Positive Traits in The Bipolar Spectrum: The Space Between Madness and Genius

Review
Mol Neuropsychiatry 2016;2:198–212 Received: January 18, 2016

Accepted: October 10, 2016
DOI: 10.1159/000452416
Published online: December 9, 2016
Positive Traits in the Bipolar Spectrum:

The Space between Madness and Genius
Tiffany A. Greenwood
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Downloaded from http://karger.com/mnp/article-pdf/2/4/198/3116921/000452416.pdf by guest on 15 September 2023

Key Words this model. Current findings are summarized from a multi-
Bipolar disorder · Creativity · Temperament · Personality · disciplinary perspective to demonstrate the feasibility of re-
Genetics · Polygenic · Psychosis search in this area to reveal the mechanisms underlying ill-
ness. © 2016 S. Karger AG, Basel
Abstract
Bipolar disorder is a severe, lifelong mood disorder for which
little is currently understood of the genetic mechanisms un- Introduction
derlying risk. By examining related dimensional phenotypes,
we may further our understanding of the disorder. Creativity Bipolar disorder is a severe mood disorder that is char-
has a historical connection with the bipolar spectrum and is acterized by alternating states of major depression and
particularly enhanced among unaffected first-degree rela- mania. Mania is accompanied by pathological elevations
tives and those with bipolar spectrum traits. This suggests in energy and mood, racing thoughts and speech, a de-
that some aspects of the bipolar spectrum may confer ad- creased need for sleep, grandiosity, and risk taking;
vantages, while more severe expressions of symptoms nega- whereas depression is associated with low energy and
tively influence creative accomplishment. Creativity is a motivation, insomnia, and feelings of extreme sadness,
complex, multidimensional construct with both cognitive failure, worthlessness, and hopelessness [1]. Psychosis is
and affective components, many of which appear to reflect a common feature of bipolar mood episodes, with up to
a shared genetic vulnerability with bipolar disorder. It is sug- 50% of patients experiencing psychotic symptoms, more
gested that a subset of bipolar risk variants confer advan- often during acute mania than depression [1, 2]. Bipolar
tages as positive traits according to an inverted-U-shaped disorder is common, affecting approximately 1% of the
curve with clinically unaffected allele carriers benefitting population in its most severe form and up to 6% when
from the positive traits and serving to maintain the risk al- considered as a spectrum [3, 4].
leles in the population. The association of risk genes with Since bipolar disorder is a lifelong illness for which
creativity in healthy individuals (e.g., NRG1), as well as an lasting remissions are uncommon, understanding the
overall sharing of common genetic variation between bipo- pathophysiology and genetic architecture is of paramount
lar patients and creative individuals, provides support for importance to diagnosis and treatment. Bipolar disorder
© 2016 S. Karger AG, Basel Tiffany A. Greenwood, PhD

2296–9209/16/0024–0198$39.50/0 Department of Psychiatry
University of California San Diego
E-Mail karger@karger.com
9500 Gilman Drive, MC 0689, La Jolla, CA 92093 (USA)
www.karger.com/mnp
E-Mail tgreenwood @ ucsd.edu
is strongly familial with an estimated heritability of 60– reportedly having struggled under the burden of illness
93% [5–8]. Yet, despite the clear contribution of genetics [19]. Numerous studies have consistently reported an
to the etiology of bipolar disorder, little of the genetic ar- overrepresentation of affective disorders and psychosis
chitecture is currently understood. Large genome-wide among successful people in creative professions, as well
association studies have suggested a significant role for as exceptional creative potential in relatives of individuals
common variation in explaining at least 25% of the ge- with bipolar disorder [19–27]. Large studies of nonemi-
netic variance in bipolar disorder, 68% of which is shared nent, or “everyday,” creativity in patients and their rela-
with schizophrenia as a general risk for psychosis [9]. tives have produced comparable findings. Recent Swed-
While such studies have identified several strong candi- ish population-based studies have demonstrated an over-
dates for susceptibility genes [10], the mechanisms by representation in creative occupations of bipolar patients
which risk variants lead to disease are complex and re- and their healthy first-degree relatives, strongly support-
main largely unknown. ing the familial association of bipolar disorder with cre-
Some of the difficulty in identifying bipolar risk genes ativity [28, 29]. Similarly, the Epidemiologic Catchment
may stem from the use of diagnostic systems that group Area Study found a disproportionate concentration of in-

patients into discrete categories, which may have some dividuals with bipolar disorder in creative occupations
utility for clinical care but do not adequately reflect the [30].
dimensional nature of psychiatric illness. Some investiga- It must be noted that creativity is not a ubiquitous trait
tors have suggested that bipolar disorder exists at the ex- in bipolar disorder. In fact, a large study of psychiatric
treme of normal population variation in temperament, patients estimated that only 8% of those with a bipolar
personality, and cognition [11–15]. Moreover, it has long spectrum disorder could be considered highly creative
been observed that certain positive traits or enhanced [31]. Concerns have also been raised regarding potential
abilities, such as creativity, exist within the bipolar spec- biases across studies, as well as a lack of consistency in
trum and in unaffected relatives. This may suggest a mod- how both mood disorders and creativity are conceptual-
el in which large doses of risk variants cause illness, but ized [32]. For example, anecdotal studies of eminently
mild or moderate doses hold advantages for unaffected creative individuals may suffer from incomplete bio-
allele carriers. Investigating these positive traits may not graphical records and be skewed towards a sampling of
only enhance our understanding of bipolar disorder as a individuals with more severe mood symptoms. Most
dimensional clinical phenotype but, as quantitative traits studies also rely on creative occupation, which may serve
that are presumably closer to the actual transmitted phe- as a poor proxy for creativity and introduce bias. Finally,
notype, they can also be expected to improve our power it has been suggested that the overrepresentation of bipo-
to identify risk genes and ultimately provide novel thera- lar disorder observed in population-based studies of cre-
peutic targets. ativity may reflect a preference for the unconventional
lifestyle provided by creative occupations, as many suffer-
ing with bipolar disorder have trouble maintaining stable
Bipolar Disorder and Creativity: “Madness versus employment. Indeed, the personality traits that seem to
Genius” be most associated with choosing a creative occupation
are openness and impulsivity [33], which are associated
Western cultural notions of “mad geniuses” and “ar- with bipolar disorder as discussed below [34–37]. How-
tistic temperaments” date back to Aristotle’s observation ever, a multitude of studies of both eminent and “every-
that “no great genius has ever existed without a strain of day” creativity consistently suggest a relationship be-
madness” [16], and a wealth of investigations into this tween creativity and risk for bipolar spectrum disorders
area, both formal and anecdotal, have supported this no- that warrants further research.
tion [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 be- Bipolar Disorder and Creativity: A Shared
tween creativity and bipolar disorder is well documented Vulnerability
in eminently creative individuals, with artists like Vincent
van Gogh, authors like F. Scott Fitzgerald and Ernest While some studies have found increased creativity in
Hemingway, poets like Walt Whitman and Sylvia Plath, those with bipolar disorder, comparable to that observed
and composers like Rachmaninoff and Tchaikovsky all in creative individuals [38–40], others have indicated that
Positive Traits and Bipolar Disorder Mol Neuropsychiatry 2016;2:198–212 199

DOI: 10.1159/000452416
Color version available online
fortunate side effect of extreme genetic loading. In short,
as once observed by Paracelsus, “the dose makes the poi-
son.”
BD
Population frequency
Optimal genetic
loading for
positive traits:
creativity Positive Traits in the Space between Madness and
personality Genius
temperament
cognitive flexibility
Several temperament and personality traits are related
to bipolar disorder, to creativity in individuals with bipo-
lar disorder, and to creativity in healthy individuals,
Genetic risk
seemingly occupying the space between madness and ge-
nius. Both bipolar and creative individuals have higher
Fig. 1. Positive traits within the bipolar spectrum and a shared vul-
cyclothymic, dysthymic, and irritable temperament

nerability. According to the inverted-U model, creativity and oth- scores compared with noncreative controls [36, 38, 50–
er positive traits would be expected to increase with genetic load- 52]. Hyperthymic temperament is further associated with
ing up to a threshold, beyond which they would start to diminish creativity in healthy subjects, as are hypomanic personal-
with the increasing impairment of illness [42, 48, 49]. Polygenic ity traits, which predict risk for bipolar disorder [53–55].
risk indicates genetic vulnerability due to common variation in ag-
gregate, which is maintained in the population by clinically unaf- Bipolar and creative individuals also have higher neurot-
fected individuals, who benefit from the positive traits. BD, bipolar icism, extraversion, and openness personality scores
disorder. compared with noncreative controls [33, 36–38, 51, 52,
56–61]. Openness to experience is a central feature of cre-
ativity, with an estimated effect size of 0.71 [33, 62–66].
Openness is also heritable in bipolar families [67].
professional success and creativity is significantly higher Although the exact nature of the relationship is un-
in their clinically unaffected first-degree relatives [28, 39, clear, intelligence and cognitive style are associated with
41–43]. Similarly, creativity and eminence occur more of- aspects of creativity [68]. Creative people tend toward di-
ten in individuals with affective temperaments, which vergent thinking, the cognitive ability of associational
may reflect the subclinical expression of bipolar disorder network activation and creative ideation, and an overin-
and the underlying genetic vulnerability [31, 42, 44–47]. clusive cognitive style, which involves remote associa-
These observations are consistent with the observed “in- tions and may facilitate originality [69]. The hallmark
verted-U” relationship between creativity and psychopa- symptoms of mania include increased word production
thology and a shared vulnerability, as shown in Figure 1 and loose associations, and, not surprisingly, manic bipo-
[42, 48, 49]. According to this model, creativity and other lar patients exhibit conceptual overinclusiveness, similar
positive traits would increase with genetic risk for bipolar to creative writers [70]. Such loose associations may result
disorder up to a threshold, beyond which they would start from a failure to filter irrelevant stimuli from the environ-
to diminish with the increasing impairment of illness. In- ment, a process known as cognitive disinhibition [49],
triguingly, this model suggests that the phenotype being which has been associated with both psychosis proneness
transmitted in the population is not bipolar disorder per [64] and creativity [71]. While intelligence, particularly
se, but rather positive traits that modulate behavior in executive function, may be associated with performance
healthy individuals, with the disorder representing the measures of creativity, like divergent thinking [72–74],
extreme on a continuum of variation in these traits [11– this effect appears only moderate (d = 0.31) [64]. In fact,
15]. This model also suggests the influence of common above-average intelligence (IQ >120) appears to be neces-
variants distributed across the entire population, which is sary but not sufficient for high creativity [75], and once
consistent both with the polygenic model of risk for bipo- this threshold is met, personality factors like openness are
lar disorder and with the observance of a stable world- more predictive of creative potential [76]. Still, higher ex-
wide prevalence rate [9]. Clinically unaffected individuals ecutive function has been shown to mediate increased
would thus serve as a genetic reservoir, maintaining bipo- creativity during mania [77]. The combination of high IQ
lar risk alleles in the population and benefiting from the and cognitive disinhibition may also predict creative
positive traits, with the disorder occurring only as an un- achievement [49]. Finally, a positive mood appears to
200 Mol Neuropsychiatry 2016;2:198–212 Greenwood

DOI: 10.1159/000452416
Color version available online
Creative genius
Drive/ Mood instability Bipolar disorder

motivation cyclothymic, dysthymic, mania, mood
irritable temperaments; cycling
hypomanic traits
High IQ
“Experiencing” personality
openness, extraversion, Depression
Ideational impulsivity, positive schizotypy
originality
Fig. 2. The space between madness and ge- Conceptual Psychosis
overinclusiveness
nius. Adaptation of Carson’s model of the Cognitive
flexibility Cognitive
shared vulnerability between creative ge- Cognitive deficits
nius and psychopathology [49] summariz- disinhibition
ing the temperament, personality, and cog-
Schizophrenia

nitive characteristics shared by creative in-
affective flattening,
dividuals and those with genetic liability to cognitive disorganization
bipolar disorder and/or psychosis. The
Shared vulnerability traits
clinical overlap between bipolar disorder Present in creative individuals and those with
and schizophrenia is also represented, as genetic liability to bipolar disorder or psychosis
are the characteristics unique to each disor-
der.
provide a significant cognitive advantage in the perfor- mechanisms by which these traits mediate creativity are
mance of divergent thinking tasks, whereas a negative unknown, and it is unclear as to whether they explain the
mood inhibits this process [78]. association of creativity with bipolar disorder.
Recent studies have made significant progress in de-
fining the relationship between bipolar disorder and cre-
ativity. In one study of bipolar families, a network analy- Bipolar Disorder, Schizophrenia, and Their Common
sis of the observed phenotypic correlations revealed clus- Connection to Creativity
ters of traits related to affective temperament, impulsivity,
risk taking, and psychosis proneness (a “bipolar spec- Schizophrenia is a severe psychotic disorder that is
trum” component) and to executive function, processing characterized by abnormalities in a patient’s thoughts,
speed, working memory, and long-term memory (a cog- perceptions, speech, affect, and behaviors, manifesting as
nitive component) [79]. Interestingly, perceptual creativ- auditory hallucinations, paranoid or bizarre delusions,
ity was found to span these clusters. Another study exam- and/or disorganized speech and thoughts. While schizo-
ining individuals with bipolar disorder and their healthy phrenia is often thought to mainly affect cognition, it also
co-twins found increased sharing of positive traits related usually contributes to chronic problems with behavior
to temperament, schizotypy, impulsivity, and sensation and emotion. Bipolar disorder and schizophrenia have
seeking that were further correlated with increased verbal historically been regarded as separate disorders with dis-
learning and fluency in the co-twins [80]. These studies tinctive underlying etiologies, yet data across many disci-
highlight the need to examine multiple dimensions of plines have increasingly advocated for a functional psy-
personality, mood, and cognition to fully understand chosis continuum spanning these diagnoses [85–90].
concepts relating to positive traits within the context of The considerable clinical overlap between bipolar dis-
creativity and illness. order and schizophrenia often causes confusion and mis-
Creativity thus appears to result from the complex in- diagnosis [91]. For example, acutely manic bipolar pa-
teraction of multiple personality, cognitive, and affective tients exhibit cognitive deficits, such as thought disorder
traits [69, 81, 82], which may reflect a shared vulnerabil- and conceptual disorganization, which are typical of
ity with bipolar disorder [49, 83, 84]. A summary of the schizophrenia [92]. To some extent, parallels can be
components that likely occupy the space between mad- drawn between the negative symptoms of schizophrenia
ness and genius is presented in Figure 2. However, the (e.g., asociality, avolition) and depression in bipolar dis-

DOI: 10.1159/000452416
order and between the positive symptoms of schizophrenia patients [132, 133], which are primarily associated
nia (e.g., delusions, hallucinations) and mania. Epidemi- with negative symptoms, may explain the relatively poor
ological and genetic data are also consistent with a sub- performance of schizophrenia patients for measures of
stantial overlap in susceptibility for bipolar disorder and creativity involving fluency and cognitive flexibility [134–
schizophrenia [6, 9, 10, 93–106]. It has been estimated 136]. If creativity and psychosis result from a shared vul-
that 63% of the shared genetic vulnerability between these nerability, cognitive protective factors, such as high IQ
disorders derives from additive genetic effects [6], with and cognitive flexibility, may lead to enhanced creativity,
68% of the shared genetic variance deriving from com- whereas the cognitive deficits often present in full-blown
mon variation [9]. It is possible that a portion of this illness may prevent the individual from fully realizing
shared common genetic variance may be a reflection of their creative potential [49, 115].
the historical connection of both bipolar disorder and Many have also argued that bipolar disorder and
psychosis to creativity. schizophrenia are associated with different types of cre-
As with bipolar disorder, large population-based stud- ativity, such as “artistic” versus “scientific,” which may be
ies have reported an overrepresentation in creative occu- mediated by varying aspects of temperament, personality,

pations of the healthy first-degree relatives of schizophre- and cognitive style [19, 118, 137–140]. In support of this
nia patients, supporting the familial association of schizo- concept, some groups have demonstrated an association
phrenia with creativity [28, 29]. Some groups have also of positive schizotypal traits with artistic domains and
reported increased creativity in schizophrenia patients negative schizotypal traits with math and science [116,
compared with normal controls [107, 108], as well as in- 141]. Verbal divergent thinking is linked to creativity in
creased creativity in the adopted children of parents with writers and scientists and is correlated with a higher IQ
schizophrenia [109, 110]. However, much research on than figural divergent thinking, which is more closely re-
creativity has focused on aspects of schizotypy, which is lated to creativity in artists and musicians [75].
thought to reflect the subclinical expression of schizo-
phrenia [111, 112], as well as the underlying genetic vul-
nerability [113]. Many studies have demonstrated strong Bipolar Disorder and Evolution
associations between schizotypal personality traits and
enhanced performance on tests of creativity and fluency, Bipolar disorder exhibits substantial fitness costs in
as well as elevated levels of schizotypy in individuals ac- terms of increased mortality and significant impairment,
tive in the creative arts [48, 55, 84, 114–124]. Interest- yet it has persisted in the population with a high heritabil-
ingly, this association between creativity and schizotypal ity and a stable prevalence [142]. This appears contrary to
traits is also observed in bipolar patients, who score high- evolution theory, in which genetic variants associated
er than controls on several measures of schizotypy [116, with a loss of fitness are presumably pruned from the gene
125, 126]. Several of the personality traits discussed above pool through the process of natural selection [143, 144].
with relationships to creativity, namely, neuroticism, Some have suggested that psychiatric illnesses result from
openness, and cyclothymic temperament, are correlated polygenic mutation-selection balance, whereby genetic
with positive schizotypal traits [127–129]. Openness also variants that reduce fitness are introduced through muta-
demonstrated high sibling correlations in a study of mul- tion and pruned from the gene pool at a rate proportion-
tigenerational SZ families, as well as high heritability al to their adverse effects on fitness [143–147]. While the
[130]. mutation rate is low, the overall target size is large, involv-
These data, like those for bipolar disorder, suggest that ing many genes and regulatory regions. This model fits
some aspects of the schizophrenia spectrum provide ad- well with the apparent impact of rare structural and de
vantages in terms of creativity, many of which are sum- novo variants on schizophrenia susceptibility [146–152],
marized in Figure 2. Other personality factors, such as the reported effects of paternal age [153], and with the
increased sociability, strong ambition, and a desire for severe fertility disadvantages that have been observed in
recognition by others, characterize those who excel be- schizophrenia [154–156]. While structural variants do
cause of their creative talent and are features observed in not appear to contribute significantly to risk for bipolar
bipolar patients and their relatives, which may partially disorder, rare variants may play a role [157–160].
explain the tighter link of bipolar disorder to creativity Other evolutionary models relating to balancing selec-
compared with schizophrenia [33, 83, 118, 131]. Addi- tion and fitness trade-offs have been widely debated. For
tionally, the deficits in executive function in schizophre- example, it has been suggested that traits associated with

DOI: 10.1159/000452416
bipolar disorder and psychosis may provide fitness ad- creativity [71] and psychosis [184–186]. Interestingly, the
vantages in terms of sexual selection, mating success, or DAT gene (SLC6A3) has shown evidence of association
social skills, particularly in certain niches [144, 161–166]. and linkage with bipolar disorder [187–189], schizophre-
Some have suggested that affective temperaments pro- nia [190], neurocognitive deficits in schizophrenia [191],
vide favorable evolutionary properties that serve to main- and, of particular relevance, sensorimotor gating deficits
tain bipolar risk alleles in the population [45, 46, 167]. in schizophrenia [192, 193]. Furthermore, decreased tha-
Others have suggested that the observed association be- lamic D2 receptor densities are observed both in patients
tween schizotypal traits and creativity may partially ex- with psychosis [194–196] and in healthy subjects with
plain the persistence of psychosis risk variants in the pop- high divergent thinking scores [197, 198]. The presynap-
ulation [117, 141, 166, 168–171]. Consistent with these tic D2 receptor is part of the inhibitory response to curb
notions, studies have shown at least moderate evidence excessive dopamine release, similar to the function of
for reduced fecundity in individuals with bipolar disorder DAT, and is the primary target of all antipsychotics [199].
and increased fecundity in their unaffected siblings, who Finally, the variants of the D2 receptor gene (DRD2) have
presumably carry a reduced burden of risk variants and been shown to be associated with both verbal creativity

may express these traits in a milder, more advantageous [197] and sensory motor gating deficits [200] in healthy
form [142, 155, 156]. Antagonistic pleiotropy provides an individuals. These observations collectively suggest that
attractive evolutionary model in this context, wherein al- higher dopamine availability may lower gating thresholds
leles associated with an increased fitness for one trait also and increase creativity in the absence of psychosis.
decrease fitness for another [143, 144, 172]. As many al- Several validated psychosis risk genes have been inves-
leles are likely involved, the fitness consequences of each tigated as part of small candidate gene studies for asso-
allele would be closer to neutral. This would allow risk ciation with creativity in healthy individuals and have
alleles to randomly drift to higher frequencies through shown marks of positive selection in humans (e.g., NRG1,
neutral drift-mutation and become common in the popu- SLC6A4) [201–203]. NRG1 in particular provides an in-
lation. As it is likely that no single trait in its extreme leads triguing candidate for a shared vulnerability, with a func-
to bipolar disorder, a highly heterogeneous clinical phe- tional promoter variant [204] that is associated with both
notype, it is also likely that no single evolutionary model an increased risk of psychosis [205, 206] and increased
can fully explain the persistence of bipolar disorder in the creativity in healthy subjects [201]. Interestingly, an un-
population. This topic awaits a better understanding of usually high percentage of genes involved in the phospha-
the interacting phenotypes and the underlying genetic tidylinositol 3-kinase (PI3K) pathway appear to have
mechanisms involved in both illness and creativity. 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
Molecular Pathways and Genetic Links [208]. Both lithium and valproate, common treatments
for bipolar disorder, are also thought to act, in part,
There is strong evidence to suggest a role for the dopa- through activation of PI3K [209–211]. While these find-
minergic system in bipolar disorder and psychosis [173– ings remain to be confirmed in larger samples, they may
175], as well as in creativity [42, 123, 176]. Mania and provide clues as to the underlying mechanisms.
psychosis both partially reflect a hyperdopaminergic state Perhaps the most convincing genetic evidence in sup-
[177, 178], whereas depression and cognitive deficits in port of a shared vulnerability between creativity and bi-
bipolar disorder may relate to dopamine deficiencies polar disorder/psychosis comes from a study conducted
[178, 179]. Acute amphetamine intoxication closely re- by Power et al. [212] of over 86,000 healthy subjects from
sembles mania, and chronic administration can provoke an Icelandic cohort with a replication sample of more
a manic episode in those with bipolar disorder and trigger than 27,000 from Sweden and the Netherlands, all of who
psychosis in healthy individuals [180]. The dopamine were genotyped. Approximately 1% of each sample was
transporter (DAT) plays a critical role in the regulation of considered creative, as defined by membership in an ar-
dopamine availability and is the site of action of amphet- tistic society or by creative profession. Using data from
amine, which increases synaptic dopamine by inhibiting recent genome-wide association studies of bipolar disor-
reuptake [181]. Excess dopamine has also been reported der and schizophrenia, polygenic risk scores were calcu-
to decrease inhibition of stimuli from the surrounding lated as the sum of associated alleles weighted by their
environment [182, 183], which is characteristic of both effect sizes. Power’s group found that higher genetic risk

DOI: 10.1159/000452416
for bipolar disorder and schizophrenia, measured as a observed increased verbal ability and schizotypal person-
polygenic risk score, was significantly associated with cre- ality in the musicians compared with the nonmusicians.
ativity, indicating shared genetic vulnerability. However, In general, structural imaging studies have revealed posi-
the primary limitation of this study, like many previous tive correlations between both creative achievement and
studies, is the use of creative occupation as the phenotype, divergent thinking and the right DLPFC, right posterior
rather than a direct measurement of creative ability. Large cingulate, right parietal lobe, bilateral caudate, and right
genomic studies evaluating the shared vulnerability mod- midbrain regions and inverse correlations with the left
el of bipolar disorder/psychosis and creativity utilizing lateral orbitofrontal gyrus, lingual gyrus, inferior parietal
more refined measurements of creative ability remain a gyrus, and fusiform gyrus [222, 224–226]. This complex
topic of future investigations. pattern that spans lobes and hemispheres likely reflects
the inherent complexity of human creativity [227].
Whether the pattern of activation in bipolar individuals
Brain Imaging Studies of Creativity engaged in creative cognition resembles that of healthy
creative individuals remains to be shown.

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 prob- Optimizing Study Design
lems in novel situations, which is independent of acquired
knowledge (crystalized intelligence) and is a component Although there have been many attempts to evaluate
of general intelligence (g) [213]. Fluid intelligence is mod- the nature of the relationship of creativity to bipolar dis-
erately correlated with the novel, original idea generation order and psychosis, very few have administered a com-
processes encompassed by divergent thinking [54, 214, prehensive battery in a reasonably large sample. Most
215]. Results suggest that this reasoning ability is associ- studies have been small, underpowered, or employed a
ated with activation of a network of frontal and parietal very limited number of phenotypes. Large population-
brain regions, specifically the dorsolateral prefrontal cor- based studies have focused solely on diagnosis and creative
tex (DLPFC), the superior parietal lobule, intraparietal occupation or involvement, which may not adequately re-
cortices, and left temporoparietal regions [216–218]. flect creative ability. Many other studies have focused on
Recent studies have attempted to directly evaluate healthy subjects and evaluated, for example, schizotypal
brain activation during divergent thinking in artists. One personality traits and creativity. While these studies col-
study compared fMRI scans of rappers during freestyle lectively provide an abundance of data to support the con-
(i.e., improvisation), which is analogous to divergent nection between bipolar disorder and creativity, the lack
thinking, with those during the recitation of memorized of consistency prevents cross-study comparisons.
lyrics [219]. A previous study by the same group had ex- To truly understand the complex relationship between
amined jazz musicians (pianists) using a similar para- bipolar disorder and creativity, all traits of potential rel-
digm of improvisation versus the performance of a stan- evance must be evaluated in the same sample using a de-
dardized piece of written music [220]. Interestingly, both sign intended to capture the full spectrum of shared phe-
sets of artists showed decreased activity in the DLPFC notypic and genetic variation. Only then can we defini-
during improvisation and increased activity in the me- tively determine which traits are relevant in this context.
dial prefrontal cortex. These studies suggested that a re- A study design including individuals with bipolar disor-
laxation of executive functions and de-focused attention, der, unaffected relatives, and both creative (i.e., artists,
allowing for uncensored processes and free associations musicians, writers, etc.) and noncreative controls would
to occur, may be the hallmark of creative cognition. Fur- be ideally suited for a direct evaluation of the shared vul-
ther evidence is provided by findings of inverse relation- nerability model shown in Figure 1. Using a polygenic
ships between divergent thinking ability and both cortical risk score method analogous to that of Power et al. [212],
thickness and white matter integrity in frontal lobe re- one would expect the positive trait values to approximate
gions [221, 222]. Another study comparing musicians an inverted-U-shaped curve with noncreative controls
with matched controls using near-infrared spectroscopy and bipolar individuals anchoring the curve at each end,
observed enhanced divergent thinking in the musicians representing the lowest and highest genetic risk, respec-
supported by increased bilateral frontal cortical activity tively. Creative controls and unaffected relatives would
[223]. In addition to enhanced creativity, this study also presumably fall in the center of the curve with higher pos-

DOI: 10.1159/000452416
itive trait values conferred by mild-to-moderate risk for of research in this area is to better understand the genetic
illness. The inclusion of twins discordant for bipolar dis- pathways contributing to risk. The low signal produced
order would be useful for disentangling genetic and envi- by genome-wide studies, with individual allelic effect siz-
ronmental effects [80]. es on the order of 0.5–1%, suggests that a large portion of
The use of a comprehensive, standardized battery the variance operates in clinically unaffected individuals
would facilitate cross-study comparisons and allow for [9, 10]. This also suggests that the phenotype is poorly
the sample sizes needed to resolve these issues. For in- understood, implicating the need to define better mea-
clusion in such a battery, a task should show evidence sures to detect the common alleles contributing to 25% of
of reliability and stability; provide a range of pheno- the risk for bipolar disorder and operating in the general
typic variation in both clinical and nonclinical sam- population. Through the assessment of positive traits, we
ples; relate to the bipolar spectrum; and, most impor- broaden the concept of bipolar disorder into a fully di-
tantly, have the potential to function as a positive trait. mensional spectrum and presumably capture specific
Options for such a battery that meet many of these cri- portions of the variance, which will facilitate the detection
teria are listed in online supplementary Table 1 (www. of the underlying genes and pathways contributing to

karger.com/doi/10.1159/000452416). For some traits, such risk. Understanding the relationship between positive
as temperament and personality, we would expect relative- traits and bipolar disorder may thus provide insight into
ly intermediate values to provide an advantage, whereas the mechanisms of illness, which may someday lead to
extreme values on either end would be expected to confer novel therapeutic targets.
a disadvantage. Other traits, such as creativity or cognitive Although this discussion has focused on positive traits,
flexibility, would be expected to function more simply, with it is important to note that the patients themselves exist at
higher (more extreme) values conferring the advantage. the extreme and may be pushed beyond the limit of posi-
The administration of an array of creative tasks is also tive value, either at euthymia or in a state-dependent man-
necessary to capture the range of creative ability and gain ner. Behavioral traits conforming to a shared vulnerabil-
insight into the mechanism by which the various person- ity model may provide excellent targets for evidence-
ality, cognitive, and affective traits associated with the bi- based therapies. For example, individuals with bipolar
polar spectrum impact creativity. While creativity is gen- disorder often exhibit poor judgment in terms of impul-
erally conceptualized as a spontaneous process that may sivity or reward-based decision-making [34, 35, 228].
be difficult to fully capture within a laboratory setting, Modulation of risk-reward valuation can easily be viewed
several standardized and validated measurements exist, according to this model, as a slight overvaluation of risk,
including figure preference and divergent thinking tasks. in appropriate balance with reward valuation, can lead to
Divergent thinking involves originality of thought, flu- great accomplishments, yet a large overvaluation of risk as
ency of ideas, and creative problem solving ability and compared with reward, which is correlated with mania,
thus represents an advantageous trait that drives inven- may have disastrous consequences [229, 230]. Even indi-
tion and achievement across many domains (e.g., writing, viduals with subsyndromal hypomanic symptoms show a
science, business, etc.). Divergent thinking tasks can be greater hedonic impact of reward and a preference for im-
conceptualized as the opposite of fluid intelligence tasks, mediate over delayed, but superior, rewards [231, 232].
which measure logical reasoning, and high performance There is thus likely a threshold along the bipolar spectrum
across both types of tasks would particularly promote at which a loss of inhibition and false positive error rates
success across a number of disciplines. In addition to increase for tasks of impulsivity and risk-reward valua-
mood and personality, assessments of creativity should tion, which would implicate a possible point of interven-
thus be combined with comprehensive cognitive assess- tion and suggest a target for behavioral therapy to improve
ments to allow for an evaluation of overall intelligence emotion-based decision-making or enhance self-control.
and the full range of individual capabilities. In general, treatments aimed at reducing subsyndromal
symptoms and relapses may indirectly improve the cogni-
tive deficits associated with the disorder. Adjunctive ther-
Implications and Future Directions apies that improve focus and concentration, such as yoga
therapy, also hold promise for improving cognitive func-
Little is currently understood of the molecular mecha- tion across several domains in both bipolar disorder and
nisms underlying bipolar disorder, and current treat- schizophrenia [233]. Additionally, cognitive behavioral
ments are far from maximally effective. Part of the value therapy and self-monitoring techniques can be used to

DOI: 10.1159/000452416
help patients modulate cognitive disorganization and per- ative work that they prefer to go untreated rather than
form better on executive function tasks [234]. Finally, al- risk limiting or losing it [244]. However, bipolar disorder
though controversial, there is evidence to suggest that usually worsens with time. While the side effects of med-
cognitive training exercises can not only increase working ications may be unpleasant for some, the consequences of
memory but also improve fluid intelligence, which in- the disorder left untreated can be fatal, as evidenced by
cludes such abilities as pattern recognition, abstract rea- the ninefold increase in suicide rate and the countless art-
soning, and problem-solving [235, 236]. Although more ists and writers with bipolar disorder who have commit-
research in this area is needed, this is potentially promis- ted suicide [19]. Studying the link between creativity and
ing for bipolar patients with complex cognitive deficits, bipolar disorder will thus promote a deeper understand-
and all tasks improving cognitive functioning in bipolar ing of patients’ needs and experiences and facilitate better
disorder may ultimately improve performance in those treatment, thereby enhancing patient compliance.
with creative abilities [77]. Thus, the investigation of be- While the “Madness versus Genius” debate dates back
havioral traits that follow this model may not only further to the time of Aristotle, research in this area is still in its
our understanding of the underlying neural networks in- infancy. Still, reports across several disciplines now pro-

volved in bipolar disorder but also facilitate treatment. vide scientific evidence to bolster what was once a collec-
tion of anecdotal evidence and lend legitimacy to these
claims. Future studies will need to evaluate potential pos-
Conclusions itive traits in the appropriate samples to identify those
that will be most useful for exploring the genetic architec-
It has long been conventional wisdom that positive ture of the shared vulnerability and the evolutionary con-
traits or enhanced abilities occur in the unaffected rela- text of bipolar disorder. An understanding of the role of
tives of individuals with bipolar disorder, as well as many bipolar risk genes in the general population as they relate
patients themselves, a view supported by numerous stud- to positive traits may provide insight into the mechanism
ies. If it can be shown that bipolar disorder is merely an of illness and thus facilitate the development of novel
extension of normal population variation in beneficial therapeutic treatments. Additionally, while the mild to
traits, it may erase some of the stigma still associated with moderate expression of these positive traits may hold ad-
this severe mental illness. Studies evaluating positive as- vantages, more extreme expressions likely contribute to
pects and character strengths associated with bipolar dis- the severe symptoms associated with illness. A better un-
order are aligned with the growing interest in research on derstanding of the nature of this relationship will enable
the impact of positive psychological traits on health [237, a suite of cognitive behavioral therapy techniques to im-
238]. Positive psychological traits of spirituality, empa- prove decision-making, self-control, and cognitive func-
thy, creativity, realism, and resilience are frequently ob- tioning in patients, effectively “bending the curve” to-
served in bipolar individuals [239]. By gaining a better wards the positive aspects of these traits where function-
appreciation for the positive aspects of mental illness and ing is increased and is truly beneficial. Further research
exploring methods to enhance these traits, we may im- in this area would thus represent an important step to-
prove clinical outcomes [240]. ward advancing our understanding of bipolar disorder,
Current practice in psychiatry is geared more towards from both etiological and population perspectives, and
controlling the symptoms of bipolar disorder, rather than toward promoting better patient care.
understanding a patient’s true needs and potential capa-
bilities. Creative expression is a source of well-being, and
many of those struggling with bipolar disorder consider Acknowledgements
increased creativity a truly positive aspect of their illness Dr. Greenwood is supported by grant R21 MH106917 from the
[241, 242]. In fact, bipolar patients often discontinue their National Institute of Mental Health. The author expresses her grat-
medications due to subjective experiences of diminished itude to Drs. Ruben Gur, Hagop Akiskal, and especially John Kel-
creativity, among other unpleasant side effects [243, 244]. soe for their guidance, support, and inspiration.
Some patients, once stabilized on lithium, will even de-
crease their own dosage toward achieving a “controlled
Disclosure Statement
cyclothymia,” risking relapse of severe symptoms, all in
the name of creative expression [19]. Others find the hy- Dr. Greenwood reports no financial relationships with com-
pomanic phase so enjoyable and so integral to their cre- mercial interests.

DOI: 10.1159/000452416
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Mol Neuropsychiatry 2016;2:198–212 Received: January 18, 2016

Positive Traits in the Bipolar Spectrum:

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© 2016 S. Karger AG, Basel Tiffany A. Greenwood, PhD

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200 Mol Neuropsychiatry 2016;2:198–212 Greenwood

Drive/ Mood instability Bipolar disorder

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