Depression is a complex disease with multiple contributing causes, including a variety of lifestyle, dietary, environmental, and genetic factors. While we still don\u2019t fully understand what causes depression, scientists have recently discovered a variety of new potential links between gut health, inflammation, and the brain — and some early evidence suggests that these links may even play a significant role in behavior and mental health. Read on to learn more about what the latest science has to say about these potential connections, and the mechanisms that might be potentially involved!<\/p>\n
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Depression<\/a> — also referred to as Unipolar Depression<\/em> and Major Depressive Disorder<\/em> — is a complex disease with many contributing factors, including a wide variety of lifestyle, dietary, genetic, and environmental factors.<\/p>\n In short, we still don’t completely understand what causes depression. Moreover, conflicting results have arisen from studies that look at the effectiveness of antidepressants for the treatment of depression.<\/p>\n The only effective treatments — neurotransmitter reuptake inhibitors — still have only relatively low efficacy, as up to 30-40 % of patients do not respond to these drugs, and 60-70% of patients do not experience full remission (R<\/a>, R<\/a>).<\/p>\n In addition, these medications can take a long time to become effective even in patients who do<\/em> respond well to them; and many patients experience a number of severe side-effects while taking them.<\/p>\n The primary diagnostic criteria for depression include (R<\/a>):<\/p>\n However, note that not every symptom is required to be present in order to be diagnosed with depression: most patients only have a subset of the full \u201ccore\u201d symptoms.<\/p>\n Some of the known factors that can increase a person\u2019s risk of experiencing depression include (R<\/a>):<\/p>\n Neurotransmitters are chemicals that our neurons use to transmit signals from one cell to another. There are over 100 different types of neurotransmitters, although some of the most well-known ones include serotonin<\/a>, dopamine<\/a>, and norepinephrine<\/a>.<\/p>\n The majority of the most common or widely-used antidepressant medications (such as citalopram<\/em><\/a> and many others) generally act by increasing the amount of the neurotransmitters serotonin and norepinephrine available in the brain (i.e. selective serotonin reuptake inhibitors<\/em> or serotonin-norepinephrine reuptake inhibitors<\/em>, or \u201cSSRIs\u201d and \u201cSNRIs\u201d, respectively).<\/p>\n However, some other antidepressants — such as bupropion<\/em> (Wellbutrin) — act primarily on dopamine and norepinephrine (i.e. norepinephrine-dopamine reuptake inhibitors<\/em>, or \u201cNDRIs\u201d).<\/p>\n Nonetheless, it remains an unanswered question whether low levels of serotonin<\/a> or norepinephrine directly cause<\/em> depression. For example, numerous scientific attempts to confirm that depressed people actually have<\/em> abnormally low levels of these neurotransmitters have sometimes failed to fully verify a connection (R<\/a>, R<\/a>).<\/p>\n Another major methodological limitation in our understanding of depression is that although antidepressants have established biochemical mechanisms (such as inhibiting monoamine oxidase<\/em><\/a> (MAO), or inhibiting the reuptake of specific neurotransmitters), both the diagnosis and treatment of depression are based largely on subjective<\/em> reports of symptoms, and not on any discrete measurements of specific biochemical markers or other \u201cobjective\u201d biological indicators (R<\/a>). In other words, it\u2019s not as simple as measuring a person\u2019s level of these compounds, and then concluding whether they \u201chave\u201d depression or not.<\/p>\n Furthermore, while most SSRIs immediately increase serotonin levels and activity in the brain, many patients don\u2019t report experiencing a significant improvement in their mood until being on their medication for several weeks or months (R<\/a>). Findings such as these suggest that serotonin levels may merely be the first link in a much more complex chain of mechanisms and biological changes that are collectively involved in depression — and serotonin may just be one piece in this larger puzzle.<\/p>\n The biological mechanisms involved in depression are still something of a mystery. Nonetheless, while the \u201cserotonin deficiency\u201d hypothesis of depression is still controversial and not 100% universally accepted by every researcher out there, at the present moment it is generally considered to be the best working hypothesis based on the overall evidence and data available so far. <\/em><\/div><\/div>\n Just as the attempts to identify specific biochemical \u201cmarkers\u201d of depression have failed, so too have many of the attempts to identify specific genes or genetic mutations responsible for depression been met with only limited success — possibly because different cases of depression may be caused by mutations in many different genes, as well as unique environmental factors (R<\/a>).<\/p>\n Several comprehensive studies (including genome-wide association studies, as well as familial and twin studies) have reported evidence suggesting that interactions between large numbers of individual genes — as well as the complex interactions of these genes with certain environmental factors — may be partly responsible for some cases or types of depression [R<\/a>].<\/p>\n For example, one systematic genome-wide association study<\/em> (GWAS) reported that a number of genes related to immune system function and inflammation<\/a> may be among the possible genetic factors that influence a person\u2019s risk of depression (R<\/a>).<\/p>\n Another comprehensive GWAS study reportedly identified a number of genes related to serotonin function, circadian rhythm<\/a>, and other neurotransmitters as possible genetic risk factors for depression<\/a>, as listed in this table [R<\/a>]:<\/p>\nDiagnostic Criteria for Depression<\/strong><\/span><\/h3>\n
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Known Risk Factors for Depression<\/strong><\/span><\/h3>\n
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Is Depression Really Caused by Low Serotonin?<\/strong><\/span><\/h3>\n
Genetics of Depression<\/strong><\/span><\/h3>\n