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Biological Causes Of Major Depressive Disorder

How Does Psychotic Depression Differ From Schizophrenia

Biological basis of depression

Schizophrenia is a psychotic disorder, while psychotic depression is a mood disorder.

Schizophrenia is a stand-alone condition, while psychotic depression is a subtype of major depressive disorder.

While both conditions result in psychotic symptoms, such as hallucinations and/or delusions, with psychotic depression these psychotic symptoms happen at the same time as major depressive episodes.

Life Expectancy And The Risk Of Suicide

Depressed individuals have a shorter life expectancy than those without depression, in part because people who are depressed are at risk of dying of suicide. Up to 60% of people who die of suicide have a mood disorder such as major depression, and the risk is especially high if a person has a marked sense of hopelessness or has both depression and borderline personality disorder. About 2â8% of adults with major depression die by suicide, and about 50% of people who die by suicide had depression or another mood disorder. The lifetime risk of suicide associated with a diagnosis of major depression in the US is estimated at 3.4%, which averages two highly disparate figures of almost 7% for men and 1% for women . The estimate is substantially lower than a previously accepted figure of 15%, which had been derived from older studies of people who were hospitalized.

Depressed people have a higher rate of dying from other causes. There is a 1.5- to 2-fold increased risk of cardiovascular disease, independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating and preventing cardiovascular disorders, further increasing their risk of medical complications.Cardiologists may not recognize underlying depression that complicates a cardiovascular problem under their care.

Immune System Processes And Depression

Spurred in part by the evidence of the strong association between depression and coronary heart disease, researchers have begun to examine the potential role of the immune system, and particularly proinflammatory cytokines, in the link between stress and depression . Recent models have proposed that chronic stress activates the immune system in a way that leads to inflammation, and that chronic inflammation in turn leads to symptoms of depression as well as pathological processes underlying heart disease . Cytokines are signaling molecules that coordinate inflammation in response to pathogens and include interleukin-1, interleukin-6 , and tumor necrosis factor-. Among other functions, they direct white blood cells toward infections, signaling them to divide and activating their killing mechanisms. Downstream products of this process, including C-reactive protein , a molecule produced by the liver in response to IL-6, are used as an index of the inflammatory response.

Although in its early stages, research on inflammatory responses suggests an additional biological process that may help to explain the link between stress and depression. And inflammatory processes may be especially important in elucidating important medical comorbidities of depression, most notably coronary heart disease.

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Are You Disabled If You Have Psychotic Depression

Major depressive disorder, under which psychotic depression falls, is considered a disability by the Americans with Disabilities Act .

A person with psychotic depression must be given reasonable accommodations, including a flexible work schedule, and is offered protection against discrimination, such as with employment or housing.

Psychological Causes Of Depression

Understanding Major Depression


Psychological Causes of Depression The actual causes of depression are still unknown today but there are a few theories that could help explain them. It is widely believed by psychologists and scientists that all mental disorders are brought about by a complex correlation of psychological, biological, and social factors. A serious loss, chronic illness, relationship problem, work stress, family crisis, financial setback, or any unwelcome life change can ignite a depressive disorder . Depression is a serious disorder in the United States and has only become more prevalent among individuals as their lives become more stressful and overwhelming. One theory for the cause of depression is the bio-psycho-social model of causation and is the most commonly recognized theory for the cause of disorders such as depression by professionals. As stated earlier, it consists of a complicated correlation of psychological, biological, and social factors.

This can be caused by fluctuated levels of hormones, which would explain why many people first experience depression during puberty. . The exact causes of depression are vast and unknown. Some types of depression have been found in families from generation to generation, which may possibly suggest that it can be inherited . With that said, major depression seems to be present generation after generation, in some families, but not with a frequency that suggests clear biological causes.

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Analysis Of Published Papers

In the past decade, the total number of papers on depression published worldwide has increased year by year as shown in Fig. 1A. Searching the Web of Science database, we found a total of 43,863 papers published in the field of depression from 2009 to 2019 or ts = ) and py = , Articles). The top 10 countries that published papers on the topic of depression are shown in Fig. 1B. Among them, researchers in the USA published the most papers, followed by China. Compared with the USA, the gap in the total number of papers published in China is gradually narrowing , but the quality gap reflected by the index is still large, and is lower than the global average . As shown in Fig. 1E, the hot research topics in depression are as follows: depression management in primary care, interventions to prevent depression, the pathogenesis of depression, comorbidity of depression and other diseases, the risks of depression, neuroimaging studies of depression, and antidepressant treatment.

Fig. 1

Analysis of published papers around the world from 2009 to 2019 in depressive disorder. A The total number of papers . B The top 10 countries publishing on the topic. C Comparison of papers in China and the USA. D Citations for the top 10 countries and comparison with the global average. E Hot topics.

Analysis Of Clinical Trial

There are 6,516 clinical trials in the field of depression in the database, and among them, 1,737 valid trials include the ongoing recruitment of subjects, upcoming recruitment of subjects, and ongoing clinical trials. These clinical trials are mainly distributed in the USA , Canada , China , France , Germany , UK , Spain , Denmark , Sweden , and Switzerland . The indications for clinical trials include various types of depression, such as minor depression, depression, severe depression, perinatal depression, postpartum depression, and depression comorbid with other psychiatric disorders or physical diseases, such as schizophrenia, epilepsy, stroke, cancer, diabetes, cardiovascular disease, and Parkinson’s disease.

Based on the database of the Chinese Clinical Trial Registry website, a total of 143 clinical trials for depression have been carried out in China. According to the type of research, they are mainly interventional and observational studies, as well as a small number of related factor studies, epidemiological studies, and diagnostic trials. The research content involves postpartum, perinatal, senile, and other age groups with clinical diagnosis and intervention studies . It also includes intervention studies on depression comorbid with coronary heart disease, diabetes, and heart failure.

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Can Certain Drugs Cause Depression

In certain people, drugs may lead to depression. For example, medications such as barbiturates, benzodiazepines, and the acne drug isotretinoin have sometimes been linked with depression, especially in older people. Likewise, medications such as corticosteroids, opioids , and anticholinergics taken to relieve stomach cramping can sometimes cause changes and fluctuations in mood. Even blood pressure medications called beta-blockers have been linked to depression.

Personal Vulnerabilities To Depression

Biological Theories of Major Depressive Disorder | Psychopathology

As noted earlier, etiological approaches to depression commonly invoke diathesis-stress models, in which stress precipitates depressive reactions among those with particular vulnerabilities. In this section, several nonbiological vulnerabilities are discussed: cognitive, interpersonal, and personality factors. As with biological factors, psychosocial vulnerabilities may contribute to the development of depression and also may be consequences of depressive states in a bidirectional process.

Cognitive Vulnerability to Depression

Considerable research on depression in the past 40 years has focused on three variants of cognitive models of depressionthe classical cognitive triad model of Aaron Beck , the versions of the helplessness/hopelessness cognitive style models of Seligman, Abramson, Alloy, and colleagues , and information-processing perspectives .

The information-processing approach to cognitive vulnerability refers to dysfunctional cognitive processes, such as biases in attention and memory, and overgeneralized thinking style . Such biases may result in selective attention to negative information and reduced access to positive memories, increasing the likelihood of dysphoric reactions to negative events.

Interpersonal Vulnerabilities to Depression

Personality Vulnerabilities

Integrative Research

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How Stress Affects The Body

Stress can be defined as an automatic physical response to any stimulus that requires you to adjust to change. Every real or perceived threat to your body triggers a cascade of stress hormones that produces physiological changes. We all know the sensations: your heart pounds, muscles tense, breathing quickens, and beads of sweat appear. This is known as the stress response.

The stress response starts with a signal from the part of your brain known as the hypothalamus. The hypothalamus joins the pituitary gland and the adrenal glands to form a trio known as the hypothalamic-pituitary-adrenal axis, which governs a multitude of hormonal activities in the body and may play a role in depression as well.

When a physical or emotional threat looms, the hypothalamus secretes corticotropin-releasing hormone , which has the job of rousing your body. Hormones are complex chemicals that carry messages to organs or groups of cells throughout the body and trigger certain responses. CRH follows a pathway to your pituitary gland, where it stimulates the secretion of adrenocorticotropic hormone , which pulses into your bloodstream. When ACTH reaches your adrenal glands, it prompts the release of cortisol.

The boost in cortisol readies your body to fight or flee. Your heart beats faster up to five times as quickly as normal and your blood pressure rises. Your breath quickens as your body takes in extra oxygen. Sharpened senses, such as sight and hearing, make you more alert.

What Does Depression Look Like

Well raise your question with a few Qs of our own: Are you female? Are you a teen? Depression can also affect different ages and genders in unique ways:

Women are more likely to ruminate . This can look like negative self-talk, sudden crying spells, feelings of guilt, or blaming oneself. Women are also more likely to have depression at the same time as an anxiety disorder, such as panic disorder, eating disorder, or obsessive-compulsive behavior.

Men with depression are more likely to show signs of irritability, anger, apathy, escapist behavior , or reckless behavior .

Younger people can struggle with depression and MDD . Children and teens may sometimes exhibit oversensitivity, social withdrawal, poor school performance, frequent physical complaints , or feelings of incompetence and despair .

Older adults and the elderly are often misdiagnosed or undertreated for depression because their symptoms can be mistaken for other disorders , or they may assume their feelings are just an inevitable part of aging. For many, sadness isnt the biggest indicator of depression instead, physical complaints are often the predominant symptom. Sleep trouble, low motivation, neglect of personal care or hygiene, and fixation on death are other signs of depression in older adults.

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Geneenvironment Interaction In Major Depression: Focus On Experience

  • 1IRCCS Fatebenefratelli San Giovanni di Dio, Brescia, Italy
  • 2Faculty of Psychology, eCampus University, Novedrate, Como, Italy
  • 3Department of Psychiatry and Neuroscience Program, McLean Hospital, Harvard Medical School, Belmont, MA, USA
  • 4Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Kings College London, London, UK
  • 5Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy

Environmental And Personal Vulnerabilities

Major depressive disorder
  • Etiological models for depression are largely diathesis-stress models in which stressful experiences trigger depression in those who may be vulnerable due to biological and psychosocial characteristics and circumstances.
  • Environmental stressors associated with depression include acute life events, chronic stress, and childhood exposure to adversity. Personal vulnerabilities associated with depression include cognitive, interpersonal, and personality factors.
  • Biological, environmental, and personal vulnerabilities interact to contribute to the development of depression and also may be affected by depressive states in a bidirectional process.

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Genetic Findings In Major Depression

Studies of variants associated with single genes are mostly equivocal in terms of effect sizes and specificity. For instance, studies of the promoter polymorphism of the serotonin transporter suggest a weak moderating effect on major depression and associated traits and more robust effects on neural endophenotypes that relate to general risk for psychopathology and vulnerability to affective disorders . Conversely, rare coding or gain-or-function mutation in genes such as SERT , monoamine oxidase A and disrupted in schizophrenia implicate single genes in severe major mental illnesses, but the observed phenotypes are complex, mixed and often severe, including combinations of depression, obsessive-compulsive disorder, substance abuse disorders, with aggression, schizoaffective and psychotic features, and in some cases suggesting strong developmental contributions. Together these studies significantly contributed to lowering boundaries between major depression and other categorical psychiatric disorders and provided leads for investigating pathophysiological mechanisms with implications beyond their original areas of investigation .

Enhancing Healthcare Team Outcomes

An interdisciplinary approach is essential for the effective and successful treatment of MDD. Primary care physicians and psychiatrists, along with nurses, therapists, social workers, and case managers, form an integral part of these collaborated services. In the majority of cases, PCPs are the first providers to whom individuals with MDD present mostly with somatic complaints. Depression screening in primary care settings is very imperative. The regular screening of the patients using depression rating scales such as PHQ-9 can be very helpful in the early diagnosis and intervention, thus improving the overall outcome of MDD. Psychoeducation plays a significant role in improving patient compliance and medication adherence. Recent evidence also supports that lifestyle modification, including moderate exercises, can help to improve mild-to-moderate depression. Suicide screening at each psychiatric visit can be helpful to lower suicide incidence. Since patients with MDD are at increased risk of suicide, close monitoring, and follow up by mental health workers becomes necessary to ensure safety and compliance with mental health treatment. The involvement of families can further add to a better outcome of the overall mental health treatment. Meta-analyses of randomized trials have shown that depression outcomes are superior when using collaborative care as compared with usual care.

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Stress As A Cause Of Depressive Disorders

Chronic stress and stressful life events early in life are strong proximal predictors of the onset of depression. Although the response to stress implies stability or maintenance of homeostasis, long-time activation of the stress system can cause harmful or even fatal consequences by elevating the risk of obesity, heart diseases, depression, and other disorders . The Hypothalamicpituitaryadrenal axis and its three main componentshypothalamic neurosecretory cells, pituitary gland, and adrenal cortexare responsible for adaptation to changed environmental conditions and for mobilization of the organism’s reserves during exposure to stress of different etiologies. The HPA system operates in the following way .1). In response to a stressor, neurons in the hypothalamic paraventricular nuclei secrete corticotropin-releasing hormone , which exerts its action on the hypophysis to initiate the release into the blood circulation of adrenocorticotropic hormone , which stimulates the release of corticosteroids, particularly cortisol, from the adrenal cortex. The final hormonal product of the HPA axis, cortisol, binds to mineralocorticoid receptors and glucocorticoid receptors to form hormonereceptor complexes, which are then transported into the cell nucleus where they interact with specific DNA regions, the glucocorticoid-response elements, to activate the expression of hormone-dependent genes .

What Is The Outlook For Someone With Major Depressive Disorder

Session 2: Neurobiology of Major Depressive Disorder and Bipolar Disorder

While someone with MDD can feel hopeless at times, its important to remember that the disorder can be treated successfully. There is hope.

To improve your outlook, its critical to stick with your treatment plan. Dont miss therapy sessions or follow-up appointments with your healthcare professional.

Never stop taking your medications unless your therapist or healthcare professional advises you to.

On days when you feel particularly depressed despite treatment, it can be helpful to call a local crisis or mental health service or the National Suicide Prevention Lifeline. Resources are available.

A friendly, supportive voice could be just what you need to get you through a difficult time.

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Epigenetic Mechanisms As Mediators Of The Effect Of The Environment On The Genome: Focus On Dna Methylation And Mirnas

The term epigenetics refers to the potentially heritable, but environmentally modifiable, regulation of genetic function and expression . Among epigenetic processes, DNA methylation is one of the major epigenetic processes studied in the context of early life adversities as a potential mechanism to explain the long-term effects on gene transcription . DNA methylation is a covalent modification of the cytosine residues that are located primarily at CpG dinucleotide sequences in mammals methylation changes within promoter and enhancer regions of the gene are particularly important as they reduce the access of transcription factors to regulatory elements and promote silencing of gene expression . The contribution of DNA methylation has been extensively investigated especially in the context of pathologies related to exposure to stressful life events including depression or post-traumatic stress disorder .

Studies conducted both in animal models and in humans have shown that ELS can leave persistent epigenetic marks on the genome, which can influence neurobiological substrates until adulthood . Indeed, early-life exposures can disrupt epigenetic programing in the brain, with long-lasting consequences for gene expression and behavior .

We summarized the above-mentioned studies on epigenetics in Table 2.

Table 2. Correlation between epigenetic modification, stress, and genetics.

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