Bipolar disorder is a severe, lifelong mood disorder for which little is currently understood of the genetic mechanisms underlying risk. By examining related dimensional phenotypes, we may further our understanding of the disorder. Creativity has a historical connection with the bipolar spectrum and is particularly enhanced among unaffected first-degree relatives and those with bipolar spectrum traits. This suggests that some aspects of the bipolar spectrum may confer advantages, while more severe expressions of symptoms negatively influence creative accomplishment. 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. 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. 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. Current findings are summarized from a multidisciplinary perspective to demonstrate the feasibility of research in this area to reveal the mechanisms underlying illness.
© 2016 S. Karger AG, Basel
Bipolar disorder is a severe mood disorder that is characterized by alternating states of major depression and mania. 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 . 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 [1,2]. Bipolar disorder is common, affecting approximately 1% of the population in its most severe form and up to 6% when considered as a spectrum [3,4].
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 strongly familial with an estimated heritability of 60-93% [5,6,7,8]. Yet, despite the clear contribution of genetics to the etiology of bipolar disorder, little of the genetic architecture is currently understood. 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 . 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.
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. Some investigators have suggested that bipolar disorder exists at the extreme of normal population variation in temperament, personality, and cognition [11,12,13,14,15]. 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. 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. Investigating these positive traits may not only enhance our understanding of bipolar disorder as a dimensional clinical phenotype but, as quantitative traits that are presumably closer to the actual transmitted phenotype, they can also be expected to improve our power to identify risk genes and ultimately provide novel therapeutic targets.
Bipolar Disorder and Creativity: “Madness versus Genius”
Western cultural notions of “mad geniuses” and “artistic temperaments” date back to Aristotle’s observation that “no great genius has ever existed without a strain of madness” , and a wealth of investigations into this area, both formal and anecdotal, have supported this notion . Overall, these studies suggest a tenfold increase in the rate of bipolar disorder among artists as compared with the general population [1,18]. The association between creativity and bipolar disorder is well documented in eminently creative individuals, with artists like Vincent van Gogh, authors like F. Scott Fitzgerald and Ernest Hemingway, poets like Walt Whitman and Sylvia Plath, and composers like Rachmaninoff and Tchaikovsky all reportedly having struggled under the burden of illness . Numerous studies have consistently reported an overrepresentation of affective disorders and psychosis among successful people in creative professions, as well as exceptional creative potential in relatives of individuals with bipolar disorder [19,20,21,22,23,24,25,26,27]. Large studies of noneminent, or “everyday,” creativity in patients and their relatives have produced comparable findings. Recent Swedish population-based studies have demonstrated an overrepresentation in creative occupations of bipolar patients and their healthy first-degree relatives, strongly supporting the familial association of bipolar disorder with creativity [28,29]. Similarly, the Epidemiologic Catchment Area Study found a disproportionate concentration of individuals with bipolar disorder in creative occupations .
It must be noted that creativity is not a ubiquitous trait in bipolar disorder. In fact, a large study of psychiatric patients estimated that only 8% of those with a bipolar spectrum disorder could be considered highly creative . Concerns have also been raised regarding potential biases across studies, as well as a lack of consistency in how both mood disorders and creativity are conceptualized . For example, anecdotal studies of eminently creative individuals may suffer from incomplete biographical records and be skewed towards a sampling of individuals with more severe mood symptoms. Most studies also rely on creative occupation, which may serve as a poor proxy for creativity and introduce bias. Finally, it has been suggested that the overrepresentation of bipolar disorder observed in population-based studies of creativity may reflect a preference for the unconventional lifestyle provided by creative occupations, as many suffering with bipolar disorder have trouble maintaining stable employment. Indeed, the personality traits that seem to be most associated with choosing a creative occupation are openness and impulsivity , which are associated with bipolar disorder as discussed below [34,35,36,37]. However, a multitude of studies of both eminent and “everyday” creativity consistently suggest a relationship between creativity and risk for bipolar spectrum disorders that warrants further research.
Bipolar Disorder and Creativity: A Shared Vulnerability
While some studies have found increased creativity in those with bipolar disorder, comparable to that observed in creative individuals [38,39,40], others have indicated that professional success and creativity is significantly higher in their clinically unaffected first-degree relatives [28,39,41,42,43]. Similarly, creativity and eminence occur more often in individuals with affective temperaments, which may reflect the subclinical expression of bipolar disorder and the underlying genetic vulnerability [31,42,44,45,46,47]. These observations are consistent with the observed “inverted-U” relationship between creativity and psychopathology and a shared vulnerability, as shown in Figure 1 [42,48,49]. According to this model, creativity and other positive traits would increase with genetic risk for bipolar disorder up to a threshold, beyond which they would start to diminish with the increasing impairment of illness. Intriguingly, this model suggests that the phenotype being transmitted in the population is not bipolar disorder per se, but rather positive traits that modulate behavior in healthy individuals, with the disorder representing the extreme on a continuum of variation in these traits [11,12,13,14,15]. This model also suggests the influence of common variants distributed across the entire population, which is consistent both with the polygenic model of risk for bipolar disorder and with the observance of a stable world-wide prevalence rate . Clinically unaffected individuals would thus serve as a genetic reservoir, maintaining bipolar risk alleles in the population and benefiting from the positive traits, with the disorder occurring only as an unfortunate side effect of extreme genetic loading. In short, as once observed by Paracelsus, “the dose makes the poison.”
Positive traits within the bipolar spectrum and a shared vulnerability. According to the inverted-U model, creativity and other positive traits would be expected to increase with genetic loading up to a threshold, beyond which they would start to diminish with the increasing impairment of illness [42,48,49]. Polygenic risk indicates genetic vulnerability due to common variation in aggregate, which is maintained in the population by clinically unaffected individuals, who benefit from the positive traits. BD, bipolar disorder.
Positive Traits in the Space between Madness and Genius
Several temperament and personality traits are related to bipolar disorder, to creativity in individuals with bipolar disorder, and to creativity in healthy individuals, seemingly occupying the space between madness and genius. Both bipolar and creative individuals have higher cyclothymic, dysthymic, and irritable temperament scores compared with noncreative controls [36,38,50,51,52]. Hyperthymic temperament is further associated with creativity in healthy subjects, as are hypomanic personality traits, which predict risk for bipolar disorder [53,54,55]. Bipolar and creative individuals also have higher neuroticism, extraversion, and openness personality scores compared with noncreative controls [33,36,37,38,51,52,56,57,58,59,60,61]. Openness to experience is a central feature of creativity, with an estimated effect size of 0.71 [33,62,63,64,65,66]. Openness is also heritable in bipolar families .
Although the exact nature of the relationship is unclear, intelligence and cognitive style are associated with aspects of creativity . Creative people tend toward divergent thinking, the cognitive ability of associational network activation and creative ideation, and an overinclusive cognitive style, which involves remote associations and may facilitate originality . The hallmark symptoms of mania include increased word production and loose associations, and, not surprisingly, manic bipolar patients exhibit conceptual overinclusiveness, similar to creative writers . Such loose associations may result from a failure to filter irrelevant stimuli from the environment, a process known as cognitive disinhibition, which has been associated with both psychosis proneness  and creativity . While intelligence, particularly executive function, may be associated with performance measures of creativity, like divergent thinking [72,73,74], this effect appears only moderate (d = 0.31) . In fact, above-average intelligence (IQ >120) appears to be necessary but not sufficient for high creativity , and once this threshold is met, personality factors like openness are more predictive of creative potential . Still, higher executive function has been shown to mediate increased creativity during mania . The combination of high IQ and cognitive disinhibition may also predict creative achievement . Finally, a positive mood appears to provide a significant cognitive advantage in the performance of divergent thinking tasks, whereas a negative mood inhibits this process .
Recent studies have made significant progress in defining the relationship between bipolar disorder and creativity. In one study of bipolar families, a network analysis of the observed phenotypic correlations revealed clusters of traits related to affective temperament, impulsivity, risk taking, and psychosis proneness (a “bipolar spectrum” component) and to executive function, processing speed, working memory, and long-term memory (a cognitive component) . Interestingly, perceptual creativity was found to span these clusters. Another study examining individuals with bipolar disorder and their healthy co-twins found increased sharing of positive traits related to temperament, schizotypy, impulsivity, and sensation seeking that were further correlated with increased verbal learning and fluency in the co-twins . These studies highlight the need to examine multiple dimensions of personality, mood, and cognition to fully understand concepts relating to positive traits within the context of creativity and illness.
Creativity thus appears to result from the complex interaction of multiple personality, cognitive, and affective traits [69,81,82], which may reflect a shared vulnerability with bipolar disorder [49,83,84]. A summary of the components that likely occupy the space between madness and genius is presented in Figure 2. However, the mechanisms by which these traits mediate creativity are unknown, and it is unclear as to whether they explain the association of creativity with bipolar disorder.
The space between madness and genius. Adaptation of Carson’s model of the shared vulnerability between creative genius and psychopathology  summarizing the temperament, personality, and cognitive characteristics shared by creative individuals and those with genetic liability to bipolar disorder and/or psychosis. The clinical overlap between bipolar disorder and schizophrenia is also represented, as are the characteristics unique to each disorder.
Bipolar Disorder, Schizophrenia, and Their Common Connection to Creativity
Schizophrenia is a severe psychotic disorder that is characterized by abnormalities in a patient’s thoughts, perceptions, speech, affect, and behaviors, manifesting as auditory hallucinations, paranoid or bizarre delusions, and/or disorganized speech and thoughts. While schizophrenia is often thought to mainly affect cognition, it also usually contributes to chronic problems with behavior and emotion. Bipolar disorder and schizophrenia have historically been regarded as separate disorders with distinctive underlying etiologies, yet data across many disciplines have increasingly advocated for a functional psychosis continuum spanning these diagnoses [85,86,87,88,89,90].
The considerable clinical overlap between bipolar disorder and schizophrenia often causes confusion and misdiagnosis . For example, acutely manic bipolar patients exhibit cognitive deficits, such as thought disorder and conceptual disorganization, which are typical of schizophrenia . To some extent, parallels can be drawn between the negative symptoms of schizophrenia (e.g., asociality, avolition) and depression in bipolar disorder and between the positive symptoms of schizophrenia (e.g., delusions, hallucinations) and mania. Epidemiological and genetic data are also consistent with a substantial overlap in susceptibility for bipolar disorder and schizophrenia [6,9,10,93,94,95,96,97,98,99,100,101,102,103,104,105,106]. It has been estimated that 63% of the shared genetic vulnerability between these disorders derives from additive genetic effects , with 68% of the shared genetic variance deriving from common variation . It is possible that a portion of this shared common genetic variance may be a reflection of the historical connection of both bipolar disorder and psychosis to creativity.
As with bipolar disorder, large population-based studies have reported an overrepresentation in creative occupations of the healthy first-degree relatives of schizophrenia patients, supporting the familial association of schizophrenia with creativity [28,29]. Some groups have also reported increased creativity in schizophrenia patients compared with normal controls [107,108], as well as increased creativity in the adopted children of parents with schizophrenia [109,110]. However, much research on creativity has focused on aspects of schizotypy, which is thought to reflect the subclinical expression of schizophrenia [111,112], as well as the underlying genetic vulnerability . Many studies have demonstrated strong associations between schizotypal personality traits and enhanced performance on tests of creativity and fluency, as well as elevated levels of schizotypy in individuals active in the creative arts [48,55,84,114,115,116,117,118,119,120,121,122,123,124]. Interestingly, this association between creativity and schizotypal traits is also observed in bipolar patients, who score higher than controls on several measures of schizotypy [116,125,126]. Several of the personality traits discussed above with relationships to creativity, namely, neuroticism, openness, and cyclothymic temperament, are correlated with positive schizotypal traits [127,128,129]. Openness also demonstrated high sibling correlations in a study of multigenerational SZ families, as well as high heritability .
These data, like those for bipolar disorder, suggest that some aspects of the schizophrenia spectrum provide advantages in terms of creativity, many of which are summarized in Figure 2. Other personality factors, such as increased sociability, strong ambition, and a desire for recognition by others, characterize those who excel because of their creative talent and are features observed in bipolar patients and their relatives, which may partially explain the tighter link of bipolar disorder to creativity compared with schizophrenia [33,83,118,131]. Additionally, the deficits in executive function in schizophrenia patients [132,133], which are primarily associated with negative symptoms, may explain the relatively poor performance of schizophrenia patients for measures of creativity involving fluency and cognitive flexibility [134,135,136]. If creativity and psychosis result from a shared vulnerability, cognitive protective factors, such as high IQ and cognitive flexibility, may lead to enhanced creativity, whereas the cognitive deficits often present in full-blown illness may prevent the individual from fully realizing their creative potential [49,115].
Many have also argued that bipolar disorder and schizophrenia are associated with different types of creativity, such as “artistic” versus “scientific,” which may be mediated by varying aspects of temperament, personality, and cognitive style [19,118,137,138,139,140]. In support of this concept, some groups have demonstrated an association of positive schizotypal traits with artistic domains and negative schizotypal traits with math and science [116,141]. Verbal divergent thinking is linked to creativity in writers and scientists and is correlated with a higher IQ than figural divergent thinking, which is more closely related to creativity in artists and musicians .