Bipolar disorder causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Nuha Al-Howthi, MD[2]
Overview
A number of factors can be involved in bipolar disorder including genetic, biochemical, psychodynamic, and environmental factors. paternal age increase the risk of bipolar disorder in one’s offspring that could be due to increased genetic mutations during spermatogenesis. Stressful life events may be associated with onset of bipolar disorder and a more severe course of illness.The disorder runs in families. More than two-thirds of people with bipolar disorder have at least one close relative with the disorder or with unipolar major depression. Bipolar disorder is associated with immune system dysregulation.
Causes
Psychosocial factors
- Paternal age increase the risk of bipolar disorder in offspring due to increased genetic mutations during spermatogenesis. As an example, a national registry study found that the risk of bipolar disorder in offspring of fathers 45 years and older was six times greater.[1]
- Stress and a history of childhood physical abuse associated with onset of bipolar disorder and a more severe course of illness.[2][3]
Heritability or inheritance
- More than two-thirds of people with bipolar disorder have at least one close relative with the disorder or with unipolar major depression.[4][./Bipolar_disorder_causes#cite_note-4 [4]]
- Genes that are involved in bipolar disorder have been studied, but no single gene has been identified.[5] it may involve many genes with small effects.[6]
- Studies found several genetic variants are associated with bipolar disorder. One possible locus is CACNA1C, which codes for a calcium channel that is involved in channel gating.[7][8] other genes are ANK3, and CLOCK genes especially bipolar type I disorder.[9][10]
- A meta-analysis suggests that other biologic pathways are cardiac β-adrenergic signaling, cardiac hypertrophy signaling, corticotropin releasing hormone signaling, endothelin 1 signaling, glutamate signaling, and phospholipase C signaling.[11]
- In addition, a meta-analysis studies identified three single-nucleotide polymorphisms on chromosomes 3 and 10. One of them is located on a brain expressed gene that encodes calcium channel subunits; calcium signaling regulates neuronal growth and development.[12][13]
Inflammation
- Bipolar disorder is associated with immune system dysregulation. Cytokines (eg, interleukin-4 and tumor necrosis factor-alpha) and cytokine receptors are elevated in patients with bipolar disorder[14]
- A meta-analysis found that levels of C reactive protein were higher in patients than controls, and the difference was small to moderate.[15]
Biochemical factors
- A number of neurotransmitters have been linked to this disorder.
- Catecholamine hypothesis, state that increase in epinephrine and norepinephrine causes mania and a decrease in epinephrine and norepinephrine causes depression.
- Drugs that increase levels of monoamines, including serotonin, norepinephrine, or dopamine, can all potentially trigger mania for instance drug of abuse like cocaine.[16]
- Patients with substance use-induced psychosis may develop schizophrenia or bipolar disorder within five years.[17]
- A postmortem study of the frontal lobes of individuals with these disorders revealed that the glutamate levels were increased[18].
Neurophysiologic factors
- A meta-analysis shows that decreased activation of gray matter in a cortical-cognitive brain network, which has been associated with the emotion regulation in patients with bipolar disorder. [19]
- There is functional and anatomic alterations in brain networks. for instance, there is activation in ventral limbic brain regions that mediate the experience of emotions. [20]
References
- ↑ Chudal R, Gissler M, Sucksdorff D, Lehti V, Suominen A, Hinkka-Yli-Salomäki S; et al. (2014). "Parental age and the risk of bipolar disorders". Bipolar Disord. 16 (6): 624–32. doi:10.1111/bdi.12182. PMID 24499422.
- ↑ Sugaya L, Hasin DS, Olfson M, Lin KH, Grant BF, Blanco C (2012). "Child physical abuse and adult mental health: a national study". J Trauma Stress. 25 (4): 384–92. doi:10.1002/jts.21719. PMC 3805363. PMID 22806701.
- ↑ Janiri D, Sani G, Danese E, Simonetti A, Ambrosi E, Angeletti G; et al. (2015). "Childhood traumatic experiences of patients with bipolar disorder type I and type II". J Affect Disord. 175: 92–7. doi:10.1016/j.jad.2014.12.055. PMID 25597794.
- ↑ McGuffin, P; Rijsdijk, F; Andrew, M; Sham, P; Katz, R; Cardno, A (2003), "The Heritability of Bipolar Affective Disorder and the Genetic Relationship to Unipolar Depression", Archives of General Psychiatry, 60 (5): 497–502
- ↑ Craddock N, Sklar P (2013). "Genetics of bipolar disorder". Lancet. 381 (9878): 1654–62. doi:10.1016/S0140-6736(13)60855-7. PMID 23663951.
- ↑ Finn CT, Smoller JW (2006). "Genetic counseling in psychiatry". Harv Rev Psychiatry. 14 (2): 109–21. doi:10.1080/10673220600655723. PMID 16603476.
- ↑ Craddock N, Sklar P (2013) Genetics of bipolar disorder. Lancet 381 (9878):1654-62. DOI:10.1016/S0140-6736(13)60855-7 PMID: 23663951
- ↑ Ferreira MA, O'Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L; et al. (2008). "Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder". Nat Genet. 40 (9): 1056–8. doi:10.1038/ng.209. PMC 2703780. PMID 18711365.
- ↑ Sklar P, Smoller JW, Fan J, Ferreira MA, Perlis RH, Chambert K; et al. (2008). "Whole-genome association study of bipolar disorder". Mol Psychiatry. 13 (6): 558–69. doi:10.1038/sj.mp.4002151. PMC 3777816. PMID 18317468.
- ↑ Roybal K, Theobold D, Graham A, DiNieri JA, Russo SJ, Krishnan V; et al. (2007). "Mania-like behavior induced by disruption of CLOCK". Proc Natl Acad Sci U S A. 104 (15): 6406–11. doi:10.1073/pnas.0609625104. PMC 1851061. PMID 17379666.
- ↑ Nurnberger JI, Koller DL, Jung J, Edenberg HJ, Foroud T, Guella I; et al. (2014). "Identification of pathways for bipolar disorder: a meta-analysis". JAMA Psychiatry. 71 (6): 657–64. doi:10.1001/jamapsychiatry.2014.176. PMC 4523227. PMID 24718920.
- ↑ Serretti A, Fabbri C (2013). "Shared genetics among major psychiatric disorders". Lancet. 381 (9875): 1339–1341. doi:10.1016/S0140-6736(13)60223-8. PMID 23453886.
- ↑ Cross-Disorder Group of the Psychiatric Genomics Consortium (2013). "Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis". Lancet. 381 (9875): 1371–1379. doi:10.1016/S0140-6736(12)62129-1. PMC 3714010. PMID 23453885.
- ↑ Modabbernia A, Taslimi S, Brietzke E, Ashrafi M (2013). "Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies". Biol Psychiatry. 74 (1): 15–25. doi:10.1016/j.biopsych.2013.01.007. PMID 23419545.
- ↑ Dargél AA, Godin O, Kapczinski F, Kupfer DJ, Leboyer M (2015). "C-reactive protein alterations in bipolar disorder: a meta-analysis". J Clin Psychiatry. 76 (2): 142–50. doi:10.4088/JCP.14r09007. PMID 25742201.
- ↑ Starzer MSK, Nordentoft M, Hjorthøj C (2018). "Rates and Predictors of Conversion to Schizophrenia or Bipolar Disorder Following Substance-Induced Psychosis". Am J Psychiatry. 175 (4): 343–350. doi:10.1176/appi.ajp.2017.17020223. PMID 29179576.
- ↑ Starzer MSK, Nordentoft M, Hjorthøj C (2018). "Rates and Predictors of Conversion to Schizophrenia or Bipolar Disorder Following Substance-Induced Psychosis". Am J Psychiatry. 175 (4): 343–350. doi:10.1176/appi.ajp.2017.17020223. PMID 29179576.
- ↑ Hashimoto K, Sawa A, Iyo M (2007). "Increased levels of glutamate in brains from patients with mood disorders". Biol Psychiatry. 62 (11): 1310–6. doi:10.1016/j.biopsych.2007.03.017. PMID 17574216.
- ↑ Houenou J, Frommberger J, Carde S, Glasbrenner M, Diener C, Leboyer M; et al. (2011). "Neuroimaging-based markers of bipolar disorder: evidence from two meta-analyses". J Affect Disord. 132 (3): 344–55. doi:10.1016/j.jad.2011.03.016. PMID 21470688.
- ↑ Houenou J, Frommberger J, Carde S, Glasbrenner M, Diener C, Leboyer M; et al. (2011). "Neuroimaging-based markers of bipolar disorder: evidence from two meta-analyses". J Affect Disord. 132 (3): 344–55. doi:10.1016/j.jad.2011.03.016. PMID 21470688.