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   14 Facts You Didn’t Know About Depression, Including Genetics, Links to Gut   
   Microbes, and Inflammation   
   Posted by Archana   
   Depression is a complex disease with multiple contributing causes, involving   
   both genetics and the environment. In this article, we discuss genetics, gut   
   microbes, the gut-brain axis, as well as links between depression and   
   inflammation.   
      
      
   Contents [hide]   
   Introduction   
   What is Depression?   
   Diagnostic Criteria for Depression   
   Risk Factors for Depression   
   Is Depression Really Caused by Low Serotonin?   
   Genetics of Depression   
   The Gut Microbiome   
   Diet Changes the Microbiome   
   Neurotransmitters and Hormones vs the Gut Microbiome – A Two-Way Interaction   
   How the Gut Microbiome Influences Depression   
   Gut Bacteria Influence Brain Development   
   Manipulation of Gut Bacteria in Mice Changes their Brain and Behaviors   
   Probiotic Supplementation Alleviates Depression in Humans   
   The Gut Microbiota-Brain Connection and Depression   
   The Gut-Brain Axis   
   Inflammation May Contribute to Depression   
   Intestinal Permeability and Depression   
   Gut Bacteria Influence the Stress Response System   
   The Gut Microbe Influences Neurotransmitter Production   
   Bacterial Waste Chemicals can Act as Neurotransmitters   
   Gut Bacteria and Inflammation Affect Serotonin Metabolism   
   How the Gut Bacteria May Affect the Brain   
   Enterochromaffin Cells (ECC) Sense Gut Bacteria and Secrete Serotonin   
   The Vagus Nerve May Link Between the Gut and the Brain   
   Technicals   
   Credits   
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   Introduction   
      
   bigstock-young-woman-suffering-from-a-s-137762819-min   
      
   What is Depression?   
      
   Depression (also named Unipolar Depression, Major Depression, and Major   
   Depressive Disorder) is a complex disease with many contributing factors,   
   including both the genetics and the environment. We still don’t completely   
   understand what causes    
   depression.   
      
   Conflicting results have arisen from studies that look at the effectiveness of   
   antidepressants for the treatment of depression.   
      
   The only effective treatments, neurotransmitter reuptake inhibitors, have low   
   efficacy since 30 – 40 % of patients do not respond to these drugs and 60   
   – 70% of patients do not experience remission (R, R).   
      
   In addition, patients typically experience many severe side effects while   
   these medications can take a long time to see an improvement in mood.   
      
   Diagnostic Criteria for Depression   
      
   Diagnostic criteria for depression include (R):   
      
   Depressed or irritable mood   
   Decreased interest in pleasurable activities and ability to experience pleasure   
   Significant weight gain or loss (>5% change in a month)   
   Insomnia or hypersomnia   
   Psychomotor agitation or retardation   
   Fatigue or loss of energy   
   Feelings of worthlessness or excessive guilt   
   Diminished ability to think or concentrate   
   Recurrent thoughts of death or suicide   
   Risk Factors for Depression   
      
   Known Risk Factors for Depression include (R):   
      
   Females are approximately twice as likely to have depression than males.   
   Highest risk age group is between 25 – 30   
   People who are divorced, separated, or widowed have higher risks of depression   
   than married or people who were never married   
   Lower income than $20,000/year, and rates of depression decline as income   
   increases.   
   Having relatives with early-onset major depression   
   Personality: middle-aged adults (31 – 41 years old) with decreased emotional   
   strength and no interpersonal dependency   
   Stressful life events   
   Early trauma   
   Cardiovascular disease, AIDS, respiratory disorders, cancer, Parkinson’s   
   Is Depression Really Caused by Low Serotonin?   
      
   Most antidepressants aim to increase the amount of the neurotransmitters   
   serotonin and norepinephrine in the synaptic cleft.   
      
   Neurotransmitters are chemicals in our body that transmit signals from one   
   nerve cell to another nerve, muscle cell, or gland cell. They play a major   
   role in shaping everyday life and functions. There are over 100    
   eurotransmitters, including dopamine,    
   norepinephrine, and serotonin.   
      
   However, it remains an unanswered question whether low serotonin and   
   norepinephrine cause depression, because numerous attempts to find confirm   
   that depressed people have low serotonin and norepinephrines have failed (R1,   
   R2).   
      
   Furthermore, while most selective serotonin reuptake inhibitors immediately   
   increase serotonin in the brain, patients don’t experience an improvement in   
   the mood until weeks after starting the medication (R).   
      
   Although antidepressants have established biochemical bases such as inhibition   
   of monoamine oxidase or reuptake of specific neurotransmitters, diagnoses, and   
   treatment of depression are subjectively based on symptoms and not on measured   
   biochemical    
   imbalances (R).   
      
   The fact that this is a complex disease with many different contributing   
   causes but one treatment may account for low treatment response rates.   
      
   Genetics of Depression   
      
   Attempts to identify genes or genetic mutations responsible for depression   
   have been met with limited success, possibly because different cases of   
   depression may be caused by mutations in different genes as well as the   
   environment (R).   
      
   Several comprehensive studies (genome-wide association, familial and twin   
   studies) indicate that interactions of multiple genes, and interactions of   
   these genes and environmental factors are responsible for depression (R, R2).   
      
   A systematic genomic study identified genes related to immune function and   
   inflammation as genetic causes of depression (R).   
      
   Another comprehensive genetic study identified genes related to serotonin   
   functions, circadian rhythm, and other neurotransmitter genes as a risk factor   
   for depression, as listed in this table (R):   
      
   Gene Name	Variant	Minor Allele Frequency   
   5-HTR2A	rs6311	0.44   
   5HT-6R	rs1805054	0.17   
   5HTTLPR/SLC6A4	44 bp ins/del	0.43   
   intron 2 VNTR	0.35   
   ACE	Ins/del intron 16	0.45   
   BDNF	rs16917204	0.24   
   rs2030324	0.46   
   rs988748	0.26   
   rs694	0.43   
   CLOCK	rs1801260	0.22   
   COMT	rs4680	0.39   
   DRD3	rs6280	0.45   
   DRD4	48 bp ins/del	0.45   
   GABRA3	CA repeat intron 8	0.29   
   GNB3	rs5443	0.48   
   HTR1A	rs6295	0.48   
   HTR1B	rs6296	0.35   
   HTR2A	rs6311	0.44   
   rs6313	0.43   
   HTR2C	rs6318	0.17   
   HTR6	rs1805054	0.17   
   MAOA	VNTR promoter	0.34   
   MTHFR	rs1801133	0.32   
   NET/SLC6A2	rs5569	0.27   
   rs2242446	0.26   
   DAT/SLC6A3	VNTR 3-UTR	0.48   
   TPH1	rs1800532	0.36   
   ACMSD (R)	rs2121337 (increased suicidal risk, Quinolinic)	   
      
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