Mental health articles

 Genetic Causes of Bipolar Disorder

An early review of the genetics of bipolar disorder by Allenreported overall concordance rates for MZ twins of 72 per cent, while concordance rates for DZ twins averaged 14 per cent. More recently, these estimates have been reduced to 40 per cent and between 5 and 10 per cent respectively. Attempts to identify the locus of the genes that contribute to risk for the disorder have suggested that it may lie on chromosomes 4, 6, 12, 13, 15, 18 and 22, although Craddock and Sklar  noted that there still remains insuffi cient evidence to confirm a specific gene involvement in the development of the disorder.

Biological Causes of Bipolar Disorder

Given the role of serotonin and norepinephrine in depression, it would seem logical to assume that they also play a role in mania.

However, the biological model that has emerged is not as simple as may have been expected. Data on norepinephrine are consistent with a simple model of mood disorders. High levels of norepinephrine are associated with elevated mood and mania; low levels result in depressed mood. No such relationship has been found for serotonin levels. Indeed, mania has been associated with low levels of serotonin  – just as in depression. This finding is perhaps relevant to psychological studies that suggest manic behaviour may be somehow ‘masking’ depressed mood. Data such as these led some researchers to suggest a permissive theory of bipolar disorder, in which low serotonin levels somehow permit the activity of norepinephrine to determine mood. Low serotonin combined with low norepinephrine results in depression; combined with high norepinephrine, it results in mania.

A second model of bipolar disorders moves from consideration of neurotransmitters to the electrical conduction of whole neurons. Two processes involved in nerve transmission may be implicated: disturbances in activity of second messengers known as phosphoinositides, that instigate the fi ring of nerves including those involved in moderating mood, and altered sodium and potassium activity in the same neurons. In mania, second messenger activity or sodium and potassium transport across the cell membrane may be excessive and result in overactivity of the neuron system; in depression, there may be low activity in the neurons.

A third factor that may contribute to bipolar disorder involves actual damage to the neurons. Sassi et al. found evidence of neuronal abnormalities in the prefrontal cortex of young people with bipolar disorder – similar to those found in adults with the disorder. Because this was found in both groups, they concluded that this damage was unlikely to represent long-term degenerative processes, and was more likely to reflect an underdevelopment of dendritic connections and synaptic connections. By contrast, Nugent et al. found evidence of neuronal damage in adults in parts of the brain, including the amygdala and hippocampus. These structures within the limbic system contribute to control over emotions and emotional behaviour. They suggested that repeated stress and elevated glucocorticoid secretion may have contributed to neuronal damage, and dysfunctional processing of these brain areas. The damage to these and other neurons appears to lead to marked cognitive decrements in individuals with bipolar disorder including defi cits in executive functioning and verbal memory.

Tags: biological causes, bipolar, Bipolar Disorder, disorder, genetic causes