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52-577: 4160 17202 ENSG00000166603 ENSMUSG00000047259 P32245 P56450 NM_005912 NM_016977 NP_005903 NP_058673 Melanocortin 4 receptor ( MC 4 R ) is a melanocortin receptor that in humans is encoded by the MC4R gene . It encodes the MC 4 R protein, a G protein-coupled receptor (GPCR) that binds α-melanocyte stimulating hormone (α-MSH). In mouse models, MC 4 receptors have been found to be involved in feeding behaviour,

104-428: A seasonal affective disorder . Outside the mood disorders: borderline personality disorder often features an extremely intense depressive mood; adjustment disorder with depressed mood is a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode; and posttraumatic stress disorder ,

156-544: A "rational response to global conditions", according to Ann Cvetkovich . Psychogeographical depression overlaps somewhat with the theory of "deprejudice", a portmanteau of depression and prejudice proposed by Cox, Abramson, Devine, and Hollon in 2012, who argue for an integrative approach to studying the often comorbid experiences. Cox, Abramson, Devine, and Hollon are concerned with the ways in which social stereotypes are often internalized , creating negative self-stereotypes that then produce depressive symptoms. Unlike

208-420: A diagnosis of a psychiatric or medical condition which may benefit from treatment. The UK National Institute for Health and Care Excellence (NICE) 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, because the risk-benefit ratio is poor. Physical activity has a protective effect against the emergence of depression in some people. There

260-561: A distinction between endogenous (internally caused) and exogenous (externally caused) types. Other psycho-dynamic theories were proposed. Existential and humanistic theories represented a forceful affirmation of individualism. Austrian existential psychiatrist Viktor Frankl connected depression to feelings of futility and meaninglessness . Frankl's logotherapy addressed the filling of an "existential vacuum" associated with such feelings, and may be particularly useful for depressed adolescents. Researchers theorized that depression

312-699: A loved one; and it is also a symptom of some physical diseases and a side effect of some drugs and medical treatments. It may feature sadness , difficulty in thinking and concentration, or a significant increase or decrease in appetite and time spent sleeping. People experiencing depression may have feelings of dejection or hopelessness and may experience suicidal thoughts . Depression can either be short term or long term. Adversity in childhood , such as bereavement, neglect, mental abuse, physical abuse, sexual abuse, or unequal parental treatment of siblings, can contribute to depression in adulthood. Childhood physical or sexual abuse in particular significantly correlates with

364-410: A main symptom. The mood disorders are a group of disorders considered to be primary disturbances of mood. These include major depressive disorder (commonly called major depression or clinical depression) where a person has at least two weeks of depressed mood or a loss of interest or pleasure in nearly all activities; and dysthymia , a state of chronic depressed mood, the symptoms of which do not meet

416-439: A medical diagnosis (cancer, HIV, diabetes, etc.), bullying, loss of a loved one, natural disasters, social isolation, rape, relationship troubles, jealousy, separation, or catastrophic injury . Similar depressive symptoms are associated with survivor's guilt . Adolescents may be especially prone to experiencing a depressed mood following social rejection , peer pressure, or bullying. Depression in childhood and adolescence

468-447: A mental disorder that sometimes follows trauma , is commonly accompanied by depressed mood. Researchers have begun to conceptualize ways in which the historical legacies of racism and colonialism may create depressive conditions. Given the lived experiences of marginalized peoples, ranging from conditions of migration , class stratification , cultural genocide , labor exploitation , and social immobility , depression can be seen as

520-401: A person pleasure or joy gives reduced pleasure or joy, and the afflicted person often experiences a loss of motivation or interest in those activities. Depressed mood is a symptom of some mood disorders , also categorized and called depression , such as major depressive disorder , bipolar disorder and dysthymia . It is a normal temporary reaction to life events, such as the loss of

572-769: A prevalence of 1.0–2.5% in people with body mass indices greater than 30, making it the most commonly known genetic defect predisposing people to obesity. In an exome-wide meta-analysis across three cohorts (UKB,GHS and MCPS), there were 16 genes for which there genetic variants was associated with BMI. Among the 16 genes, the analysis identified two for which rare mutations are known to cause monogenic obesity: MC4R and PCSK1 (proprotein convertase subtilisin/kexin type 1). One study provides genetic evidence linking  rare coding variation to BMI and obesity-related phenotypes. MC4R gene mutations are associated with early-onset severe obesity they effect of mutations on opacity in these two heterozygous coding genes among mutations in

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624-436: A process of self-recognition and identifying familiar stimuli. By maintaining one's personal past and identity, it is a technique that stimulates people to view their lives in a more objective and balanced way, causing them to pay attention to positive information in their life stories, which would successfully reduce depressive mood levels. There is limited evidence that continuing antidepressant medication for one year reduces

676-472: A result of these factors. It is possible that some early generation beta-blockers induce depression in some patients, though the evidence for this is weak and conflicting. There is strong evidence for a link between alpha interferon therapy and depression. One study found that a third of alpha interferon-treated patients had developed depression after three months of treatment. ( Beta interferon therapy appears to have no effect on rates of depression.) There

728-434: A study on academic journal Molecular Psychiatry that depression is not caused by a serotonin imbalance in the human body, unlike what most of the psychiatry community points to, and that therefore anti-depressants do not work against the illness. However, such study was met with criticism from some psychiatrists, who argued the study's methodology used an indirect trace of serotonin, instead of taking direct measurements of

780-437: Is a precursor peptide pro-hormone which is cleaved into several other peptide hormones. All of the endogenous ligands of MC 4 are produced by cleaving this one precursor peptide. These endogenous agonists include α-MSH , β-MSH , γ-MSH , and ACTH . GPCRs can bind a wide variety of extracellular ligands including physiological cations. Biological and pharmacological studies have previously implicated both Zn and Ca in

832-445: Is associated with low extraversion , and people who have high levels of neuroticism are more likely to experience depressive symptoms and are more likely to receive a diagnosis of a depressive disorder. Additionally, depression is associated with low conscientiousness. Some factors that may arise from low conscientiousness include disorganization and dissatisfaction with life. Individuals may be more exposed to stress and depression as

884-500: Is crucial for the access of treatments. The mhGAP adopted its approach of improving detection rates of depression by training general practitioners. However, there is still weak evidence supporting this training. According to 2011 study, people who are high in hypercompetitive traits are also likely to measure higher for depression and anxiety. The term depression was derived from the Latin verb deprimere , "to press down". From

936-404: Is limited evidence suggesting yoga may help some people with depressive disorders or elevated levels of depression, but more research is needed. Reminiscence of old and fond memories is another alternative form of treatment, especially for the elderly who have lived longer and have more experiences in life. It is a method that causes a person to recollect memories of their own life, leading to

988-509: Is limited treatment options for the most common form of monogenic obesity,  MC4R mutations symptoms can be treated with a Glucagon-like Peptide-1 Receptor Agonist liraglutide which cause weight loss by reducing appetite. They found that the effects of liraglutide 3.0 mg daily for 16 weeks causes weight reducing and glucose lowering and may be relevant treatment in the most common form of monogenic obesity. The MC 4 receptor has been shown to interact with proopiomelanocortin (POMC). POMC

1040-794: Is moderately strong evidence that finasteride when used in the treatment of alopecia increases depressive symptoms in some patients. Evidence linking isotretinoin , an acne treatment, to depression is strong. Other medicines that seem to increase the risk of depression include anticonvulsants , antimigraine drugs , antipsychotics and hormonal agents such as gonadotropin-releasing hormone agonist . Several drugs of abuse can cause or exacerbate depression, whether in intoxication, withdrawal, and from chronic use. These include alcohol, sedatives (including prescription benzodiazepines ), opioids (including prescription pain killers and illicit drugs such as heroin), stimulants (such as cocaine and amphetamines), hallucinogens, and inhalants . Depressed mood can be

1092-660: Is shown to be lower than those who do not. Likewise, those from smaller towns and rural areas tend to have higher rates of depression, anxiety, and psychological unwellness. Studies have consistently shown that physicians have had the highest depression and suicide rates compared to people in many other lines of work—for suicide, 40% higher for male physicians and 130% higher for female physicians. Life events and changes that may cause depressed mood includes, but are not limited to, childbirth, menopause, financial difficulties, unemployment, stress (such as from work, education, military service, family, living conditions, marriage, etc.),

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1144-541: Is similar to adult major depressive disorder, although young sufferers may exhibit increased irritability or behavioral dyscontrol instead of the more common sad, empty, or hopeless feelings seen with adults. Children who are under stress, experiencing loss, or have other underlying disorders are at a higher risk for depression. Childhood depression is often comorbid with mental disorders outside of other mood disorders; most commonly anxiety disorder and conduct disorder . Depression also tends to run in families. Depression

1196-472: Is the study of how epigenetics (heritable characteristics that do not involve changes in DNA sequence) contribute to depression. Behavioral theories of depression explain the etiology of depression with behavioral science ; adherents promote the use of behavioral therapies for treatment. Evolutionary approaches to depression are attempts by evolutionary psychologists and evolutionary psychiatrists to use

1248-516: The MC4R gene (C293R and S94N) are: • Rapid weight gains from early age (the most important feature). • Development of severe obesity (BMI ≫97th percentile) at early ages, usually <3 years of age. • Persistent food-seeking behavior, mostly reported from six months of age. • Parental/siblings anthropometric data: suspect if relatives present normal anthropometric data. • Tall stature/increased growth velocity ( MC4R monogenic diabetes). There

1300-513: The Patient Health Questionnaire (PHQ-9). Both of these measures are psychological tests that ask personal questions of the participant, and have mostly been used to measure the severity of depression. The Beck Depression Inventory is a self-report scale that helps a therapist identify the patterns of depression symptoms and monitor recovery. The responses on this scale can be discussed in therapy to devise interventions for

1352-503: The 14th century, "to depress" meant to subjugate or to bring down in spirits. It was used in 1665 in English author Richard Baker's Chronicle to refer to someone having "a great depression of spirit", and by English author Samuel Johnson in a similar sense in 1753. In Ancient Greece, disease was thought due to an imbalance in the four basic bodily fluids, or humors . Personality types were similarly thought to be determined by

1404-431: The brain, and are also thought to be responsible for effects on mood and cognition. Depression (mood) Depression is a mental state of low mood and aversion to activity. It affects about 3.5% of the global population , or about 280 million people of all ages (as of 2020). Depression affects a person's thoughts , behavior , feelings , and sense of well-being . Experiences that would normally bring

1456-579: The central oxytocin system, have been found to promote pair bond formation in prairie voles and, due to these prosocial effects, have been suggested as possible treatments for social deficits in autism spectrum disorders and schizophrenia . In 2008, MC4R mutations were reported to be associated with inherited human obesity . They were found in heterozygotes , suggesting an autosomal dominant inheritance pattern. However, based on other research and observations, these mutations seem to have an incomplete penetrance and some degree of codominance . It has

1508-490: The central nervous system) but might not be bound intracellularly ( Ca concentration: 100 nm), thus suggesting a potential regulatory role for Ca in α-MSH–binding dynamics. Signaling along the phospholipase C pathway can significantly raise the intracellular Ca concentration, and this may constitute positive feedback from signaling of MC 4 receptor or other receptors that result in Ca flux. This discovery highlights

1560-556: The chance of death by suicide by two to three times. In 2017, the British Medical Association found that 49% of UK chronic pain patients also had depression. As many as 1/3 of stroke survivors will later develop post-stroke depression . Because strokes may cause damage to the parts of the brain involved in processing emotions, reward, and cognition, stroke may be considered a direct cause of depression. A number of psychiatric syndromes feature depressed mood as

1612-493: The dominant humor in a particular person. Derived from the Ancient Greek melas , "black", and kholé , "bile", melancholia was described as a distinct disease with particular mental and physical symptoms by Hippocrates in his Aphorisms , where he characterized all "fears and despondencies, if they last a long time" as being symptomatic of the ailment. During the 18th century, the humoral theory of melancholia

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1664-416: The function of multiple members of the melanocortin receptor family. There is Ca in the agonist-bound structure. The researches hypothesize that Ca stabilizes the ligand-binding pocket and functions as an endogenous cofactor for the binding of α-MSH to MC 4 receptor. Ca is likely to bind when the receptor is exposed to extracellular Ca concentrations (~1.2 mM in the extracellular space of

1716-404: The genetic reverberations for subsequent generations. Likewise, research by scientists at Emory University suggests that memories of trauma can be inherited, rendering offspring vulnerable to psychological predispositions for stress disorders , schizophrenia , and PTSD . Measures of depression include, but are not limited to: Beck Depression Inventory-11 and the 9-item depression scale in

1768-1042: The global population has depression, according to a report released by the UN World Health Organization (WHO), which shows an 18 percent increase in the number of people living with depression between 2005 and 2015. Depression is a major mental-health cause of disease burden . Its consequences further lead to significant burden in public health , including a higher risk of dementia , premature mortality arising from physical disorders, and maternal depression impacts on child growth and development. Approximately 76% to 85% of depressed people in low- and middle-income countries do not receive treatment; barriers to treatment include: inaccurate assessment, lack of trained health-care providers, social stigma and lack of resources. The stigma comes from misguided societal views that people with mental illness are different from everyone else, and they can choose to get better only if they wanted to. Due to this more than half of

1820-558: The likelihood of experiencing depression over the survivor's lifetime. People who have experienced four or more adverse childhood experiences are 3.2 to 4.0 times more likely to suffer from depression. Poor housing quality, non-functionality, lack of green spaces , and exposure to noise and air pollution are linked to depressive moods, emphasizing the need for consideration in planning to prevent such outcomes. Locality has also been linked to depression and other negative moods. The rate of depression among those who reside in large urban areas

1872-714: The melanocortin receptor system each with differing specificities for melanocortins : These receptors are inhibited by endogenous inverse agonists agouti signalling peptide and agouti-related peptide , and activated by synthetic (i.e. afamelanotide ) and endogenous agonist melanocyte-stimulating hormones . Several selective ligands for the melanocortin receptors are known, and some synthetic compounds have been investigated as potential tanning, anti-obesity and aphrodisiac drugs, with tanning effects mainly from stimulation of MC 1 , while anorectic and aphrodisiac effects appear to involve both MC 3 and MC 4 . MC 1 , MC 3 and MC 4 are widely expressed in

1924-560: The most distressing symptoms of depression. There are multiple schools of depression theory. Beck's cognitive triad theorizes that an individual with depression has "automatic, spontaneous, and seemingly uncontrollable negative thoughts" about the self, the world or environment, and the future. The Tripartite Model of Anxiety and Depression helps to explain the common comorbidity of anxiety and depression by separating symptoms into three groups: negative affect, positive affect, and physiological hyperarousal. The epigenetics of depression

1976-454: The people with depression do not receive help with their disorders. The stigma leads to a strong preference for privacy. An analysis of 40,350 undergraduates from 70 institutions by Posselt and Lipson found that undergraduates who perceived their classroom environments as highly competitive had a 37% higher chance of developing depression and a 69% higher chance of developing anxiety. Several studies have suggested that unemployment roughly doubles

2028-563: The plasticity and multipronged regulation and control of this receptor and will aid in next-generation structure-based drug design of therapeutics for MC4R -related obesity. This article incorporates text from the United States National Library of Medicine , which is in the public domain . Melanocortin receptor Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors . There are five known members of

2080-839: The receptor in complex with the agonist setmelanotide and the antagonist SHU9119 have been determined. The MC 4 receptor agonist bremelanotide (PT-141), sold under the brand name Vyleesi , was approved in the United States as a treatment for low sexual desire in women in 2019. Melanotan II , a synthetic analog of α-MSH, is marketed to the general population for sexual enhancement by internet retailers . PL-6983 and PF-00446687 are under investigation as potential treatments for both female and male sexual dysfunction , including hypoactive sexual desire disorder and erectile dysfunction . The non-selective melanocortin receptor agonist afamelanotide (NDP-α-MSH) has been found to induce brain-derived neurotrophic factor (BDNF) expression in

2132-554: The region previously identified in the 2009 studies. The rs489693 polymorphism, in particular, sustained a statistically robust signal across three replication cohorts and demonstrated consistent recessive effects. This finding was replicated again by another research group in the following year. In accordance with the above, MC 4 receptor agonists have garnered interest as potential treatments for obesity and insulin resistance, while MC 4 receptor antagonists have attracted interest as potential treatments for cachexia . The structures of

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2184-696: The regulation of metabolism, sexual behaviour, and male erectile function. In 2009, two very large genome-wide association studies of body mass index (BMI) confirmed the association of variants about 150 kilobases downstream of the MC4R gene with insulin resistance , obesity , and other anthropometric traits. MC4R may also have clinical utility as a biomarker for predicting individual susceptibility to drug-induced adverse effects causing weight gain and related metabolic abnormalities. Another GWAS performed in 2012 identified twenty SNPs located ~190 Kb downstream of MC4R in association with severe antipsychotic -induced weight gain. This locus overlapped with

2236-440: The resources available to a population to seek comfort, health, stability, and sense of security. The historical memory of this trauma conditions the psychological health of future generations, making psychogeographical depression an intergenerational experience as well. This work is supported by recent studies in genetic science which has demonstrated an epigenetic link between the trauma suffered by Holocaust survivors and

2288-601: The result of a number of infectious diseases, nutritional deficiencies , neurological conditions, and physiological problems, including hypoandrogenism (in men), Addison's disease , Cushing's syndrome , pernicious anemia , hypothyroidism , hyperparathyroidism , Lyme disease , multiple sclerosis , Parkinson's disease , celiac disease , chronic pain, stroke, diabetes, cancer, and HIV. Studies have found that anywhere from 30 to 85 percent of patients suffering from chronic pain are also clinically depressed. A 2014 study by Hooley et al. concluded that chronic pain increased

2340-496: The risk of depression recurrence with no additional harm. Recommendations for psychological treatments or combination treatments in preventing recurrence are not clear. Depression is the leading cause of disability worldwide, the United Nations (UN) health agency reported, estimating that it affects more than 300 million people worldwide – the majority of them women, young people and the elderly. An estimated 4.4 percent of

2392-783: The risk of developing depression. The World Health Organization has constructed guidelines – known as The Mental Health Gap Action Programme (mhGAP) – aiming to increase services for people with mental, neurological and substance-use disorders. Depression is listed as one of conditions prioritized by the programme. Trials conducted show possibilities for the implementation of the programme in low-resource primary-care settings dependent on primary-care practitioners and lay health-workers. Examples of mhGAP-endorsed therapies targeting depression include Group Interpersonal Therapy as group treatment for depression and "Thinking Health", which utilizes cognitive behavioral therapy to tackle perinatal depression. Furthermore, effective screening in primary care

2444-401: The rodent brain via activation of the MC 4 receptor and mediate "intense" neurogenesis and cognitive recovery in an animal model of Alzheimer's disease . MC 4 receptor antagonists produce pronounced antidepressant - and anxiolytic -like effects in animal models of depression and anxiety . And agonists of the MC 4 receptor such as melanotan II and PF-00446687 , via activation of

2496-475: The severity of a major depressive episode . Another mood disorder, bipolar disorder , features one or more episodes of abnormally elevated mood, cognition , and energy levels, but may also involve one or more episodes of depression. Individuals with bipolar depression are often misdiagnosed with unipolar depression. When the course of depressive episodes follows a seasonal pattern, the disorder (major depressive disorder, bipolar disorder, etc.) may be described as

2548-523: The theory of evolution to further understand mood disorders . The biology of depression is the attempt to identify a biochemical origin of depression, as opposed to theories that emphasize psychological or situational causes. Depressed mood may not require professional treatment, and may be a normal temporary reaction to life events, a symptom of some medical condition, or a side effect of some drugs or medical treatments. A prolonged depressed mood, especially in combination with other symptoms, may lead to

2600-558: The theory of "deprejudice", a psychogeographical theory of depression attempts to broaden study of the subject beyond an individual experience to one produced on a societal scale, seeing particular manifestations of depression as rooted in dispossession; historical legacies of genocide , slavery , and colonialism are productive of segregation, both material and psychic material deprivation, and concomitant circumstances of violence, systemic exclusion, and lack of access to legal protections. The demands of navigating these circumstances compromise

2652-637: Was caused by a chemical imbalance in neurotransmitters in the brain, a theory based on observations made in the 1950s of the effects of reserpine and isoniazid in altering monoamine neurotransmitter levels and affecting depressive symptoms. During the 1960s and 70s, manic-depression came to refer to just one type of mood disorder (now most commonly known as bipolar disorder ) which was distinguished from (unipolar) depression. The terms unipolar and bipolar had been coined by German psychiatrist Karl Kleist . In July 2022, British psychiatrist Joanna Moncrieff , also psychiatrist Mark Horowtiz and others proposed in

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2704-677: Was increasingly being challenged by mechanical and electrical explanations; references to dark and gloomy states gave way to ideas of slowed circulation and depleted energy. German physician Johann Christian Heinroth , however, argued melancholia was a disturbance of the soul due to moral conflict within the patient. In the 20th century, the German psychiatrist Emil Kraepelin distinguished manic depression. The influential system put forward by Kraepelin unified nearly all types of mood disorder into manic–depressive insanity . Kraepelin worked from an assumption of underlying brain pathology, but also promoted

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