Bipolar disorder has a number of contributing factors, including genetic, biochemical, psychodynamic, and environmental elements.
* Genetics
o Bipolar disorder, especially bipolar I, has a major genetic component. The evidence indicating a genetic role in bipolar disorder takes several forms.
o First-degree relatives of people with BPI are approximately 7 times more likely to develop BPI than the general population. Remarkably, offspring of a parent with bipolar disorder have a 50% chance of having another major psychiatric disorder.
o Twin studies demonstrate a concordance of 33-90% for BPI in identical twins.
o Adoption studies prove that a common environment is not the only factor that makes bipolar disorder occur in families. Children whose biologic parents have either bipolar I or a major depressive disorder remain at increased risk of developing an affective disorder, even if they are reared in a home with adopted parents who are not affected. For more information on bipolar disorder in children, see Medscape's CME Activity New Findings in Childhood Bipolar Disorder.
o Numerous genetic studies of BPI suggest that multiple different genetic loci, each of small effect, contribute to the affected phenotype. Four genome-wide association studies of bipolar disorder have now been published and a collaborative analysis of the 3 largest studies implicate 2 genes coding for proteins that either regulate or are subunits of ion channels ANK3 and CACNA1C. 2, 3, 4, 5 These findings suggest that bipolar disorder might be, in part, an ion channelopathy, similar to epilepsy. Another interesting candidate gene for mania is the CLOCK gene involved in circadian periodicity.7 A mouse CLOCK mutant was recently shown to exhibit features of mania.
o An interesting finding in psychiatric genetics heralds the future revision of DSM-IV-TR according to an etiological rather than descriptive basis. Using probands from the Maudsley Twin Register in London, Cardno and colleagues showed that schizophrenic, schizoaffective, and manic syndromes share genetic risk factors and that the genetic liability for schizoaffective disorder was the same as the other 2 syndromes.14 This finding suggests an independent genetic liability for psychosis shared by both mood and schizophrenia spectrum disorders as Berrettini15 previously speculated.
o A study by Tsuang et al further indicates the genetic contribution to manic-depressive illness with psychotic features. Their findings show the link between schizophrenia and bipolar disorder.16
o As discussed above, gene expression studies also demonstrate that persons with bipolar disorder, major depression, and schizophrenia share similar decreases in the expression of oligodendrocyte-myelin-related genes and abnormalities of white matter in various brain regions.
* Biochemical causes
o Multiple biochemical pathways likely contribute to bipolar disorder, which is why detecting one particular abnormality is difficult.
o A number of neurotransmitters have been linked to this disorder, largely based on patients' responses to psychoactive agents.
o Evidence is mounting of the contribution of glutamate to both bipolar and major depressions. A postmortem study of the frontal lobes with both these disorders revealed that the glutamate levels were increased.17
o The blood pressure drug reserpine, which depletes catecholamines from nerve terminals, was noted incidentally to cause depression. This led to the catecholamine hypothesis, which holds that an increase in epinephrine and norepinephrine causes mania and a decrease in epinephrine and norepinephrine causes depression.
o Drugs like cocaine, which also act on this neurotransmitter system, exacerbate mania.
o Other agents that exacerbate mania include L-dopa, which implicates dopamine and serotonin-reuptake inhibitors, which, in turn, implicate serotonin.
o Calcium channel blockers have b
Answered by
Moksha G
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10:57 AM on January 04, 2009
