Major Depressive Disorder
Disease Details
Family Health Simplified
- Description
- Major depressive disorder is a mood disorder characterized by persistent feelings of sadness, loss of interest, and various emotional and physical problems that interfere with daily functioning.
- Type
- Major Depressive Disorder (MDD) is classified as a mood disorder. It has a complex genetic transmission that is polygenic, meaning it is influenced by multiple genes, each contributing a small effect to the overall risk. While MDD tends to run in families, its inheritance pattern is not straightforward Mendelian but rather involves multiple genetic and environmental factors.
- Signs And Symptoms
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Major Depressive Disorder (MDD) is characterized by a variety of signs and symptoms that significantly impact daily functioning. These include:
- Persistent feelings of sadness, hopelessness, or emptiness
- Loss of interest or pleasure in most or all normal activities, including hobbies and social interactions
- Significant weight loss or gain, or changes in appetite
- Insomnia or excessive sleeping (hypersomnia)
- Fatigue or loss of energy nearly every day
- Feelings of worthlessness or excessive guilt
- Difficulty thinking, concentrating, or making decisions
- Recurrent thoughts of death or suicide, or suicidal behavior
These symptoms must persist for at least two weeks for a diagnosis of MDD. - Prognosis
- Studies have shown that 80% of those with a first major depressive episode will have at least one more during their life, with a lifetime average of four episodes. Other general population studies indicate that around half those who have an episode recover (whether treated or not) and remain well, while the other half will have at least one more, and around 15% of those experience chronic recurrence. Studies recruiting from selective inpatient sources suggest lower recovery and higher chronicity, while studies of mostly outpatients show that nearly all recover, with a median episode duration of 11 months. Around 90% of those with severe or psychotic depression, most of whom also meet criteria for other mental disorders, experience recurrence. Cases when outcome is poor are associated with inappropriate treatment, severe initial symptoms including psychosis, early age of onset, previous episodes, incomplete recovery after one year of treatment, pre-existing severe mental or medical disorder, and family dysfunction.A high proportion of people who experience full symptomatic remission still have at least one not fully resolved symptom after treatment. Recurrence or chronicity is more likely if symptoms have not fully resolved with treatment. Current guidelines recommend continuing antidepressants for four to six months after remission to prevent relapse. Evidence from many randomized controlled trials indicates continuing antidepressant medications after recovery can reduce the chance of relapse by 70% (41% on placebo vs. 18% on antidepressant). The preventive effect probably lasts for at least the first 36 months of use.Major depressive episodes often resolve over time, whether or not they are treated. Outpatients on a waiting list show a 10–15% reduction in symptoms within a few months, with approximately 20% no longer meeting the full criteria for a depressive disorder. The median duration of an episode has been estimated to be 23 weeks, with the highest rate of recovery in the first three months. According to a 2013 review, 23% of untreated adults with mild to moderate depression will remit within 3 months, 32% within 6 months and 53% within 12 months.
- Onset
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Onset: Major depressive disorder (MDD) can occur at any age, but its common onset is during late adolescence to mid-20s. It may also arise later in adulthood.
Nan: If "nan" refers to "not a number," additional context is needed to provide relevant information. If it refers to something else, please clarify. - Prevalence
- The prevalence of major depressive disorder (MDD) varies widely depending on the population and region. Globally, it affects approximately 5% of adults each year. In the United States, about 7% of adults experience MDD annually. Lifetime prevalence rates can be higher, with some studies indicating that up to 20% of people may experience an episode of major depression at some point in their lives.
- Epidemiology
- Major depressive disorder affected approximately 163 million people in 2017 (2% of the global population). The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France. In most countries the number of people who have depression during their lives falls within an 8–18% range.In the United States, 8.4% of adults (21 million individuals) have at least one episode within a year-long period; the probability of having a major depressive episode is higher for females than males (10.5% to 6.2%), and highest for those aged 18 to 25 (17%). Among adolescents between the ages of 12 and 17, 17% of the U.S. population (4.1 million individuals) had a major depressive episode in 2020 (females 25.2%, males 9.2%). Among individuals reporting two or more races, the US prevalence is highest.Major depression is about twice as common in women as in men, although it is unclear why this is so, and whether factors unaccounted for are contributing to this. The relative increase in occurrence is related to pubertal development rather than chronological age, reaches adult ratios between the ages of 15 and 18, and appears associated with psychosocial more than hormonal factors. In 2019, major depressive disorder was identified (using either the DSM-IV-TR or ICD-10) in the Global Burden of Disease Study as the fifth most common cause of years lived with disability and the 18th most common for disability-adjusted life years.People are most likely to develop their first depressive episode between the ages of 30 and 40, and there is a second, smaller peak of incidence between ages 50 and 60. The risk of major depression is increased with neurological conditions such as stroke, Parkinson's disease, or multiple sclerosis, and during the first year after childbirth. It is also more common after cardiovascular illnesses, and is related more to those with a poor cardiac disease outcome than to a better one. Depressive disorders are more common in urban populations than in rural ones and the prevalence is increased in groups with poorer socioeconomic factors, e.g., homelessness. Depression is common among those over 65 years of age and increases in frequency beyond this age. The risk of depression increases in relation to the frailty of the individual. Depression is one of the most important factors which negatively impact quality of life in adults, as well as the elderly. Both symptoms and treatment among the elderly differ from those of the rest of the population.Major depression was the leading cause of disease burden in North America and other high-income countries, and the fourth-leading cause worldwide as of 2006. In the year 2030, it is predicted to be the second-leading cause of disease burden worldwide after HIV, according to the WHO. Delay or failure in seeking treatment after relapse and the failure of health professionals to provide treatment are two barriers to reducing disability.
- Intractability
- Major Depressive Disorder (MDD) is not considered inherently intractable. While it can be challenging to treat and may require a combination of therapies, many individuals respond well to appropriate treatment, which can include medication, psychotherapy, lifestyle changes, and other interventions. Treatment resistance can occur, but various strategies and emerging therapies are available to manage such cases effectively.
- Disease Severity
- Major Depressive Disorder (MDD) is characterized by a persistent and intense feeling of sadness or lack of interest in external stimuli. Disease severity in MDD can vary greatly among individuals and typically ranges from mild to severe. Mild cases involve fewer symptoms and minimal disability in daily functioning, whereas severe cases can greatly impact an individual's ability to function in daily life, potentially leading to significant disability and suicidal thoughts or actions. Severity often dictates the intensity and type of treatment required.
- Healthcare Professionals
- Disease Ontology ID - DOID:1470
- Pathophysiology
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The pathophysiology of depression is not completely understood, but current theories center around monoaminergic systems, the circadian rhythm, immunological dysfunction, HPA-axis dysfunction and structural or functional abnormalities of emotional circuits.
Derived from the effectiveness of monoaminergic drugs in treating depression, the monoamine theory posits that insufficient activity of monoamine neurotransmitters is the primary cause of depression. Evidence for the monoamine theory comes from multiple areas. First, acute depletion of tryptophan—a necessary precursor of serotonin and a monoamine—can cause depression in those in remission or relatives of people who are depressed, suggesting that decreased serotonergic neurotransmission is important in depression. Second, the correlation between depression risk and polymorphisms in the 5-HTTLPR gene, which codes for serotonin receptors, suggests a link. Third, decreased size of the locus coeruleus, decreased activity of tyrosine hydroxylase, increased density of alpha-2 adrenergic receptor, and evidence from rat models suggest decreased adrenergic neurotransmission in depression. Furthermore, decreased levels of homovanillic acid, altered response to dextroamphetamine, responses of depressive symptoms to dopamine receptor agonists, decreased dopamine receptor D1 binding in the striatum, and polymorphism of dopamine receptor genes implicate dopamine, another monoamine, in depression. Lastly, increased activity of monoamine oxidase, which degrades monoamines, has been associated with depression. However, the monoamine theory is inconsistent with observations that serotonin depletion does not cause depression in healthy persons, that antidepressants instantly increase levels of monoamines but take weeks to work, and the existence of atypical antidepressants which can be effective despite not targeting this pathway.One proposed explanation for the therapeutic lag, and further support for the deficiency of monoamines, is a desensitization of self-inhibition in raphe nuclei by the increased serotonin mediated by antidepressants. However, disinhibition of the dorsal raphe has been proposed to occur as a result of decreased serotonergic activity in tryptophan depletion, resulting in a depressed state mediated by increased serotonin. Further countering the monoamine hypothesis is the fact that rats with lesions of the dorsal raphe are not more depressive than controls, the finding of increased jugular 5-HIAA in people who are depressed that normalized with selective serotonin reuptake inhibitor (SSRI) treatment, and the preference for carbohydrates in people who are depressed. Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public. A 2022 review found no consistent evidence supporting the serotonin hypothesis, linking serotonin levels and depression.Immune system abnormalities have been observed, including increased levels of cytokines involved in generating sickness behavior (which shares overlap with depression). The effectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine inhibitors in treating depression, and normalization of cytokine levels after successful treatment further suggest immune system abnormalities in depression.HPA-axis abnormalities have been suggested in depression given the association of CRHR1 with depression and the increased frequency of dexamethasone test non-suppression in people who are depressed. However, this abnormality is not adequate as a diagnosis tool, because its sensitivity is only 44%. These stress-related abnormalities are thought to be the cause of hippocampal volume reductions seen in people who are depressed. Furthermore, a meta-analysis yielded decreased dexamethasone suppression, and increased response to psychological stressors. Further abnormal results have been obscured with the cortisol awakening response, with increased response being associated with depression.Theories unifying neuroimaging findings have been proposed. The first model proposed is the limbic-cortical model, which involves hyperactivity of the ventral paralimbic regions and hypoactivity of frontal regulatory regions in emotional processing. Another model, the cortico-striatal model, suggests that abnormalities of the prefrontal cortex in regulating striatal and subcortical structures result in depression. Another model proposes hyperactivity of salience structures in identifying negative stimuli, and hypoactivity of cortical regulatory structures resulting in a negative emotional bias and depression, consistent with emotional bias studies. - Carrier Status
- Major Depressive Disorder (MDD) does not involve carrier status as it is not a single-gene disorder. Instead, it is a complex condition influenced by a combination of genetic, environmental, and psychological factors.
- Mechanism
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Major depressive disorder (MDD) is a complex and multifactorial mental health condition. The mechanisms underlying MDD involve various neural, psychological, genetic, and environmental factors.
**Mechanism:**
1. **Neurotransmitter Imbalance**: Alterations in the levels of neurotransmitters such as serotonin, norepinephrine, and dopamine are often implicated in MDD. These neurotransmitters play key roles in mood regulation.
2. **Neuroendocrine Dysfunction**: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which controls the body’s stress response, is frequently observed in MDD. Elevated levels of cortisol, a stress hormone, are common.
3. **Neuroplasticity and Brain Structure**: Changes in synaptic plasticity, as well as structural brain differences (e.g., reduced volume in the hippocampus and prefrontal cortex), are associated with MDD. These changes can affect cognitive function and emotional regulation.
**Molecular Mechanisms:**
1. **Genetic Factors**: Certain genetic variations can increase susceptibility to MDD. Polymorphisms in genes related to neurotransmitter systems (e.g., the serotonin transporter gene, 5-HTT) and neurotrophic factors (e.g., brain-derived neurotrophic factor, BDNF) are notable.
2. **Inflammatory Markers**: Elevated levels of pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-alpha) have been found in individuals with MDD, suggesting that inflammation may play a role in the pathophysiology of the disorder.
3. **Epigenetic Modifications**: Epigenetic changes, such as DNA methylation and histone modification, can affect gene expression without altering the DNA sequence, potentially contributing to MDD.
4. **Neurogenesis**: Impaired neurogenesis, especially in the hippocampus, is associated with MDD. Reduced levels of neurotrophic factors such as BDNF can lead to decreased neuron formation and survival.
5. **Glutamatergic System**: Dysregulation of the glutamatergic system, which is involved in excitatory neurotransmission, has been implicated. Overactivity of NMDA receptors and altered synaptic plasticity are potential contributors.
Research into the mechanisms and molecular underpinnings of MDD is ongoing, and understanding these processes is crucial for developing more effective treatments. - Treatment
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Major depressive disorder (MDD) is typically treated using a combination of the following strategies:
1. **Medications**: Antidepressants are commonly prescribed, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and atypical antidepressants.
2. **Psychotherapy**: Cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), and other types of counseling can be effective in treating MDD.
3. **Lifestyle Changes**: Exercise, a healthy diet, and adequate sleep can support overall well-being and may enhance the effects of other treatments.
4. **Other Treatments**: In severe cases, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or other brain stimulation therapies might be considered.
5. **Support Networks**: Involvement in support groups or networks can provide social support and help in managing symptoms.
Treatment plans are often personalized to meet the specific needs of the individual. - Compassionate Use Treatment
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For major depressive disorder (MDD), compassionate use treatments and off-label or experimental treatments are options considered when conventional therapies have failed. Here are some examples:
1. **Ketamine and Esketamine (Spravato):** Originally an anesthetic, ketamine is used off-label at low doses for treatment-resistant depression. Esketamine, an isomer of ketamine, is FDA-approved for use in treatment-resistant depression.
2. **Psilocybin:** The active compound in magic mushrooms is being researched for its potential antidepressant effects. Though still experimental, some studies show promise in treatment-resistant cases.
3. **Transcranial Magnetic Stimulation (TMS):** An FDA-approved treatment that non-invasively stimulates nerve cells in the brain. When standard treatments are ineffective, TMS may be used.
4. **Vagus Nerve Stimulation (VNS):** Initially used for epilepsy, VNS involves implanting a device that sends electrical impulses to the vagus nerve. It has shown potential benefits for treatment-resistant depression.
5. **Omega-3 Fatty Acids:** While not typically first-line treatments, omega-3 supplements are sometimes used off-label due to their potential mood-stabilizing properties.
6. **Anti-inflammatory drugs:** Emerging research suggests that inflammation might play a role in MDD. Anti-inflammatory medications are being studied as potential treatments.
7. **MDMA:** Known for its recreational use, MDMA is being researched in clinical trials for its efficacy in treating PTSD and MDD due to its ability to increase emotional openness.
These treatments are typically considered when standard therapies such as SSRIs, SNRIs, or cognitive behavioral therapy have not been effective. Always consult with a healthcare provider for personalized medical advice and treatment options. - Lifestyle Recommendations
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For major depressive disorder, lifestyle recommendations include:
1. **Regular Exercise**: Engaging in physical activity for at least 30 minutes a day can release endorphins, improve mood, and reduce symptoms of depression.
2. **Healthy Diet**: Eating a balanced diet rich in fruits, vegetables, lean proteins, and whole grains can positively affect mental health.
3. **Adequate Sleep**: Establishing a regular sleep schedule and ensuring 7-9 hours of quality sleep per night can help manage depression symptoms.
4. **Stress Management**: Techniques such as meditation, yoga, and deep-breathing exercises can help reduce stress levels.
5. **Social Support**: Maintaining social connections and seeking support from friends, family, or support groups can provide emotional comfort.
6. **Avoid Alcohol and Drugs**: Reducing or eliminating the use of alcohol and recreational drugs can prevent exacerbation of depressive symptoms.
7. **Mindfulness and Relaxation Activities**: Practices like mindfulness meditation, progressive muscle relaxation, and engaging in hobbies can improve overall well-being.
8. **Routine and Structure**: Establishing a daily routine can provide a sense of normalcy and purpose.
9. **Professional Help**: Regular therapy sessions with a psychologist or counselor, and following prescribed medications and treatments by a psychiatrist can significantly aid in managing the disorder. - Medication
- Major depressive disorder (MDD) is commonly treated with medications known as antidepressants. These include selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline, serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). The choice of medication often depends on the individual's specific symptoms, side effect profile, and any co-existing medical conditions. It may take some time to find the most effective medication and dosage. Regular follow-up with a healthcare provider is essential for monitoring response and adjusting treatment as necessary.
- Repurposable Drugs
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Current research into repurposing drugs for Major Depressive Disorder (MDD) has identified several candidates, although their efficacy and safety must be validated through clinical trials. Some promising examples include:
1. **Ketamine**: Originally an anesthetic, ketamine has shown rapid-acting antidepressant effects in treatment-resistant MDD.
2. **Modafinil**: Typically used to treat narcolepsy, modafinil has potential off-label use for MDD, particularly for cognitive symptoms.
3. **Minocycline**: An antibiotic that has anti-inflammatory properties, minocycline is being explored for its potential benefits in MDD.
4. **Pindolol**: A beta-blocker used for hypertension, pindolol has been investigated for its ability to augment the effects of SSRIs in MDD treatment.
These repurposed drugs offer new avenues for treatment, especially for those who do not respond to traditional antidepressants. - Metabolites
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Major depressive disorder (MDD) is associated with alterations in various metabolites, which can be detected in bodily fluids like blood and cerebrospinal fluid. These metabolites include those involved in neurotransmitter pathways, such as serotonin, dopamine, and norepinephrine. The exact levels and profiles of these metabolites can vary, but abnormalities in the metabolism of amino acids, lipids, and energy production molecules have also been reported in individuals with MDD.
If you intended "nan" to mean something specific, could you please provide more context or clarify your question? - Nutraceuticals
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For major depressive disorder (MDD), several nutraceuticals have been studied for their potential benefits. These include:
1. **Omega-3 Fatty Acids**: Found in fish oil, these have been linked to improved mood and cognitive function.
2. **S-Adenosyl Methionine (SAMe)**: This naturally occurring compound has been shown to have antidepressant effects.
3. **St. John’s Wort**: An herbal remedy that may help with mild to moderate depression, though it can interact with other medications.
4. **Folate and Vitamin B12**: These vitamins are essential for brain health and may help reduce symptoms of depression.
5. **Vitamin D**: Low levels of Vitamin D have been associated with depression; supplementation may be beneficial.
6. **Magnesium**: Some studies suggest that magnesium supplementation can improve mood in individuals with depression.
It is important to consult with a healthcare professional before starting any nutraceuticals, as they can interact with medications and other treatments for MDD. - Peptides
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Major depressive disorder (MDD) has been studied in relation to various peptides, which are small chains of amino acids. Important peptides in MDD research include:
1. **Corticotropin-Releasing Hormone (CRH):** Elevated levels can be associated with stress and have been found in people with MDD.
2. **Substance P:** Involved in pain perception and mood regulation, and higher levels have been noted in those with MDD.
3. **Brain-Derived Neurotrophic Factor (BDNF):** Typically decreased in MDD, BDNF plays a crucial role in neuron survival and plasticity.
Nanotechnology is being explored in MDD treatment for its potential to improve drug delivery systems, allowing for targeted delivery to the brain, reducing side effects, and enhancing the efficacy of existing treatments. Nanoparticles can cross the blood-brain barrier more effectively, making them promising candidates for future therapeutic strategies.