Depression (mood)
Depression is far more than just feeling sad; it's a pervasive mental state characterized by persistent low mood and a significant aversion to activity, profoundly impacting nearly 300 million people globally. It can reshape a person's thoughts, behaviors, and overall sense of well-being, often diminishing life's simple joys and motivation. Understanding its multifaceted origins, from deeply personal experiences to broader societal forces, is crucial for addressing this silent, yet widespread, challenge. Depression is a complex condition with diverse roots, affecting millions worldwide and significantly impacting daily life beyond mere sadness. A wide array of factors, from adverse childhood experiences and specific life events to chronic illnesses and even societal structures, can contribute to depressive states. While management approaches vary, a holistic understanding of depression's biological, psychological, and social dimensions is essential for effective care and reducing its global burden.
AI Summary
Depression is far more than just feeling sad; it's a pervasive mental state characterized by persistent low mood and a significant aversion to activity, profoundly impacting nearly 300 million people globally. It can reshape a person's thoughts, behaviors, and overall sense of well-being, often diminishing life's simple joys and motivation. Understanding its multifaceted origins, from deeply personal experiences to broader societal forces, is crucial for addressing this silent, yet widespread, challenge.
- Depression is a complex condition with diverse roots, affecting millions worldwide and significantly impacting daily life beyond mere sadness.
- A wide array of factors, from adverse childhood experiences and specific life events to chronic illnesses and even societal structures, can contribute to depressive states.
- While management approaches vary, a holistic understanding of depression's biological, psychological, and social dimensions is essential for effective care and reducing its global burden.
What is Depression?
At its core, depression is a mental state marked by a low mood and a strong disinterest in activities. It's not just a bad day or a passing feeling—it's a persistent state that can warp a person's thoughts, emotions, and overall sense of contentment. Imagine the world losing its color, its flavor...
When experiencing depression, the simple joys in life often fade, and motivation can plummet. Individuals might feel profound sadness, dejection, or hopelessness, struggling with focus, sleep patterns, or appetite. In its more severe forms, it can even lead to thoughts of self-harm or suicide.
More Than a Mood: Diverse Origins
It's important to understand that depression isn't a single entity. Sometimes, it's a symptom of underlying mood disorders like major depressive disorder or bipolar disorder. Other times, it's a perfectly normal, albeit temporary, reaction to significant life events, such as the loss of a loved one or a major life transition.
Contributing Factors: The Tapestry of Life
Early Life & Environment
Our early experiences weave a significant part of our mental health tapestry. Adversity in childhood, such as neglect, abuse, or unequal treatment, can profoundly increase the risk of depression later in life. Studies show that individuals who endured four or more adverse childhood experiences are significantly more likely to suffer from depression.
Even our physical surroundings play a role. Poor housing, a lack of green spaces, and exposure to noise and air pollution are all linked to depressive moods. Interestingly, some research suggests that residents of large urban areas may report lower rates of depression than those in smaller towns or rural areas, highlighting the complex interplay of community and mental well-being.
Significant Life Events
Major life changes and stressors are frequent triggers for depressive moods. This can range from the profound experience of childbirth or menopause to the intense pressures of financial hardship, unemployment, or demanding work and academic environments. Even positive life changes can bring a period of adjustment and mood shifts.
Receiving a serious medical diagnosis—like cancer or HIV—or enduring social isolation, bullying, or the breakdown of a relationship can also precipitate depressive symptoms. These events can leave individuals feeling overwhelmed, helpless, and deeply saddened, sometimes leading to what's known as 'survivor's guilt' after traumatic events.
Certain professions face higher risks too. For example, studies have consistently shown that physicians, despite their role in healing, experience significantly higher rates of depression and suicide compared to many other lines of work—a sobering statistic that underscores the immense pressure they endure.
Workplace Stressors
Our jobs can be powerful sources of both fulfillment and stress. High-quality research points to adverse working conditions as significant contributors to depressive symptoms and disorders. Excessive workloads, a lack of autonomy, and an unfavorable balance between effort and reward are common culprits, as is workplace bullying.
Childhood and Adolescent Depression
Depression in children and adolescents often mirrors adult major depressive disorder, though it can manifest differently. Young sufferers might exhibit increased irritability or behavioral control issues rather than the typical adult feelings of sadness or emptiness. Stress, loss, or other underlying conditions put children at higher risk.
Childhood depression frequently co-occurs with other mental health conditions, most commonly anxiety and conduct disorders. There's also a notable familial link, suggesting that genetic predispositions or shared environmental factors can play a role across generations.
Personality Traits
Certain personality traits are linked to a higher likelihood of experiencing depression. Individuals with lower levels of extraversion, for instance, may be more susceptible. Similarly, those with high levels of neuroticism, characterized by emotional instability and negative emotional reactions, are more prone to depressive symptoms and diagnoses.
Additionally, low conscientiousness—which can manifest as disorganization or dissatisfaction with life—is associated with depression. These factors can leave individuals more exposed to chronic stress, further entrenching depressive states.
Medical & Substance-Induced Causes
Sometimes, depression can be a side effect of medical treatments. For instance, alpha interferon therapy is strongly linked to depression, with some studies showing a third of patients developing it within three months. Certain medications for acne (isotretinoin), hair loss (finasteride), epilepsy, migraines, and even some hormonal agents also carry an increased risk.
Substance use can also cause or worsen depression, whether through intoxication, withdrawal, or chronic use. This includes alcohol, sedatives, opioids, stimulants, hallucinogens, and inhalants—all of which can disrupt brain chemistry and mood regulation, creating a challenging cycle for those affected.
Non-Psychiatric Illnesses
Depressed mood can often be a direct consequence of various physical health conditions. This list is extensive, encompassing infectious diseases, nutritional deficiencies, neurological conditions, and endocrine imbalances. Examples include hypothyroidism, Parkinson's disease, celiac disease, diabetes, cancer, and HIV. It truly shows how intertwined our physical and mental health are.
Chronic pain, in particular, has a strong and tragic link to depression. Studies indicate that anywhere from 30% to 85% of chronic pain sufferers also experience clinical depression, and chronic pain can increase the risk of suicide by two to three times. It's a debilitating combination that requires careful and integrated care.
Even a stroke, a seemingly purely physical event, can directly cause depression. As many as one-third of stroke survivors develop 'post-stroke depression.' This is because a stroke can damage areas of the brain vital for processing emotions, rewards, and cognitive functions, leading to profound mood changes.
Psychiatric Syndromes
Depressed mood is a core symptom in several psychiatric syndromes. Major depressive disorder, often called clinical depression, involves at least two weeks of persistent low mood or loss of interest. Dysthymia, on the other hand, is a chronic, milder form of depression.
Bipolar disorder, while known for its elevated mood episodes, also includes depressive phases that can be severe and prolonged. Beyond mood disorders, conditions like borderline personality disorder, adjustment disorder, and post-traumatic stress disorder (PTSD) frequently feature intense depressive symptoms, highlighting the pervasive nature of low mood across various mental health challenges.
Societal & Historical Context
Beyond individual factors, researchers are increasingly recognizing how historical legacies can create depressive conditions. Think about the lasting impacts of racism, colonialism, and systemic oppression—these aren't just abstract concepts. For marginalized communities, they translate into real-world experiences of violence, exclusion, and a lack of resources.
This perspective suggests that depression can, in some cases, be a 'rational response to global conditions,' as coined by Ann Cvetkovich. It encompasses 'psychogeographical depression,' where the historical memory of trauma can affect the psychological health of future generations, making it an intergenerational experience.
Emerging genetic science even supports this, demonstrating an epigenetic link between trauma suffered by Holocaust survivors and genetic reverberations in subsequent generations. This points to a profound connection between societal history and individual well-being that we are only just beginning to fully comprehend.
Understanding Depression: Theories & Measurement
Theories of Depression
Scientists and clinicians have developed numerous theories to explain depression. Aaron Beck's cognitive triad, for example, suggests that depression stems from automatic, negative thoughts about oneself, the world, and the future. Other models, like the Tripartite Model, help explain why anxiety and depression often co-exist.
The 'biology of depression' explores biochemical origins, searching for imbalances in neurotransmitters. Historically, the 'chemical imbalance' theory—particularly involving serotonin—gained widespread traction. However, recent research has challenged this simplified view, prompting a deeper re-evaluation of how antidepressants truly work.
In 2022, a study in 'Molecular Psychiatry' suggested that depression isn't caused by a serotonin imbalance, unlike what was previously thought. While this ignited debate among psychiatrists, it underscores the complexity of brain chemistry and the need for ongoing research—and importantly, experts advise against discontinuing treatment without professional guidance.
Measuring Depression
To assess the severity and patterns of depression, mental health professionals use various tools. Common self-report scales include the Beck Depression Inventory-II (BDI-II) and the 9-item depression scale in the Patient Health Questionnaire (PHQ-9). These measures help therapists understand symptoms, track progress, and tailor interventions.
Paths to Well-being: Management
Not every instance of low mood requires professional treatment. Sometimes, it's a transient reaction to life, or a symptom of a treatable medical condition. However, a prolonged depressed mood, especially when combined with other symptoms, often signals an underlying issue that could greatly benefit from intervention.
For mild depression, guidelines from bodies like the UK's National Institute for Health and Care Excellence (NICE) suggest that antidepressants shouldn't always be the first line of defense due to a less favorable risk-benefit ratio. Lifestyle interventions often hold significant power.
Physical activity, for example, has a protective effect against depression, with increased daily steps linked to lower symptoms. Other non-pharmacological approaches include yoga, which shows limited but promising evidence, and 'reminiscence therapy'—particularly beneficial for the elderly—where recalling positive memories can foster a more balanced view of life.
Article
Depression (mood)
Depression is a mental state of low mood and aversion to activity. It affects about 3.5% of the global population, or about 280 million people worldwide, as of 2020. Depression affects a person's thoughts, behavior, feelings, and sense of well-being. The pleasure or joy that a person gets from certain experiences is reduced, and the afflicted person often experiences a loss of motivation or interest in those activities. People with depression may experience sadness, feelings of dejection or lack of hope, difficulty in thinking and concentration, hypersomnia or insomnia, overeating or anorexia, or suicidal thoughts.
Depression can have multiple, sometimes overlapping, origins. Depression can be a normal temporary reaction to life events, such as the loss of a loved one. Additionally, depression can be a symptom of some mood disorders, such as major depressive disorder, bipolar disorder, and dysthymia. Depression is also a symptom of some physical diseases and a side effect of some drugs and medical treatments.
Contributing factors
Depression (mood)
Allegory on melancholy, from c. 1729–1740, etching and engraving, in the Metropolitan Museum of Art (New York City)
Life events
Adversity in childhood, such as bereavement, neglect, mental abuse, physical abuse, sexual abuse, or unequal parental treatment of siblings, can contribute to depression in adulthood. Childhood physical or sexual abuse in particular significantly correlates with the likelihood of experiencing depression over the survivor's lifetime. People who have experienced four or more adverse childhood experiences are 3.2 to 4.0 times more likely to have depression. Poor housing quality, non-functionality, lack of green spaces, and exposure to air pollution and noise are linked to depressive moods, emphasizing the need for consideration in planning to prevent such outcomes. Locality has also been linked to depression and other negative moods. The rate of depression among those who reside in large urban areas is shown to be lower than those who do not. Likewise, those from smaller towns and rural areas tend to have higher rates of depression, anxiety, and psychological unwellness.
Studies have consistently shown that physicians have had the highest depression and suicide rates compared to people in many other lines of work—for suicide, 40% higher for male physicians and 130% higher for female physicians.
Life events and changes that may cause depressed mood includes, but are not limited to, childbirth, menopause, financial difficulties, unemployment, stress (such as from work, education, military service, family, living conditions, marriage, etc.), a medical diagnosis (cancer, HIV, diabetes, etc.), bullying, loss of a loved one, natural disasters, social isolation, rape, relationship troubles, jealousy, separation, or catastrophic injury. Similar depressive symptoms are associated with survivor's guilt. Adolescents may be especially prone to experiencing a depressed mood following social rejection, peer pressure, or bullying.
Work and depression
A body of high-quality longitudinal research has linked adverse working to increased depressive symptoms and disorders. Workplace stressors that increase depression risk include excessive workloads, little autonomy, an unfavorable effort-reward imbalance, and workplace bullying.
Childhood and adolescence
Depression in childhood and adolescence is similar to adult major depressive disorder, although young sufferers may exhibit increased irritability or behavioral dyscontrol instead of the more common sad, empty, or hopeless feelings seen with adults. Children who are under stress, experiencing loss or grief, or have other underlying disorders are at a higher risk for depression. Depression in young people is often comorbid with mental disorders outside of other mood disorders, most commonly anxiety disorders, especially social anxiety disorder, and conduct disorder. Depression also tends to run in families.
Personality
Depression is associated with low extraversion, and people who have high levels of neuroticism are more likely to experience depressive symptoms and are more likely to receive a diagnosis of a depressive disorder. Additionally, depression is associated with low conscientiousness. Some factors that may arise from low conscientiousness include disorganization and dissatisfaction with life. Individuals may be more exposed to stress and depression as a result of these factors.
LGBT
About 60% of LGBTQ youth has reported to feel sad, depressed, or hopeless almost every day for 2 weeks or more in the last year, compared to 26% in the general population.
Side effect of medical treatment
It is possible that some early generation beta-blockers induce depression in some patients, though the evidence for this is weak and conflicting. There is strong evidence for a link between alpha interferon therapy and depression. One study found that a third of alpha interferon-treated patients had developed depression after three months of treatment. (Beta interferon therapy appears to have no effect on rates of depression.) There is moderately strong evidence that finasteride when used in the treatment of alopecia increases depressive symptoms in some patients. Evidence linking isotretinoin, an acne treatment, to depression is strong. Other medicines that seem to increase the risk of depression include anticonvulsants, antimigraine drugs, antipsychotics, and hormonal agents such as gonadotropin-releasing hormone agonist.
Substance-induced
Several drugs of abuse can cause or exacerbate depression, whether in intoxication, withdrawal, and from chronic use. These include alcohol, sedatives (including prescription benzodiazepines), opioids (including prescription pain killers and illicit drugs such as heroin), stimulants (such as cocaine and amphetamines), hallucinogens, and inhalants.
Non-psychiatric illnesses
Depressed mood can be the result of a number of infectious diseases, nutritional deficiencies, neurological conditions, and physiological problems, including hypoandrogenism (in men), Addison's disease, Cushing's syndrome, pernicious anemia, hypothyroidism, hyperparathyroidism, Lyme disease, multiple sclerosis, Parkinson's disease, celiac disease, chronic pain, stroke, diabetes, cancer, and HIV. Autistic burnout may also be misdiagnosed as depression.
Studies have found that anywhere from 30 to 85 percent of patients suffering from chronic pain are also clinically depressed. A 2014 study by Hooley et al. concluded that chronic pain increased the chance of death by suicide by two to three times. In 2017, the British Medical Association found that 49% of UK chronic pain patients also had depression.
As many as 1/3 of stroke survivors will later develop post-stroke depression. Because strokes may cause damage to the parts of the brain involved in processing emotions, reward, and cognition, stroke may be considered a direct cause of depression.
Psychiatric syndromes
A number of psychiatric syndromes feature depressed mood as a main symptom. The mood disorders are a group of disorders considered to be primary disturbances of mood. These include major depressive disorder (commonly called major depression or clinical depression) where a person has at least two weeks of depressed mood or a loss of interest or pleasure in nearly all activities; and dysthymia, a state of chronic depressed mood, the symptoms of which do not meet the severity of a major depressive episode. Another mood disorder, bipolar disorder, features one or more episodes of abnormally elevated mood, cognition, and energy levels, but may also involve one or more episodes of depression. Individuals with bipolar depression are often misdiagnosed with unipolar depression. When the course of depressive episodes follows a seasonal pattern, the disorder (major depressive disorder, bipolar disorder, etc.) may be described as a seasonal affective disorder.
Outside the mood disorders: borderline personality disorder often features an extremely intense depressive mood; adjustment disorder with depressed mood is a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode; and posttraumatic stress disorder, a mental disorder that sometimes follows trauma, is commonly accompanied by depressed mood.
Historical legacy
Research suggests possible associations between Neanderthal genetics and some forms of depression.
Authors and researchers have begun to conceptualize ways in which the historical legacies of racism and colonialism may create depressive conditions. Given the lived experiences of marginalized peoples, ranging from conditions of migration, class stratification, cultural genocide, labor exploitation, and social immobility, depression can be seen as a "rational response to global conditions", according to Ann Cvetkovich.
Psychogeographical depression overlaps somewhat with the theory of "deprejudice", a portmanteau of "depression" and "prejudice" proposed by Cox, Abramson, Devine, and Hollon in 2012, who argue for an integrative approach to studying the often comorbid experiences. Cox, Abramson, Devine, and Hollon are concerned with the ways in which social stereotypes are often internalized, creating negative self-stereotypes that then produce depressive symptoms.
Unlike the theory of "deprejudice", a psychogeographical theory of depression attempts to broaden study of the subject beyond an individual experience to one produced on a societal scale, seeing particular manifestations of depression as rooted in dispossession; historical legacies of genocide, slavery, and colonialism are productive of segregation, both material and psychic material deprivation, and concomitant circumstances of violence, systemic exclusion, and lack of access to legal protections. The demands of navigating these circumstances compromise the resources available to a population to seek comfort, health, stability, and sense of security. The historical memory of this trauma conditions the psychological health of future generations, making psychogeographical depression an intergenerational experience as well.
This work is supported by recent studies in genetic science which has demonstrated an epigenetic link between the trauma suffered by Holocaust survivors and genetic reverberations in subsequent generations.
Measures
Depression (mood)
Measures of depression include, but are not limited to: Beck Depression Inventory-11 and the 9-item depression scale in the Patient Health Questionnaire (PHQ-9). Both of these measures are psychological tests that ask personal questions of the participant, and have mostly been used to measure the severity of depression. The Beck Depression Inventory is a self-report scale that helps a therapist identify the patterns of depression symptoms and monitor recovery. The responses on this scale can be discussed in therapy to devise interventions for the most distressing symptoms of depression.
Theories
Depression (mood)
There are multiple schools of depression theory. Beck's cognitive triad theorizes that an individual with depression has "automatic, spontaneous, and seemingly uncontrollable negative thoughts" about the self, the world or environment, and the future. The Tripartite Model of Anxiety and Depression helps to explain the common comorbidity of anxiety and depression by separating symptoms into three groups: negative affect, positive affect, and physiological hyperarousal. The epigenetics of depression is the study of how epigenetics (heritable characteristics that do not involve changes in DNA sequence) contribute to depression. Behavioral theories of depression explain the etiology of depression with behavioral science; adherents promote the use of behavioral therapies for treatment. Evolutionary approaches to depression are attempts by evolutionary psychologists and evolutionary psychiatrists to use the theory of evolution to further understand mood disorders. The biology of depression is the attempt to identify a biochemical origin of depression, as opposed to theories that emphasize psychological or situational causes.
Management
Depression (mood)
Depressed mood may not require professional treatment, and may be a normal temporary reaction to life events, a symptom of some medical condition, or a side effect of some drugs or medical treatments. A prolonged depressed mood, especially in combination with other symptoms, may lead to a diagnosis of a psychiatric or medical condition which may benefit from treatment.
The UK National Institute for Health and Care Excellence (NICE) 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, because the risk-benefit ratio is poor.
Physical activity has a protective effect against the emergence of depression in some people. Increased daily step counts have been associated with lower depressive symptoms.
Recent research indicates that mindfulness and mindfulness-based interventions can significantly reduce depression across diverse population groups. Other research suggests that rumination is a significant risk factor for depression, and that reductions in rumination appear to contribute to the beneficial effects of mindfulness meditation on depressive symptoms.
Reminiscence of old and fond memories is another alternative form of treatment, especially for the elderly who have lived longer and have more experiences in life. It is a method that causes a person to recollect memories of their own life, leading to a process of self-recognition and identifying familiar stimuli. By maintaining one's personal past and identity, it is a technique that stimulates people to view their lives in a more objective and balanced way, causing them to pay attention to positive information in their life stories, which would successfully reduce depressive mood levels.
Depression is a common condition among the elderly living in long-term care (LTC) facilities. Although antidepressant medications are frequently prescribed, many residents prefer non-pharmacological treatments such as psychological therapies. A systematic review of 19 randomized controlled trials found that therapies like cognitive behavioural therapy, behavioural therapy, and reminiscence therapy may reduce depressive symptoms and improve short-term quality of life. However, the evidence was of very low certainty, and some participants were more likely to drop out of therapy. There was no clear effect on symptoms, with only short term improvements seen with psychological therapies. Further high-quality studies are needed.
There is limited evidence that continuing antidepressant medication for one year reduces the risk of depression recurrence with no additional harm. Recommendations for psychological treatments or combination treatments in preventing recurrence are not clear. For chronic and treatment-resistant forms of depression, specialized psychotherapies such as cognitive behavioral analysis system of psychotherapy (CBASP) have been developed to address enduring interpersonal patterns that maintain depressive symptoms.
Epidemiology
Depression (mood)
Depression is the leading cause of disability worldwide, the United Nations (UN) health agency reported, estimating that it affects more than 300 million people worldwide – the majority of them women, young people and the elderly. An estimated 4.4 percent of the global population has depression, according to a report released by the UN World Health Organization (WHO), which shows an 18 percent increase in the number of people living with depression between 2005 and 2015.
Depression is a major mental-health cause of disease burden. Its consequences further lead to significant burden in public health, including a higher risk of dementia, premature mortality arising from physical disorders, and maternal depression impacts on child growth and development. Approximately 76% to 85% of depressed people in low- and middle-income countries do not receive treatment; barriers to treatment include: inaccurate assessment, lack of trained health-care providers, social stigma and lack of resources.
The stigma comes from misguided societal views that people with mental illness are different from everyone else, and they can choose to get better only if they wanted to. Due to this more than half of the people with depression do not receive help with their disorders. The stigma leads to a strong preference for privacy. An analysis of 40,350 undergraduates from 70 institutions by Posselt and Lipson found that undergraduates who perceived their classroom environments as highly competitive had a 37% higher chance of developing depression and a 69% higher chance of developing anxiety. Several studies have suggested that unemployment roughly doubles the risk of developing depression.
The World Health Organization has constructed guidelines – known as The Mental Health Gap Action Programme (mhGAP) – aiming to increase services for people with mental, neurological and substance-use disorders. Depression is listed as one of conditions prioritized by the programme. Trials conducted show possibilities for the implementation of the programme in low-resource primary-care settings dependent on primary-care practitioners and lay health-workers. Examples of mhGAP-endorsed therapies targeting depression include Group Interpersonal Therapy as group treatment for depression and "Thinking Health", which utilizes cognitive behavioral therapy to tackle perinatal depression. Furthermore, effective screening in primary care is crucial for the access of treatments. The mhGAP adopted its approach of improving detection rates of depression by training general practitioners. However, there is still weak evidence supporting this training.
According to 2011 study, people who are high in hypercompetitive traits are also likely to measure higher for depression and anxiety.
History
Depression (mood)
The term depression was derived from the Latin verb deprimere, "to press down". From the 14th century, "to depress" meant to subjugate or to bring down in spirits. It was used in 1665 in English author Richard Baker's Chronicle to refer to someone having "a great depression of spirit", and by English author Samuel Johnson in a similar sense in 1753.
In Ancient Greece, disease was thought due to an imbalance in the four basic bodily fluids, or humors. Personality types were similarly thought to be determined by the dominant humor in a particular person. Derived from the Ancient Greek melas, "black", and kholé, "bile", melancholia was described as a distinct disease with particular mental and physical symptoms by Hippocrates in his Aphorisms, where he characterized all "fears and despondencies, if they last a long time" as being symptomatic of the ailment.
During the 18th century, the humoral theory of melancholia was increasingly being challenged by mechanical and electrical explanations; references to dark and gloomy states gave way to ideas of slowed circulation and depleted energy. German physician Johann Christian Heinroth, however, argued melancholia was a disturbance of the soul due to moral conflict within the patient.
In the 20th century, the German psychiatrist Emil Kraepelin distinguished manic depression. The influential system put forward by Kraepelin unified nearly all types of mood disorder into manic–depressive insanity. Kraepelin worked from an assumption of underlying brain pathology, but also promoted a distinction between endogenous (internally caused) and exogenous (externally caused) types.
Other psycho-dynamic theories were proposed. Existential and humanistic theories represented a forceful affirmation of individualism. Austrian existential psychiatrist Viktor Frankl connected depression to feelings of futility and meaninglessness. Frankl's logotherapy addressed the filling of an "existential vacuum" associated with such feelings, and may be particularly useful for depressed adolescents.
Researchers theorized that depression was caused by a chemical imbalance in neurotransmitters in the brain, a theory based on observations made in the 1950s of the effects of reserpine and isoniazid in altering monoamine neurotransmitter levels and affecting depressive symptoms. During the 1960s and 70s, manic-depression came to refer to just one type of mood disorder (now most commonly known as bipolar disorder) which was distinguished from (unipolar) depression. The terms unipolar and bipolar had been coined by German psychiatrist Karl Kleist.
In July 2022, a systematic review by British psychiatrist Joanna Moncrieff, researcher Mark Horowitz and others in the academic journal Molecular Psychiatry found that depression is not caused by a serotonin imbalance in the human body. However, the study was met with criticism from some psychiatrists, who argued the study's methodology used an indirect trace of serotonin, instead of taking direct measurements of the molecule. Moncrieff said that no one should "suddenly interrupt [...]" antidepressant treatment.