![]() ![]() ![]() This may suggest a model in which large doses of risk variants cause illness, but mild or moderate doses hold advantages for unaffected allele carriers. Moreover, it has long been observed that certain positive traits or enhanced abilities, such as creativity, exist within the bipolar spectrum and in unaffected relatives. Some investigators have suggested that bipolar disorder exists at the extreme of normal population variation in temperament, personality, and cognition. Some of the difficulty in identifying bipolar risk genes may stem from the use of diagnostic systems that group patients into discrete categories, which may have some utility for clinical care but do not adequately reflect the dimensional nature of psychiatric illness. While such studies have identified several strong candidates for susceptibility genes, the mechanisms by which risk variants lead to disease are complex and remain largely unknown. Large genome-wide association studies have suggested a significant role for common variation in explaining at least 25% of the genetic variance in bipolar disorder, 68% of which is shared with schizophrenia as a general risk for psychosis. Yet, despite the clear contribution of genetics to the etiology of bipolar disorder, little of the genetic architecture is currently understood. Bipolar disorder is strongly familial with an estimated heritability of 60-93%. ![]() Since bipolar disorder is a lifelong illness for which lasting remissions are uncommon, understanding the pathophysiology and genetic architecture is of paramount importance to diagnosis and treatment. Bipolar disorder is common, affecting approximately 1% of the population in its most severe form and up to 6% when considered as a spectrum. Psychosis is a common feature of bipolar mood episodes, with up to 50% of patients experiencing psychotic symptoms, more often during acute mania than depression. Mania is accompanied by pathological elevations in energy and mood, racing thoughts and speech, a decreased need for sleep, grandiosity, and risk taking whereas depression is associated with low energy and motivation, insomnia, and feelings of extreme sadness, failure, worthlessness, and hopelessness. Current findings are summarized from a multidisciplinary perspective to demonstrate the feasibility of research in this area to reveal the mechanisms underlying illness.īipolar disorder is a severe mood disorder that is characterized by alternating states of major depression and mania. The association of risk genes with creativity in healthy individuals (e.g., NRG1), as well as an overall sharing of common genetic variation between bipolar patients and creative individuals, provides support for this model. It is suggested that a subset of bipolar risk variants confer advantages as positive traits according to an inverted-U-shaped curve with clinically unaffected allele carriers benefitting from the positive traits and serving to maintain the risk alleles in the population. Creativity is a complex, multidimensional construct with both cognitive and affective components, many of which appear to reflect a shared genetic vulnerability with bipolar disorder. This suggests that some aspects of the bipolar spectrum may confer advantages, while more severe expressions of symptoms negatively influence creative accomplishment. Creativity has a historical connection with the bipolar spectrum and is particularly enhanced among unaffected first-degree relatives and those with bipolar spectrum traits. By examining related dimensional phenotypes, we may further our understanding of the disorder. Bipolar disorder is a severe, lifelong mood disorder for which little is currently understood of the genetic mechanisms underlying risk. ![]()
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