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.

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 [1]. 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 [9]. While such studies have identified several strong candidates for susceptibility genes [10], 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.

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” [16], and a wealth of investigations into this area, both formal and anecdotal, have supported this notion [17]. 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 [19]. 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 [30].

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 [31]. 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 [32]. 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 [33], 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.

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 [9]. 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.”

Fig. 1

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.

Fig. 1

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.

Close modal

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 [67].

Although the exact nature of the relationship is unclear, intelligence and cognitive style are associated with aspects of creativity [68]. 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 [69]. 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 [70]. Such loose associations may result from a failure to filter irrelevant stimuli from the environment, a process known as cognitive disinhibition [49], which has been associated with both psychosis proneness [64] and creativity [71]. 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) [64]. In fact, above-average intelligence (IQ >120) appears to be necessary but not sufficient for high creativity [75], and once this threshold is met, personality factors like openness are more predictive of creative potential [76]. Still, higher executive function has been shown to mediate increased creativity during mania [77]. The combination of high IQ and cognitive disinhibition may also predict creative achievement [49]. 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 [78].

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) [79]. 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 [80]. 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.

Fig. 2

The space between madness and genius. Adaptation of Carson's model of the shared vulnerability between creative genius and psychopathology [49] 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.

Fig. 2

The space between madness and genius. Adaptation of Carson's model of the shared vulnerability between creative genius and psychopathology [49] 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.

Close modal

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 [91]. For example, acutely manic bipolar patients exhibit cognitive deficits, such as thought disorder and conceptual disorganization, which are typical of schizophrenia [92]. 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 [6], with 68% of the shared genetic variance deriving from common variation [9]. 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 [113]. 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 [130].

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 [75].

Bipolar disorder exhibits substantial fitness costs in terms of increased mortality and significant impairment, yet it has persisted in the population with a high heritability and a stable prevalence [142]. This appears contrary to evolution theory, in which genetic variants associated with a loss of fitness are presumably pruned from the gene pool through the process of natural selection [143,144]. Some have suggested that psychiatric illnesses result from polygenic mutation-selection balance, whereby genetic variants that reduce fitness are introduced through mutation and pruned from the gene pool at a rate proportional to their adverse effects on fitness [143,144,145,146,147]. While the mutation rate is low, the overall target size is large, involving many genes and regulatory regions. This model fits well with the apparent impact of rare structural and de novo variants on schizophrenia susceptibility [146,147,148,149,150,151,152], the reported effects of paternal age [153], and with the severe fertility disadvantages that have been observed in schizophrenia [154,155,156]. While structural variants do not appear to contribute significantly to risk for bipolar disorder, rare variants may play a role [157,158,159,160].

Other evolutionary models relating to balancing selection and fitness trade-offs have been widely debated. For example, it has been suggested that traits associated with bipolar disorder and psychosis may provide fitness advantages in terms of sexual selection, mating success, or social skills, particularly in certain niches [144,161,162,163,164,165,166]. Some have suggested that affective temperaments provide favorable evolutionary properties that serve to maintain bipolar risk alleles in the population [45,46,167]. Others have suggested that the observed association between schizotypal traits and creativity may partially explain the persistence of psychosis risk variants in the population [117,141,166,168,169,170,171]. Consistent with these notions, studies have shown at least moderate evidence for reduced fecundity in individuals with bipolar disorder and increased fecundity in their unaffected siblings, who presumably carry a reduced burden of risk variants and may express these traits in a milder, more advantageous form [142,155,156]. Antagonistic pleiotropy provides an attractive evolutionary model in this context, wherein alleles associated with an increased fitness for one trait also decrease fitness for another [143,144,172]. As many alleles are likely involved, the fitness consequences of each allele would be closer to neutral. This would allow risk alleles to randomly drift to higher frequencies through neutral drift-mutation and become common in the population. As it is likely that no single trait in its extreme leads to bipolar disorder, a highly heterogeneous clinical phenotype, it is also likely that no single evolutionary model can fully explain the persistence of bipolar disorder in the population. This topic awaits a better understanding of the interacting phenotypes and the underlying genetic mechanisms involved in both illness and creativity.

There is strong evidence to suggest a role for the dopaminergic system in bipolar disorder and psychosis [173,174,175], as well as in creativity [42,123,176]. Mania and psychosis both partially reflect a hyperdopaminergic state [177,178], whereas depression and cognitive deficits in bipolar disorder may relate to dopamine deficiencies [178,179]. Acute amphetamine intoxication closely resembles mania, and chronic administration can provoke a manic episode in those with bipolar disorder and trigger psychosis in healthy individuals [180]. The dopamine transporter (DAT) plays a critical role in the regulation of dopamine availability and is the site of action of amphetamine, which increases synaptic dopamine by inhibiting reuptake [181]. Excess dopamine has also been reported to decrease inhibition of stimuli from the surrounding environment [182,183], which is characteristic of both creativity [71] and psychosis [184,185,186]. Interestingly, the DAT gene (SLC6A3) has shown evidence of association and linkage with bipolar disorder [187,188,189], schizophrenia [190], neurocognitive deficits in schizophrenia [191], and, of particular relevance, sensorimotor gating deficits in schizophrenia [192,193]. Furthermore, decreased thalamic D2 receptor densities are observed both in patients with psychosis [194,195,196] and in healthy subjects with high divergent thinking scores [197,198]. The presynaptic D2 receptor is part of the inhibitory response to curb excessive dopamine release, similar to the function of DAT, and is the primary target of all antipsychotics [199]. Finally, the variants of the D2 receptor gene (DRD2) have been shown to be associated with both verbal creativity [197] and sensory motor gating deficits [200] in healthy individuals. These observations collectively suggest that higher dopamine availability may lower gating thresholds and increase creativity in the absence of psychosis.

Several validated psychosis risk genes have been investigated as part of small candidate gene studies for association with creativity in healthy individuals and have shown marks of positive selection in humans (e.g., NRG1, SLC6A4) [201,202,203]. NRG1 in particular provides an intriguing candidate for a shared vulnerability, with a functional promoter variant [204] that is associated with both an increased risk of psychosis [205,206] and increased creativity in healthy subjects [201]. Interestingly, an unusually high percentage of genes involved in the phosphatidylinositol 3-kinase (PI3K) pathway appear to have been subject to selective sweeps [207], and a dysregulated activation of this pathway, mediated in part through the effects of NRG1, has been implicated in psychosis risk [208]. Both lithium and valproate, common treatments for bipolar disorder, are also thought to act, in part, through activation of PI3K [209,210,211]. While these findings remain to be confirmed in larger samples, they may provide clues as to the underlying mechanisms.

Perhaps the most convincing genetic evidence in support of a shared vulnerability between creativity and bipolar disorder/psychosis comes from a study conducted by Power et al. [212] of over 86,000 healthy subjects from an Icelandic cohort with a replication sample of more than 27,000 from Sweden and the Netherlands, all of who were genotyped. Approximately 1% of each sample was considered creative, as defined by membership in an artistic society or by creative profession. Using data from recent genome-wide association studies of bipolar disorder and schizophrenia, polygenic risk scores were calculated as the sum of associated alleles weighted by their effect sizes. Power's group found that higher genetic risk for bipolar disorder and schizophrenia, measured as a polygenic risk score, was significantly associated with creativity, indicating shared genetic vulnerability. However, the primary limitation of this study, like many previous studies, is the use of creative occupation as the phenotype, rather than a direct measurement of creative ability. Large genomic studies evaluating the shared vulnerability model of bipolar disorder/psychosis and creativity utilizing more refined measurements of creative ability remain a topic of future investigations.

Creativity is difficult to directly measure in terms of brain activity. Some studies have instead evaluated fluid intelligence, the ability to think logically and solve problems in novel situations, which is independent of acquired knowledge (crystalized intelligence) and is a component of general intelligence (g) [213]. Fluid intelligence is moderately correlated with the novel, original idea generation processes encompassed by divergent thinking [54,214,215]. Results suggest that this reasoning ability is associated with activation of a network of frontal and parietal brain regions, specifically the dorsolateral prefrontal cortex (DLPFC), the superior parietal lobule, intraparietal cortices, and left temporoparietal regions [216,217,218].

Recent studies have attempted to directly evaluate brain activation during divergent thinking in artists. One study compared fMRI scans of rappers during freestyle (i.e., improvisation), which is analogous to divergent thinking, with those during the recitation of memorized lyrics [219]. A previous study by the same group had examined jazz musicians (pianists) using a similar paradigm of improvisation versus the performance of a standardized piece of written music [220]. Interestingly, both sets of artists showed decreased activity in the DLPFC during improvisation and increased activity in the medial prefrontal cortex. These studies suggested that a relaxation of executive functions and de-focused attention, allowing for uncensored processes and free associations to occur, may be the hallmark of creative cognition. Further evidence is provided by findings of inverse relationships between divergent thinking ability and both cortical thickness and white matter integrity in frontal lobe regions [221,222]. Another study comparing musicians with matched controls using near-infrared spectroscopy observed enhanced divergent thinking in the musicians supported by increased bilateral frontal cortical activity [223]. In addition to enhanced creativity, this study also observed increased verbal ability and schizotypal personality in the musicians compared with the nonmusicians. In general, structural imaging studies have revealed positive correlations between both creative achievement and divergent thinking and the right DLPFC, right posterior cingulate, right parietal lobe, bilateral caudate, and right midbrain regions and inverse correlations with the left lateral orbitofrontal gyrus, lingual gyrus, inferior parietal gyrus, and fusiform gyrus [222,224,225,226]. This complex pattern that spans lobes and hemispheres likely reflects the inherent complexity of human creativity [227]. Whether the pattern of activation in bipolar individuals engaged in creative cognition resembles that of healthy creative individuals remains to be shown.

Although there have been many attempts to evaluate the nature of the relationship of creativity to bipolar disorder and psychosis, very few have administered a comprehensive battery in a reasonably large sample. Most studies have been small, underpowered, or employed a very limited number of phenotypes. Large population-based studies have focused solely on diagnosis and creative occupation or involvement, which may not adequately reflect creative ability. Many other studies have focused on healthy subjects and evaluated, for example, schizotypal personality traits and creativity. While these studies collectively provide an abundance of data to support the connection between bipolar disorder and creativity, the lack of consistency prevents cross-study comparisons.

To truly understand the complex relationship between bipolar disorder and creativity, all traits of potential relevance must be evaluated in the same sample using a design intended to capture the full spectrum of shared phenotypic and genetic variation. Only then can we definitively determine which traits are relevant in this context. A study design including individuals with bipolar disorder, unaffected relatives, and both creative (i.e., artists, musicians, writers, etc.) and noncreative controls would be ideally suited for a direct evaluation of the shared vulnerability model shown in Figure 1. Using a polygenic risk score method analogous to that of Power et al. [212], one would expect the positive trait values to approximate an inverted-U-shaped curve with noncreative controls and bipolar individuals anchoring the curve at each end, representing the lowest and highest genetic risk, respectively. Creative controls and unaffected relatives would presumably fall in the center of the curve with higher positive trait values conferred by mild-to-moderate risk for illness. The inclusion of twins discordant for bipolar disorder would be useful for disentangling genetic and environmental effects [80].

The use of a comprehensive, standardized battery would facilitate cross-study comparisons and allow for the sample sizes needed to resolve these issues. For inclusion in such a battery, a task should show evidence of reliability and stability; provide a range of phenotypic variation in both clinical and nonclinical samples; relate to the bipolar spectrum; and, most importantly, have the potential to function as a positive trait. Options for such a battery that meet many of these criteria are listed in online supplementary Table 1 ( For some traits, such as temperament and personality, we would expect relatively intermediate values to provide an advantage, whereas extreme values on either end would be expected to confer a disadvantage. Other traits, such as creativity or cognitive flexibility, would be expected to function more simply, with higher (more extreme) values conferring the advantage.

The administration of an array of creative tasks is also necessary to capture the range of creative ability and gain insight into the mechanism by which the various personality, cognitive, and affective traits associated with the bipolar spectrum impact creativity. While creativity is generally conceptualized as a spontaneous process that may be difficult to fully capture within a laboratory setting, several standardized and validated measurements exist, including figure preference and divergent thinking tasks. Divergent thinking involves originality of thought, fluency of ideas, and creative problem solving ability and thus represents an advantageous trait that drives invention and achievement across many domains (e.g., writing, science, business, etc.). Divergent thinking tasks can be conceptualized as the opposite of fluid intelligence tasks, which measure logical reasoning, and high performance across both types of tasks would particularly promote success across a number of disciplines. In addition to mood and personality, assessments of creativity should thus be combined with comprehensive cognitive assessments to allow for an evaluation of overall intelligence and the full range of individual capabilities.

Little is currently understood of the molecular mechanisms underlying bipolar disorder, and current treatments are far from maximally effective. Part of the value of research in this area is to better understand the genetic pathways contributing to risk. The low signal produced by genome-wide studies, with individual allelic effect sizes on the order of 0.5-1%, suggests that a large portion of the variance operates in clinically unaffected individuals [9,10]. This also suggests that the phenotype is poorly understood, implicating the need to define better measures to detect the common alleles contributing to 25% of the risk for bipolar disorder and operating in the general population. Through the assessment of positive traits, we broaden the concept of bipolar disorder into a fully dimensional spectrum and presumably capture specific portions of the variance, which will facilitate the detection of the underlying genes and pathways contributing to risk. Understanding the relationship between positive traits and bipolar disorder may thus provide insight into the mechanisms of illness, which may someday lead to novel therapeutic targets.

Although this discussion has focused on positive traits, it is important to note that the patients themselves exist at the extreme and may be pushed beyond the limit of positive value, either at euthymia or in a state-dependent manner. Behavioral traits conforming to a shared vulnerability model may provide excellent targets for evidence-based therapies. For example, individuals with bipolar disorder often exhibit poor judgment in terms of impulsivity or reward-based decision-making [34,35,228]. Modulation of risk-reward valuation can easily be viewed according to this model, as a slight overvaluation of risk, in appropriate balance with reward valuation, can lead to great accomplishments, yet a large overvaluation of risk as compared with reward, which is correlated with mania, may have disastrous consequences [229,230]. Even individuals with subsyndromal hypomanic symptoms show a greater hedonic impact of reward and a preference for immediate over delayed, but superior, rewards [231,232]. There is thus likely a threshold along the bipolar spectrum at which a loss of inhibition and false positive error rates increase for tasks of impulsivity and risk-reward valuation, which would implicate a possible point of intervention and suggest a target for behavioral therapy to improve emotion-based decision-making or enhance self-control. In general, treatments aimed at reducing subsyndromal symptoms and relapses may indirectly improve the cognitive deficits associated with the disorder. Adjunctive therapies that improve focus and concentration, such as yoga therapy, also hold promise for improving cognitive function across several domains in both bipolar disorder and schizophrenia [233]. Additionally, cognitive behavioral therapy and self-monitoring techniques can be used to help patients modulate cognitive disorganization and perform better on executive function tasks [234]. Finally, although controversial, there is evidence to suggest that cognitive training exercises can not only increase working memory but also improve fluid intelligence, which includes such abilities as pattern recognition, abstract reasoning, and problem-solving [235,236]. Although more research in this area is needed, this is potentially promising for bipolar patients with complex cognitive deficits, and all tasks improving cognitive functioning in bipolar disorder may ultimately improve performance in those with creative abilities [77]. Thus, the investigation of behavioral traits that follow this model may not only further our understanding of the underlying neural networks involved in bipolar disorder but also facilitate treatment.

It has long been conventional wisdom that positive traits or enhanced abilities occur in the unaffected relatives of individuals with bipolar disorder, as well as many patients themselves, a view supported by numerous studies. If it can be shown that bipolar disorder is merely an extension of normal population variation in beneficial traits, it may erase some of the stigma still associated with this severe mental illness. Studies evaluating positive aspects and character strengths associated with bipolar disorder are aligned with the growing interest in research on the impact of positive psychological traits on health [237,238]. Positive psychological traits of spirituality, empathy, creativity, realism, and resilience are frequently observed in bipolar individuals [239]. By gaining a better appreciation for the positive aspects of mental illness and exploring methods to enhance these traits, we may improve clinical outcomes [240].

Current practice in psychiatry is geared more towards controlling the symptoms of bipolar disorder, rather than understanding a patient's true needs and potential capabilities. Creative expression is a source of well-being, and many of those struggling with bipolar disorder consider increased creativity a truly positive aspect of their illness [241,242]. In fact, bipolar patients often discontinue their medications due to subjective experiences of diminished creativity, among other unpleasant side effects [243,244]. Some patients, once stabilized on lithium, will even decrease their own dosage toward achieving a “controlled cyclothymia,” risking relapse of severe symptoms, all in the name of creative expression [19]. Others find the hypomanic phase so enjoyable and so integral to their creative work that they prefer to go untreated rather than risk limiting or losing it [244]. However, bipolar disorder usually worsens with time. While the side effects of medications may be unpleasant for some, the consequences of the disorder left untreated can be fatal, as evidenced by the ninefold increase in suicide rate and the countless artists and writers with bipolar disorder who have committed suicide [19]. Studying the link between creativity and bipolar disorder will thus promote a deeper understanding of patients' needs and experiences and facilitate better treatment, thereby enhancing patient compliance.

While the “Madness versus Genius” debate dates back to the time of Aristotle, research in this area is still in its infancy. Still, reports across several disciplines now provide scientific evidence to bolster what was once a collection of anecdotal evidence and lend legitimacy to these claims. Future studies will need to evaluate potential positive traits in the appropriate samples to identify those that will be most useful for exploring the genetic architecture of the shared vulnerability and the evolutionary context of bipolar disorder. An understanding of the role of bipolar risk genes in the general population as they relate to positive traits may provide insight into the mechanism of illness and thus facilitate the development of novel therapeutic treatments. Additionally, while the mild to moderate expression of these positive traits may hold advantages, more extreme expressions likely contribute to the severe symptoms associated with illness. A better understanding of the nature of this relationship will enable a suite of cognitive behavioral therapy techniques to improve decision-making, self-control, and cognitive functioning in patients, effectively “bending the curve” towards the positive aspects of these traits where functioning is increased and is truly beneficial. Further research in this area would thus represent an important step toward advancing our understanding of bipolar disorder, from both etiological and population perspectives, and toward promoting better patient care.

Dr. Greenwood is supported by grant R21 MH106917 from the National Institute of Mental Health. The author expresses her gratitude to Drs. Ruben Gur, Hagop Akiskal, and especially John Kelsoe for their guidance, support, and inspiration.

Dr. Greenwood reports no financial relationships with commercial interests.

Goodwin FK, Jamison KR: Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression. New York, Oxford University Press, 2007.
Pope HG Jr, Lipinski JF Jr: Diagnosis in schizophrenia and manic-depressive illness: a reassessment of the specificity of “schizophrenic” symptoms in the light of current research. Arch Gen Psychiatry 1978;35:811-828.
Placidi GF, Signoretta S, Liguori A, Gervasi R, Maremmani I, Akiskal HS: The semi-structured affective temperament interview (TEMPS-I). Reliability and psychometric properties in 1,010 14-26-year old students. J Affect Disord 1998;47:1-10.
Depue RA, Slater JF, Wolfstetter-Kausch H, Klein D, Goplerud E, Farr D: A behavioral paradigm for identifying persons at risk for bipolar depressive disorder: a conceptual framework and five validation studies. J Abnorm Psychol 1981;90:381-437.
Taylor L, Faraone SV, Tsuang MT: Family, twin, and adoption studies of bipolar disease. Curr Psychiatry Rep 2002;4:130-133.
Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM: Common genetic determinants of schizophrenia and bipolar disorder in swedish families: a population-based study. Lancet 2009;373:234-239.
McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A: The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry 2003;60:497-502.
Kieseppa T, Partonen T, Haukka J, Kaprio J, Lonnqvist J: High concordance of bipolar I disorder in a nationwide sample of twins. Am J Psychiatry 2004;161:1814-1821.
Cross-Disorder Group of the Psychiatric Genomics Consortium: Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet 2013;45:984-994.
Psychiatric GWAS Consortium Bipolar Disorder Working Group: Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 2011;43:977-983.
Akiskal HS: The bipolar spectrum - the shaping of a new paradigm in psychiatry. Curr Psychiatry Rep 2002;4:1-3.
Akiskal HS, Pinto O: Soft bipolar spectrum: footnotes to Kraepelin on the interface of hypomania, temperament and depression; in Marneros A, Angst J (eds): Bipolar Disorders: 100 Years after Manic-Depressive Insanity. Dordrecht, Kluwer Academic, 2000, pp 37-62.
Burmeister M, McInnis MG, Zollner S: Psychiatric genetics: progress amid controversy. Nat Rev Genet 2008;9:527-540.
Crow TJ: From Kraepelin to Kretschmer leavened by Schneider: the transition from categories of psychosis to dimensions of variation intrinsic to Homo sapiens. Arch Gen Psychiatry 1998;55:502-504.
Kretschmer E: Physique and Character: An Investigation of the Nature of Constitution and of the Theory of Temperament. New York, K Paul, Trench, Trubner, 1926.
Motto AL, Clark JR: The paradox of genius and madness: Seneca and his influence. Cuadernos Filologa Clasica Estudios Latinos 1992;2:189-200.
Bentall RP: Madness Explained: Psychosis and Human Nature. London, Penguin, 2003.
Rothenberg A: Creativity, self creation, and the treatment of mental illness. Med Hum 2006;32:14-19.
Jamison KR: Touched with fire: Manic-Depressive Illness and the Artistic Temperament, ed 1. New York, Free Press, 1993.
Andreasen NC: Creativity and mental illness: prevalence rates in writers and their first-degree relatives. Am J Psychiatry 1987;144:1288-1292.
Post F: Creativity and psychopathology. A study of 291 world-famous men. Br J Psychiatry 1994;165:22-34.
Ludwig AM: Creative achievement and psychopathology: comparison among professions. Am J Psychother 1992;46:330-356.
Jamison KR: Mood disorders and patterns of creativity in British writers and artists. Psychiatry 1989;52:125-134.
Wills GI: Forty lives in the bebop business: mental health in a group of eminent jazz musicians. Br J Psychiatry 2003;183:255-259.
Ludwig AM: The Price of Greatness: Resolving the Creativity and Madness Controversy. New York, Guilford Press, 1995.
Karlsson JL: Genetic association of giftedness and creativity with schizophrenia. Hereditas 1970;66:177-182.
Andreasen NC: The Creating Brain: The Neuroscience of Genius. New York, Dana Press, 2005.
Kyaga S, Landen M, Boman M, Hultman CM, Langstrom N, Lichtenstein P: Mental illness, suicide and creativity: 40-year prospective total population study. J Psychiatr Res 2013;47:83-90.
Kyaga S, Lichtenstein P, Boman M, Hultman C, Langstrom N, Landen M: Creativity and mental disorder: family study of 300,000 people with severe mental disorder. Br J Psychiatry 2011;199:373-379.
Tremblay CH, Grosskopf S, Yang K: Brainstorm: Occupational choice, bipolar illness and creativity. Econ Hum Biol 2010;8:233-241.
Akiskal HS, Akiskal K: Reassessing the prevalence of bipolar disorders: clinical significance and artistic creativity. Psychiatry Psychobiol 1988;3:29-36.
Johnson SL, Murray G, Fredrickson B, Youngstrom EA, Hinshaw S, Bass JM, Deckersbach T, Schooler J, Salloum I: Creativity and bipolar disorder: touched by fire or burning with questions? Clin Psychol Rev 2012;32:1-12.
Feist GJ: A meta-analysis of personality in scientific and artistic creativity. Pers Soc Psychol Rev 1998;2:290-309.
Peluso MA, Hatch JP, Glahn DC, Monkul ES, Sanches M, Najt P, Bowden CL, Barratt ES, Soares JC: Trait impulsivity in patients with mood disorders. J Affect Disord 2007;100:227-231.
Swann AC, Anderson JC, Dougherty DM, Moeller FG: Measurement of inter-episode impulsivity in bipolar disorder. Psychiatry Res 2001;101:195-197.
Nowakowska C, Strong CM, Santosa CM, Wang PW, Ketter TA: Temperamental commonalities and differences in euthymic mood disorder patients, creative controls, and healthy controls. J Affect Disord 2005;85:207-215.
Barnett JH, Huang J, Perlis RH, Young MM, Rosenbaum JF, Nierenberg AA, Sachs G, Nimgaonkar VL, Miklowitz DJ, Smoller JW: Personality and bipolar disorder: dissecting state and trait associations between mood and personality. Psychol Med 2011;41:1593-1604.
Srivastava S, Childers ME, Baek JH, Strong CM, Hill SJ, Warsett KS, Wang PW, Akiskal HS, Akiskal KK, Ketter TA: Toward interaction of affective and cognitive contributors to creativity in bipolar disorders: a controlled study. J Affect Disord 2010;125:27-34.
Simeonova DI, Chang KD, Strong C, Ketter TA: Creativity in familial bipolar disorder. J Psychiatr Res 2005;39:623-631.
Santosa CM, Strong CM, Nowakowska C, Wang PW, Rennicke CM, Ketter TA: Enhanced creativity in bipolar disorder patients: a controlled study. J Affect Disord 2007;100:31-39.
Verdoux H, Bourgeois M: Comparative study on the occupational levels of unipolar and bipolar probands and relatives. Ann Med Psychol (Paris) 1995;153:67-70.
Richards R, Kinney DK, Lunde I, Benet M, Merzel AP: Creativity in manic-depressives, cyclothymes, their normal relatives, and control subjects. J Abnorm Psychol 1988;97:281-288.
Coryell W, Endicott J, Keller M, Andreasen N, Grove W, Hirschfeld RM, Scheftner W: Bipolar affective disorder and high achievement: a familial association. Am J Psychiatry 1989;146:983-988.
Akiskal HS, Akiskal KK, Haykal RF, Manning JS, Connor PD: TEMPS-A: progress towards validation of a self-rated clinical version of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire. J Affect Disord 2005;85:3-16.
Akiskal KK, Akiskal HS: The theoretical underpinnings of affective temperaments: Implications for evolutionary foundations of bipolar disorder and human nature. J Affect Disord 2005;85:231-239.
Akiskal HS, Akiskal KK: In search of Aristotle: temperament, human nature, melancholia, creativity and eminence. J Affect Disord 2007;100:1-6.
Akiskal HS, Akiskal K: Tempéraments et humeur des musiciens de blues. Nervure 1994;8:28-304.
Nettle D: Strong Imagination: Madness, Creativity and Human Nature. Oxford, Oxford University Press, 2001.
Carson SH: Creativity and psychopathology: a shared vulnerability model. Can J Psychiatry 2011;56:144-153.
Akiskal HS, Kilzieh N, Maser JD, Clayton PJ, Schettler PJ, Traci Shea M, Endicott J, Scheftner W, Hirschfeld RM, Keller MB: The distinct temperament profiles of bipolar I, bipolar II and unipolar patients. J Affect Disord 2006;92:19-33.
Strong CM, Nowakowska C, Santosa CM, Wang PW, Kraemer HC, Ketter TA: Temperament-creativity relationships in mood disorder patients, healthy controls and highly creative individuals. J Affect Disord 2007;100:41-48.
Srivastava S, Ketter TA: The link between bipolar disorders and creativity: evidence from personality and temperament studies. Curr Psychiatry Rep 2010;12:522-530.
Vellante M, Zucca G, Preti A, Sisti D, Rocchi MB, Akiskal KK, Akiskal HS: Creativity and affective temperaments in non-clinical professional artists: an empirical psychometric investigation. J Affect Disord 2011;135:28-36.
Furnham A, Batey M, Anand K, Manfield J: Personality, hypomania, intelligence and creativity. Pers Individl Dif 2008;44:1060-1069.
Schuldberg D: Six subclinical spectrum traits in normal creativity. Creativity Res J 2001;13:5-16.
Gelade GA: Creativity in conflict: the personality of the commercial creative. J Genet Psychol 1997;158:67-78.
Andreasen NC, Glick ID: Bipolar affective disorder and creativity: implications and clinical management. Compr Psychiatry 1988;29:207-217.
Bakker FC: Development of personality in dancers: a longitudinal study. Pers Individ Dif 1991;12:671-681.
Hammond J, Edelmann RJ: The act of being: personality characteristics professional actors, amateur actors and non-actors; in Wilson G (ed): Psychology and performing arts. Amsterdam, Swets and Zeitlinger, 1991, pp 123-131.
Kemp A: The personality structure of the musician. I. Identifying a profile of traits for the performer. Psychol Music 1981;9:3-14.
Marchant-Haycox SE, Wilson GD: Personality and stress in performing artists. Pers Individ Dif 1992;13:1061-1068.
Dollinger SJ, Urban KK, James TA: Creativity and openness: further validation of two creative product measures. Creativity Res J 2004;16:35-47.
King R, Curtis D, Knoblich G: Complexity preference in substance abusers and controls: relationships to diagnosis and personality variables. Percept Mot Skills 1991;72:35-39.
Ma H: The effect size of variables associated with creativity: a meta-analysis. Creat Res J 2009;21:30-42.
Parson RJ, Tittler BI, Cook VJ: A multi-trait multi-method evaluation of creativity and openness. Psychol Rep 1984;54:403-410.
McCrae RR: Creativity, divergent thinking, and openness to experience. J Personal Soc Psychol 1987;52:1258-1265.
Hare E, Contreras J, Raventos H, Flores D, Jerez A, Nicolini H, Ontiveros A, Almasy L, Escamilla M: Genetic structure of personality factors and bipolar disorder in families segregating bipolar disorder. J Affect Disord 2012;136:1027-1033.
Kaufman JC, Plucker JA: Intelligence and creativity; in Sternberg RJ, Kaufman SB (eds): The Cambridge Handbook of Intelligence. Cambridge, Cambridge University Press, 2011, pp 771-783.
Eysenck HJ: Genius: The Natural History of Creativity. Cambridge, Cambridge University Press, 1995.
Andreasen NJ, Powers PS: Creativity and psychosis: an examination of conceptual style. Arch Gen Psychiatry 1975;32:70-73.
Carson SH, Peterson JB, Higgins DM: Decreased latent inhibition is associated with increased creative achievement in high-functioning individuals. J Pers Soc Psychol 2003;85:499-506.
Benedek M, Franz F, Heene M, Neubauer AC: Differential effects of cognitive inhibition and intelligence on creativity. Pers Individ Dif 2012;53:480-485.
Silvia PJ: Another look at creativity and intelligence: exploring higher-order models and probable confounds. Pers Indiv Diff 2008;44:1012-1021.
Gilhooly KJ, Fioratou E, Anthony SH, Wynn V: Divergent thinking: strategies and executive involvement in generating novel uses for familiar objects. Br J Psychol 2007;98:611-625.
Guilford JP: The Nature of Human Intelligence. New York, McGraw-Hill, 1967.
Jauk E, Benedek M, Dunst B, Neubauer AC: The relationship between intelligence and creativity: new support for the threshold hypothesis by means of empirical breakpoint detection. Intelligence 2013;41:212-221.
Soeiro-de-Souza MG, Dias VV, Bio DS, Post RM, Moreno RA: Creativity and executive function across manic, mixed and depressive episodes in bipolar I disorder. J Affect Disord 2011;135:292-297.
Vosburg SK: The effects of positive and negative mood on divergent-thinking performance. Creativity Res J 1998;11:165-172.
Fears SC, Service SK, Kremeyer B, Araya C, Araya X, Bejarano J, Ramirez M, Castrillon G, Gomez-Franco J, Lopez MC, Montoya G, Montoya P, Aldana I, Teshiba TM, Abaryan Z, Al-Sharif NB, Ericson M, Jalbrzikowski M, Luykx JJ, Navarro L, Tishler TA, Altshuler L, Bartzokis G, Escobar J, Glahn DC, Ospina-Duque J, Risch N, Ruiz-Linares A, Thompson PM, Cantor RM, Lopez-Jaramillo C, Macaya G, Molina J, Reus VI, Sabatti C, Freimer NB, Bearden CE: Multisystem component phenotypes of bipolar disorder for genetic investigations of extended pedigrees. JAMA Psychiatry 2014;71:375-387.
Higier RG, Jimenez AM, Hultman CM, Borg J, Roman C, Kizling I, Larsson H, Cannon TD: Enhanced neurocognitive functioning and positive temperament in twins discordant for bipolar disorder. Am J Psychiatry 2014;171:1191-1198.
Barron F, Harrington DM: Creativity, intelligence, and personality. Annu Rev Psychol 1981;32:439-476.
Russ S: Affect and Creativity: The Role of Affect and Play in the Creative Process. Hillsdale, Lawrence Erlbaum Associates, 1993.
Murray G, Johnson SL: The clinical significance of creativity in bipolar disorder. Clin Psychol Rev 2010;30:721-732.
Barrantes-Vidal N: Creativity & madness revisited from current psychological perspectives. J Consciousness Stud 2004;11:58-78.
Craddock N, Owen MJ: The beginning of the end for the Kraepelinian dichotomy. Br J Psychiatry 2005;186:364-366.
Crow TJ: The continuum of psychosis and its genetic origins. The sixty-fifth Maudsley lecture. Br J Psychiatry 1990;156:788-797.
Ivleva E, Thaker G, Tamminga CA: Comparing genes and phenomenology in the major psychoses: schizophrenia and bipolar 1 disorder. Schizophr Bull 2008;34:734-742.
Kendler KS, Karkowski LM, Walsh D: The structure of psychosis: latent class analysis of probands from the Roscommon family study. Arch Gen Psychiatry 1998;55:492-499.
Keshavan MS, Morris DW, Sweeney JA, Pearlson G, Thaker G, Seidman LJ, Eack SM, Tamminga C: A dimensional approach to the psychosis spectrum between bipolar disorder and schizophrenia: the Schizo-Bipolar Scale. Schizophr Res 2011;133:250-254.
Loughland CM, Williams LM: A cluster analytic study of schizotypal trait dimensions. Pers Individ Dif 1997;23:877-883.
Bromet EJ, Kotov R, Fochtmann LJ, Carlson GA, Tanenberg-Karant M, Ruggero C, Chang SW: Diagnostic shifts during the decade following first admission for psychosis. Am J Psychiatry 2011;168:1186-1194.
Carlson GA, Goodwin FK: The stages of mania. A longitudinal analysis of the manic episode. Arch Gen Psychiatry 1973;28:221-228.
Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium: Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011;43:969-976.
Cardno AG, Rijsdijk FV, Sham PC, Murray RM, McGuffin P: A twin study of genetic relationships between psychotic symptoms. Am J Psychiatry 2002;159:539-545.
Kendler KS, McGuire M, Gruenberg AM, O'Hare A, Spellman M, Walsh D: The Roscommon family study. IV. Affective illness, anxiety disorders, and alcoholism in relatives. Arch Gen Psychiatry 1993;50:952-960.
Maier W, Lichtermann D, Minges J, Hallmayer J, Heun R, Benkert O, Levinson DF: Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. Arch Gen Psychiatry 1993;50:871-883.
Potash JB, Willour VL, Chiu YF, Simpson SG, MacKinnon DF, Pearlson GD, DePaulo JR Jr, McInnis MG: The familial aggregation of psychotic symptoms in bipolar disorder pedigrees. Am J Psychiatry 2001;158:1258-1264.
Somnath CP, Janardhan Reddy YC, Jain S: Is there a familial overlap between schizophrenia and bipolar disorder? J Affect Disord 2002;72:243-247.
Weissman MM, Gershon ES, Kidd KK, Prusoff BA, Leckman JF, Dibble E, Hamovit J, Thompson WD, Pauls DL, Guroff JJ: Psychiatric disorders in the relatives of probands with affective disorders. The Yale University-National Institute of Mental Health Collaborative Study. Arch Gen Psychiatry 1984;41:13-21.
Winokur G, Tsuang MT, Crowe RR: The Iowa 500: affective disorder in relatives of manic and depressed patients. Am J Psychiatry 1982;139:209-212.
Badner JA, Gershon ES: Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 2002;7:405-411.
Craddock N, O'Donovan MC, Owen MJ: Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophr Bull 2006;32:9-16.
Cross-Disorder Group of the Psychiatric Genomics Consortium: Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013;381:1371-1379.
Gershon ES, DeLisi LE, Hamovit J, Nurnberger JI Jr, Maxwell ME, Schreiber J, Dauphinais D, Dingman CW 2nd, Guroff JJ: A controlled family study of chronic psychoses. Schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 1988;45:328-336.
Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger JI Jr, Goldin LR, Bunney WE Jr: A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands. Arch Gen Psychiatry 1982;39:1157-1167.
Owen MJ, Craddock N, Jablensky A: The genetic deconstruction of psychosis. Schizophr Bull 2007;33:905-911.
Jena SPK, Ramchandra S: Creativity among schizophrenics and non-psychiatric individuals: a compartive study. J Person Clin Stud 1995;11:59-63.
Merten T: Factors influencing word-association responses: a reanalysis. Creat Res J 1995;8:249-263.
McNeil TF: Prebirth and postbirth influence on the relationship between creative ability and recorded mental illness. J Pers 1971;39:391-406.
Kinney DK, Richards R, Lowing PA, LeBlanc D, Zimbalist ME: Creativity in offspring of schizophrenic and control parents: an adoption study. Creat Res J 2001;13:17-25.
Raine A: Schizotypal personality: neurodevelopmental and psychosocial trajectories. Annu Rev Clin Psychol 2006;2:291-326.
van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L: A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychol Med 2009;39:179-195.
Vollema MG, Sitskoorn MM, Appels MC, Kahn RS: Does the schizotypal personality questionnaire reflect the biological-genetic vulnerability to schizophrenia? Schizophr Res 2002;54:39-45.
Schuldberg D, French C, Stone BL, Heberle J: Creativity and schizotypal traits. Creativity test scores and perceptual aberration, magical ideation, and impulsive nonconformity. J Nerv Ment Dis 1988;176:648-657.
Nelson B, Rawlings D: Relating schizotypy and personality to the phenomenology of creativity. Schizophr Bull 2010;36:388-399.
Nettle D: Schizotypy and mental health amongst poets, visual artists, and mathematicians. J Res Pers 2006;40:876-890.
O'Reilly T, Dunbar R, Bentall RP: Schizotypy and creativity: an evolutionary connection? Pers Individ Dif 2001;31:1067-1078.
Sass LA: Schizophrenia, modernism, and the “creative imagination”: on creativity and psychopathology. Creat Res J 2001;13:55-74.
Tsakanikos E, Claridge G: More words, less words: Verbal fluency as a function of “positive” and “negative” schizotypy. Pers Individ Dif 2005;39:705-713.
Green MJ, Williams LM: Schizotypy and creativity as effects of reduced cognitive inhibition. Pers Individ Dif 1999;27:263-276.
Batey M, Furnham A: The relationship between measures of creativity and schizotypy. Pers Individ Dif 2008;45:816-821.
Batey M, Furnham A: The relationship between creativity, schizotypy and intelligence. Individ Dif Res 2009;7:272-284.
Burch G, Pavelis C, Hemsley DR, Corr PJ: Schizotypy and creativity in visual artists. Br J Psychol 2006;97:177-190.
Woody E, Claridge G: Psychoticism and thinking. Br J Soc Clin Psychol 1977;16:241-248.
Rybakowski JK, Klonowska P: Bipolar mood disorder, creativity and schizotypy: an experimental study. Psychopathology 2011;44:296-302.
Mahon K, Perez-Rodriguez MM, Gunawardane N, Burdick KE: Dimensional endophenotypes in bipolar disorder: affective dysregulation and psychosis proneness. J Affect Disord 2013;151:695-701.
Asai T, Sugimori E, Bando N, Tanno Y: The hierarchic structure in schizotypy and the five-factor model of personality. Psychiatry Res 2011;185:78-83.
Ross SR, Lutz CJ, Bailley SE: Positive and negative symptoms of schizotypy and the five-factor model: a domain and facet level analysis. J Pers Assess 2002;79:53-72.
Morvan Y, Tibaoui F, Bourdel MC, Loo H, Akiskal KK, Akiskal HS, Krebs MO: Confirmation of the factorial structure of temperamental autoquestionnaire TEMPS-A in non-clinical young adults and relation to current state of anxiety, depression and to schizotypal traits. J Affect Disord 2011;131:37-44.
Aukes MF, Alizadeh BZ, Sitskoorn MM, Selten JP, Sinke RJ, Kemner C, Ophoff RA, Kahn RS: Finding suitable phenotypes for genetic studies of schizophrenia: heritability and segregation analysis. Biol Psychiatry 2008;64:128-136.
Johnson SL, Eisner LR, Carver CS: Elevated expectancies among persons diagnosed with bipolar disorder. Br J Clin Psychol 2009;48:217-222.
Wobrock T, Ecker UK, Scherk H, Schneider-Axmann T, Falkai P, Gruber O: Cognitive impairment of executive function as a core symptom of schizophrenia. World J Biol Psychiatry 2009;10:442-451.
Gooding DC, Kwapil TR, Tallent KA: Wisconsin card sorting test deficits in schizotypic individuals. Schizophr Res 1999;40:201-209.
Abraham A, Windmann S, McKenna P, Gunturkun O: Creative thinking in schizophrenia: the role of executive dysfunction and symptom severity. Cogn Neuropsychiatry 2007;12:235-258.
Tsakanikos E, Reed P: Dimensional approaches to experimental psychopathology of schizophrenia: shift learning and report of psychotic-like experiences in college students. J Behav Ther Exp Psychiatry 2005;36:300-312.
Jaracz J, Patrzala A, Rybakowski JK: Creative thinking deficits in patients with schizophrenia: neurocognitive correlates. J Nerv Ment Dis 2012;200:588-593.
Thys E, Sabbe B, De Hert M: Creativity and psychiatric illness: the search for a missing link - an historical context for current research. Psychopathology 2012;46:136-144.
Prentky RA: Creativity and Psychopathology: A Neurocognitive Perspective. New York, Praeger, 1980.
Claridge G: Creativity and madness: clues from modern psychiatric diagnosis; in Steptoe A (ed): Genius and the Mind: Studies of Creativity and Temperament. Oxford, Oxford University Press, 1998, pp 227-250.
Glazer E: Rephrasing the madness and creativity debate: what is the nature of the creativity construct? Pers Individ Dif 2009;46:755-764.
Brod JH: Creativity and schizotypy; in Claridge GS (ed): Schizotypy: Implications for Illness and Health. Oxford, Oxford University Press, 1997, pp 276-298.
Baron M, Risch N, Mendlewicz J: Differential fertility in bipolar affective illness. J Affect Disord 1982;4:103-112.
Keller MC, Miller G: Resolving the paradox of common, harmful, heritable mental disorders: which evolutionary genetic models work best? Behav Brain Sci 2006;29:385-404; discussion 405-352.
Uher R: The role of genetic variation in the causation of mental illness: an evolution-informed framework. Mol Psychiatry 2009;14:1072-1082.
Pritchard JK: Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet 2001;69:124-137.
Rees E, Kirov G, O'Donovan MC, Owen MJ: De novo mutation in schizophrenia. Schizophr Bull 2012;38:377-381.
Rees E, Moskvina V, Owen MJ, O'Donovan MC, Kirov G: De novo rates and selection of schizophrenia-associated copy number variants. Biol Psychiatry 2011;70:1109-1114.
International Schizophrenia Consortium: Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 2008;455:237-241.
Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, et al: Large recurrent microdeletions associated with schizophrenia. Nature 2008;455:232-236.
Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, Nord AS, Kusenda M, Malhotra D, Bhandari A, Stray SM, Rippey CF, Roccanova P, Makarov V, Lakshmi B, Findling RL, Sikich L, Stromberg T, Merriman B, Gogtay N, Butler P, Eckstrand K, Noory L, Gochman P, Long R, Chen Z, Davis S, Baker C, Eichler EE, Meltzer PS, Nelson SF, Singleton AB, Lee MK, Rapoport JL, King MC, Sebat J: Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 2008;320:539-543.
Vrijenhoek T, Buizer-Voskamp JE, van der Stelt I, Strengman E, Sabatti C, Geurts van Kessel A, Brunner HG, Ophoff RA, Veltman JA: Recurrent CNVs disrupt three candidate genes in schizophrenia patients. Am J Hum Genet 2008;83:504-510.
Kirov G, Gumus D, Chen W, Norton N, Georgieva L, Sari M, O'Donovan MC, Erdogan F, Owen MJ, Ropers HH, Ullmann R: Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum Mol Genet 2008;17:458-465.
Malaspina D, Corcoran C, Fahim C, Berman A, Harkavy-Friedman J, Yale S, Goetz D, Goetz R, Harlap S, Gorman J: Paternal age and sporadic schizophrenia: evidence for de novo mutations. Am J Med Genet 2002;114:299-303.
Bundy H, Stahl D, MacCabe JH: A systematic review and meta-analysis of the fertility of patients with schizophrenia and their unaffected relatives. Acta Psychiatr Scand 2011;123:98-106.
MacCabe JH, Koupil I, Leon DA: Lifetime reproductive output over two generations in patients with psychosis and their unaffected siblings: the Uppsala 1915-1929 Birth Cohort Multigenerational Study. Psychol Med 2009;39:1667-1676.
Power RA, Kyaga S, Uher R, MacCabe JH, Langstrom N, Landen M, McGuffin P, Lewis CM, Lichtenstein P, Svensson AC: Fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse vs their unaffected siblings. JAMA Psychiatry 2013;70:22-30.
Zhang D, Cheng L, Qian Y, Alliey-Rodriguez N, Kelsoe JR, Greenwood T, Nievergelt C, Barrett TB, McKinney R, Schork N, Smith EN, Bloss C, Nurnberger J, Edenberg HJ, Foroud T, Sheftner W, Lawson WB, Nwulia EA, Hipolito M, Coryell W, Rice J, Byerley W, McMahon F, Schulze TG, Berrettini W, Potash JB, Belmonte PL, Zandi PP, McInnis MG, Zollner S, Craig D, Szelinger S, Koller D, Christian SL, Liu C, Gershon ES: Singleton deletions throughout the genome increase risk of bipolar disorder. Mol Psychiatry 2009;14:376-380.
Ament SA, Szelinger S, Glusman G, Ashworth J, Hou L, Akula N, Shekhtman T, Badner JA, Brunkow ME, Mauldin DE, Stittrich AB, Rouleau K, Detera-Wadleigh SD, Nurnberger JI, Jr., Edenberg HJ, Gershon ES, Schork N, Bipolar Genome Study, Price ND, Gelinas R, Hood L, Craig D, McMahon FJ, Kelsoe JR, Roach JC: Rare variants in neuronal excitability genes influence risk for bipolar disorder. Proc Natl Acad Sci USA 2015;112:3576-3581.
Grozeva D, Kirov G, Ivanov D, Jones IR, Jones L, Green EK, St Clair DM, Young AH, Ferrier N, Farmer AE, McGuffin P, Holmans PA, Owen MJ, O'Donovan MC, Craddock N: Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia. Arch Gen Psychiatry 2010;67:318-327.
Goes FS, Pirooznia M, Parla JS, Kramer M, Ghiban E, Mavruk S, Chen YC, Monson ET, Willour VL, Karchin R, Flickinger M, Locke AE, Levy SE, Scott LJ, Boehnke M, Stahl E, Moran JL, Hultman CM, Landen M, Purcell SM, Sklar P, Zandi PP, McCombie WR, Potash JB: Exome sequencing of familial bipolar disorder. JAMA Psychiatry 2016;73:590-597.
Gardner R Jr: Mechanisms in manic-depressive disorder: an evolutionary model. Arch Gen Psychiatry 1982;39:1436-1441.
Nettle D, Clegg H: Schizotypy, creativity and mating success in humans. Proc Biol Sci 2006;273:611-615.
Shaner A, Miller G, Mintz J: Schizophrenia as one extreme of a sexually selected fitness indicator. Schizophr Res 2004;70:101-109.
Brody JF: Evolutionary recasting: ADHD, mania and its variants. J Affect Disord 2001;65:197-215.
Miller G: Aesthetic fitness: How sexual selection shaped artistic virtuosity as a fitness indicator and aesthetic preference as mate choice criteria. Bull Psychol Arts 2001;2:20-25.
Jarvik LF, Deckard BS: The Odyssean personality. A survival advantage for carriers of genes predisposing to schizophrenia? Neuropsychobiology 1977;3:179-191.
Kelsoe JR: Arguments for the genetic basis of the bipolar spectrum. J Affect Disord 2003;73:183-197.
Karlsson JL: Creative intelligence in relatives of mental patients. Hereditas 1984;100:83-86.
Karlsson JL: Mental abilities of male relatives of psychotic patients. Acta Psychiatr Scand 2001;104:466-468.
Chadwick PK: Schizophrenia: A Positive Perspective. London, Routledge, 1997.
Hammer M, Zubin J: Evolution, culture and psychopathology. J Gen Psychol 1968;78:151-164.
van Dongen J, Boomsma DI: The evolutionary paradox and the missing heritability of schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2013;162B:122-136.
Cousins DA, Butts K, Young AH: The role of dopamine in bipolar disorder. Bipolar Disord 2009;11:787-806.
McKenna PJ: Pathology, phenomenology and the dopamine hypothesis of schizophrenia. Br J Psychiatry 1987;151:288-301.
Diehl DJ, Gershon S: The role of dopamine in mood disorders. Compr Psychiatry 1992;33:115-120.
Folley BS, Park S: Verbal creativity and schizotypal personality in relation to prefrontal hemispheric laterality: a behavioral and near-infrared optical imaging study. Schizophr Res 2005;80:271-282.
Howes OD, Kambeitz J, Kim E, Stahl D, Slifstein M, Abi-Dargham A, Kapur S: The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry 2012;69:776-786.
Randrup A, Braestrup C: Uptake inhibition of biogenic amines by newer antidepressant drugs: relevance to the dopamine hypothesis of depression. Psychopharmacology (Berl) 1977;53:309-314.
Williams GV, Goldman-Rakic PS: Modulation of memory fields by dopamine d1 receptors in prefrontal cortex. Nature 1995;376:572-575.
Angrist B: Clinical variations of amphetamine psychosis; in Cho AK, Segal DS (eds): Amphetamine and Its Analogs. San Diego, Academic Press, 1994, pp 387-414.
Giros B, el Mestikawy S, Godinot N, Zheng K, Han H, Yang-Feng T, Caron MG: Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. Mol Pharmacol 1992;42:383-390.
Swerdlow NR, Platten A, Hanlon FM, Martinez ZA, Printz MP, Auerbach P: Sensitivity to sensorimotor gating-disruptive effects of apomorphine in two outbred parental rat strains and their F1 and N2 progeny. Neuropsychopharmacology 2003;28:226-234.
Ellenbroek BA, Budde S, Cools AR: Prepulse inhibition and latent inhibition: The role of dopamine in the medial prefrontal cortex. Neuroscience 1996;75:535-542.
Geyer MA, Braff DL: Startle habituation and sensorimotor gating in schizophrenia and related animal models. Schizophr Bull 1987;13:643-668.
Grillon C, Courchesne E, Ameli R, Geyer MA, Braff DL: Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence. Arch Gen Psychiatry 1990;47:171-179.
Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR: Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl) 2001;156:117-154.
Greenwood TA, Alexander M, Keck PE, McElroy S, Sadovnick AD, Remick RA, Kelsoe JR: Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder. Am J Med Genet 2001;105:145-151.
Greenwood TA, Schork NJ, Eskin E, Kelsoe JR: Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samples. Mol Psychiatry 2006;11:125-133.
Kelsoe JR, Sadovnick AD, Kristbjarnarson H, Bergesch P, Mroczkowski-Parker Z, Drennan M, Rapaport MH, Flodman P, Spence MA, Remick RA: Possible locus for bipolar disorder near the dopamine transporter on chromosome 5. Am J Med Genet 1996;67:533-540.
Stober G, Sprandel J, Jabs B, Pfuhlmann B, Moller-Ehrlich K, Knapp M: Family-based study of markers at the 5′-flanking region of the human dopamine transporter gene reveals potential association with schizophrenic psychoses. Eur Arch Psychiatry Clin Neurosci 2006;256:422-427.
Greenwood TA, Lazzeroni LC, Murray SS, Cadenhead KS, Calkins ME, Dobie DJ, Green MF, Gur RE, Gur RC, Hardiman G, Kelsoe JR, Leonard S, Light GA, Nuechterlein KH, Olincy A, Radant AD, Schork NJ, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Freedman R, Braff DL: Analysis of 94 candidate genes and 12 endophenotypes for schizophrenia from the consortium on the genetics of schizophrenia. Am J Psychiatry 2011;168:930-946.
Greenwood TA, Light GA, Swerdlow NR, Radant AD, Braff DL: Association analysis of 94 candidate genes and schizophrenia-related endophenotypes. PLoS One 2012;7:e29630.
Greenwood TA, Swerdlow NR, Gur RE, Cadenhead KS, Calkins ME, Dobie DJ, Freedman R, Green MF, Gur RC, Lazzeroni LC, Nuechterlein KH, Olincy A, Radant AD, Ray A, Schork NJ, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Sugar CA, Tsuang DW, Tsuang MT, Turetsky BI, Light GA, Braff DL: Genome-wide linkage analyses of 12 endophenotypes for schizophrenia from the consortium on the genetics of schizophrenia. Am J Psychiatry 2013;170:521-532.
Buchsbaum MS, Christian BT, Lehrer DS, Narayanan TK, Shi B, Mantil J, Kemether E, Oakes TR, Mukherjee J: D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia. Schizophr Res 2006;85:232-244.
Yasuno F, Suhara T, Okubo Y, Sudo Y, Inoue M, Ichimiya T, Takano A, Nakayama K, Halldin C, Farde L: Low dopamine D(2) receptor binding in subregions of the thalamus in schizophrenia. Am J Psychiatry 2004;161:1016-1022.
Talvik M, Nordstrom AL, Olsson H, Halldin C, Farde L: Decreased thalamic D2/D3 receptor binding in drug-naive patients with schizophrenia: A PET study with [11C]FLB 457. Int J Neuropsychopharmacol 2003;6:361-370.
Reuter M, Roth S, Holve K, Hennig J: Identification of first candidate genes for creativity: a pilot study. Brain Res 2006;1069:190-197.
de Manzano O, Cervenka S, Karabanov A, Farde L, Ullen F: Thinking outside a less intact box: Thalamic dopamine D2 receptor densities are negatively related to psychometric creativity in healthy individuals. PLoS One 2010;5:e10670.
Madras BK: History of the discovery of the antipsychotic dopamine D2 receptor: a basis for the dopamine hypothesis of schizophrenia. J Hist Neurosci 2013;22:62-78.
Volter C, Riedel M, Wostmann N, Aichert DS, Lobo S, Costa A, Schmechtig A, Collier DA, Hartmann AM, Giegling I, Moller HJ, Quednow BB, Rujescu D, Kumari V, Ettinger U: Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach. Int J Neuropsychopharmacol 2012;15:1427-1440.
Keri S: Genes for psychosis and creativity: a promoter polymorphism of the neuregulin 1 gene is related to creativity in people with high intellectual achievement. Psychol Sci 2009;20:1070-1073.
Crespi B, Summers K, Dorus S: Adaptive evolution of genes underlying schizophrenia. Proc Biol Sci 2007;274:2801-2810.
Bachner-Melman R, Dina C, Zohar AH, Constantini N, Lerer E, Hoch S, Sella S, Nemanov L, Gritsenko I, Lichtenberg P, Granot R, Ebstein RP: AVPR1A and SLC6A4 gene polymorphisms are associated with creative dance performance. PLoS Genet 2005;1:e42.
Law AJ, Lipska BK, Weickert CS, Hyde TM, Straub RE, Hashimoto R, Harrison PJ, Kleinman JE, Weinberger DR: Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5′ SNPs associated with the disease. Proc Natl Acad Sci USA 2006;103:6747-6752.
Keri S, Kiss I, Kelemen O: Effects of a neuregulin 1 variant on conversion to schizophrenia and schizophreniform disorder in people at high risk for psychosis. Mol Psychiatry 2009;14:118-119.
Hall J, Whalley HC, Job DE, Baig BJ, McIntosh AM, Evans KL, Thomson PA, Porteous DJ, Cunningham-Owens DG, Johnstone EC, Lawrie SM: A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms. Nat Neurosci 2006;9:1477-1478.
Voight BF, Kudaravalli S, Wen X, Pritchard JK: A map of recent positive selection in the human genome. PLoS Biol 2006;4:e72.
Kalkman HO: The role of the phosphatidylinositide 3-kinase-protein kinase B pathway in schizophrenia. Pharmacol Ther 2006;110:117-134.
Chalecka-Franaszek E, Chuang DM: Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci USA 1999;96:8745-8750.
De Sarno P, Li X, Jope RS: Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium. Neuropharmacology 2002;43:1158-1164.
Kozlovsky N, Amar S, Belmaker RH, Agam G: Psychotropic drugs affect Ser9-phosphorylated GSK-3 beta protein levels in rodent frontal cortex. Int J Neuropsychopharmacol 2006;9:337-342.
Power RA, Steinberg S, Bjornsdottir G, Rietveld CA, Abdellaoui A, Nivard MM, Johannesson M, Galesloot TE, Hottenga JJ, Willemsen G, Cesarini D, Benjamin DJ, Magnusson PK, Ullen F, Tiemeier H, Hofman A, van Rooij FJ, Walters GB, Sigurdsson E, Thorgeirsson TE, Ingason A, Helgason A, Kong A, Kiemeney LA, Koellinger P, Boomsma DI, Gudbjartsson D, Stefansson H, Stefansson K: Polygenic risk scores for schizophrenia and bipolar disorder predict creativity. Nat Neurosci 2015;18:953-955.
Gur RC, Richard J, Calkins ME, Chiavacci R, Hansen JA, Bilker WB, Loughead J, Connolly JJ, Qiu H, Mentch FD, Abou-Sleiman PM, Hakonarson H, Gur RE: Age group and sex differences in performance on a computerized neurocognitive battery in children age 8-21. Neuropsychology 2012;26:251-265.
Kuncel NR, Hezlett SA, Ones DS: Academic performance, career potential, creativity, and job performance: can one construct predict them all? J Pers Soc Psychol 2004;86:148-161.
Batey M, Chamorro-Premuzic T, Furnham A: Intelligence and personality as predictors of divergent thinking: the role of general, fluid and crystallised intelligence. Think Skills Creat 2009;4:60-69.
Gur RC, Gur RE, Obrist WD, Hungerbuhler JP, Younkin D, Rosen AD, Skolnick BE, Reivich M: Sex and handedness differences in cerebral blood flow during rest and cognitive activity. Science 1982;217:659-661.
Gur RC, Alsop D, Glahn D, Petty R, Swanson CL, Maldjian JA, Turetsky BI, Detre JA, Gee J, Gur RE: An fMRI study of sex differences in regional activation to a verbal and a spatial task. Brain Lang 2000;74:157-170.
Jung RE, Haier RJ: The Parieto-Frontal Integration Theory (P-FIT) of intelligence: converging neuroimaging evidence. Behav Brain Sci 2007;30:135-154; discussion 154-187.
Liu S, Chow HM, Xu Y, Erkkinen MG, Swett KE, Eagle MW, Rizik-Baer DA, Braun AR: Neural correlates of lyrical improvisation: an fMRI study of freestyle rap. Sci Rep 2012;2:834.
Limb CJ, Braun AR: Neural substrates of spontaneous musical performance: an fMRI study of jazz improvisation. PLoS One 2008;3:e1679.
Jung RE, Grazioplene R, Caprihan A, Chavez RS, Haier RJ: White matter integrity, creativity, and psychopathology: disentangling constructs with diffusion tensor imaging. PLoS One 2010;5:e9818.
Jung RE, Segall JM, Jeremy Bockholt H, Flores RA, Smith SM, Chavez RS, Haier RJ: Neuroanatomy of creativity. Hum Brain Mapp 2010;31:398-409.
Gibson C, Folley BS, Park S: Enhanced divergent thinking and creativity in musicians: a behavioral and near-infrared spectroscopy study. Brain Cogn 2009;69:162-169.
Gansler DA, Moore DW, Susmaras TM, Jerram MW, Sousa J, Heilman KM: Cortical morphology of visual creativity. Neuropsychologia 2011;49:2527-2532.
Moore DW, Bhadelia RA, Billings RL, Fulwiler C, Heilman KM, Rood KM, Gansler DA: Hemispheric connectivity and the visual-spatial divergent-thinking component of creativity. Brain Cogn 2009;70:267-272.
Takeuchi H, Taki Y, Sassa Y, Hashizume H, Sekiguchi A, Fukushima A, Kawashima R: Regional gray matter volume of dopaminergic system associate with creativity: evidence from voxel-based morphometry. Neuroimage 2010;51:578-585.
Jung RE, Mead BS, Carrasco J, Flores RA: The structure of creative cognition in the human brain. Front Hum Neurosci 2013;7:330.
Johnson SL, Edge MD, Holmes MK, Carver CS: The behavioral activation system and mania. Annu Rev Clin Psychol 2012;8:243-267.
Mason L, O'Sullivan N, Montaldi D, Bentall RP, El-Deredy W: Decision-making and trait impulsivity in bipolar disorder are associated with reduced prefrontal regulation of striatal reward valuation. Brain 2014;137:2346-2355.
O'Sullivan N, Szczepanowski R, El-Deredy W, Mason L, Bentall RP: fMRI evidence of a relationship between hypomania and both increased goal-sensitivity and positive outcome-expectancy bias. Neuropsychologia 2011;49:2825-2835.
Mason L, O'Sullivan N, Blackburn M, Bentall R, El-Deredy W: I want it now! Neural correlates of hypersensitivity to immediate reward in hypomania. Biol Psychiatry 2012;71:530-537.
Mason L, O'Sullivan N, Bentall RP, El-Deredy W: Better than I thought: positive evaluation bias in hypomania. PLoS One 2012;7:e47754.
Bhatia T, Agarwal A, Shah G, Wood J, Richard J, Gur RE, Gur RC, Nimgaonkar VL, Mazumdar S, Deshpande SN: Adjunctive cognitive remediation for schizophrenia using yoga: an open, non-randomized trial. Acta Neuropsychiatr 2012;24:91-100.
Perry W, Potterat EG, Braff DL: Self-monitoring enhances Wisconsin Card Sorting Test performance in patients with schizophrenia: performance is improved by simply asking patients to verbalize their sorting strategy. J Int Neuropsychol Soc 2001;7:344-352.
Jaeggi SM, Buschkuehl M, Jonides J, Perrig WJ: Improving fluid intelligence with training on working memory. Proc Natl Acad Sci USA 2008;105:6829-6833.
Au J, Sheehan E, Tsai N, Duncan GJ, Buschkuehl M, Jaeggi SM: Improving fluid intelligence with training on working memory: a meta-analysis. Psychon Bull Rev 2015;22:366-377.
Seligman ME, Csikszentmihalyi M: Positive psychology. An introduction. Am Psychol 2000;55:5-14.
Seligman ME, Steen TA, Park N, Peterson C: Positive psychology progress: empirical validation of interventions. Am Psychol 2005;60:410-421.
Galvez JF, Thommi S, Ghaemi SN: Positive aspects of mental illness: a review in bipolar disorder. J Affect Disord 2011;128:185-190.
Duckworth AL, Steen TA, Seligman ME: Positive psychology in clinical practice. Annu Rev Clin Psychol 2005;1:629-651.
Parker G, Paterson A, Fletcher K, Blanch B, Graham R: The “magic button question” for those with a mood disorder - would they wish to re-live their condition? J Affect Disord 2012;136:419-424.
Nelson B, Rawlings D: Its own reward: a phenomenological study of artistic creativity. J Phenomenol Psychol 2007;38:217-255.
Schou M: Artistic productivity and lithium prophylaxis in manic-depressive illness. Br J Psychiatry 1979;135:97-103.
Polatin P, Fieve RR: Patient rejection of lithium carbonate prophylaxis. JAMA 1971;218:864-866.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.