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In
psychopathology Psychopathology is the study of mental illness. It includes the signs and symptoms of all mental disorders. The field includes Abnormal psychology, abnormal cognition, maladaptive behavior, and experiences which differ according to social norms ...
, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are
delusion A delusion is a fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some other m ...
s,
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s, and disorganized or incoherent thoughts or speech. Psychosis is a description of a person's state or symptoms, rather than a particular mental illness, and it is not related to
psychopathy Psychopathy, or psychopathic personality, is a personality construct characterized by impaired empathy and remorse, along with bold, disinhibited, and egocentric traits. These traits are often masked by superficial charm and immunity ...
(a
personality Personality is any person's collection of interrelated behavioral, cognitive, and emotional patterns that comprise a person’s unique adjustment to life. These interrelated patterns are relatively stable, but can change over long time per ...
construct characterized by impaired
empathy Empathy is generally described as the ability to take on another person's perspective, to understand, feel, and possibly share and respond to their experience. There are more (sometimes conflicting) definitions of empathy that include but are ...
and
remorse Remorse is a distressing emotion experienced by an individual who regrets actions which they have done in the past which they deem to be shameful, hurtful, or wrong. Remorse is closely allied to guilt and self-directed resentment. When a perso ...
, along with bold,
disinhibited Disinhibition, also referred to as behavioral disinhibition, is medically recognized as an orientation towards immediate gratification, leading to impulsive behaviour driven by current thoughts, feelings, and external stimuli, without regard for ...
, and egocentric traits). Common causes of chronic (i.e. ongoing or repeating) psychosis include
schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
or
schizoaffective disorder Schizoaffective disorder is a mental disorder characterized by symptoms of both schizophrenia (psychosis) and a mood disorder, either bipolar disorder or depression. The main diagnostic criterion is the presence of psychotic symptoms for at leas ...
,
bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
, and
brain damage Brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating trauma-induced damage. A common ...
(usually as a result of
alcoholism Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...
). Acute (temporary) psychosis can also be caused by severe distress,
sleep deprivation Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either Chronic (medicine), chronic ...
,
sensory deprivation Sensory deprivation or perceptual isolation is the deliberate reduction or removal of stimuli from one or more of the senses. Simple devices such as blindfolds or hoods and earmuffs can cut off sight and hearing, while more complex devices can ...
, some
medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
s, and drug use (including
alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...
,
cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae that is widely accepted as being indigenous to and originating from the continent of Asia. However, the number of species is disputed, with as many as three species be ...
,
hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...
s, and
stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
s). Acute psychosis is termed primary if it results from a psychiatric condition and secondary if it is caused by another medical condition or drugs. The diagnosis of a mental-health condition requires excluding other potential causes. Tests can be done to check whether psychosis is caused by
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
diseases, toxins, or other health problems. Treatment may include antipsychotic medication,
psychotherapy Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of Psychology, psychological methods, particularly when based on regular Conversation, personal interaction, to help a person change behavior, increase hap ...
, and
social support Social support is the perception and actuality that one is cared for, has assistance available from other people, and, most popularly, that one is part of a supportive social network. These supportive resources can be emotional (e.g., nurturance), ...
. Early treatment appears to improve outcomes. Medications appear to have a moderate effect. Outcomes depend on the underlying cause. Psychosis is not well-understood at the
neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
level, but
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
(along with other
neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotransmitters are rele ...
) is known to play an important role. In the United States about 3% of people develop psychosis at some point in their lives. Psychosis has been described as early as the 4th century BC by
Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...
and possibly as early as 1500 BC in the
Ebers Papyrus The Ebers Papyrus, also known as Papyrus Ebers, is an Egyptian medical papyrus of herbal knowledge dating to (the late Second Intermediate Period or early New Kingdom). Among the oldest and most important medical papyri of Ancient Egypt, it ...
.


Signs and symptoms


Hallucinations

A
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
is defined as sensory perception in the absence of external stimuli. Hallucinations are different from
illusion An illusion is a distortion of the senses, which can reveal how the mind normally organizes and interprets sensory stimulation. Although illusions distort the human perception of reality, they are generally shared by most people. Illusions may ...
s and perceptual distortions, which are the misperception of external stimuli. Hallucinations may occur in any of the senses and take on almost any form. They may consist of simple sensations (such as lights, colors, sounds, tastes, or smells) or more detailed experiences (such as seeing and interacting with animals and people, hearing voices, and having complex tactile sensations). Hallucinations are generally characterized as being vivid and uncontrollable.
Auditory hallucination An auditory hallucination, or paracusia, is a form of hallucination that involves perceiving sounds without auditory stimulus. While experiencing an auditory hallucination, the affected person hears a sound or sounds that did not come from the ...
s, particularly experiences of hearing voices, are the most common and often prominent feature of psychosis. Up to 15% of the general population may experience auditory hallucinations (though not all are due to psychosis). The prevalence of auditory hallucinations in patients with schizophrenia is generally put around 70%, but may go as high as 98%. Reported prevalence in bipolar disorder ranges between 11% and 68%. During the early 20th century, auditory hallucinations were second to visual hallucinations in frequency, but they are now the most common manifestation of schizophrenia, although rates vary between cultures and regions. Auditory hallucinations are most commonly intelligible voices. When voices are present, the average number has been estimated at three. Content, like frequency, differs significantly, especially across cultures and demographics. People who experience auditory hallucinations can frequently identify the loudness, location of origin, and may settle on identities for voices. Western cultures are associated with auditory experiences concerning religious content, frequently related to sin. Hallucinations may command a person to do something potentially dangerous when combined with delusions. So-called "minor hallucinations", such as extracampine hallucinations, or false perceptions of people or movement occurring outside of one's visual field, frequently occur in neurocognitive disorders, such as Parkinson's disease. Visual hallucinations occur in roughly a third of people with schizophrenia, although rates as high as 55% are reported. The prevalence in bipolar disorder is around 15%. Content commonly involves animate objects, although perceptual abnormalities such as changes in lighting, shading, streaks, or lines may be seen. Visual abnormalities may conflict with
proprioceptive Proprioception ( ) is the sense of self-movement, force, and body position. Proprioception is mediated by proprioceptors, a type of sensory receptor, located within muscles, tendons, and joints. Most animals possess multiple subtypes of propri ...
information, and visions may include experiences such as the ground tilting. Lilliputian hallucinations are less common in schizophrenia, and are more common in various types of
encephalopathy Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...
, such as peduncular hallucinosis. A visceral hallucination, also called a cenesthetic hallucination, is characterized by visceral sensations in the absence of stimuli. Cenesthetic hallucinations may include sensations of burning, or re-arrangement of internal organs.


Delusions

Psychosis may involve
delusion A delusion is a fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some other m ...
al beliefs. A delusion is a ''fixed, false idiosyncratic belief'', which does not change even when presented with incontrovertible evidence to the contrary. Delusions are context- and culture-dependent: a belief that inhibits critical functioning and is widely considered delusional in one population may be common (and even adaptive) in another, or in the same population at a later time. Since
normative Normativity is the phenomenon in human societies of designating some actions or outcomes as good, desirable, or permissible, and others as bad, undesirable, or impermissible. A Norm (philosophy), norm in this sense means a standard for evaluatin ...
views may contradict available evidence, a belief need not contravene cultural standards in order to be considered delusional. However, the
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiat ...
considers a belief delusional only if it is not widely accepted within a cultural or subcultural context. Prevalence in schizophrenia is generally considered at least 90%, and around 50% in bipolar disorder. The DSM-5 characterizes certain delusions as "bizarre" if they are clearly implausible, or are incompatible with the surrounding cultural context. The concept of bizarre delusions has many criticisms, the most prominent being judging its presence is not highly reliable even among trained individuals. A delusion may involve diverse thematic content. The most common type is a
persecutory delusion A persecutory delusion is a type of delusional condition in which the affected person believes that harm is going to occur to oneself by a persecutor, despite a clear lack of evidence. The person may believe that they are being targeted by an ...
, in which a person believes that an entity seeks to harm them. Others include
delusions of reference Ideas of reference and delusions of reference describe the phenomenon of an individual experiencing innocuous events or mere coincidences and believing they have strong personal significance. It is "the notion that everything one perceives in the ...
(the belief that some element of one's experience represents a deliberate and specific act by or message from some other entity), delusions of grandeur (the belief that one possesses special power or influence beyond one's actual limits),
thought broadcasting Thought broadcasting is a type of Delusion, delusional condition in which the affected person believes that others can hear their inner thoughts, despite a clear lack of evidence. The person may believe that either those nearby can perceive the ...
(the belief that one's thoughts are audible) and
thought insertion Thought insertion is defined by the ICD-10 as the delusion that one's thoughts are not one's own, but rather belong to someone else and have been inserted into one's mind. The person experiencing the thought insertion delusion will not necessaril ...
(the belief that one's thoughts are not one's own). A delusion may also involve misidentification of objects, persons, or environs that the afflicted should reasonably be able to recognize; such examples include Cotard's syndrome (the belief that oneself is partly or wholly
dead Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sho ...
) and clinical lycanthropy (the belief that oneself is or has transformed into an animal). The subject matter of delusions seems to reflect the current culture in a particular time and location. For example, in the early 1900s in the United States,
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...
was a common theme in delusions. During the Second World War, it was Germany. In the
Cold War The Cold War was a period of global Geopolitics, geopolitical rivalry between the United States (US) and the Soviet Union (USSR) and their respective allies, the capitalist Western Bloc and communist Eastern Bloc, which lasted from 1947 unt ...
era, communists became a frequent focus. Now, in recent years, technology is a common subject matter of delusions. Some psychologists, such as those who practice the Open Dialogue method, believe that the content of psychosis represents an underlying thought process, that may in part, be responsible for psychosis, though the accepted medical position is that psychosis is due to a brain disorder. Historically,
Karl Jaspers Karl Theodor Jaspers (; ; 23 February 1883 – 26 February 1969) was a German-Swiss psychiatrist and philosopher who had a strong influence on modern theology, psychiatry, and philosophy. His 1913 work ''General Psychopathology'' influenced many ...
classified psychotic delusions into ''primary'' and ''secondary'' types. Primary delusions are defined as arising suddenly and not being comprehensible in terms of normal mental processes, whereas secondary delusions are typically understood as being influenced by the person's background or current situation (e.g., ethnicity, religious, superstitious, or political beliefs).


Disorganized speech/thought and Disorganized behavior

Disorganization is categorized into either disorganized speech (disorganized speech stemming from disorganized thought), and grossly disorganized motor behavior. Disorganized speech or thought, also formally called
thought disorder A thought disorder (TD) is a disturbance in cognition which affects language, thought and communication. Psychiatric and psychological glossaries in 2015 and 2017 identified thought disorders as encompassing poverty of ideas, paralogia (a reason ...
, is disorganization of thinking that is ''inferred'' from speech. Characteristics of disorganized speech include rapidly switching topics which is called derailment or loose association, switching to topics that are unrelated which is called tangential thinking, incomprehensible speech which is called incoherence and referred to as a word salad. Disorganized motor behavior includes repetitive, odd, or sometimes purposeless movement. Disorganized motor behavior rarely includes catatonia, and although it was a prominent symptom historically, it is rarely seen today. Whether this may be due to the use of historical treatments or the lack thereof is unknown.
Catatonia Catatonia is a complex syndrome most commonly seen in people with underlying mood disorders, such as major depressive disorder, or psychotic disorders, such as schizophrenia. People with catatonia exhibit abnormal movement and behaviors, wh ...
describes a profoundly agitated state in which the experience of reality is generally considered impaired. There are two primary manifestations of catatonic behavior. The classic presentation is a person who does not move or interact with the world in any way while awake. This type of catatonia presents with waxy flexibility. Waxy flexibility is when someone physically moves part of a catatonic person's body and the person stays in the position even if it is bizarre and otherwise nonfunctional (such as moving a person's arm straight up in the air and the arm staying there). The other type of catatonia is more of an outward presentation of the profoundly agitated state described above. It involves excessive and purposeless motor behaviour, as well as an extreme mental preoccupation that prevents an intact experience of reality. An example is someone walking very fast in circles to the exclusion of anything else with a level of mental preoccupation (meaning not focused on anything relevant to the situation) that was not typical of the person prior to the symptom onset. In both types of catatonia, there is generally no reaction to anything that happens outside of them. It is important to distinguish catatonic agitation from severe bipolar mania, although someone could have both.


Negative symptoms

Negative symptoms include reduced emotional expression, decreased motivation (
avolition Avolition or amotivation, as a symptom of various forms of psychopathology, is the decrease in the ability to initiate and persist in self-directed purposeful activities. Such activities that appear to be neglected usually include routine activit ...
), and reduced spontaneous speech (poverty of speech, alogia). Individuals with this condition lack interest and spontaneity, and have the inability to feel pleasure (
anhedonia Anhedonia is a diverse array of deficits in hedonic function, including reduced motivation or ability to experience pleasure. While earlier definitions emphasized the inability to experience pleasure, anhedonia is currently used by researcher ...
). Altered Behavioral Inhibition System functioning could possibly cause reduced sustained attention in psychosis and overall contribute to more negative reactions.


Psychosis in adolescents

Psychosis is relatively rare in adolescents but not uncommon. Young people who have psychosis may have trouble connecting with the world around them and may experience hallucinations or delusions. Adolescents with psychosis may also have cognitive deficits that may make it harder for the youth to socialize and work. Potential impairments include a reduced speed of mental processing, the lack of ability to focus without getting distracted (limited
attention span Attention span is the amount of time spent concentrating on a task before becoming distracted. Distractibility occurs when attention is uncontrollably diverted to another activity or sensation. ''Attention training'' is said to be part of educa ...
), and deficits in verbal memory. If an adolescent is experiencing psychosis, they most likely have comorbidity, meaning that they could have multiple mental illnesses. Because of this, it may be difficult to determine whether it is psychosis or autism spectrum disorder, social or generalized anxiety disorder, or obsessive-compulsive disorder.


Causes

The symptoms of psychosis may be caused by serious
psychiatric disorders A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...
such as
schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
, a number of medical illnesses, and trauma. Psychosis may also be temporary or transient, and be caused by medications or
substance use disorder Substance use disorder (SUD) is the persistent use of drugs despite substantial harm and adverse consequences to self and others. Related terms include ''substance use problems'' and ''problematic drug or alcohol use''. Along with substance-ind ...
( substance-induced psychosis).


Normal states

Brief hallucinations are not uncommon in those without any psychiatric disease, including healthy children. Causes or triggers include: * Falling asleep and waking: hypnagogic and
hypnopompic Hypnopompia (also known as hypnopompic state) is the state of consciousness leading out of sleep, a term coined by the psychical researcher Frederic William Henry Myers, Frederic Myers. Its mirror is the hypnagogic state at sleep onset; though ...
hallucinations * Bereavement, in which hallucinations of a deceased loved one are common * Severe
sleep deprivation Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either Chronic (medicine), chronic ...
* Extreme stress (see below) * Abnormal brainwaves * Abnormal brain networks *
Traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity ranging from mild traumatic brain injury (mTBI/concussion) to severe traumati ...


Trauma and stress

Traumatic life events have been linked with an elevated risk of developing psychotic symptoms. Childhood trauma has specifically been shown to be a predictor of adolescent and adult psychosis. Individuals with psychotic symptoms are three times more likely to have experienced childhood trauma (e.g., physical or sexual abuse, physical or emotional neglect) than those in the general population. Increased individual vulnerability toward psychosis may interact with traumatic experiences promoting an onset of future psychotic symptoms, particularly during sensitive developmental periods. Importantly, the relationship between traumatic life events and psychotic symptoms appears to be dose-dependent in which multiple traumatic life events accumulate, compounding symptom expression and severity. However, acute, stressful events can also trigger brief psychotic episodes. Trauma prevention and early intervention may be an important target for decreasing the incidence of psychotic disorders and ameliorating its effects. A healthy person could become psychotic if he or she is placed in an empty room with no light and sound. After about 15 minutes, psychosis can occur, this is a phenomenon known as
sensory deprivation Sensory deprivation or perceptual isolation is the deliberate reduction or removal of stimuli from one or more of the senses. Simple devices such as blindfolds or hoods and earmuffs can cut off sight and hearing, while more complex devices can ...
.
Neuroticism Neuroticism is a personality trait associated with negative emotions. It is one of the Big Five traits. Individuals with high scores on neuroticism are more likely than average to experience such feelings as anxiety, worry, fear, anger, shame ...
, a personality trait associated with vulnerability to stressors, is an independent predictor of the development of psychosis.


Psychiatric disorders

Traditionally psychotic disorders have been believed to have one of two roots: organic or functional. Organic disorders being those caused by physical conditions directly affecting the brain with psychosis as a secondary feature, and functional disorders being primary psychological or psychiatric disorders (disorders of the functioning of the mind) in the absence of physiological causes. Subtle physical abnormalities have been found in illnesses traditionally considered functional, such as
schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
. The
DSM-IV-TR The ''Diagnostic and Statistical Manual of Mental Disorders'' (''DSM''; latest edition: ''DSM-5-TR'', published in March 2022) is a publication by the American Psychiatric Association (APA) for the classification of mental disorders using a c ...
avoids the functional/organic distinction, and instead lists traditional psychotic illnesses, psychosis due to general medical conditions, and substance-induced psychosis. Primary psychiatric causes of psychosis include the following:
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

''The ICD-10 Classification of Mental and Behavioural Disorders: Clinical descriptions and diagnostic guidelines (CDDG)''
, 1992.
*
schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
*
mood disorders A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where the main underlying characteristic is a disturbance in the person's mood. The classification is in the ''Diagnostic ...
including
psychotic depression Psychotic depression, also known as depressive psychosis, is a major depressive episode that is accompanied by psychotic symptoms.Hales E and Yudofsky JA, eds, The American Psychiatric Press Textbook of Psychiatry, Washington, DC: American Psych ...
and
bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
in the manic and mixed episodes of
bipolar I disorder Bipolar I disorder (BD-I; pronounced "type one bipolar disorder") is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other ti ...
and depressive episodes of both bipolar I and bipolar II *
schizoaffective disorder Schizoaffective disorder is a mental disorder characterized by symptoms of both schizophrenia (psychosis) and a mood disorder, either bipolar disorder or depression. The main diagnostic criterion is the presence of psychotic symptoms for at leas ...
*
delusional disorder Delusional disorder, traditionally synonymous with paranoia, is a mental illness in which a person has delusions, but with no accompanying prominent hallucinations, thought disorder, mood disorder, or significant flattening of affect. Ameri ...
* brief psychotic disorder *
schizophreniform disorder Schizophreniform disorder is a mental disorder diagnosed when symptoms of schizophrenia are present for a significant portion of time (at least a month), but signs of disturbance are not present for the full six months required for the diagnosis ...
Psychotic symptoms may also be seen in: *
Personality disorders Personality disorders (PD) are a class of mental health conditions characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the culture. T ...
including
Schizotypal personality disorder Schizotypal personality disorder (StPD or SPD), also known as schizotypal disorder, is a cluster A personality disorder, cluster A personality disorder characterized by thought disorder, paranoia, a characteristic form of social anxiety, dereali ...
and
borderline personality disorder Borderline personality disorder (BPD) is a personality disorder characterized by a pervasive, long-term pattern of significant interpersonal relationship instability, an acute fear of Abandonment (emotional), abandonment, and intense emotiona ...
*
Post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...
*
obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental disorder in which an individual has intrusive thoughts (an ''obsession'') and feels the need to perform certain routines (''Compulsive behavior, compulsions'') repeatedly to relieve the dis ...
* dissociative identity disorder * paraphrenia


Subtypes

Subtypes of psychosis include: * Postpartum psychosis, occurring shortly after giving birth, primarily associated with maternal
bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
* Monothematic delusions * Myxedematous psychosis *
Stimulant psychosis Stimulant psychosis is a mental disorder characterized by psychotic symptoms such as hallucinations, paranoid ideation, delusions, disorganized thinking, and grossly disorganized behaviour. It typically occurs following an overdose or several ...
* Tardive psychosis * Shared psychosis


Cycloid psychosis

Cycloid psychosis is typically an acute, self-limiting form of psychosis with psychotic and mood symptoms that progress from normal to full-blown, usually between a few hours to days, and not related to drug intake or
brain injury Brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating trauma-induced damage. A common ...
. While proposed as a distinct entity, clinically separate from schizophrenia and affective disorders, cycloid psychosis is not formally acknowledged by current ICD or DSM criteria. Its unclear place in psychiatric nosology has likely contributed to the limited scientific investigation and literature on the topic.


Postpartum psychosis

Postpartum psychosis is a rare yet serious and debilitating form of psychosis. Symptoms range from fluctuating moods and insomnia to mood-incongruent delusions related to the individual or the infant. Women experiencing postpartum psychosis are at increased risk for suicide or infanticide. Many women who experience first-time psychosis from postpartum often have bipolar disorder, meaning they could experience an increase of psychotic episodes even after postpartum.


Medical conditions

A very large number of medical conditions can cause psychosis, sometimes called ''secondary psychosis''. Examples include: * disorders causing ''
delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...
'' (''toxic psychosis''), in which consciousness is disturbed * neurodevelopmental disorders and chromosomal abnormalities, including velocardiofacial syndrome * neurodegenerative disorders, such as
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
,
dementia with Lewy bodies Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior change (individual), behavior, cognition, movement, and dysautonomia, regulation of automatic bodily functions. Unlike some other dementias, mem ...
, and
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
* focal neurological disease, such as
stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
,
brain tumor A brain tumor (sometimes referred to as brain cancer) occurs when a group of cells within the Human brain, brain turn cancerous and grow out of control, creating a mass. There are two main types of tumors: malignant (cancerous) tumors and benign ...
s,
multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...
, and some forms of
epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...
* malignancy (typically via masses in the brain, paraneoplastic syndromes) * infectious and postinfectious syndromes, including infections causing
delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...
,
viral encephalitis Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningiti ...
,
HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
,
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
,
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...
* endocrine disease, such as
hypothyroidism Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...
,
hyperthyroidism Hyperthyroidism is a endocrine disease in which the thyroid gland produces excessive amounts of thyroid hormones. Thyrotoxicosis is a condition that occurs due to elevated levels of thyroid hormones of any cause and therefore includes hyperth ...
,
Cushing's syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...
,
hypoparathyroidism Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary m ...
and
hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands ( primary hyperparathyroidism) or as response to external stimuli ( secondary hyperparathyroi ...
; sex hormones also affect psychotic symptoms and sometimes giving birth can provoke psychosis, termed postpartum psychosis * inborn errors of metabolism, such as Wilson's disease, porphyria, and homocysteinemia. * nutritional deficiency, such as
vitamin B12 deficiency Vitamins are organic molecules (or a set of closely related molecules called vitamers) that are essential to an organism in small quantities for proper metabolic function. Essential nutrients cannot be synthesized in the organism in suff ...
* other acquired metabolic disorders, including
electrolyte An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble Salt (chemistry), salts, acids, and Base (chemistry), bases, dissolved in a polar solven ...
disturbances such as
hypocalcemia Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6  mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), while levels less than 2.1  ...
,
hypernatremia Hypernatremia, also spelled hypernatraemia, is a high concentration of sodium in the blood. Early symptoms may include a strong feeling of thirst, weakness, nausea, and loss of appetite. Severe symptoms include confusion, muscle twitching, and ...
,
hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the Serum (blood), blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symp ...
,
hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an a ...
,
hypomagnesemia Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, and nystagmus. Complications may in ...
, hypermagnesemia,
hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L def ...
, and
hypophosphatemia Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Symptoms may include weakness, trouble breathing, and loss of appetite. Complications may include seizures, coma, rhabdomyolysis, or soft ...
, but also
hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...
, hypoxia, and failure of the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
or
kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
s *
autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...
and related disorders, such as
systemic lupus erythematosus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...
(lupus, SLE),
sarcoidosis Sarcoidosis (; also known as Besnier–Boeck–Schaumann disease) is a disease involving abnormal collections of White blood cell, inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph n ...
, Hashimoto's encephalopathy, anti-NMDA-receptor encephalitis, and
non-celiac gluten sensitivity Non-celiac gluten sensitivity (NCGS) or gluten sensitivity is a controversial disorder which can cause both gastrointestinal and other problems. NCGS is included in the spectrum of gluten-related disorders. The definition and diagnostic criteria ...
* poisoning by a range of plants, fungi, metals, organic compounds, and a few animal toxins * sleep disorders, such as in
narcolepsy Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep. The symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-r ...
(in which
REM sleep Rapid eye movement sleep (REM sleep or REMS) is a unique phase of sleep in mammals (including humans) and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the s ...
intrudes into wakefulness) * parasitic diseases, such as
neurocysticercosis Neurocysticercosis (NCC) is a Parasitic disease, parasitic infection of the central nervous system, nervous system caused by the larvae of the tapeworm ''Taenia solium,'' also known as the "pork tapeworm". The disease is primarily transmitted ...


Psychoactive drugs

Various psychoactive substances (both legal and illegal) have been implicated in causing, exacerbating, or precipitating psychotic states or disorders in users, with varying levels of evidence. This may be upon intoxication for a more prolonged period after use, or upon withdrawal. Individuals who experience substance-induced psychosis tend to have a greater awareness of their psychosis and tend to have higher levels of suicidal thinking compared to those who have a primary psychotic illness. Drugs commonly alleged to induce psychotic symptoms include
alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...
,
cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae that is widely accepted as being indigenous to and originating from the continent of Asia. However, the number of species is disputed, with as many as three species be ...
,
cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
,
amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
s,
cathinone Cathinone (; also known as β-ketoamphetamine) is a monoamine alkaloid found in the shrub ''Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the main contributor to t ...
s,
psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluc ...
s (such as
LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...
and
psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...
),
κ-opioid receptor The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP for its ligand ketazocine, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four re ...
agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
s (such as enadoline and
salvinorin A Salvinorin A is the main active psychotropic molecule in '' Salvia divinorum''. Salvinorin A is considered an atypical dissociative hallucinogen. It is structurally distinct from other naturally occurring hallucinogens (such as DMT, psil ...
) and
NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to receptor antagonist, antagonize, or inhibit the action of, the NMDA, ''N''-Methyl-D-aspartate receptor (NMDA receptor, NMDAR). They are commonly used as anesthetics for humans and anima ...
s (such as
phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hall ...
and
ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...
).
Caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...
may worsen symptoms in those with schizophrenia and cause psychosis at very high doses in people without the condition. Cannabis and other illicit recreational drugs are often associated with psychosis in adolescents and cannabis use before 15 years old may increase the risk of psychosis in adulthood.


Alcohol

Approximately three percent of people with
alcoholism Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...
experience psychosis during acute intoxication or withdrawal. Alcohol related psychosis may manifest itself through a kindling mechanism. The mechanism of alcohol-related psychosis is due to the
long-term effects of alcohol consumption The long-term effects of alcohol consumption on health are predominantly detrimental, with the severity and range of harms generally increasing with the cumulative amount of alcohol consumed over a lifetime. The extent of these effects varies depen ...
resulting in distortions to neuronal membranes,
gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...
, as well as
thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin – an Nutrient#Micronutrients, essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosp ...
deficiency. It is possible that hazardous alcohol use via a kindling mechanism can cause the development of a chronic substance-induced psychotic disorder, i.e. schizophrenia. The effects of an alcohol-related psychosis include an increased risk of depression and suicide as well as causing psychosocial impairments.
Delirium tremens Delirium tremens (DTs; ) is a rapid onset of confusion usually caused by withdrawal from alcohol. When it occurs, it is often three days into the withdrawal symptoms and lasts for two to three days. Physical effects may include shaking, sh ...
, a symptom of chronic alcoholism that can appear in the acute withdrawal phase, shares many symptoms with alcohol-related psychosis suggesting a common mechanism.


Cannabis

According to current studies, cannabis use is associated with increased risk of psychotic disorders, and the more often cannabis is used the more likely a person is to develop a psychotic illness. Furthermore, people with a history of cannabis use develop psychotic symptoms earlier than those who have never used cannabis. Some debate exists regarding the causal relationship between cannabis use and psychosis with some studies suggesting that cannabis use hastens the onset of psychosis primarily in those with pre-existing vulnerability. Indeed, cannabis use plays an important role in the development of psychosis in vulnerable individuals, and cannabis use in adolescence should be discouraged. Some studies indicate that the effects of two active compounds in cannabis,
tetrahydrocannabinol Tetrahydrocannabinol (THC) is a cannabinoid found in cannabis. It is the principal psychoactive constituent of ''Cannabis'' and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) de ...
(THC) and
cannabidiol Cannabidiol (CBD) is a phytocannabinoid, one of 113 identified cannabinoids in ''Cannabis'', along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. Medically, it is an anticonvulsant used to treat multiple f ...
(CBD), have opposite effects with respect to psychosis. While THC can induce psychotic symptoms in healthy individuals, limited evidence suggests that CBD may have antipsychotic effects.


Methamphetamine

Methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...
induces a psychosis in 26–46 percent of heavy users. Some of these people develop a long-lasting psychosis that can persist for longer than six months. Those who have had a short-lived psychosis from methamphetamine can have a relapse of the methamphetamine psychosis years later after a stressful event such as severe insomnia or a period of hazardous alcohol use despite not relapsing back to methamphetamine. Individuals who have a long history of methamphetamine use and who have experienced psychosis in the past from methamphetamine use are highly likely to re-experience methamphetamine psychosis if drug use is recommenced. Methamphetamine-induced psychosis is likely gated by genetic vulnerability, which can produce long-term changes in brain neurochemistry following repetitive use. Methamphetamine users with more ADHD-related behaviours in childhood experience methamphetamine-related psychosis more frequently.


Psychedelics

A 2024 meta-analysis found an incidence of psychedelic-induced psychosis at 0.002% in population studies, 0.2% in uncontrolled clinical trials, and 0.6% in randomised controlled trials. This meta-analysis found that in uncontrolled clinical trials involving only patients with schizophrenia, 3.8% developed prolonged psychotic reactions. A 2024 study found that psychedelic use was not generally associated with a change in the number of psychotic symptoms. This study found that psychedelic use interacted with a family history of bipolar disorder, such that in those with a family history of bipolar disorder, psychedelic use was associated with an increase in the number of psychotic symptoms, while in those with a personal history of psychosis but no family history of psychotic disorders, psychedelic use was associated with a decrease in the number of psychotic symptoms. A 2023 study found an interaction between lifetime psychedelic use and family history of psychosis or bipolar disorder on psychotic symptoms over the past two weeks. Psychotic symptoms were highest among individuals with both a family history of psychosis or bipolar disorder and lifetime psychedelic use, while they were lowest among those with lifetime psychedelic use but no family history of these disorders.


Medication

Administration, or sometimes withdrawal, of a large number of medications may provoke psychotic symptoms. Drugs that can induce psychosis experimentally or in a significant proportion of people include: * stimulants, such as
amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
and other sympathomimetics, *
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
agonists, *
ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...
, *
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
s (often with mood changes in addition), * and some anticonvulsants such as vigabatrin.


Pathophysiology


Neuroimaging

The first brain image of an individual with psychosis was completed as far back as 1935 using a technique called
pneumoencephalography Pneumoencephalography (sometimes abbreviated PEG; also referred to as an "air study") was a common medical procedure in which most of the cerebrospinal fluid (CSF) was drained from around the brain by means of a lumbar puncture and replaced with ...
(a painful and now obsolete procedure where
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
is drained from around the brain and replaced with air to allow the structure of the brain to show up more clearly on an
X-ray An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...
picture). Both first episode psychosis, and high risk status is associated with reductions in grey matter volume (GMV). First episode psychotic and high risk populations are associated with similar but distinct abnormalities in GMV. Reductions in the right middle temporal gyrus, right
superior temporal gyrus The superior temporal gyrus (STG) is one of three (sometimes two) gyri in the temporal lobe of the human brain, which is located laterally to the head, situated somewhat above the external ear. The superior temporal gyrus is bounded by: * the l ...
(STG), right parahippocampus, right
hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
, right
middle frontal gyrus The middle frontal gyrus makes up about one-third of the frontal lobe of the human brain. (A gyrus is one of the prominent "bumps" or "ridges" on the cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer la ...
, and left
anterior cingulate cortex In human brains, the anterior cingulate cortex (ACC) is the frontal part of the cingulate cortex that resembles a "collar" surrounding the frontal part of the corpus callosum. It consists of Brodmann areas 24, 32, and 33. It is involved ...
(ACC) are observed in high risk populations. Reductions in first episode psychosis span a region from the right STG to the right insula, left insula, and cerebellum, and are more severe in the right ACC, right STG, insula and cerebellum. Another meta analysis reported bilateral reductions in insula, operculum, STG, medial frontal cortex, and ACC, but also reported increased GMV in the right
lingual gyrus The lingual gyrus, also known as the ''medial'' occipitotemporal gyrus, is a brain structure that is linked to processing vision, especially related to letters. It is thought to also play a role in analysis of logical conditions (i.e., logical or ...
and left
precentral gyrus The precentral gyrus is a prominent gyrus on the surface of the posterior frontal lobe of the brain. It is the site of the primary motor cortex that in humans is cytoarchitecturally defined as Brodmann area 4. Structure The precentral gyrus li ...
. The Kraepelinian dichotomy is made questionable by grey matter abnormalities in bipolar and schizophrenia; schizophrenia is distinguishable from bipolar in that regions of grey matter reduction are generally larger in magnitude, although adjusting for gender differences reduces the difference to the left
dorsomedial prefrontal cortex The dorsomedial prefrontal cortex (dmPFC or DMPFC is a section of the prefrontal cortex in some species' brain anatomy. It includes portions of Brodmann areas BA8, BA9, BA10, BA24 and BA32, although some authors identify it specifically w ...
, and right
dorsolateral prefrontal cortex The dorsolateral prefrontal cortex (DLPFC or DL-PFC) is an area in the prefrontal cortex of the primate brain. It is one of the most recently derived parts of the human brain. It undergoes a prolonged period of maturation which lasts into adulthoo ...
. During attentional tasks, first episode psychosis is associated with hypoactivation in the right middle frontal gyrus, a region generally described as encompassing the dorsolateral prefrontal cortex (dlPFC).Altered Behavioral Inhibition System functioning could possibly cause reduced sustained attention in psychosis and overall contribute to more negative reactions. In congruence with studies on grey matter volume, hypoactivity in the right insula, and right inferior parietal lobe is also reported. During cognitive tasks, hypoactivities in the right insula, dACC, and the left precuneus, as well as reduced deactivations in the right
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
, right
thalamus The thalamus (: thalami; from Greek language, Greek Wikt:θάλαμος, θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the wikt:dorsal, dorsal part of the diencephalon (a division of ...
, right inferior frontal and left precentral gyri are observed. These results are highly consistent and replicable possibly except the abnormalities of the right inferior frontal gyrus. Decreased grey matter volume in conjunction with bilateral hypoactivity is observed in anterior insula, dorsal medial frontal cortex, and dorsal ACC. Decreased grey matter volume and bilateral hyperactivity is reported in posterior insula, ventral medial frontal cortex, and ventral ACC.


Hallucinations

Studies during acute experiences of hallucinations demonstrate increased activity in primary or secondary sensory cortices. As auditory hallucinations are most common in psychosis, most robust evidence exists for increased activity in the left middle temporal gyrus, left
superior temporal gyrus The superior temporal gyrus (STG) is one of three (sometimes two) gyri in the temporal lobe of the human brain, which is located laterally to the head, situated somewhat above the external ear. The superior temporal gyrus is bounded by: * the l ...
, and left
inferior frontal gyrus The inferior frontal gyrus (IFG; also gyrus frontalis inferior) is the lowest positioned gyrus of the frontal gyri, of the frontal lobe, and is part of the prefrontal cortex. Its superior border is the inferior frontal sulcus (which divides it ...
(i.e.
Broca's area Broca's area, or the Broca area (, also , ), is a region in the frontal lobe of the dominant Cerebral hemisphere, hemisphere, usually the left, of the Human brain, brain with functions linked to speech production. Language processing in the brai ...
). Activity in the
ventral striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamater ...
,
hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
, and ACC are related to the lucidity of hallucinations, and indicate that activation or involvement of emotional circuitry are key to the impact of abnormal activity in sensory cortices. Together, these findings indicate abnormal processing of internally generated sensory experiences, coupled with abnormal emotional processing, results in hallucinations. One proposed model involves a failure of feedforward networks from sensory cortices to the inferior frontal cortex, which normally cancel out sensory cortex activity during internally generated speech. The resulting disruption in expected and perceived speech is thought to produce lucid hallucinatory experiences.


Delusions

The two-factor model of delusions posits that dysfunction in both belief formation systems and belief evaluation systems are necessary for delusions. Dysfunction in evaluations systems localized to the right lateral prefrontal cortex, regardless of delusion content, is supported by neuroimaging studies and is congruent with its role in conflict monitoring in healthy persons. Abnormal activation and reduced volume is seen in people with delusions, as well as in disorders associated with delusions such as
frontotemporal dementia Frontotemporal dementia (FTD), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of the brain's frontal lobe, frontal and tempor ...
, psychosis and
Lewy body dementia Lewy body dementia (LBD) is an umbrella term for two similar and common subtypes of dementia: dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Both are characterized by changes in thinking, movement, behavior, and mood. The ...
. Furthermore, lesions to this region are associated with "jumping to conclusions", damage to this region is associated with post-stroke delusions, and hypometabolism this region associated with caudate strokes presenting with delusions. The aberrant salience model suggests that delusions are a result of people assigning excessive importance to irrelevant stimuli. In support of this hypothesis, regions normally associated with the
salience network The salience network (SN), also referred to as the midcingulo-insular network (M-CIN) or cingulo-opercular network in anatomical parcellation schemes, is a large scale network of the human brain that is primarily composed of the anterior insula ...
demonstrate reduced grey matter in people with delusions, and the neurotransmitter
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
, which is widely implicated in salience processing, is also widely implicated in psychotic disorders. Specific regions have been associated with specific types of delusions. The volume of the hippocampus and parahippocampus is related to paranoid delusions in
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
, and has been reported to be abnormal post mortem in one person with delusions. Capgras delusions have been associated with occipito-temporal damage, and may be related to failure to elicit normal emotions or memories in response to faces.


Negative symptoms

Psychosis is associated with
ventral striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamater ...
(VS), which is the part of the brain that is involved with the desire to naturally satisfy the body's needs. When high reports of
negative symptoms Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...
were recorded, there were significant irregularities in the left VS. Anhedonia, the inability to feel pleasure, is a commonly reported symptom in psychosis; experiences are present in most people with schizophrenia. Anhedonia arises as a result of the inability to feel motivation and drive towards both the desire to engage in as well as to complete tasks and goals. Previous research has indicated that a deficiency in the neural representation in regards to goals and the motivation to achieve them, has demonstrated that when a reward is not present, a strong reaction is noted in the ventral striatum; reinforcement learning is intact when contingencies about stimulus-reward are implicit, but not when they require explicit neural processing; reward prediction errors are what the actual reward is versus what the reward was predicted to be. In most cases positive prediction errors are considered an abnormal occurrence. A positive prediction error response occurs when there is an increased activation in a brain region, typically the
striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
, in response to unexpected rewards. A negative prediction error response occurs when there is a decreased activation in a region when predicted rewards do not occur. Anterior Cingulate Cortex (ACC) response, taken as an indicator of effort allocation, does not increase with reward or reward probability increase, and is associated with negative symptoms; deficits in Dorsolateral Prefrontal Cortex (dlPFC) activity and failure to improve performance on cognitive tasks when offered monetary incentives are present; and dopamine mediated functions are abnormal.


Neurobiology

Psychosis has been traditionally linked to the overactivity of the
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
, in particular to its effect in the
mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The v ...
, spanning from the
ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is th ...
to the ventral
striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
. Additionally, recent evidence suggests a crucial involvement of the pathway spanning from the
substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra a ...
to the dorsal
striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
. The two major sources of evidence given to support this theory are that
dopamine receptor D2 Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, ...
blocking drugs (i.e.,
antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...
s) tend to reduce the intensity of psychotic symptoms, and that drugs that accentuate dopamine release, or inhibit its reuptake (such as
amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
s and
cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
) can trigger psychosis in some people (see
stimulant psychosis Stimulant psychosis is a mental disorder characterized by psychotic symptoms such as hallucinations, paranoid ideation, delusions, disorganized thinking, and grossly disorganized behaviour. It typically occurs following an overdose or several ...
). However, there is substantial evidence that dopaminergic overactivity does not fully explain psychosis, and that neurodegerative pathophysiology plays a significant role. This is evidenced by the fact that psychosis commonly occurs in neurodegenerative diseases of the dopaminergic nervous system, such as Parkinson's disease, which involved reduced, rather than increased, dopaminergic activity. The
endocannabinoid system The endocannabinoid system (ECS) is a biological system composed of endocannabinoids, which are neurotransmitters that bind to cannabinoid receptors, and cannabinoid receptor proteins that are expressed throughout the central nervous system ( ...
is also implicated in psychosis. This is evidenced by the propensity of CB1 receptor agonists such as THC to induce psychotic symptoms, and the efficacy of CB1 receptor antagonists such as CBD in ameliorating psychosis. NMDA receptor dysfunction has been proposed as a mechanism in psychosis. This theory is reinforced by the fact that
dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens that distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...
NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to receptor antagonist, antagonize, or inhibit the action of, the NMDA, ''N''-Methyl-D-aspartate receptor (NMDA receptor, NMDAR). They are commonly used as anesthetics for humans and anima ...
s such as
ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...
, PCP and
dextromethorphan Dextromethorphan, sold under the brand name Robitussin among others, is a cough suppressant used in many cough and Common cold, cold medicines. In 2022, the US Food and Drug Administration (FDA) approved the combination dextromethorphan/bupropi ...
(at large overdoses) induce a psychotic state. The symptoms of dissociative intoxication are also considered to mirror the symptoms of schizophrenia, including
negative symptoms Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...
. NMDA receptor antagonism, in addition to producing symptoms reminiscent of psychosis, mimics the neurophysiological aspects, such as reduction in the amplitude of P50, P300, and MMN
evoked potential An evoked potential or evoked response is an electrical potential in a specific pattern recorded from a specific part of the nervous system, especially the brain, of a human or other animals following presentation of a stimulus such as a light fl ...
s. Hierarchical Bayesian neurocomputational models of sensory feedback, in agreement with neuroimaging literature, link NMDA receptor hypofunction to delusional or hallucinatory symptoms via proposing a failure of NMDA mediated top down predictions to adequately cancel out enhanced bottom up AMPA mediated predictions errors. Excessive prediction errors in response to stimuli that would normally not produce such a response is thought to root from conferring excessive salience to otherwise mundane events. Dysfunction higher up in the hierarchy, where representation is more abstract, could result in delusions. The common finding of reduced GAD67 expression in psychotic disorders may explain enhanced AMPA mediated signaling, caused by reduced GABAergic inhibition. The connection between dopamine and psychosis is generally believed to be complex. While dopamine receptor D2 suppresses
adenylate cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...
activity, the D1 receptor increases it. If D2-blocking drugs are administered, the blocked dopamine spills over to the D1 receptors. The increased adenylate cyclase activity affects genetic expression in the nerve cell, which takes time. Hence antipsychotic drugs take a week or two to reduce the symptoms of psychosis. Moreover, newer and equally effective antipsychotic drugs actually block slightly less dopamine in the brain than older drugs whilst also blocking 5-HT2A receptors, suggesting the 'dopamine hypothesis' may be oversimplified. Soyka and colleagues found no evidence of dopaminergic dysfunction in people with alcohol-induced psychosis and Zoldan et al. reported moderately successful use of
ondansetron Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by chemotherapy, radiation therapy, migraines, or surgery. It is also effective for treating gastroenteritis. It can be giv ...
, a 5-HT3 receptor antagonist, in the treatment of
levodopa Levodopa, also known as L-DOPA and sold under many brand names, is a dopaminergic medication which is used in the treatment of Parkinson's disease (PD) and certain other conditions like dopamine-responsive dystonia and restless legs syndrome. ...
psychosis in
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
patients. A review found an association between a first-episode of psychosis and prediabetes. Prolonged or high dose use of
psychostimulants Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...
can alter normal functioning, making it similar to the manic phase of bipolar disorder. NMDA antagonists replicate some of the so-called "negative" symptoms like
thought disorder A thought disorder (TD) is a disturbance in cognition which affects language, thought and communication. Psychiatric and psychological glossaries in 2015 and 2017 identified thought disorders as encompassing poverty of ideas, paralogia (a reason ...
in subanesthetic doses (doses insufficient to induce
anesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...
), and
catatonia Catatonia is a complex syndrome most commonly seen in people with underlying mood disorders, such as major depressive disorder, or psychotic disorders, such as schizophrenia. People with catatonia exhibit abnormal movement and behaviors, wh ...
in high doses. Psychostimulants, especially in one already prone to psychotic thinking, can cause some "positive" symptoms, such as delusional beliefs, particularly those persecutory in nature.


Culture

Cross-cultural studies into schizophrenia have found that individual experiences of psychosis and 'hearing voices' vary across cultures. In countries such as the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
where there exists a predominantly biomedical understanding of the body, the mind and in turn, mental health, subjects were found to report their hallucinations as having 'violent content' and self-describing as 'crazy'. This lived experience is at odds with the lived experience of subjects in Accra, Ghana, who describe the voices they hear as having 'spiritual meaning' and are often reported as positive in nature; or subjects in Chennai, India, who describe their hallucinations as kin, family members or close friends, and offering guidance. These differences are attributed to 'social kindling' or how one's social context shapes how an individual interprets and experiences sensations such as hallucinations. This concept aligns with pre-existing cognitive theory such as reality modelling and is supported by recent research that demonstrates that individuals with psychosis can be taught to attend to their hallucinations differently, which in turn alters the hallucinations themselves. Such research creates pathways for social or community-based treatment, such as reality monitoring, for individuals with schizophrenia and other psychotic disorders, providing alternatives to, or supplementing traditional pharmacologic management. Cross-cultural studies explore the way in which psychosis varies in different cultures, countries and religions. The cultural differences are based on the individual or shared illness narratives surrounding cultural meanings of illness experience.Jenkins J (2018) 'Anthropology and Psychiatry: A contemporary convergence for global mental health', in Bhugra D and Bhui K (eds) Textbook of Cultural Psychiatry, 2nd edn, Cambridge University Press, London. In countries such as
India India, officially the Republic of India, is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area; the List of countries by population (United Nations), most populous country since ...
,
Cambodia Cambodia, officially the Kingdom of Cambodia, is a country in Southeast Asia on the Mainland Southeast Asia, Indochinese Peninsula. It is bordered by Thailand to the northwest, Laos to the north, and Vietnam to the east, and has a coastline ...
and
Muslim Muslims () are people who adhere to Islam, a Monotheism, monotheistic religion belonging to the Abrahamic religions, Abrahamic tradition. They consider the Quran, the foundational religious text of Islam, to be the verbatim word of the God ...
majority countries, they each share alternative epistemologies. These are known as knowledge systems that focus on the connections between mind, body, culture, nature, and society. Cultural perceptions of mental disorders such as psychosis or schizophrenia are believed to be caused by
jinn Jinn or djinn (), alternatively genies, are supernatural beings in pre-Islamic Arabian religion and Islam. Their existence is generally defined as parallel to humans, as they have free will, are accountable for their deeds, and can be either ...
(spirits) in Muslim majority countries. Furthermore, those in
Arab Arabs (,  , ; , , ) are an ethnic group mainly inhabiting the Arab world in West Asia and North Africa. A significant Arab diaspora is present in various parts of the world. Arabs have been in the Fertile Crescent for thousands of years ...
-Muslim societies perceive those who act differently than the social norm as "crazy" or as abnormal behaviour. This differs from the lived experience of individuals in India and how they attain their perspectives on mental health issues through a variety of spiritual and healing traditions. In Cambodia, hallucinations are linked with spirit visitation, a term they call "cultural kindling". These examples of differences are attributed to culture and the way it shapes conceptions of mental disorders. These cultural differences can be useful in bridging the gap of cultural understanding and psychiatric signs and symptoms.


Diagnosis

To make a diagnosis of a mental illness in someone with psychosis other potential causes must be excluded. An initial assessment includes a comprehensive history and physical examination by a health care provider. Tests may be done to exclude substance use, medication, toxins, surgical complications, or other medical illnesses. A person with psychosis is referred to as psychotic.
Delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...
should be ruled out, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, indicating other underlying factors, including medical illnesses. Excluding medical illnesses associated with psychosis is performed by using blood tests to measure: * thyroid-stimulating hormone to exclude hypo- or
hyperthyroidism Hyperthyroidism is a endocrine disease in which the thyroid gland produces excessive amounts of thyroid hormones. Thyrotoxicosis is a condition that occurs due to elevated levels of thyroid hormones of any cause and therefore includes hyperth ...
, * vitamin B12 serum and urinary
MMA Mixed martial arts (MMA) is a full-contact fighting sport based on striking and grappling; incorporating techniques from various combat sports from around the world. In the early 20th century, various inter-stylistic contests took place t ...
to role out
pernicious anemia Pernicious anemia is a disease where not enough red blood cells are produced due to a deficiency of Vitamin B12, vitamin B12. Those affected often have a gradual onset. The most common initial symptoms are Fatigue, feeling tired and weak. Other ...
or
vitamin B12 deficiency Vitamins are organic molecules (or a set of closely related molecules called vitamers) that are essential to an organism in small quantities for proper metabolic function. Essential nutrients cannot be synthesized in the organism in suff ...
, * basic electrolytes and serum calcium to rule out a metabolic disturbance, *
full blood count A complete blood count (CBC), also known as a full blood count (FBC) or full haemogram (FHG), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blo ...
including ESR to rule out a systemic infection or chronic disease, and *
serology Serology is the scientific study of Serum (blood), serum and other body fluids. In practice, the term usually refers to the medical diagnosis, diagnostic identification of Antibody, antibodies in the serum. Such antibodies are typically formed in r ...
to exclude
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...
or HIV infection. Other investigations include: * EEG to exclude
epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...
, and an *
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...
or
CT scan A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
of the head to exclude brain lesions. Because psychosis may be precipitated or exacerbated by common classes of medications, medication-induced psychosis should be ruled out, particularly for first-episode psychosis. Both substance- and medication-induced psychosis can be excluded to a high level of certainty, using toxicology screening. Because some
dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...
s may also induce psychosis or mania, but cannot be ruled out with laboratory tests, a psychotic individual's family, partner, or friends should be asked whether the patient is currently taking any dietary supplements. Common mistakes made when diagnosing people who are psychotic include: * Not properly excluding
delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...
, * Not appreciating medical abnormalities (e.g., vital signs), * Not obtaining a medical history and family history, * Indiscriminate screening without an organizing framework, * Missing a toxic psychosis by not screening for substances ''and'' medications, * Not asking their family or others about dietary supplements, * Premature diagnostic closure, and * Not revisiting or questioning the initial diagnostic impression of primary psychiatric disorder. Only after relevant and known causes of psychosis are excluded, a mental health clinician may make a psychiatric
differential diagnosis In healthcare, a differential diagnosis (DDx) is a method of analysis that distinguishes a particular disease or condition from others that present with similar clinical features. Differential diagnostic procedures are used by clinicians to di ...
using a person's family history, incorporating information from the person with psychosis, and information from family, friends, or significant others. Types of psychosis in psychiatric disorders may be established by formal rating scales. The Brief Psychiatric Rating Scale (BPRS) assesses the level of 18 symptom constructs of psychosis such as
hostility Hostility is seen as a form of emotionally charged aggressive behavior. In everyday speech, it is more commonly used as a synonym for anger and aggression. It appears in several psychological theories. For instance it is a Facet (psychology), f ...
, suspicion,
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
, and
grandiosity In psychology, grandiosity is a sense of superiority, uniqueness, or invulnerability that is unrealistic and not based on personal capability. It may be expressed by exaggerated beliefs regarding one's abilities, the belief that few other peopl ...
. It is based on the clinician's interview with the patient and observations of the patient's behavior over the previous 2–3 days. The patient's family can also answer questions on the behavior report. During the initial assessment and the follow-up, both positive and negative symptoms of psychosis can be assessed using the 30 item Positive and Negative Symptom Scale ( PANSS). The
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiat ...
characterizes disorders as psychotic or on the schizophrenia spectrum if they involve hallucinations, delusions, disorganized thinking, grossly disorganized motor behavior, or negative symptoms. The DSM-5 does not include psychosis as a definition in the glossary, although it defines "psychotic features", as well as "psychoticism" with respect to personality disorder. The
ICD-10 ICD-10 is the 10th revision of the International Classification of Diseases (ICD), a medical classification list by the World Health Organization (WHO). It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social cir ...
has no specific definition of psychosis. The PSQ (Psychosis Screening Questionnaire) is the most common tool in detecting psychotic symptoms and it includes five root questions that assess the presence of PLE (mania, thought insertion, paranoia, strange experiences and perceptual disturbances) The different tools used to assess symptom severity include the Revised Behavior and Symptom Identification Scale (BASIS-R), a 24-item self-report instrument with six scales: psychosis, depression/functioning, interpersonal problems, alcohol/drug use, self-harm, and emotional lability. The Symptom Checklist-90-Revised (SCL-90-R), a 90-item self assessment tool that measures psychoticism and paranoid ideation in addition to seven other symptom scales. Finally, the Brief Symptom Inventory (BSI), a 53-item self-administered scale developed from the SCL-90-R. The BSI has good psychometric properties and is an acceptable brief alternative to the SCL-90-R. These seem to be the most accurate tools at the moment, but a research in 2007 that focused on quantifying self-reports of auditory verbal hallucinations (AVH) in persons with psychosis, suggest that The Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) is also potentially a reliable and useful measure for specifically quantifying AVHs in relation to psychosis.
Factor analysis Factor analysis is a statistical method used to describe variability among observed, correlated variables in terms of a potentially lower number of unobserved variables called factors. For example, it is possible that variations in six observe ...
of symptoms generally regarded as psychosis frequently yields a five factor solution, albeit five factors that are distinct from the five domains defined by the DSM-5 to encompass psychotic or schizophrenia spectrum disorders. The five factors are frequently labeled as hallucinations, delusions, disorganization, excitement, and emotional distress. The DSM-5 emphasizes a psychotic spectrum, wherein the low end is characterized by schizoid personality disorder, and the high end is characterized by schizophrenia. Gouzoulis-Mayfrank et al. said that the pleasant or emotionally positive experiences that are common in psychosis, particularly in the early stages, are more easily overlooked in clinical practice than the negative experiences.Friesen P. Psychosis and psychedelics: Historical entanglements and contemporary contrasts. Transcultural Psychiatry. 2022;59(5):592-609. https://doi.org/10.1177/13634615221129116 Nev Jones and Mona Shattel wrote that there is less curiosity towards the complications, or towards the richness of the good things as well as the bad things.


Prevention

The evidence for the effectiveness of early interventions to prevent psychosis appeared inconclusive. But psychosis caused by drugs can be prevented. Whilst early intervention in those with a psychotic episode might improve short-term outcomes, little benefit was seen from these measures after five years. However, there is evidence that
cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders. Cognitive behavioral therapy focuses on challenging and chang ...
(CBT) may reduce the risk of becoming psychotic in those at high risk, and in 2014 the UK National Institute for Health and Care Excellence (NICE) recommended preventive CBT for people at risk of psychosis.


Treatment

The treatment of psychosis depends on the specific diagnosis (such as schizophrenia, bipolar disorder or substance intoxication). The first-line treatment for many psychotic disorders is antipsychotic medication, which can reduce the positive symptoms of psychosis in about 7 to 14 days. For youth or adolescents, treatment options include medications, psychological interventions, and social interventions.


Medication

The choice of which
antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...
to use is based on benefits, risks, and costs. It is debatable whether, as a class, typical or
atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neurol ...
s are better. Tentative evidence supports that
amisulpride Amisulpride, sold under the brand names Socian and Barhemsys, is a medication used in the treatment of schizophrenia, acute psychotic episodes, depression, and nausea and vomiting. It is specifically used at lower doses intravenously to prev ...
,
olanzapine Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomitin ...
,
risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is t ...
and
clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...
may be more effective for positive symptoms but result in more side effects. Typical antipsychotics have equal drop-out and symptom relapse rates to atypicals when used at low to moderate dosages. There is a good response in 40–50%, a partial response in 30–40%, and treatment resistance (failure of symptoms to respond satisfactorily after six weeks to two or three different antipsychotics) in 20% of people. Clozapine is an effective treatment for those who respond poorly to other drugs ("treatment-resistant" or "refractory" schizophrenia), but it has the potentially serious side effect of
agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing neutropenia in the circulating blood. I ...
(lowered
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
count) in less than 4% of people. Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of extrapyramidal side effects while some atypicals are associated with considerable weight gain, diabetes and risk of
metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...
; this is most pronounced with olanzapine, while risperidone and quetiapine are also associated with weight gain. Risperidone has a similar rate of extrapyramidal symptoms to haloperidol.


Psychotherapy

Psychological treatments such as
acceptance and commitment therapy Acceptance and commitment therapy (ACT, typically pronounced as the word "act") is a form of psychotherapy, as well as a branch of clinical behavior analysis. It is an empirically-based psychological intervention that uses acceptance and mindfu ...
(ACT) are possibly useful in the treatment of psychosis, helping people to focus more on what they can do in terms of valued life directions despite challenging symptomology. Metacognitive training (MCT) is associated with reduced
delusion A delusion is a fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some other m ...
s,
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s and
negative symptoms Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...
as well as improved
self-esteem Self-esteem is confidence in one's own worth, abilities, or morals. Self-esteem encompasses beliefs about oneself (for example, "I am loved", "I am worthy") as well as emotional states, such as triumph, despair, pride, and shame. Smith and Macki ...
and functioning in individuals with schizophrenia spectrum disorders. There are many psychosocial interventions that seek to treat the symptoms of psychosis: need adapted treatment, Open Dialogue, psychoanalysis/psychodynamic psychotherapy, major role therapy, soteria, psychosocial outpatient and inpatient treatment, milieu therapy, and cognitive behavioral therapy ( CBT). In relation to the success of CBT for psychosis, a randomized controlled trial for a Web-based CBTp (Cognitive Behavioral Therapy for Psychosis) skills program named Coping With Voices (CWV) suggest that the program has promise for increasing access to CBTp. It also associated benefits in the management of distressing psychotic symptoms and improved social functioning. When CBT and the other psychosocial interventions these are used without antipsychotic medications, they may be somewhat effective for some people, especially for CBT, need-adapted treatment, and soteria.


Early intervention

Early intervention in psychosis is based on the observation that identifying and treating someone in the early stages of a psychosis can improve their longer term outcome. This approach advocates the use of an intensive multi-disciplinary approach during what is known as the
critical period In developmental psychology and developmental biology, a critical period is a maturational stage in the lifespan of an organism during which the nervous system is especially sensitive to certain environmental stimuli. If, for some reason, the org ...
, where intervention is the most effective, and prevents the long-term morbidity associated with chronic psychotic illness.


Systematic reform

Addressing systematic reform is essential to creating effective prevention as well as supporting treatments and recovery for those with psychosis. Waghorn et al. suggest that education interventions can be a building block to support those with psychosis to successfully participate in society. In their study they analyse the relationship between successful education attainment and psychosis. Findings suggest proportionately more school aged persons with psychosis discontinued their education, compared to those without psychosis. Waghorn et al. finds that specialised supported education for those with psychotic disorders can help lead to successful education attainment. Additionally, future employment outcomes are relative to such education attainment. Established approaches to supported education in the US include three basic models, self-contained classrooms, onsite support model and the mobile support model. Each model includes the participation of mental health service staff or educational facility staff in the student's education arrangements. Potential benefits of specialised supported education found from this study include coordination with other service providers (e.g. income support, housing, etc.) to prevent disrupting education, providing specialised career counselling, development of coping skills in the academic environment. These examples provide beneficial ways for people with psychosis to finish studies successfully as well as counter future experiences of psychosis.


History


Etymology

The word ''psychosis'' was introduced to the psychiatric literature in 1841 by Karl Friedrich Canstatt in his work ''Handbuch der Medizinischen Klinik''. He used it as a shorthand for 'psychic neurosis'. At that time neurosis meant any disease of the
nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...
, and Canstatt was thus referring to what was considered a psychological manifestation of brain disease. Ernst von Feuchtersleben is also widely credited as introducing the term in 1845, as an alternative to
insanity Insanity, madness, lunacy, and craziness are behaviors caused by certain abnormal mental or behavioral patterns. Insanity can manifest as violations of societal norms, including a person or persons becoming a danger to themselves or to other ...
and
mania Mania, also known as manic syndrome, is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome defined as a state of Abnormality (behavior), abnormally elevated arousal, affect (psychology), affect, and energy level. During a mani ...
. The term stems from
Modern Latin Neo-LatinSidwell, Keith ''Classical Latin-Medieval Latin-Neo Latin'' in ; others, throughout. (also known as New Latin and Modern Latin) is the style of written Latin used in original literary, scholarly, and scientific works, first in Italy d ...
''psychosis'', "a giving soul or life to, animating, quickening" and that from
Ancient Greek Ancient Greek (, ; ) includes the forms of the Greek language used in ancient Greece and the classical antiquity, ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Greek ...
ψυχή (), "soul" and the suffix -ωσις (-'), in this case "abnormal condition". In its adjective form "psychotic", references to psychosis can be found in both clinical and non-clinical discussions. However, in a ''non''-clinical context, "psychotic" is a nonspecific colloquialism used to mean "insane".


Classification

The word was also used to distinguish a condition considered a disorder of the mind, as opposed to ''
neurosis Neurosis (: neuroses) is a term mainly used today by followers of Freudian thinking to describe mental disorders caused by past anxiety, often that has been repressed. In recent history, the term has been used to refer to anxiety-related con ...
'', which was considered a disorder of the nervous system. The psychoses thus became the modern equivalent of the old notion of madness, and hence there was much debate on whether there was only one (unitary) or many forms of the new disease. One type of broad usage would later be narrowed down by Koch in 1891 to the 'psychopathic inferiorities'—later renamed abnormal personalities by Schneider. The division of the major psychoses into manic depressive illness (now called
bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
) and dementia praecox (now called
schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
) was made by
Emil Kraepelin Emil Wilhelm Georg Magnus Kraepelin (; ; 15 February 1856 – 7 October 1926) was a German psychiatrist. H. J. Eysenck's Encyclopedia of Psychology identifies him as the founder of modern scientific psychiatry, psychopharmacology and psychiatric ...
, who attempted to create a synthesis of the various mental disorders identified by 19th-century
psychiatrists A psychiatrist is a physician who specializes in psychiatry. Psychiatrists are physicians who evaluate patients to determine whether their symptoms are the result of a physical illness, a combination of physical and mental ailments or strictly ...
, by grouping diseases together based on classification of common symptoms. Kraepelin used the term 'manic depressive insanity' to describe the whole spectrum of
mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where the main underlying characteristic is a disturbance in the person's mood. The classification is in the ''Diagnostic ...
s, in a far wider sense than it is usually used today. In Kraepelin's classification this would include 'unipolar'
clinical depression Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
, as well as bipolar disorder and other mood disorders such as
cyclothymia Cyclothymia (, ), also known as cyclothymic disorder, psychothemia / psychothymia, bipolar III, affective personality disorder and cyclothymic personality disorder, is a mental disorder, mental and Abnormal behaviour, behavioural Disease#Disorder ...
. These are characterised by problems with mood control and the psychotic episodes appear associated with disturbances in mood, and patients often have periods of normal functioning between psychotic episodes even without medication.
Schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
is characterized by psychotic episodes that appear unrelated to disturbances in mood, and most non-medicated patients show signs of disturbance between psychotic episodes.


Treatment

Written record of supernatural causes and resultant treatments can be traced back to the
New Testament The New Testament (NT) is the second division of the Christian biblical canon. It discusses the teachings and person of Jesus in Christianity, Jesus, as well as events relating to Christianity in the 1st century, first-century Christianit ...
. Mark 5:8–13 describes a man displaying what would today be described as psychotic symptoms.
Christ Jesus ( AD 30 or 33), also referred to as Jesus Christ, Jesus of Nazareth, and many other names and titles, was a 1st-century Jewish preacher and religious leader. He is the Jesus in Christianity, central figure of Christianity, the M ...
cured this "
demon A demon is a malevolent supernatural entity. Historically, belief in demons, or stories about demons, occurs in folklore, mythology, religion, occultism, and literature; these beliefs are reflected in Media (communication), media including f ...
ic madness" by casting out the demons and hurling them into a herd of swine. Exorcism is still utilized in some religious circles as a treatment for psychosis presumed to be demonic possession. A research study of out-patients in psychiatric clinics found that 30 percent of religious patients attributed the cause of their psychotic symptoms to evil spirits. Many of these patients underwent exorcistic healing rituals that, though largely regarded as positive experiences by the patients, had no effect on symptomology. Results did, however, show a significant worsening of psychotic symptoms associated with exclusion of medical treatment for coercive forms of exorcism. The medical teachings of the fourth-century philosopher and physician Hippocrates of Cos proposed a natural, rather than supernatural, cause of human illness. In Hippocrates' work, the
Hippocratic corpus The Hippocratic Corpus (Latin: ''Corpus Hippocraticum''), or Hippocratic Collection, is a collection of around 60 early Ancient Greek medical works strongly associated with the physician Hippocrates and his teachings. The Hippocratic Corpus cov ...
, a holistic explanation for health and disease was developed to include madness and other "diseases of the mind". Hippocrates writes: Hippocrates espoused a theory of humoralism wherein disease is resultant of a shifting balance in bodily fluids including
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
,
phlegm Phlegm (; , ''phlégma'', "inflammation", "humour caused by heat") is mucus produced by the respiratory system, excluding that produced by the throat nasal passages. It often refers to respiratory mucus expelled by coughing, otherwise known as ...
, black bile, and yellow bile. According to humoralism, each fluid or "
humour Humour (English in the Commonwealth of Nations, Commonwealth English) or humor (American English) is the tendency of experiences to provoke laughter and provide amusement. The term derives from the humorism, humoral medicine of the ancient Gre ...
" has temperamental or behavioral correlates. In the case of psychosis, symptoms are thought to be caused by an excess of both blood and yellow bile. Thus, the proposed surgical intervention for psychotic or manic behavior was
bloodletting Bloodletting (or blood-letting) was the deliberate withdrawal of blood from a patient to prevent or cure illness and disease. Bloodletting, whether by a physician or by leeches, was based on an ancient system of medicine in which blood and othe ...
. 18th-century physician, educator, and widely considered "founder of American psychiatry",
Benjamin Rush Benjamin Rush (April 19, 1813) was an American revolutionary, a Founding Father of the United States and signatory to the U.S. Declaration of Independence, and a civic leader in Philadelphia, where he was a physician, politician, social refor ...
, also prescribed bloodletting as a first-line treatment for psychosis. Although not a proponent of humoralism, Rush believed that active purging and bloodletting were efficacious corrections for disruptions in the circulatory system, a complication he believed was the primary cause of "insanity". Although Rush's treatment modalities are now considered antiquated and brutish, his contributions to psychiatry, namely the biological underpinnings of psychiatric phenomenon including psychosis, have been invaluable to the field. In honor of such contributions, Benjamin Rush's image is in the official seal of the
American Psychiatric Association The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. It has more than 39,200 members who are in ...
. Early 20th-century treatments for severe and persisting psychosis were characterized by an emphasis on shocking the nervous system. Such therapies include
insulin shock therapy Insulin shock therapy or insulin coma therapy was a form of psychiatric treatment in which patients were repeatedly injected with large doses of insulin in order to produce daily comas over several weeks.Neustatter WL (1948) ''Modern psychiatry ...
, cardiazol shock therapy, and
electroconvulsive therapy Electroconvulsive therapy (ECT) is a psychiatry, psychiatric treatment that causes a generalized seizure by passing electrical current through the brain. ECT is often used as an intervention for mental disorders when other treatments are inadequ ...
. Despite considerable risk, shock therapy was considered highly efficacious in the treatment of psychosis including
schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
. The acceptance of high-risk treatments led to more invasive medical interventions including psychosurgery. In 1888, Swiss psychiatrist Gottlieb Burckhardt performed the first medically sanctioned psychosurgery in which the
cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...
was excised. Although some patients showed improvement of symptoms and became more subdued, one patient died and several developed
aphasia Aphasia, also known as dysphasia, is an impairment in a person's ability to comprehend or formulate language because of dysfunction in specific brain regions. The major causes are stroke and head trauma; prevalence is hard to determine, but aph ...
or seizure disorders. Burckhardt would go on to publish his clinical outcomes in a scholarly paper. This procedure was met with criticism from the medical community and his academic and surgical endeavors were largely ignored. In the late 1930s, Egas Moniz conceived the leucotomy (AKA prefrontal lobotomy) in which the fibers connecting the
frontal lobe The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a Sulcus (neur ...
s to the rest of the brain were severed. Moniz's primary inspiration stemmed from a demonstration by neuroscientists John Fulton and Carlyle's 1935 experiment in which two chimpanzees were given leucotomies and pre- and post-surgical behavior was compared. Prior to the leucotomy, the chimps engaged in typical behavior including throwing feces and fighting. After the procedure, both chimps were pacified and less violent. During the Q&A, Moniz asked if such a procedure could be extended to human subjects, a question that Fulton admitted was quite startling. Moniz would go on to extend the controversial practice to humans with various psychotic disorders, an endeavor for which he received a
Nobel Prize The Nobel Prizes ( ; ; ) are awards administered by the Nobel Foundation and granted in accordance with the principle of "for the greatest benefit to humankind". The prizes were first awarded in 1901, marking the fifth anniversary of Alfred N ...
in 1949. Between the late 1930s and early 1970s, the leucotomy was a widely accepted practice, often performed in non-
sterile Sterile or sterility may refer to: *Asepsis, a state of being free from biological contaminants * Sterile (archaeology), a sediment deposit which contains no evidence of human activity *Sterilization (microbiology), any process that eliminates or ...
environments such as small
outpatient A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other healt ...
clinics and patient homes. Psychosurgery remained standard practice until the discovery of antipsychotic pharmacology in the 1950s. The first clinical trial of
antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...
s (also commonly known as neuroleptics) for the treatment of psychosis took place in 1952.
Chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...
(brand name: Thorazine) passed clinical trials and became the first antipsychotic medication approved for the treatment of both acute and chronic psychosis. Although the mechanism of action was not discovered until 1963, the administration of chlorpromazine marked the advent of the
dopamine antagonist A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and have been used in t ...
, or first generation antipsychotic. While clinical trials showed a high response rate for both acute psychosis and disorders with psychotic features, the
side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...
s were particularly harsh, which included high rates of often irreversible Parkinsonian symptoms such as
tardive dyskinesia Tardive dyskinesia (TD) is an iatrogenic disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips, which occurs following treatment with medication. Additional mo ...
. With the advent of
atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neurol ...
s (also known as second generation antipsychotics) came a dopamine antagonist with a comparable response rate but a far different, though still extensive, side-effect profile that included a lower risk of Parkinsonian symptoms but a higher risk of cardiovascular disease. Atypical antipsychotics remain the first-line treatment for psychosis associated with various psychiatric and
neurological disorder Neurological disorders represent a complex array of medical conditions that fundamentally disrupt the functioning of the nervous system. These disorders affect the brain, spinal cord, and nerve networks, presenting unique diagnosis, treatment, and ...
s including schizophrenia,
bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
,
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...
,
anxiety disorder Anxiety disorders are a group of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal functions are significantly impaired. Anxiety may cause phys ...
s,
dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
, and some
autism spectrum Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing d ...
disorders. Dopamine is now one of the primary neurotransmitters implicated in psychotic symptomology. Blocking dopamine receptors (namely, the dopamine D2 receptors) and decreasing dopaminergic activity continues to be an effective but highly unrefined effect of antipsychotics, which are commonly used to treat psychosis. Recent pharmacological research suggests that the decrease in dopaminergic activity does not eradicate psychotic
delusion A delusion is a fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some other m ...
s or
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s, but rather attenuates the reward mechanisms involved in the development of delusional thinking; that is, connecting or finding meaningful relationships between unrelated stimuli or ideas. The author of this research paper acknowledges the importance of future investigation: Freud's former student Wilhelm Reich explored independent insights into the physical effects of neurotic and traumatic upbringing, and published his holistic psychoanalytic treatment with a schizophrenic. With his incorporation of breathwork and insight with the patient, a young woman, she achieved sufficient self-management skills to end the therapy. Lacan extended Freud's ideas to create a psychoanalytic model of psychosis based upon the concept of "
foreclosure Foreclosure is a legal process in which a lender attempts to recover the balance of a loan from a borrower who has Default (finance), stopped making payments to the lender by forcing the sale of the asset used as the Collateral (finance), coll ...
", the rejection of the symbolic concept of the father. Psychiatrist David Healy has criticised pharmaceutical companies for promoting simplified biological theories of mental illness that seem to imply the primacy of pharmaceutical treatments while ignoring social and developmental factors that are known important influences in the etiology of psychosis.


Society and culture

Symptoms of psychosis can also include visions or quasi-visual experiences, felt presences, alterations of time, alterations of space, or alterations of spatiotemporal qualities of objects and things. While there are many overwhelmingly negative experiences of psychosis, some experiences of psychosis can be overwhelmingly positive and can be experienced as uplifting or as healing or as difficult but meaningful. Jones and Shattell said that mutual dialogue in clinical practice would in theory allow the meaning and complexity of psychotic experiences to emerge.


Disability

The classification of psychosis as a social disability is a common occurrence. Psychosis is considered to be among the top 10 causes of social disability among adult men and women in developed countries. The traditional, negative narrative around disability has been shown to adversely influence employment and education for people experiencing psychosis. Social disability by way of social disconnection is a significant public health concern and is associated with a broad range of negative outcomes, including premature mortality. Social disconnection refers to the ongoing absence of family or social relationships with marginal participation in social activities. Research on psychosis found that reduced participation in social networks, not only negatively effects the individual on a physical and mental level, it has been shown that failure to be included in social networks influences the individual's ability to participate in the wider community through employment and education opportunities. Equal opportunity to participate in meaningful relationships with friends, family and partners, as well as engaging in social constructs such as employment, can provide significant physical and mental value to people's lives. And how breaking the disability mindset around people experiencing psychosis is imperative for their overall, long-term health and well-being as well as the contributions they are able to make to their immediate social connections and the wider community.


Research

Further research in the form of randomized controlled trials is needed to determine the effectiveness of treatment approaches for helping ''adolescents'' with psychosis. Through 10 randomized clinical trials, studies showed that Early Intervention Services (EIS) for patients with early-phase schizophrenia spectrum disorders have generated promising outcomes. EIS are specifically intended to fulfill the needs of patients with early-phase psychosis. In addition, one meta-analysis that consisted of four randomized clinical trials has examined and discovered the efficacy of EIS to Therapy as Usual (TAU) for early-phase psychosis, revealing that EIS techniques are superior to TAU. A study suggests that combining cognitive behavioral therapy (CBT) with SlowMo, an app that helps notice their "unhelpful quick-thinking", might be more effective for treating paranoia in people with psychosis than CBT alone.


References


Bibliography

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Further reading

* * * * ; Personal accounts : * emi-autobiographical* * * * *


External links


National Institute of Mental Health
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