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Depression and the Brain: Effects On Mental Health and Cognition
Mental Health

Depression and the Brain: Effects On Mental Health and Cognition

Published: 25/04/2024

Written by: Creyos

Depression is commonly understood as a mental health issue associated with feelings like low mood, but research suggests it can also lead to cognitive impairment. It’s too simplistic to say that depression is only either psychological or physiological (i.e. due to chemical imbalances). The connection between depression and the brain is intertwined and complex.

Patients may experience depression through emotional, mental, or physical symptoms, and bring these concerns to a physician or psychologist. Depression has long been diagnosed using tools such as clinical interviews, but cognitive assessments can supplement these measures by providing insight into the characteristics of cognitive impairment characteristic of depressive disorders, aiding in diagnosis, and tracking treatment efficacy. 

In this article, we discuss the symptoms of depression, what those symptoms look like in the brain, and how depression impacts cognitive function.

What is Depression?

An estimated 21 million adults in the United States experienced a major depressive episode in 2021, according to the National Institute of Mental Health. Depression in its various forms is even more common.

Depression is a mental health condition marked by persistent feelings of sadness, hopelessness, and disinterest in activities. 

While sometimes used interchangeably with major depressive disorder (MDD), a major depressive episode is defined as a period of at least two weeks where a noticeable and substantial shift in mood occurs. 

There are actually several types of mood disorder that include depressed mood as a symptom:

  1. Major Depressive Disorder (MDD): This is another name for clinical depression. Its symptoms include a persistent feeling of sadness, a lack of interest in activities, changes in appetite, sleep disturbances, and difficulty concentrating.
  2. Bipolar Disorder: This disorder is characterized by mood changes that cycle between severe highs (mania) and lows (depression). The depressive periods are similar to MDD.
  3. Postpartum Depression: This type of depression occurs in women after childbirth. Symptoms include extreme sadness, anxiety, and exhaustion that may interfere with daily care activities.
  4. Persistent Depressive Disorder (Dysthymia): This is a long-term, chronic form of depression. Symptoms are milder than major depression but are present on most days and can persist for years.
  5. Seasonal Affective Disorder (SAD): This type of depression is related to changes in seasons, typically beginning during the winter months when there's less natural sunlight.
  6. Psychotic Depression: This is a severe form of depression accompanied by psychosis, such as disturbing false fixed beliefs (delusions) or hallucinations.
  7. Premenstrual Dysphoric Disorder (PMDD): This is a severe extension of premenstrual syndrome (PMS). PMDD can cause extreme mood shifts that can disrupt work and damage relationships.
  8. Situational Depression: Although not a technical term in psychiatry, it refers to a depressed mood in response to a stressful event, such as a death in the family, a divorce, or job loss.

What are the Common Symptoms Reported to Clinicians? 

While major depression is characterized by low mood, there are other common symptoms that may be seen in some patients diagnosed with depression:

  • Loss of interest and pleasure in previously enjoyable activities
  • Decreased self-esteem
  • Reduced vitality or libido
  • Mood swings
  • Irritability
  • Delusions
  • Suicidal thoughts or ideation
  • Withdrawal from social situations
  • Changes in appetite
  • Insomnia or hypersomnia 

A study on cognitive impairment caused by depression found that the disorder also resulted in:

  • Attention and concentration disorders
  • Decrease in spatial working memory and short term memory
  • Decrease in verbal reasoning

Research found that these effects are also bidirectional—meaning that they both result from and are predictors for depression. Individuals suffering from depression may experience few symptoms or a wide range, depending on the person or the severity of their condition.

What Happens to the Brain During Depression?

The brain changes in terms of structure and cognitive function as a result of persistent depression. While the physical changes are only observable through brain imaging, physicians can potentially recognize neuroanatomical changes taking place based on a patient’s cognitive or behavioral symptoms.

Physical changes in brain anatomy resulting from depression tend to take place in the areas responsible for regulating emotions and stress hormones—namely, the prefrontal cortex, hippocampus, and amygdala

Brain imaging techniques like structural and functional magnetic resonance imaging (MRI and fMRI) have been used in research to identify specific patterns of brain activity and detect structural and functional abnormalities associated with depression.

Physical changes may correspond to changes in cognition, emotions, and behavior, that can show up as various symptoms—from mood swings to difficulty concentrating. Fortunately, research shows that antidepressant treatment and cognitive behavioral therapy can help reverse some of these changes.

While clinicians are trained to understand which areas of the brain are most affected by depression, many patients are also interested in learning about what brain regions and functions are affected by depression. Communicating this information to patients can engage them further in treatment followthrough.

In the following sections, we’ll look more closely at what is different in the brains of patients suffering from depression, the associated effects on cognitive function, and how this relationship may impact a patient’s daily life.


The hippocampus, a critical region in the brain for forming new memories and linking emotions to them, is significantly altered in the brain of a patient experiencing depression. For individuals with MDD, the hippocampus is at risk of atrophy and reduction in size, according to one study. This is attributed to prolonged exposure to cortisol, which can inhibit neuron production (nerve cells) and cause existing nerve cells to shrink or die. These changes may result in symptoms like impairments to memory and mood regulation. 

Prefrontal Cortex

The prefrontal cortex (PFC), a critical component in understanding depression, is divided into subregions such as the ventromedial prefrontal cortex (vmPFC), which plays a pivotal role in managing emotions, and the dorsolateral prefrontal cortex (dlPFC), which is recruited for some complex cognitive functions. 

Both functional and structural anomalies have been observed in the PFC of individuals suffering from depression, according to this review. Furthermore, the PFC plays a significant role in generating negative affect, which is symptomatic of depression. As such, any dysfunction in the PFC is closely related to the onset and manifestation of depressive states.

Limbic System

According to research on depression in Alzheimer's patients, negative ruminations common to depression are linked with overactivity in the amygdala. This may lead to heightened emotional responses and a negative bias in emotional processing. Furthermore, chronic stress and depression may lead to alterations in the hippocampus. These changes can contribute to the persistent feelings of sadness, hopelessness, and other emotional symptoms commonly observed in depression.


Individuals suffering from depression tend to exhibit an overactive amygdala, particularly in instances where depression and anxiety coexist. This heightened activity can lead to increased emotional reactivity, contributing to the negative emotional bias often observed in individuals suffering from depression. Differences in the amygdala can also be linked with the way it communicates with other parts of the brain, further influencing emotional processing and stress response.

Gray Matter Volume (GMV)

Chronic stress, a common feature of depression, increases the production of cortisol, which can lead to a reduction in gray matter volume. This is often observed in brain regions such as the prefrontal cortex and the hippocampus. Consequently, the decrease in gray matter volume can contribute to the cognitive impairments and emotional dysfunctions commonly seen in major depressive disorder patients.

Stress and Inflammation

Chronic stress and inflammation in the brain are closely linked to depression. Major depressive disorder is associated with autoimmune diseases, characterized by an activated immune system. Chronic stress may also elevate basal cortisol levels and heighten sensitivity to psychological stress, both of which are linked to depression. 

Moreover, inflammation, particularly in persistent depressive disorders, may influence the following complications:

  • Clinically significant fatigue
  • Immune suppression
  • Reactivity

Understanding the mechanisms underlying chronic stress and depression can help clinicians address factors causing stress independently as well as in combination with depression.

Effects of Depression on Cognitive Function

Physical changes in the brain typically aren’t observable when a patient seeks healthcare services for depression (after all, a physician or therapist likely won’t refer for brain imaging during routine health visits). However, changes in memory, focus, and attention are all cognitive changes that may provide insight into neurological shifts.


Individuals suffering from depression often experience difficulties with short-term memory, episodic memory, verbal memory, and varying subsets of executive function. One study using Creyos found that depression was linked with lower performance scores in episodic memory, working memory, and verbal short term memory.

Patients may present with issues including: 

  • Forgetfulness
  • Difficulty recalling details
  • Struggles with memory consolidation

These experiences can further amplify the challenges faced during a depressive episode.

Focus and Attention

An inability to focus is a common symptom of depression, and can sometimes co-occur with “brain fog”. Cognitive impairment resulting from depression can be measured with assessments including the Stroop test and is associated with lower performance scores.

Individuals may struggle with concentrating on tasks, making decisions, or remembering details. Difficulties with attention that are characteristic of depression can lead to challenges in both professional and personal settings, further exacerbating the distress caused by the depressive state. 

Negative Emotional Bias

Negative emotional bias, a common characteristic of depression, refers to the tendency of those affected to interpret emotional stimuli and information negatively. This bias persists across various cognitive domains and even during remitted states of depression. It can reinforce an individual’s depressive symptoms as well as affect: 

  • Perception of events
  • Memory
  • Self esteem 

Depression, Motivation, and Anxiety


Depression can significantly impact motivation, a cognitive function crucial for initiating and maintaining goal-oriented behavior. Individuals with depression often experience a marked decrease in motivation, which can manifest as a loss of interest in activities they once enjoyed, difficulty in starting tasks, or a general feeling of apathy. This reduction in motivation is not a sign of laziness or lack of willpower, but a symptom of the illness. 


Anxiety and depression often coexist. Anxiety disorders are marked by excessive worry and fear about everyday situations. Both conditions can significantly interfere with an individual's quality of life, and they often share common symptoms such as difficulty concentrating, sleep disturbances, and changes in appetite.

Depression and Sleep Depression

Sleep Disruption

One of the common symptoms of depression is insomnia. Almost three-quarters of depressed individuals experience disrupted sleep. This lack of sleep can contribute to a more pessimistic mood and outlook, potentially heightening the likelihood of further developing depression.

Excessive sleepiness, also known as hypersomnia, is reported in approximately 13.7% of patients diagnosed with depression, according to the Journal of Affective Disorders. This condition is characterized by prolonged night sleep, difficulty waking up, and frequent, often uncontrollable, daytime sleepiness. 

Hypersomnia in depression is not just about sleeping for long hours but also about the quality of sleep. Despite spending excessive time sleeping, individuals with hypersomnia often report feeling unrefreshed or groggy upon waking. This symptom can further exacerbate feelings of fatigue and lack of energy, which are common in those suffering from depression.

How Do Clinicians Evaluate Depression and Its Effects on Cognition?

Emotional and psychological impacts are often the focus of treatments for depression. However, as cognitive deficits are researched more in depth, it’s clearer than ever that focusing on addressing and restoring cognitive health is key to depression treatment. Impacts on cognitive performance—ranging from limited attention, working memory, disrupted verbal memory— are common in psychiatric disorders, can compromise quality of life, and are undertreated.

Clinicians can reach for a variety of tools when evaluating depression and its impact on cognition. These methods include:

  • Cognitive assessments
  • Questionnaires
  • Psychological assessment
  • Clinical interviews
  • Environmental and social assessment
  • Digital health tools

Below we’ll expand on a few of these key methods for evaluating depression.

Cognitive Assessment

Computerized cognitive assessments can complement subjective measures like interviews and self-report questionnaires, providing a comprehensive understanding of the patient’s cognitive function. These methods are excellent for quantifying and tracking the severity of cognitive symptoms in a patient.

Cognitive assessments help clinicians evaluate the impact of depression on cognitive functions such as:

  • Depressive symptoms measured by the PHQ-9 predicted a decline in Paired Associates, Grammatical Reasoning, Token Search, and Digit Span
  • Current depression was related to lower scores in Grammatical Reasoning, Digit Span, Paired Associates, and Token Search. Late onset depression was particularly detrimental to Grammatical Reasoning

These cognitive healthcare solutions can help providers better understand their patients’ experiences, tailor treatment strategies, and monitor progress over time. They can also support patients in understanding their condition and feeling empowered in managing their depression symptoms.

Creyos Health provides a suite of cognitive assessments that help clinicians measure depression and its role in other conditions.Regular assessment at intervals throughout care is valuable for informing treatment decisions and monitoring the evolution of cognitive function in the context of depression treatment.

To the extent that depression manifests in the brain, cognitive testing can detect deficits that may result from differences in the brains of depressed patients. Read the Brain Region Guide to understand the link between Creyos tasks and the brain.

Questionnaires and Self Report

The Patient Health Questionnaire (PHQ-9) is a self-administered tool used to assess the severity of depressive symptoms and monitor progress over time. Released by Pfizer in 2010, the PHQ-9 is widely utilized by various healthcare professionals as a standard method for screening.This questionnaire, available with Creyos Health, aids clinicians in evaluating and quantifying the severity of depressive symptoms in a patient and tracking these symptoms over time.

Tools like the General Anxiety Disorder GAD-7 Questionnaire and the Perceived Stress Scale (PSS) can evaluate other aspects of patient health that may be associated with depression, track treatment progress, and substantiate treatment efficacy. 

Psychological Assessment and Clinical Interviews

Clinical interviews are traditionally a first step in identifying the need for further testing for depression, measuring cognitive health and mental health, and potentially recommending further psychological support, such as therapy.

Psychotherapy plays a pivotal role in diagnosing and evaluating depression. While numerous styles of psychotherapy exist, the primary objective is to understand the patient's mental state, assess the intensity of their negative thoughts, and identify potential triggers or patterns that could indicate depression.

These techniques aid in a comprehensive evaluation of a patient's depressive state, offering crucial insights into the nature and severity of their condition.

Easing the Cognitive Impacts of Depression

While major depressive disorder can significantly impact the neurology and behavior of your patients, these changes don’t have to be permanent.

Patients can manage this disorder with the help of lifestyle changes or medical treatments, as well as careful monitoring with the tools available.  Since depression is a complex illness, patients will need thorough follow-up and reassessment to monitor their progression.

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