Depression is a neuropsychiatric disorder characterized by negative mood, loss of interest in doing things, and metabolic, hormonal, and immune disturbances that can degrade a person's quality of life and increase their risk of disease and death. The World Health Organization estimates that approximately 322 million people – more than 4 percent of the global population – currently live with depression,[1] the most common mental health disorder worldwide. Between 2005 and 2015 (the most recent years for which robust meta-analyses are available), the number of people living with depression worldwide increased by more than 18 percent.[1] It is estimated that only one-third of people struggling with depression receive treatment.[2]

Your subscription could not be saved. Please try again.

* You'll also receive updates from Rhonda & FoundMyFitness

Clinicians diagnose depression as major depressive disorder based on a set of diagnostic criteria including one of two primary symptoms – depressed mood (e.g., sadness, irritability) and/or anhedonia (i.e., loss of interest or pleasure in doing things) – and four or more secondary symptoms – appetite or weight changes; sleep difficulties (e.g., insomnia or sleeping too much); psychomotor agitation (e.g., restlessness, pacing) or retardation (e.g., difficulty caring for oneself); fatigue or loss of energy; diminished ability to think or concentrate; difficulty making decisions; feelings of worthlessness or excessive guilt; and suicidal ideation, intent, or behavior.[3]

Prevention at a glance

A variety of lifestyle behaviors and risk factors may affect the development of depression, including:

  • Aerobic exercise alleviated depressive symptoms better than standard depression care in a meta-analysis of twenty-four studies including over 4,000 patients. Aerobic exercise was particularly effective in alleviating depressive symptoms in people with cardiovascular disease.[4]
  • People with abdominal obesity have a 38 percent greater risk of developing depression than those with a lean BMI. This relationship remained even after taking gender and age into account.[5]
  • Increased burden of white matter hyperintensities and lacunar infarcts, symptoms of cerebral small vessel disease, was associated with greater depression risk among 3,800 participants without dementia. Cerebral microbleeds, a marker of advanced small vessel disease, were associated with severe depression symptoms.[6]
  • Polyphenols, such as those found in berries and green tea, were found to reduce the risk of depression and alleviate depression severity among 39 studies – both observational and interventional.[7]
  • People who drink sugar-sweetened beverages (about three cans per day of cola) have an approximately 25 percent higher risk of depression than non-consumers.[8]
  • Whole-body hyperthermia has been shown in a few clinical trials to alleviate symptoms of depression.[9][10]
  • Higher vitamin D levels were associated with lower rates of depression. Additionally, a meta-analysis of randomized controlled trials (a very robust form of scientific evidence) suggests that vitamin D supplementation alleviates depression severity; however, the number of trials included in the analysis was small, highlighting the need for additional trials.
  • High zinc intake was associated with a 28 percent lower risk of depression in a meta-analysis of observational and interventional studies. Additionally, zinc supplementation significantly lowered depressive symptom scores among depressed patients.[11] ## Depression increases the risk of disease and death

Several adverse medically and socially significant outcomes are associated with depression, which may elicit multigenerational effects due to genetic and epigenetic influences.[12] People with depression are at greater risk of developing numerous chronic diseases, including cardiovascular disease, type 2 diabetes, cognitive decline, and osteoporosis. In addition, chronic, severe depression that is untreated or accompanied by severe physical pain may increase the risk of suicide. More than half (56 to 87 percent) of people who attempt or die by suicide have depression.[13]

A confluence of factors contributes to depression

Despite the recent increase in its prevalence, depression is not a newly identified condition. References to depressive illness were common among the medical texts of ancient Greek physicians, who believed that depression arises from disturbances in the natural balance of the body's four fluids, or humors, which included blood, phlegm, yellow bile, and black bile. To their thinking, too much of the latter – the black bile – produced a dark state of melancholia, a construct that dominated medical thought until the 1600s.[14]

Today, the etiology of depression remains only partially elucidated but is likely multifactorial, stemming from a confluence of psychological, physiological, and environmental elements. In addition, having a chronic medical condition increases a person's risk of developing depression. Conversely, depression can be a symptom of certain medical conditions, such as Parkinson's disease, multiple sclerosis, hypothyroidism, or Cushing's disease. [15] [16] [17]

Inflammation

Another key player in the pathophysiology of depression is inflammation, a critical element of the body's immune system. Inflammation is a conserved biological response that developed during humans' ancient past when regular exposure to pathogens dictated highly coordinated behavioral and immunological responses to ensure survival. The fallout of these responses is an "inflammatory bias"– a propensity for the body to launch an indiscriminate response to a stressor, regardless of its source.[18]

Inflammation involves immune cells, cell-signaling proteins, and proinflammatory factors. Whereas acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever, chronic inflammation occurs on the cellular level in response to internal and external stressors and is often "invisible." Chronic inflammation is instrumental in the development of many diseases, including depression. Elevated biomarkers of inflammation, commonly observed in people with depression, chronically activate the body's inflammatory response system, promoting the development of depressive symptoms and inducing changes in brain and neuroendocrine function.[19] [20]

Compelling evidence suggests that the relationship between inflammation and depression is indeed causal. At least two double-blinded, placebo-controlled studies investigated the effects of injecting healthy adults with either lipopolysaccharide (also known as endotoxin – a component of bacterial cell membranes that elicits an immune response) or interferon-gamma, a proinflammatory cytokine.[21] [22] Injection of either the endotoxin or the interferon-gamma increased the study participants' circulating levels of proinflammatory cytokines, including interleukin (IL)-6 and tumor necrosis factor-alpha. Interestingly, in both studies, participants also experienced an acute increase in depressive symptoms, anxiety, feelings of social disconnection, and anhedonia (a lack of reactivity to pleasurable stimuli) [23] that coincided with the peak of the inflammatory response.

"Injection of either endotoxin or interferon-gamma increased participants' circulating levels of proinflammatory cytokines, and participants experienced an acute increase in depressive symptoms, anxiety, feelings of social disconnection, and anhedonia." Click To Tweet

Neurogenesis

Whereas the early view of the mammalian central nervous system presumed that it was a static complex incapable of change, a growing body of evidence suggests that it retains its capacity for synaptic pruning – the process that eliminates extra neurons and synaptic connections and establishes new neural circuits to increase the efficiency of neuronal transmissions – throughout life.[20]

Establishing these new circuits depends upon adequate neurogenesis, the process of forming new neurons. Neurogenesis is essential during embryonic development but continues in certain brain regions throughout the human lifespan. In particular, areas within the hypothalamus and the olfactory bulb serve as "neurogenic niches," where nascent neurons can undergo differentiation and integration.[24] Derangements in adult neurogenesis and subsequent connectivity losses or failures have been implicated in depression and may further impede responsiveness to antidepressant therapies.[20] [25]

Mice with impaired adult neurogenesis exhibit sustained stress hormone levels and display depressive-like symptoms.[26] In addition, mice exposed to an acute psychosocial stressor at the time of nerve cell generation produced fewer new cells. Furthermore, the cells were less likely to survive long-term if the stressor occurred after nerve cell generation.[27]

Several factors contribute to impaired neurogenesis, including hyperactivity of the HPA axis; insufficient production of neurotrophins (neural growth factors), particularly brain-derived neurotrophic factor, or BDNF; inflammation; and perturbed gut microbial signaling.[20]

Circadian rhythms

Circadian rhythms, the body's 24-hour biological, hormonal, and behavioral cycles, modulate various physiological processes, including producing hormones that regulate sleep, hunger, metabolism, and others. Roughly 10 to 40 percent of gene expression in mammals is under circadian control, including genes in the brain, liver, and muscle.[28][29] As such, circadian rhythmicity may have profound implications for mental health and mood.[30]

External cues, termed zeitgebers, or "time givers," provide cues to the body's internal clocks to regulate behavioral, hormonal, and biochemical processes. Food intake and light exposure are the two most potent zeitgebers, and alterations in a person's exposure to these cues, whether from shift work, late-night eating, or other variations from the regular day-night cycles of activity that entrain our bodies, elicit harmful effects on human health.

For example, light directly influences the production of melatonin, a hormone that regulates the body's response to darkness and ultimately influences mood. People who experience seasonal affective disorder, commonly known as SAD, show significant improvement following melatonin administration.[31] In addition, people who have depression often exhibit cyclical patterns of depressive symptoms, typically manifesting more severe symptoms in the morning hours.[32] [33]

Emotional or physical trauma, especially early in life, plays a vital role in the pathophysiology of depression. It is a robust risk factor for developing depression in adulthood, especially in response to additional stress.[34]

"Emotional or physical trauma, especially early in life, plays a key role in the pathophysiology of depression. It is a robust risk factor for developing depression in adulthood, especially in response to additional stress." Click To Tweet

The body responds to stress by activating a complex set of self-regulating, adaptive processes, including behavioral and physiological components, to ensure survival. A key element in the stress response is the activation of the hypothalamus-pituitary-adrenal, or HPA, axis, a complex set of interactions that sits at the interface between stress and brain function.

Activation of the HPA axis begins when the hypothalamus releases the neurohormones corticotropin-releasing factor and arginine vasopressin into the blood vessels that connect the hypothalamus and the pituitary gland. The two neurohormones stimulate the anterior pituitary gland to produce and secrete adrenocorticotropic hormone into the bloodstream, promoting the synthesis and release of glucocorticoid hormones – primarily cortisol – from the adrenal glands. Prolonged cortisol secretion increases the risk of developing depression. Several neurotransmitters, including gamma-aminobutyric acid, endogenous opioids, norepinephrine, and serotonin, among others, work in concert in a series of negative feedback loops to modulate the activation of the HPA axis.[35]

However, hyperactivity of the HPA axis is common in psychiatric disorders, including depression.[36] For example, in animal studies involving rodents and non-human primates, young animals separated from their mothers for long periods exhibit HPA axis activity changes that persist into adulthood and resemble those observed in depressed people, including hyperactivity of the HPA axis.[37] Similarly, clinical studies of women sexually or physically abused in childhood exhibit enhanced HPA axis activation in adulthood.[38]

Genetic predisposition

Genetic factors contribute to a person's susceptibility to depression. Findings from a meta-analysis that investigated the genetic epidemiology of depression indicate that roughly one-third to one-half of the risk for developing depression is due to genetic influences. Environmental exposures, such as early life trauma, parenting styles, socioeconomic status, and others – also play a role. However, these exposures are unique to each individual, suggesting that depression is likely due to gene-environment interactions.[39] A different meta-analysis that used data on more than 800,000 people from three large genome-wide association studies of depression identified 269 genes, 102 independent variants, and 15 gene sets that were associated with depression, some of which influence synaptic structure and neurotransmission.[40]

"A meta-analysis that used data on more than 800,000 people from three large genome-wide association studies of depression identified 269 genes, 102 independent variants, and 15 gene sets associated with depression." Click To Tweet

Interestingly, genetic factors and circadian rhythms are intrinsically linked. For example, the NPAS2 gene encodes for the protein Npas2, which functions in the brain as a generator and maintainer of circadian rhythm. It descends from the same ancestral gene as the CLOCK gene, which encodes for the protein Clock, a key regulator of circadian rhythms. In the absence of Clock, the production of Npas2 increases to maintain rhythms in the suprachiasmatic nucleus, the part of the brain that acts as the master regulator or "pacemaker" of circadian rhythms. Mice that lack the NPAS2 gene exhibit sleep disturbances.[41]

Furthermore, in a study of more than 500 Spanish adults, those who carried two of the G alleles (G;G) for the NPAS2 gene had a 2.88-fold increased risk of major depression or bipolar disorder. Carriers of only one allele experienced a similar but lesser magnitude effect, with a 1.44-fold increased risk.[42]

Pharmaceuticals

Depression is a side effect of many prescription drugs, especially isotretinoin (an anti-acne drug); varenicline (commonly known as Chantix®, a smoking-cessation drug); rimonabant and taranabant (anti-obesity drugs); and many classes of cardiovascular drugs, including beta-blockers, calcium channel blockers, and angiotensin II inhibitors.[43] Cardiovascular drugs are commonly prescribed for older adults, and, as mentioned above, the widespread practice of polypharmacy among many older adults places this population at greater risk of developing depression.[43]

"Depression is a side effect of many prescription drugs; isotretinoin (anti-acne drug); varenicline (smoking-cessation drug); and cardiovascular drugs (beta-blockers, calcium channel blockers, and angiotensin II inhibitors.)" Click To Tweet

Gut microbes

The gut-brain axis, a bidirectional signaling pathway between the gastrointestinal tract and the nervous system, is critical to mental health. Key elements of this pathway are the tens of trillions of bacteria, viruses, and fungi that comprise the intestinal microbiota. Stress, diet, and mood can work together or independently to influence the gut microbial population, ultimately promoting dysbiosis – an imbalance in its overall composition – and a lack of microbial diversity.[44] Dysbiosis and low diversity contribute to altered immune function, deranged appetite and metabolism, and mood changes.[45]

Gut microbes also influence dietary choices, which, in turn, influence which microbes survive.[46] [47] Adherence to a Western diet, which is high in processed foods, refined sugar, and saturated fats, promotes a misfit population of microbes that chronically activates the body's immune system.[48] [49] This cycle of stress, poor dietary choices, and immune responses sets the stage for self-sustaining systemic inflammation and low mood.

Nutrition

Research demonstrates that people with depression are often deficient in several key nutrients involved in modulating inflammation, neurogenesis, and aspects of metabolism, including folate, vitamins B6 and B12, and omega-3 fatty acids. [50] [51] A prospective study of more than 16,000 people in Spain demonstrated that deficiency in more than four essential micronutrients was associated with increased risk for developing depression.[52]

"Research demonstrates that people with depression are often deficient in several key nutrients involved in modulating inflammation, neurogenesis, and aspects of metabolism, including folate, vitamins B6 and B12, and omega-3 fatty acids" Click To Tweet

Depressed people often exhibit unhealthy dietary patterns, such as poor or excessive appetite, skipping meals, "emotional eating," or preferential consumption of sweet foods.[53] Some of these behaviors are likely due to derangements in brain function. For example, whereas depression-related loss of appetite is associated with poor interoception (the ability to perceive sensations from inside the body, including hunger), depression-related increases in appetite are associated with hyperactivity in the brain's reward circuitry.[54]

Multiple studies have found low serum levels of zinc in people with depression. [55] This association has also been noted among cases of treatment-resistant depression, and the level of zinc deficiency seems linked to the severity of depressive symptoms. [56] [57] [58] In one preclinical study, zinc chloride supplementation was found to significantly improve depression symptoms when combined with antidepressant drugs including SSRIs, tricyclic antidepressants (TCAs), and the atypical antidepressant bupropion (brand name Wellbutin), which is a norepinephrine-dopamine reuptake inhibitor (NDRI).[59] Zinc supplementation combined with the use of a multivitamin has also been shown to reduce anger and depression compared to the use of a multivitamin alone.[60]

Special populations

Women

The global prevalence of depression among women is nearly twice that in men, with an annual prevalence of 5.5 percent and 3.2 percent, respectively.[61] This difference persists across races, cultures, and socioeconomic status, suggesting that the risk may stem from biological sex differences. Women also experience specific forms of depression-related illness, including premenstrual dysphoric disorder, postpartum depression, postmenopausal depression, and anxiety, which often coincide with periods of major hormonal changes, such as those that occur during puberty, before menstruation, following pregnancy, and at perimenopause, indicating female hormonal fluctuations may serve as a trigger for depression.

"The global prevalence of depression among women is nearly twice that in men, with an annual prevalence of 5.5% and 3.2%, respectively" Click To Tweet

Animal studies consistently implicate female hormones in the etiology of depression. For example, in studies involving small groups of female macaques (which tend to form lifelong relationships with defined social orders comprised of dominant and subordinate members), subordinate females tend to develop behavioral patterns and physiological characteristics commonly observed in human depression, including low activity levels, increased heart rate, stress-response disturbances, and higher death rates.[62] These phenotypic traits were associated with lower serotonin receptor levels and lower hippocampal volume, the latter of which was more extensive in postmenopausal monkeys, suggesting that ovarian hormones, including estrogen, may lessen depression risk.[63] [64] Some evidence indicates that hormone replacement therapy, particularly during the perimenopausal period, may be useful in preventing postmenopausal depression in women.[65]

Children & adolescents

Approximately two to four percent of children and eight percent of adolescents living in the United States report having depression in any given year.[66] Children and adolescents who experience a depressive episode are more likely to have recurrent depression as adults and are at greater risk for suicide.[66] Depression risk factors for this population are varied and include female sex, family history of depression, chronic health conditions, overweight or obesity, experiencing a traumatic event (including natural disasters), witnessing or being a victim of violence, uncertainty about sexual orientation or gender identity, and living with family members who have mental or substance abuse disorders, among others.[66]

Older adults

Depression is less common in older adults (65 years and older) than younger adults. Suicide rates, however, are higher among older adults than any other demographic.[67] Depression in older adults may be masked by other health conditions, complicating diagnosis and treatment.[67] The common practice of polypharmacy – the simultaneous use of multiple drugs (typically five or more) by a single patient – in older adults may increase their risk of developing depression.[43]

Prognosis

Nearly everyone has experienced an episode of low mood and has simultaneously recovered. Clinical depression, however, is more often a chronic disorder that may last months, years, or even a lifetime. The long-term prognosis is unfavorable, and few people with depression experience full recovery. Despite the overly optimistic view of depression and recovery in the lay world and even in the medical field, more than 80 percent of people who experience an episode of depression will likely still suffer from the disorder six years later.[68]

Managing depressive symptoms

Selective serotonin reuptake inhibitors (SSRIs) in conjunction with cognitive behavioral therapy are typically the first line of treatment for people who have depression. The response to treatment with SSRIs is moderate and variable, ranging from 40 to 60 percent, with remission rates ranging from 30 to 45 percent.[69]

Several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating the symptoms of depression (including treatment-resistant depression) and include public health interventions, physical activity, dietary modification, meditation, sauna use, and light therapy, among others.

Public health interventions

Strategies for treating older adults with depression that utilize structured activities (such as exercise) and problem-solving strategies, in conjunction with psychotherapy and/or antidepressants, effectively reduce the number of days the participants experienced depressive symptoms. In a study involving more than 400 older adults seen in primary care clinics, those randomized to intervention programs involving exercise or problem-solving strategies experienced an average of 115 more depression-free days per year than those who received the typical care.[43]

"In a study involving more than 400 older adults, those randomized to intervention programs involving exercise or problem-solving strategies experienced an average of 115 more depression-free days per year than those who received the typical care." Click To Tweet

Physical activity

Exercise, particularly endurance or high-intensity aerobic exercise, may impact kynurenine metabolism in a way that is beneficial for creating resilience against stress-induced depression.

Several observational studies have found that physically active people are less likely to develop depression. For example, a Mendelian randomization study – a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population – demonstrated that higher levels of physical activity may be causally linked with a reduced risk for depression.[70] Numerous randomized-controlled trials have found that exercise mitigates depressive symptoms, facilitates recovery from depressive disorders, and prevents relapse. For example, a meta-analysis of 25 randomized controlled trials comparing exercise versus control groups found that exercise reduced depressive symptoms, and this effect was particularly robust for moderate- to vigorous-intensity aerobic exercise.[71]

Exercise and physical activity promote a wide range of neurogenic and neuroprotective responses that mediate depressive symptoms, such as increases in tryptophan transport into the brain to support serotonin, prevention of the formation of neurotoxins associated with depression, increases in anti-inflammatory factors, and increases in the neurotrophin BDNF. [72] [73] [74] [75]

Dietary modification

Many scientific studies suggest that adherence to a diet rich in fruits, vegetables, and fatty fish is associated with reduced depressive symptoms. [76] [77] In a 12-week randomized controlled trial involving people who had moderate to severe depression who received either dietary support that encouraged the consumption of healthy foods versus social support only, those who received the dietary support had fewer symptoms of depression at the end of the trial.[78]

Fruits and vegetables provide essential nutrients such as folate and B vitamins, but, perhaps more importantly, they deliver bioactive compounds such as [polyphenols]https://www.foundmyfitness.com/topics/polyphenols), carotenoids, isothiocyanates, stilbenes, and others. These compounds elicit hormetic responses in the body that trigger mild cellular stress, which, in turn, induces beneficial stress response pathways that reduce inflammation and protect cells from damage.[79]

Omega-3 fatty acids

Fatty fish (such as salmon) provide omega-3 fatty acids with essential anti-inflammatory, immunomodulatory, and neuroprotective properties.[80] Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 fatty acids in fatty fish and fish oil supplements, promote the production of anti-inflammatory mediators such as resolvins and protectins.[81] In a trial involving 28 people with depression, participants who took an omega-3 fatty acid supplement experienced marked improvements in their depressive symptoms compared to those who took a placebo.[82] In a separate trial involving 20 people with recurrent depression, participants who took an omega-3 fatty acid supplement in conjunction with their antidepressant therapy showed marked reductions in their symptoms.[83] Findings from a meta-analysis of studies investigating the therapeutic value of omega-3 fatty acids suggest that administration of high-dose supplemental omega-3 fatty acids in conjunction with antidepressant therapies offer the greatest promise in treating the symptoms of depression.[84]

"A meta-analysis of studies investigating the therapeutic value of omega-3 fatty acids suggest that supplemental omega-3 fatty acids in conjunction with antidepressant therapies offer the greatest promise in treating the symptoms of depression." Click To Tweet

Probiotics

Probiotics (present in fermented foods and dietary supplements) are live microorganisms that impart health benefits when consumed. A randomized, triple-blind, placebo-controlled trial involving 20 healthy adults who took a probiotic supplement containing 2.5 billion bacteria per gram of Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) for four weeks experienced reduced reactivity to sad mood, as evidenced by reduced rumination and aggressive thoughts. These findings suggest that probiotic intake may help reduce negative thoughts associated with a sad mood.[85]

Sauna use

Sauna use has been shown to reduce symptoms of depression, likely through its effects on the expression of heat shock proteins, transcriptional regulators, and pro- and anti-inflammatory factors.

In a randomized controlled trial involving 28 people diagnosed with mild depression, participants who received four weeks of sauna sessions experienced reduced symptoms of depression – such as improved appetite and reduced body aches and anxiety – compared to the control group, which received bed rest instead of sauna therapy.[9] Similarly, in a randomized, double-blind study of 30 healthy adults diagnosed with depression, participants exposed to a single session of whole-body hyperthermia in which core body temperature increased to 38.5°C (101.3°F) experienced an acute antidepressant effect that was apparent within a week of treatment and persisted for six weeks after treatment.[10]

"In a randomized, double-blind study on depression, a single session of whole-body hyperthermia elevating core body temperature to 101.3°F caused an acute antidepressant effect within a week and persisted for six weeks after treatment." Click To Tweet

Light therapy

Exposure to bright light, particularly blue light, boosts alertness and improves mood by acting as a robust circadian trigger in the morning and daytime hours. A study involving 20 healthy men and women who were kept in an environment free of time cues for about ten days found that seven hours of exposure to approximately 10,000 lux of bright light, roughly equivalent to the amount of light available at dawn or dusk, reduced participants' cortisol levels. Participants exposed to dim light, similar to candlelight, experienced little change in cortisol levels.[86]

Bright light may interfere with sleep patterns at night, however, by triggering the release of melanopsin, a light-sensitive protein that shifts the activity of cells in the brain's suprachiasmatic nucleus into an active day pattern. More than 80 percent of depressed patients report poor sleep quality, a common feature of depression.[87] Poor sleep quality is a decisive risk factor for suicide.[42]

Bright light therapy has long been appreciated as a helpful intervention for people experiencing seasonal affective disorder. Recent research suggests it may be effective in treating non-seasonal depression. In a randomized controlled trial involving 122 adults with depression, bright light treatment, both as monotherapy and combined with the SSRI fluoxetine (commonly known as Prozac®), markedly reduced the participants' symptoms of depression. The combination treatment had the most consistent effects.[88]

Meditation

As described above, emotional stress is a trigger that can increase the risk of developing depression. Some intervention trials have utilized mindfulness and meditation to mitigate stress and reduce this risk. In a study involving 76 adults with moderate stress levels, those who received mindfulness meditation training experienced greater improvements in their depressive symptoms than those who received only health education. A meta-analysis of 47 studies involving more than 3,500 people found mindfulness meditation moderately effective at reducing anxiety, depression, and pain.[89]

Transcranial direct current stimulation

Non-invasive brain stimulation is an effective therapy to mitigate depression. Transcranial direct current stimulation, or tDCS, utilizes a weak electrical current delivered to scalp electrodes via a portable battery-powered stimulator.[90] It modulates brain activity in a desired region or neural network by strengthening or weakening synaptic transmissions between neurons, thereby enhancing the synapses' ability to change their strength – a critical feature of neuronal development and normal brain functions.[91] [92]

In a double-blind, randomized, sham-controlled trial involving 30 adults who demonstrated poor response to SSRI therapy, participants who received tDCS showed marked improvements in their depressive symptoms, and these improvements persisted one month after the treatment.[93]

The ability to interpret or "read" emotions such as anger, disgust, or happiness on others' faces is often impaired in people with depression. A randomized cross-over placebo-controlled study involving 17 adults with depression demonstrated that tDCS improved emotion recognition deficits commonly associated with depression.[94]

Psychedelics

Psychedelic drugs, a class of hallucinogenic compounds that includes lysergic acid diethylamide, otherwise known as LSD, mescaline, psilocybin, and others, have long been known for their psychoactive properties. These drugs work partly by activating the 5-HT2A serotonin receptors, which modulate various physiological functions, including mood. Recent research suggests that these drugs may help treat the symptoms of depression.

A randomized, double-blind, cross-over trial that investigated the effects of psilocybin in people diagnosed with life-threatening cancer found that the drug mitigated symptoms of depression and anxiety. Approximately 80 percent of the study participants continued to experience these positive effects on mood six months later.[95] In addition, in an open-label feasibility trial involving 12 adults with treatment-resistant depression, participants experienced marked decreases in symptoms of depression, anxiety, and anhedonia following psilocybin administration.[96]

Modulation of the immune system by psychedelics

Interestingly, a growing body of evidence suggests that psychedelic drugs may also modulate the immune system, which may have relevance for depression.[97] Cell studies have demonstrated that an amphetamine psychedelic drug suppresses TNF-alpha-related inflammation and inhibits the production of the proinflammatory cytokine, IL-6, and others through its activation of the serotonin 5-HT2A receptor, in the same fashion as other psychedelic drugs.[98] Similar effects were observed in mice following the administration of an amphetamine psychedelic.[99]

Conclusions

Depression is a complex disorder that affects the lives of millions of people worldwide. Its causes are likely multifactorial and involve the interplay between environment, genetics, neuroendocrine systems, and intracellular signaling pathways. Whereas typical treatment options for depressive symptoms include psychological and pharmacological approaches, a growing body of evidence supports non-pharmacological interventions.

  1. ^ a b Friedrich, M.J. (2017). Depression Is The Leading Cause Of Disability Around The World Jama 317, 15.
  2. ^ Chan, Gary; Mekonen, Tesfa; Connor, Jason P.; Hides, Leanne; Leung, Janni (2021). Estimating The Global Treatment Rates For Depression: A Systematic Review And Meta-Analysis Journal Of Affective Disorders 295, .
  3. ^ Tolentino, Julio C.; Schmidt, Sérgio Luis (2018). DSM-5 Criteria And Depression Severity: Implications For Clinical Practice Frontiers In Psychiatry 9, .
  4. ^ Lavoie, Kim L; Bacon, Simon L; Béland, Mélanie; Briand, Samantha; White, Una J; Gemme, Claudia (2019). Aerobic Exercise Alleviates Depressive Symptoms In Patients With A Major Non-Communicable Chronic Disease: A Systematic Review And Meta-Analysis British Journal Of Sports Medicine 54, 5.
  5. ^ Anderson, Debra; Xu, Qunyan; Lurie-Beck, Janine (2011). The Relationship Between Abdominal Obesity And Depression In The General Population: A Systematic Review And Meta-Analysis Obesity Research & Clinical Practice 5, 4.
  6. ^ Vernooij, Meike W.; Ikram, M. Arfan; Tiemeier, Henning; Niessen, Wiro; Direk, Nese; Verhaaren, Benjamin F J, et al. (2016). Markers Of Cerebral Small Vessel Disease And Severity Of Depression In The General Population Psychiatry Research: Neuroimaging 253, .
  7. ^ Bayes, Jessica; Schloss, Janet; Sibbritt, David (2019). Effects Of Polyphenols In A Mediterranean Diet On Symptoms Of Depression: A Systematic Literature Review Advances In Nutrition 11, 3.
  8. ^ Hu, Danqing; Cheng, Lixiao; Jiang, Wenjie (2019). Sugar-sweetened Beverages Consumption And The Risk Of Depression: A Meta-Analysis Of Observational Studies Journal Of Affective Disorders 245, .
  9. ^ a b Masuda, Akinori; Nakazato, Masamitsu; Kihara, Takashi; Minagoe, Shinichi; Tei, Chuwa (2005). Repeated Thermal Therapy Diminishes Appetite Loss And Subjective Complaints In Mildly Depressed Patients Psychosomatic Medicine 67, 4.
  10. ^ a b Rentscher, Kelly; Janssen, Clemens W.; Lowry, Christopher A.; Mehl, Matthias R.; Allen, John J. B.; Kelly, Kimberly L., et al. (2016). Whole-Body Hyperthermia For The Treatment Of Major Depressive Disorder JAMA Psychiatry 73, 8.
  11. ^ Clark, Cain C T; Keshtkaran, Zahra; Yosaee, Somaye; Ashourpour, Mahkameh; Keshani, Parisa; Soltani, Sepideh (2022). Zinc In Depression: From Development To Treatment: A Comparative/ Dose Response Meta-Analysis Of Observational Studies And Randomized Controlled Trials General Hospital Psychiatry 74, .
  12. ^ Nestler EJ (2014). Epigenetic mechanisms of depression. JAMA Psychiatry 71, 4.
  13. ^ Rihmer, Zoltán (2007). Suicide Risk In Mood Disorders Current Opinion In Psychiatry 20, 1.
  14. ^ Willmuth, Lewis R. (1979). Medical Views Of Depression In The Elderly: Historical Notes Journal Of The American Geriatrics Society 27, 11.
  15. ^ Siegert RJ; Abernethy DA (2005). Depression in multiple sclerosis: a review. J Neurol Neurosurg Psychiatry 76, 4.
  16. ^ Lim, Lee-Ling; Loh, Huai Heng; Yee, Anne; Loh, Huai Seng (2019). Association Between Subclinical Hypothyroidism And Depression: An Updated Systematic Review And Meta-Analysis BMC Psychiatry 19, 1.
  17. ^ Fallo, Francesco; Boscaro, Marco; Sonino, Nicoletta; Fava, Giovanni A.; Raffi, Anna Rita (1998). Clinical Correlates Of Major Depression In Cushing’s Disease Psychopathology 31, 6.
  18. ^ Raison, Charles L.; Miller, Andrew H. (2013). Malaise, Melancholia And Madness: The Evolutionary Legacy Of An Inflammatory Bias Brain, Behavior, And Immunity 31, .
  19. ^ Miller, Andrew H.; Raison, Charles L. (2015). The Role Of Inflammation In Depression: From Evolutionary Imperative To Modern Treatment Target Nature Reviews Immunology 16, 1.
  20. ^ a b c d Villanueva R (2013). Neurobiology of major depressive disorder. Neural Plast 2013, .
  21. ^ Moieni, Mona; Jevtic, Ivana; Olmstead, Richard; Breen, Elizabeth C; Irwin, Michael; Eisenberger, Naomi I (2015). Sex Differences In Depressive And Socioemotional Responses To An Inflammatory Challenge: Implications For Sex Differences In Depression Neuropsychopharmacology 40, 7.
  22. ^ Capuron, Lucile; Pagnoni, Giuseppe; Woolwine, Bobbi; Drake, Daniel F.; Spivey, James R.; Crowe, Ronald J., et al. (2012). Dopaminergic Mechanisms Of Reduced Basal Ganglia Responses To Hedonic Reward During Interferon Alfa Administration Archives Of General Psychiatry 69, 10.
  23. ^ Inagaki, Tristen K; Irwin, Michael; Eisenberger, Naomi I.; Berkman, Elliot T.; Rameson, Lian T.; Mashal, Nehjla M. (2010). Inflammation-Induced Anhedonia: Endotoxin Reduces Ventral Striatum Responses To Reward Biological Psychiatry 68, 8.
  24. ^ Bambico FR; Belzung C (2013). Novel insights into depression and antidepressants: a synergy between synaptogenesis and neurogenesis? Curr Top Behav Neurosci 15, .
  25. ^ Belzung, Catherine; Surget, Alexandre; Arancio, Ottavio; Santarelli, Luca; Saxe, Michael; Gross, Cornelius, et al. (2003). Requirement Of Hippocampal Neurogenesis For The Behavioral Effects Of Antidepressants Science 301, 5634.
  26. ^ Cameron, Heather A; Snyder, Jason S; Soumier, Amélie; Brewer, Michelle; Pickel, James (2011). Adult Hippocampal Neurogenesis Buffers Stress Responses And Depressive Behaviour Nature 476, 7361.
  27. ^ Thomas RM; Hotsenpiller G; Peterson DA (2007). Acute psychosocial stress reduces cell survival in adult hippocampal neurogenesis without altering proliferation. J Neurosci 27, 11.
  28. ^ Labrecque N; Cermakian N (2015). Circadian Clocks in the Immune System. J Biol Rhythms 30, 4.
  29. ^ Zhang, Ray; Lahens, Nicholas F.; Ballance, Heather I.; Hughes, Michael E.; Hogenesch, John B. (2014). A Circadian Gene Expression Atlas In Mammals: Implications For Biology And Medicine Proceedings Of The National Academy Of Sciences 111, 45.
  30. ^ Germain, Anne; Kupfer, David J. (2008). Circadian Rhythm Disturbances In Depression Human Psychopharmacology: Clinical And Experimental 23, 7.
  31. ^ Jackman, Angie; Lewy, Alfred J.; Emens, Jonathan; Yuhas, Krista (2006). Circadian Uses Of Melatonin In Humans Chronobiology International 23, 1-2.
  32. ^ Gordijn MC; Beersma DG; Bouhuys AL; Reinink E; Van den Hoofdakker RH (1994). A longitudinal study of diurnal mood variation in depression; characteristics and significance. J Affect Disord 31, 4.
  33. ^ Tölle, R.; Goetze, U. (1987). On The Daily Rhythm Of Depression Symptomatology Psychopathology 20, 5-6.
  34. ^ Nemeroff, Charles B; Heim, Christine; Mletzko, Tanja; Miller, Andrew H.; Newport, D. Jeffrey (2008). The Link Between Childhood Trauma And Depression: Insights From HPA Axis Studies In Humans Psychoneuroendocrinology 33, 6.
  35. ^ Stephens MA; Wand G (2012). Stress and the HPA axis: role of glucocorticoids in alcohol dependence. Alcohol Res 34, 4.
  36. ^ Lightman, Stafford; Pariante, Carmine (2008). The HPA Axis In Major Depression: Classical Theories And New Developments Trends In Neurosciences 31, 9.
  37. ^ Nemeroff, Charles B; Heim, Christine (2002). Neurobiology Of Early Life Stress: Clinical Studies Seminars In Clinical Neuropsychiatry 7, 2.
  38. ^ Nemeroff, Charles B; Heim, Christine; Mletzko, Tanja; Purselle, David; Musselman, Dominique L. (2008). The Dexamethasone/Corticotropin-Releasing Factor Test In Men With Major Depression: Role Of Childhood Trauma Biological Psychiatry 63, 4.
  39. ^ Sullivan, Patrick F.; Neale, Michael C.; Kendler, Kenneth S. (2000). Genetic Epidemiology Of Major Depression: Review And Meta-Analysis American Journal Of Psychiatry 157, 10.
  40. ^ 23andMe Research Team; Major Depressive Disorder Working Group Of The Psychiatric Genomics Consortium; McIntosh, Andrew M; Lewis, Cathryn M; Wray, Naomi R; Trzaskowski, Maciej, et al. (2019). Genome-wide Meta-Analysis Of Depression Identifies 102 Independent Variants And Highlights The Importance Of The Prefrontal Brain Regions Nature Neuroscience 22, 3.
  41. ^ Franken, Paul; Dudley, Carol A.; Erbel-Sieler, Claudia; Estill, Sandi Jo; Reick, Martin; Pitts, SiNae, et al. (2003). Altered Patterns Of Sleep And Behavioral Adaptability In NPAS2-Deficient Mice Science 301, 5631.
  42. ^ a b Martorell, Lourdes; Soria, Virginia; Urretavizcaya, Mikel; Garcia, Cecilia; Martínez-Amorós, Èrika; Escaramís, Geòrgia, et al. (2010). Differential Association Of Circadian Genes With Mood Disorders: CRY1 And NPAS2 Are Associated With Unipolar Major Depression And CLOCK And VIP With Bipolar Disorder Neuropsychopharmacology 35, 6.
  43. ^ a b c d Rogers D; Pies R (2008). General medical with depression drugs associated. Psychiatry (Edgmont) 5, 12.
  44. ^ Elinav, Eran; Rothschild, Daphna; Vila, Arnau Vich; Korem, Tal; Zeevi, David; Shilo, Smadar, et al. (2018). Environment Dominates Over Host Genetics In Shaping Human Gut Microbiota Nature 555, 7695.
  45. ^ Madison, Annelise; Kiecolt-Glaser, Janice K (2019). Stress, Depression, Diet, And The Gut Microbiota: Human–Bacteria Interactions At The Core Of Psychoneuroimmunology And Nutrition Current Opinion In Behavioral Sciences 28, .
  46. ^ Tennoune, N; Chan, P; Legrand, R; Akkermann, K; Järv, A; Ouelaa, W, et al. (2014). Bacterial ClpB Heat-Shock Protein, An Antigen-Mimetic Of The Anorexigenic Peptide α-MSH, At The Origin Of Eating Disorders Translational Psychiatry 4, 10.
  47. ^ Zwiers, Marcel P.; Boekhorst, Jos; Timmerman, Harro M.; Netea, Mihai G.; Buitelaar, Jan K.; Arias Vasquez, Alejandro, et al. (2017). Gut Microbiome In ADHD And Its Relation To Neural Reward Anticipation Plos One 12, 9.
  48. ^ Brown, Kirsty; DeCoffe, Daniella; Molcan, Erin; Gibson, Deanna L. (2012). Diet-Induced Dysbiosis Of The Intestinal Microbiota And The Effects On Immunity And Disease Nutrients 4, 8.
  49. ^ Kolodziejczyk, Aleksandra A; Levy, Maayan; Thaiss, Christoph A.; Elinav, Eran (2017). Dysbiosis And The Immune System Nature Reviews Immunology 17, 4.
  50. ^ Payette, H; Morais, J A; Gaudreau, P; Shatenstein, B; Gray-Donald, K; Gougeon, Laura (2015). Intakes Of Folate, Vitamin B6 And B12 And Risk Of Depression In Community-Dwelling Older Adults: The Quebec Longitudinal Study On Nutrition And Aging European Journal Of Clinical Nutrition 70, 3.
  51. ^ Godos, Justyna; Castellano, Sabrina; Galvano, Fabio; Grosso, Giuseppe (2019). Linking Omega-3 Fatty Acids And Depression Omega Fatty Acids In Brain And Neurological Health , .
  52. ^ Sánchez-Villegas, Almudena; Pérez-Cornago, Aurora; Zazpe, Itziar; Santiago, Susana; Lahortiga, Francisca; Martínez-González, Miguel Angel (2017). Micronutrient Intake Adequacy And Depression Risk In The SUN Cohort Study European Journal Of Nutrition 57, 7.
  53. ^ Penninx, Bwjh; Visser, Marjolein; Brouwer, I A; Paans, Nadine Pg; Gibson-Smith, Deborah; Bot, Mariska, et al. (2019). Depression And Eating Styles Are Independently Associated With Dietary Intake Appetite 134, .
  54. ^ Simmons, W. Kyle; Avery, Jason; Burrows, Kaiping; Kerr, Kara L.; Bodurka, Jerzy; Savage, Cary R., et al. (2016). Depression-Related Increases And Decreases In Appetite: Dissociable Patterns Of Aberrant Activity In Reward And Interoceptive Neurocircuitry American Journal Of Psychiatry 173, 4.
  55. ^ McLoughlin, I. J.; Hodge, J. S. (1990). Zinc In Depressive Disorder Acta Psychiatrica Scandinavica 82, 6.
  56. ^ DOI: 10.1016/s0006-3223(96)00365-4
  57. ^ Amani, Reza; Nematpour, Sorour; Saeidi, Somaye; Nazari, Zahra (2009). Correlation Between Dietary Zinc Intakes And Its Serum Levels With Depression Scales In Young Female Students Biological Trace Element Research 137, 2.
  58. ^ DOI: 10.1016/0165-0327(94)90117-1
  59. ^ Machado, Daniele G.; Capra, Juliano C.; Cunha, Mauricio Peña; Rodrigues, Ana Lúcia S; Bettio, Luis (2008). Interaction Of Zinc With Antidepressants In The Tail Suspension Test Progress In Neuro-Psychopharmacology And Biological Psychiatry 32, 8.
  60. ^ Sawada, T; Yokoi, K (2010). Effect Of Zinc Supplementation On Mood States In Young Women: A Pilot Study European Journal Of Clinical Nutrition 64, 3.
  61. ^ DOI: 10.1016/s0140-6736(13)61611-6
  62. ^ Shively, Carol A.; Register, Thomas C.; Friedman, David P.; Morgan, Timothy M.; Thompson, Jalonda; Lanier, Tasha (2005). Social Stress-Associated Depression In Adult Female Cynomolgus Monkeys (Macaca Fascicularis) Biological Psychology 69, 1.
  63. ^ Willard, Stephanie L.; Friedman, David P.; Henkel, Craig K.; Shively, Carol A. (2009). Anterior Hippocampal Volume Is Reduced In Behaviorally Depressed Female Cynomolgus Macaques Psychoneuroendocrinology 34, 10.
  64. ^ Shively, Carol A.; Friedman, David P.; Gage, H. Donald; Bounds, Michael C.; Brown-Proctor, Clive; Blair, Joseph B., et al. (2006). Behavioral Depression And Positron Emission Tomography–Determined Serotonin 1A Receptor Binding Potential In Cynomolgus Monkeys Archives Of General Psychiatry 63, 4.
  65. ^ Gordon, Jennifer L.; Girdler, Susan S. (2014). Hormone Replacement Therapy In The Treatment Of Perimenopausal Depression Current Psychiatry Reports 16, 12.
  66. ^ a b c Siu, Albert L.; On Behalf Of The U.S. Preventive Services Task Force (2016). Screening For Depression In Children And Adolescents: U.S. Preventive Services Task Force Recommendation Statement Annals Of Internal Medicine 164, 5.
  67. ^ a b Chapman DP; Perry GS (2008). Depression as a major component of public health for older adults. Prev Chronic Dis 5, 1.
  68. ^ Schoevers, Robert; Verduijn, Judith; Verhoeven, Josine E.; Milaneschi, Yuri; Van Hemert, Albert M.; Beekman, Aartjan T. F., et al. (2017). Reconsidering The Prognosis Of Major Depressive Disorder Across Diagnostic Boundaries: Full Recovery Is The Exception Rather Than The Rule BMC Medicine 15, 1.
  69. ^ Carvalho, A. F.; Cavalcante, J. L.; Castelo, M. S.; Lima, M. C. O. (2007). Augmentation Strategies For Treatment-Resistant Depression: A Literature Review Journal Of Clinical Pharmacy And Therapeutics 32, 5.
  70. ^ For The Major Depressive Disorder Working Group Of The Psychiatric Genomics Consortium; Klimentidis, Yann; Choi, Karmel W.; Chen, Chia-Yen; Stein, Murray B.; Wang, Min-Jung, et al. (2019). Assessment Of Bidirectional Relationships Between Physical Activity And Depression Among Adults JAMA Psychiatry 76, 4.
  71. ^ Vancampfort, Davy; Richards, Justin; Rosenbaum, Simon; Schuch, Felipe Barreto; Ward, Philip; Stubbs, Brendon (2016). Exercise As A Treatment For Depression: A Meta-Analysis Adjusting For Publication Bias Journal Of Psychiatric Research 77, .
  72. ^ Melancon, Michel O.; Lorrain, Dominique; Dionne, Isabelle J. (2012). Exercise Increases Tryptophan Availability To The Brain In Older Men Age 57–70 Years Medicine & Science In Sports & Exercise 44, 5.
  73. ^ Ruas, Jorge; Westerblad, Håkan; Andersson, Daniel; Schlittler, Maja; Goiny, Michel; Agudelo, Leandro Z., et al. (2016). Endurance Exercise Increases Skeletal Muscle Kynurenine Aminotransferases And Plasma Kynurenic Acid In Humans American Journal Of Physiology-Cell Physiology 310, 10.
  74. ^ Jankord, Ryan; Jemiolo, Bozena (2004). Influence Of Physical Activity On Serum IL-6 And IL-10 Levels In Healthy Older Men Medicine & Science In Sports & Exercise 36, 6.
  75. ^ Schmolesky MT; Webb DL; Hansen RA (2013). The effects of aerobic exercise intensity and duration on levels of brain-derived neurotrophic factor in healthy men. J Sports Sci Med 12, 3.
  76. ^ Goldhaber-Fiebert, Jeremy; Lewis, Megan A; Ma, Jun; Rosas, Lisa Goldman; Lv, Nan; Xiao, Lan, et al. (2019). Effect Of Integrated Behavioral Weight Loss Treatment And Problem-Solving Therapy On Body Mass Index And Depressive Symptoms Among Patients With Obesity And Depression Jama 321, 9.
  77. ^ For The MooDFOOD Prevention Trial Investigators; Penninx, Bwjh; Van Grootheest, Gerard; Visser, Marjolein; Brouwer, I A; Owens, Matthew, et al. (2019). Effect Of Multinutrient Supplementation And Food-Related Behavioral Activation Therapy On Prevention Of Major Depressive Disorder Among Overweight Or Obese Adults With Subsyndromal Depressive Symptoms Jama 321, 9.
  78. ^ Hodge, A M; Cotton, Sue; Mihalopoulos, Cathrine; Opie, Rachelle; Dash, Sarah; Jacka, Felice N., et al. (2017). A Randomised Controlled Trial Of Dietary Improvement For Adults With Major Depression (The ‘SMILES’ Trial) BMC Medicine 15, 1.
  79. ^ Son, Tae Gen; Camandola, Simonetta; Mattson, Mark P. (2008). Hormetic Dietary Phytochemicals NeuroMolecular Medicine 10, 4.
  80. ^ Simopoulos, Artemis P. (2002). Omega-3 Fatty Acids In Inflammation And Autoimmune Diseases Journal Of The American College Of Nutrition 21, 6.
  81. ^ Calder, Philip C (2017). Omega-3 Fatty Acids And Inflammatory Processes: From Molecules To Man Biochemical Society Transactions 45, 5.
  82. ^ DOI: 10.1016/s0924-977x(03)00032-4
  83. ^ Nemets, Boris; Stahl, Ziva; Belmaker, R. H. (2002). Addition Of Omega-3 Fatty Acid To Maintenance Medication Treatment For Recurrent Unipolar Depressive Disorder American Journal Of Psychiatry 159, 3.
  84. ^ Mocking, R J T; Koeter, M W J; Ruhé, H G; Schene, A H; Harmsen, I; Assies, J (2016). Meta-analysis And Meta-Regression Of Omega-3 Polyunsaturated Fatty Acid Supplementation For Major Depressive Disorder Translational Psychiatry 6, 3.
  85. ^ Bosch, Jos A.; Van Hemert, Saskia; Steenbergen, Laura; Sellaro, Roberta; Colzato, Lorenza (2015). A Randomized Controlled Trial To Test The Effect Of Multispecies Probiotics On Cognitive Reactivity To Sad Mood Brain, Behavior, And Immunity 48, .
  86. ^ Jung, Christopher M.; Cajochen, Christian; Wright, Kenneth P.; Lockley, Steven W; Czeisler, Charles; Scheer, Frank, et al. (2010). Acute Effects Of Bright Light Exposure On Cortisol Levels Journal Of Biological Rhythms 25, 3.
  87. ^ Nutt D; Wilson S; Paterson L (2008). Sleep disorders as core symptoms of depression. Dialogues Clin Neurosci 10, 3.
  88. ^ Lam, Raymond; Tam, Edwin M.; Levitt, Anthony J.; Levitan, Robert D.; Michalak, Erin E.; Cheung, Amy H., et al. (2016). Efficacy Of Bright Light Treatment, Fluoxetine, And The Combination In Patients With Nonseasonal Major Depressive Disorder JAMA Psychiatry 73, 1.
  89. ^ Bass, Eric; Singh, Sonal; Berger, Zackary; Goyal, Madhav; Sibinga, Erica M. S.; Gould, Neda F., et al. (2014). Meditation Programs For Psychological Stress And Well-being JAMA Internal Medicine 174, 3.
  90. ^ Taylor, John-Paul; Elder, Greg J (2014). Transcranial Magnetic Stimulation And Transcranial Direct Current Stimulation: Treatments For Cognitive And Neuropsychiatric Symptoms In The Neurodegenerative Dementias? Alzheimer's Research & Therapy 6, 5-8.
  91. ^ Zimerman, Maximo; Hummel, Friedhelm C. (2014). Brain Stimulation And Its Role In Neurological Diseases The Stimulated Brain , .
  92. ^ Wong, T.P.; Howland, Jg; Wang, Y.T. (2009). NMDA Receptors And Disease+C464 Encyclopedia Of Neuroscience , .
  93. ^ Sharafi, Elham; Taghva, Arsia; Arbabi, Mohammad; Dadarkhah, Afsaneh; Ghaderi, Jamshid (2019). Transcranial Direct Current Stimulation For Treatment-Resistant Major Depression: A Double-Blind Randomized Sham-Controlled Trial Clinical EEG And Neuroscience 50, 6.
  94. ^ McLoughlin, D M; Brennan, Sean; Bogue, John; O'Connor, Stephanie; McHugh, Caroline; Glennon, Mark, et al. (2016). Anodal Transcranial Direct Current Stimulation Of The Left Dorsolateral Prefrontal Cortex Enhances Emotion Recognition In Depressed Patients And Controls Journal Of Clinical And Experimental Neuropsychology 39, 4.
  95. ^ Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D, et al. (2016). Psilocybin Produces Substantial And Sustained Decreases In Depression And Anxiety In Patients With Life-Threatening Cancer: A Randomized Double-Blind Trial Journal Of Psychopharmacology 30, 12.
  96. ^ DOI: 10.1016/s2215-0366(16)30065-7
  97. ^ Nichols, Charles; Flanagan, Thomas W. (2018). Psychedelics As Anti-Inflammatory Agents International Review Of Psychiatry 30, 4.
  98. ^ Nichols, Charles; Yu, Bangning; Becnel, Jaime; Zerfaoui, Mourad; Rohatgi, Rasika; Boulares, A. Hamid (2008). Serotonin 5-Hydroxytryptamine2A Receptor Activation Suppresses Tumor Necrosis Factor-α-Induced Inflammation With Extraordinary Potency Journal Of Pharmacology And Experimental Therapeutics 327, 2.
  99. ^ Nau, Felix; Yu, Bangning; Martin, David; Nichols, Charles (2013). Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo Plos One 8, 10.

Topics related to Depression

view all
  • Berberine
    Berberine is a plant-based compound with pharmacological actions that share many features with metformin.
  • Breast milk and breastfeeding
    Breast milk is a complex, dynamic fluid containing nutritional and non-nutritional components that support infant development. Breastfeeding benefits both infants and mothers.
  • Sauna
    Sauna use exposes the body to extreme heat and, in turn, induces protective responses that improve health and may increase healthspan.
  • Brain-derived neurotrophic factor (BDNF)
    BDNF is a growth factor known for its influence on neuronal health and for its role in mediating the beneficial cognitive effects associated with exercise.
  • Omega-3 fatty acids
    Omega-3 fatty acids play critical roles in human health and may be beneficial in ameliorating symptoms associated with chronic health conditions and in combating aging-related diseases.
  • Hydrolyzed collagen
    Hydrolyzed collagen, a mixture of peptides derived from collagen, may improve skin aging, decrease arthritis-induced pain, increase bone mineral density, and reduce hypertension.