Post-stroke depression (PSD) is a form of depression that may occur after a

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 ...

. PSD significantly impacts stroke recovery and the overall quality of life of those affected. It is particularly associated with strokes affecting the

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 ...

or the anterior regions of the brain, including the

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

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...

. Treatment can include medications such as

SSRIs Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

, SNRIs,

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...

s, and/or

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 ...

Symptoms and signs

Symptoms of post-stroke depression are the same as those of

major 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 ...

. The severity and symptoms vary from person to person, but definitionally and most commonly involve a depressed mood and/or an overall loss of interest or pleasure in activities. The classically defined symptoms of depression, which may be present in varying severity and number, are: # Down, sad, or depressed mood #

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 ...

(loss of interest or pleasure) #

Insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

''or''

hypersomnia Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition ...

# Tiredness, fatigue, or lack of energy # Loss of appetite ''or'' excessive appetite # Guilt or

self-loathing Self-hatred is a state of personal self-loathing or low self-esteem. In psychology and psychiatry The term "self-hatred" is used infrequently by psychologists and psychiatrists, who would usually describe people who hate themselves as "people wi ...

# Difficulty concentrating #

Psychomotor agitation Psychomotor agitation is a symptom in various disorders and health conditions. It is characterized by unintentional and purposeless motions and restlessness, often but not always accompanied by emotional distress and is always an indicative for ...

''or''

psychomotor retardation Psychomotor retardation involves a slowing down of thought and a reduction of physical movements in an individual. It can cause a visible slowing of physical and emotional reactions, including speech and affect. Psychomotor retardation is most ...

# Feeling hopeless, thoughts of death or dying, or thoughts of

self-harm Self-harm refers to intentional behaviors that cause harm to oneself. This is most commonly regarded as direct injury of one's own skin tissues, usually without suicidal intention. Other terms such as cutting, self-abuse, self-injury, and s ...

suicide Suicide is the act of intentionally causing one's own death. Risk factors for suicide include mental disorders, physical disorders, and substance abuse. Some suicides are impulsive acts driven by stress (such as from financial or ac ...

Incidence and risk factors

PSD has a reported incidence of 18% to 33%, though it is commonly underdiagnosed due to overlapping symptoms between stroke and depression. A comprehensive meta-analysis found that over half of stroke patients experience at least one episode of depression. Various

risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...

s increase the likelihood of developing PSD, including: * Female sex * Prior history of mental illness, especially ''pre-''stroke depression * Suffering from large or multiple strokes * Anterior or basal ganglia region strokes * Diffuse

white matter White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...

damage * Higher levels of post-stroke

disability Disability is the experience of any condition that makes it more difficult for a person to do certain activities or have equitable access within a given society. Disabilities may be Cognitive disability, cognitive, Developmental disability, d ...

Location, size, overall severity, and impact on

cognitive function Cognitive skills are skills of the mind, as opposed to other types of skills such as motor skills, social skills or life skills. Some examples of cognitive skills are literacy, self-reflection, logical reasoning, abstract thinking, critical th ...

of a stroke may better predict the likelihood of post-stroke depression than other risk factors.

Pathogenesis

The exact mechanisms behind PSD are not completely understood, as the condition results from a complex interplay of neurochemical, structural, and inflammatory disruptions of brain function. In particular, the function of the

limbic system The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''P ...

, which is commonly implicated 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 ...

, may be disrupted either directly or indirectly by a stroke. Key mechanisms implicated in PSD include glutamate toxicity, HPA axis dysfunction, abnormal neurotrophic response, decreased monoamine levels. Collectively, these mechanisms are most pronounced in 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 ...

, limbic system, and

. Strokes affecting these regions of the brain are thus more likely to cause PSD. Some evidence also suggests that strokes of the left side of the brain are more commonly associated with PSD, and with greater severity, than the right; this is the classically accepted view. However, other studies have found no association between left or right side and PSD, or have even identified the right side as being more closely linked to PSD.

Glutamate toxicity

Glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

is an excitatory neurotransmitter that, in excessive amounts, causes

excitotoxicity In excitotoxicity, neuron, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamic acid, glutamate become pathologically high, resulting in excessive stimulation of cell surface recept ...

by promoting

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

influx into neurons. This influx can lead to neuronal death, contributing to brain damage of the emotional regulation and reward pathways in the prefrontal cortex,

amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...

, and especially the

. Damage to these brain structures can lead to the development of depression.

HPA axis dysregulation

The hypothalamic-pituitary-adrenal (HPA) axis is responsible for regulating stress responses. HPA axis dysfunction is associated with both sustained elevation of

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

levels and

chronic inflammation Chronic systemic inflammation is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions such ...

, both of which are associated with major depressive disorder. Dysregulation of the HPA axis can perpetuate a cycle of neuroinflammation that exacerbates depressive symptoms.

Abnormal neurotrophic response

Neurotrophic factors Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and cell differentiation, differentiation of both developing and mature neurons. Most ...

, which support the growth, maturation, and survival of

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s, are impaired in PSD. This disruption particularly affects the hippocampus and prefrontal cortex, leading to diminished

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...

and

neuroplasticity Neuroplasticity, also known as neural plasticity or just plasticity, is the ability of neural networks in the brain to change through neurogenesis, growth and reorganization. Neuroplasticity refers to the brain's ability to reorganize and rewir ...

, which are critical for emotional regulation and cognitive function.

Lower monoamine levels

PSD is associated with decreased levels of

monoamine neurotransmitter Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ...

s such as

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

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 ...

, and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

. These neurotransmitters are vital for mood regulation, cognitive functions, and the brain's reward system. Lower levels in the frontal cortex and limbic system contribute to depression seen in PSD and in patients with other forms of depression.

Screening and diagnosis

Screening for PSD should be a standard, routine, and repeated part of post-stroke care, with tools like the

Hamilton Depression Rating Scale The Hamilton Rating Scale for Depression (HRSD), also called the Hamilton Depression Rating Scale (HDRS), sometimes also abbreviated as HAM-D, is a multiple-item questionnaire used to provide an indication of depression, and as a guide to evalua ...

(HDRS) and the Patient Health Questionnaire-9 (PHQ-9) recommended for this purpose; there is no consensus on a single screening tool to use, and some experts recommend using two different scales before establishing a diagnosis, to reduce the risk of a

false positive A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resu ...

result. Diagnosis is clinical, and can be established in any patient who develops sustained depressive symptoms after a stroke. While these criteria can appear simple, diagnosis may be challenging due to the overlap between stroke-related neurological symptoms and depression, which can present with or without a typical depressed mood. Additionally, sensory and

cognitive impairment Cognitive impairment is an inclusive term to describe any characteristic that acts as a barrier to the cognition process or different areas of cognition. Cognition, also known as cognitive function, refers to the mental processes of how a person ...

s seen in many stroke patients may complicate mental health assessments.

Differentiating from post-stroke apathy

It is essential to differentiate PSD from post-stroke apathy (PSA). While PSA involves diminished goal-directed behavior and a lack of spontaneous movement or speech, it does not encompass low mood, thoughts of death or suicide, or feelings of guilt and worthlessness, which are associated with depression. Neurologically, PSA is more associated with extensive white matter degeneration than PSD.

Treatment

Treatment strategies for PSD typically involve one or both of the following. * Medications:

Selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

s (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and

s (TCAs) have shown efficacy in managing PSD. * Cognitive Behavioral Therapy (CBT): Although CBT has demonstrated benefits in PSD patients, stroke-related symptoms such as

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 physical limitations may hinder or prevent active participation in therapy sessions. Some, but not all, sources recommend the prophylactic use of antidepressant medications (primarily SSRIs and SNRIs) in patients with strokes considered to be high risk for PSD.{{Cite journal , last1=Salter , first1=Katherine L. , last2=Foley , first2=Norine C. , last3=Zhu , first3=Lynn , last4=Jutai , first4=Jeffrey W. , last5=Teasell , first5=Robert W. , date=Nov 2013 , title=Prevention of Poststroke Depression: Does Prophylactic Pharmacotherapy Work? , url=http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2012.03.013 , journal=Journal of Stroke and Cerebrovascular Diseases , volume=22 , issue=8 , pages=1243–1251 , doi=10.1016/j.jstrokecerebrovasdis.2012.03.013 , pmid=22554569 , issn=1052-3057, url-access=subscription

Outlook

Patients with post-stroke depression have higher rates of mortality and decreased baseline

compared to non-depressed stroke patients. However, both of these consequences can be significantly improved with antidepressants such as SSRIs.

Disability Disability is the experience of any condition that makes it more difficult for a person to do certain activities or have equitable access within a given society. Disabilities may be Cognitive disability, cognitive, Developmental disability, d ...

remains a challenge for many stroke patients, and PSD can worsen medical problems that cause disability. Like cognitive function, other disabling impairments may be significantly lessened among patients prescribed SSRIs or other antidepressants.

References

Major depressive disorder Mood disorders Complications of stroke