Brain Illness and Creativity: Mechanisms and Treatment Risks

Brain diseases and their treatment may help or hurt creativity in ways that shape quality of life. Increased creative drive is associated with bipolar disorder, depression, psychosis, temporal lobe epilepsy, frontotemporal dementia, Parkinson disease treatments, and autism. Creativity depends on goal-driven approach motivation from midbrain dopaminergic systems. Fear-driven avoidance motivation is of less aid to creativity. When serotonin and norepinephrine lower motivation and flexible behaviour, they can inhibit creativity. Hemispheric lateralization and frontotemporal connections must interact to create new ideas and conceptual schemes. The right brain and temporal lobe contribute skill in novelty detection, while the left brain and frontal lobe foster approach motivation and more easily generate new patterns of action from the novel perceptions. Genes and phenotypes that increase plasticity and creativity in tolerant environments with relaxed selection pressure may confer risk in rigorous environments. Few papers substantively address this important but fraught topic. Antidepressants (ADs) that inhibit fear-driven motivation, such as selective serotonin reuptake inhibitors, sometimes inhibit goal-oriented motivation as well. ADs that boost goal-directed motivation, such as bupropion, may remediate this effect. Benzodiazepines and alcohol may be counterproductive. Although dopaminergic agonists sometimes stimulate creativity, their doing so may inappropriately disinhibit behaviour. Dopamine antagonists may suppress creative motivation; lithium and anticonvulsant mood stabilizers may do so less. Physical exercise and REM sleep may help creativity. Art therapy and psychotherapy are not well studied. Preserving creative motivation can help creativity and other aspects of well-being in all patients, not just artists or researchers.

Can J Psychiatry. 2011;56(3): 132-143.

Highlights

* Psychiatric and neurological drug choice may alter patients' creativity, sometimes in counterintuitive ways.

* To preserve creativity, treatments that enhance dopaminergic function are more helpful than those that decrease dopaminergic function.

* Traits that in stressful environments increase vulnerability to illness may, in permissive environments, help creativity.

Key Words: creativity, motivation, hypomania, writer's block, mood disorder, bipolar disorder, antidepressant, treatment, dopamine, hemispheric laterality, frontotemporal connections

Abbreviations

5-HT serotonin

AD antidepressant

ADHD attention-deficit hyperactivity disorder

BD bipolar disorder

BDZ benzodiazepine

DA dopamine

DBS deep brain stimulation

FTD frontotemporal dementia

LI latent inhibition

SNRI serotonin-norepinephrine reuptake inhibitor

SSRI selective serotonin reuptake inhibitor

TMS transcranial magnetic stimulation

As research uncovers the ways in which creativity can emerge from illness, it also reveals the relation between lack of creativity and illness. Both topics are politically charged. Some commentators do not want to infer that illness can cause creativity because they consider creativity part of the full expression of human health. Conversely, clinicians may not want to treat loss of creativity as a medical symptom if they fear embroilment in the so-called cosmetic psychiatry debate. Rescuing an artist's creativity that has been damaged by disease is not clearly distinct from enhancing the creativity of someone whose creativeness is already well above average.

Nonetheless, the relation between creativity and illness is a practical issue that clinicians should consider with each patient they see, not just when they treat artists or publishor-perish academics. For instance, a businessman may lose his job if he is prescribed a DA antagonist and then comes up with fewer new marketing ideas. Even if a drug does not cause creativity loss, the fear that it might do so can make patients discontinue it. Loss of creative drive is a marker for the loss of other important aspects of positive motivation, such as the ability to feel pleasure and curiosity.' When clinicians treat patients with disorders that affect their creativity, they need to protect patients' creativity, both from the side effects of treatment and from the very conditions that partly gave rise to the creativity.

As knowledge of the brain has increased, it has become difficult and often counterproductive to separate psychiatric and neurological diseases. Thus this review will address both. Examining nonpsychiatric diseases that are linked to altered creativity can help reveal how brains generate new ideas, and how clinicians can help preserve that ability. Creativity depends on basic phenomena, such as general psychomotor activity and the physiological distinction between rewardbased and punishment-avoidance motivation.

Creative output depends on motivation and talent. The perceptual and associative skills that underlie creative talent have a substantial literature already, and are more fully discussed in this In Review's companion article.2 Creative people are those with the strongest drive to create, who work at it constantly.3-4 Increased creative motivation correlates with improved productivity. Such motivation is less well studied, especially at a biological level. Nevertheless, medical interventions more easily help motivation than skill, because it is easier for drugs to change the subcortical monoaminergic systems that underlie drives than to safely change the intricate cortical circuits that underlie talent.

Evidence suggests that creative output depends strongly on motivation. Increased motivation can secondarily increase talent, when creators who work hard increase their skill through practice effects.5 As drive raises productivity, it can increase the number of creative ideas independently of increased creative skill, per se, because even if talent and average idea quality are not higher in a very productive person, chance ensures that the total number of creative ideas increases with the total number of ideas.6 Of course, the number of uncreative ideas increases with productivity as well. As W H Auden wrote, "The chances are that, in the course of his lifetime, the major poet will write more bad poems than the minor."7- p "

In the following discussion, creativity will mean a brain state that generates actions that are novel and useful to a community. This 3-factor definition includes the important cultural context within which creativity must always be judged. The definition also clarifies part of the creativitymadness link. The production of ideas or actions that are novel but useless - eccentric - is part of the vernacular conception of madness. The line between uselessness and usefulness is often a fine one, and is ultimately determined by society, not the creator. Many ideas become creative only after the cultural context has changed enough to make them useful. A paradigmatic example is the Xerox machine, which for many years was seen only as an expensive mimeograph.

Medical Conditions Linked to Creativity

Table I lists disorders that have been associated with creative behaviour. The disorders generally affect the brain more than illness in other organs. Some observers, though, have argued that any illness can stimulate creativity.8 In the 1 9th century, for instance, tubercular fevers were thought to produce a hectic creative state. All illnesses can release patients from creativity constraints, such as holding a job, and patients' suffering can motivate a search for inventive solutions, or at least distractions. In any disease state, though, patients create less when they are most ill. As Sylvia Plath said, "When you are insane, you are busy being insane - all the time . . . When I was crazy, that's all I was."9- P"2

Illnesses Traditionally Considered Psychiatric

Hypomania. Increased creativity is associated with BD, more specifically with mild expression of BD traits, such as hypomania and cyclothymia. IU While fully manic episodes tend to disrupt creativity with their severity, hypomania's more moderate expression of self-confidence and hyperassociativeness fosters focused goal-directed activity.

History of Depressive Episodes. Creative people often have a history of unipolar depression, although the association is less strong than with BD.10 Patients are rarely creative within a depressive episode itself, because of depression's slowed motivation and rigid thinking. Unipolar depression's reputation for boosting creativity may in part depend on its association with cyclothymia and rebound periods of increased energy after depressions. In general, negative emotions drive creativity less effectively than positive ones."

Psychosis. Some observers have reported a correlation between psychotic traits and creativity.12 Data to support this association are modest for schizophrenia, but somewhat stronger for mild schizotypal traits and for close relatives of people with schizophrenia.11 It may not be psychosis, per se, that predicts creativity best, but traits associated with psychosis. These include low LI (a decreased tendency to screen out unexpected perceptions) and openness to unusual ideas.14 Manic psychosis may be more closely related to creative imagination than schizophrenic psychosis.15

Substance abuse is common in creative artists. However, it may not cause creativity; it may instead be the case that many artists have illnesses that increase addictions.16 Artists sometimes use hallucinogens to come up with novel imagery for their work. Because of the high number of 20th-century alcoholic American writers, popular US opinion associates alcohol use with creativity. In other cultures, the correlation between alcohol and creative writing is not as strong.17 Even moderate blood alcohol content tends to lower creativity, rather than raise it.18 Simultaneously, writers' belief that they have recently consumed alcohol makes self-judgment of their work rosier.1'' Alcohol's effect on creativity is thus an example of William Stafford's adage that it is easy to cure writer's block if you just lower your standards.

Attention-Deficit Hyperactivity Disorder. ADHD increases activity, but does not selectively increase goal-directed focused activity. Although many parents of children with ADHD believe that ADHD raises creativity, research does not support this claim.20 Nor does scientific evidence confirm the equally common belief that drugs that treat ADHD lower creativity.21

Illnesses Traditionally Considered Neurological

Temporal Lobe Epilepsy . One-tenth of patients with temporal lobe epilepsy exhibit a personality cluster that includes hypergraphia, a pressured drive to write. The phenomenon is interictal, and anticonvulsants do not decrease it.22 Epileptic hypergraphia correlates with hypomanic traits and is inversely correlated with depression.23 Numerous prolific creative writers, such as Charles Dickens and Fyodor Dostoevsky, suffered from epilepsy.

Frontotemporal Dementia. Evidence for altered temporal lobe function in creativity comes from variants of FTD that stimulate de novo artistic output. Patients with FTD can become suddenly and intensely motivated to paint or draw.24 By contrast, in Alzheimer dementia, artistic talent typically deteriorates. FTD is likely to produce new artistic output only when degeneration is relatively worse in the patient's temporal lobes than in the frontal lobes. About one-third of patients with FTD have organic hypomania, and depression is rare.25

Amyotrophic or Primary Lateral Sclerosis. Amyotrophic lateral sclerosis or primary lateral sclerosis have neurodegeneration in the temporal lobes as well as in motor areas. Such patients, like the patients with FTD, occasionally manifest new artistic creativity as other parts of their brain fail.26 Some patients passionately create art long after their paralysis has made movement nearly impossible - using tongue movements, for instance, to drive the cursor in a computer painting program.

Parkinson Disease Medications. Although untreated Parkinson disease is associated with depression and apathy, treatment of Parkinson disease with DA agonists can produce highly focused goal-directed behaviour, such as hypersexuality and gambling, often along with other manic symptoms.27 In some patients with Parkinson disease, the chief compulsive behaviour is a de novo passionate artistic drive to write, compose music, or paint.28-2'' The art-making decreases when agonists are discontinued. DA agonists more rarely trigger such focused goal-directed behaviour in patients without brain disease, perhaps because their autoregulation of DA levels dampens the drug's effect.

Autistic Savant Syndrome. Popular opinion links Asperger syndrome and autism with creativity, because of the existence of savant syndrome in some patients. In fact, Asperger patients usually have decreased creative imagination, compared with unaffected subjects.30 Savant syndrome increases detail-oriented processing skills in a focused domain, such as calendar calculation, arithmetic, or musical performance.31 The cognitive skills are generally demonstrated in a behaviourally rigid way.32

Mechanisms

Table 2 lists brain mechanisms associated with creative behaviour. Knowledge of the shared features that underlie illnesses associated with creativity may guide clinical attempts to preserve creativity while the illnesses are treated.

Behavioural Mechanisms

All the medical conditions associated with creativity increase focused goal-directed behaviour. However, not all types of motivation foster creativity to the same degree. Avoidance motivation, such as fear, produces less creative behaviour than approach motivation.33 Intrinsic motivation, typically pleasure in performing the task, increases creative activity, whereas extrinsic motivation, such as tight deadlines or even monetary reward, may decrease it.3-34

Approach motivation includes not only positive drives, such as desire and curiosity, but also negative ones, such as anger. Positive moods help creativity more than negative moods. However, the effect of a mood's positive valence is weaker than the effect of its intensity. Thus high-energy negative moods, such as anger, can drive more creative ideas than low-energy positive moods, such as contentment.35 Hypomanic activity, the state that appears most closely associated with creative acts, may have psychomotor activation as its central feature, rather than positive mood.36 Increased creative talent is, in many patients, a secondary consequence of the disorders' effect on motivation. Autistic savants would seem an exception in whom talent arises from nowhere, apparently independent of motivation and hard work. However, savants' skills arise, in large part, from the single-minded pursuit with which they practice their talent repetitively.37 Savants' dedication is often overlooked because their language deficits make it hard for them to report motivational states.

Hemispheric Laterality

Neuropsychological work in the 1 970s led to the hypothesis that the right hemisphere was the site for creative and artistic activities, while the left hemisphere was analytical and rule-based. Functional imaging studies show that right hemisphere activity increases more than left in some creative tasks.38 Left and right hemisphere activities tend to be mutually inhibitory (Figure 1). The right brain creativity model predicted that left brain activity would in fact be anticreative. Therapists influenced by this theory attempted to help patients become more creative through exercises to suppress left brain activity. However, evidence against the right brain hypothesis came from patients with corpus callosotomies. The right hemisphere in callosotomy patients is protected from left hemisphere inhibition, but such patients have decreased rather than increased creativity.31'

The simple right brain creativity model did not easily explain training effects. While untrained subjects process most features of music and painting with the right hemisphere, skilled musicians and painters process more of them on the left.4"�41 This reflects the right hemisphere's role in attention and novelty detection, and the left hemisphere's processing of predictable stimuli.42 To a novice, most things are novel - it is difficult for a beginner to recognize or generate patterns in a complex domain.

The right brain creativity model also did not coordinate well with the later discovery that approach motivation is lateralized. Left frontal cortex activity promotes curiosity and pursuit, while right frontal activity promotes avoidance and withdrawal.43 This partly parallels the left hemisphere's stimulation of positive emotions, whereas right hemisphere activity tends to promote negative emotions.44

The right hemisphere facilitates both novelty detection and avoidance behaviour, suggesting that if the right brain were left to its own devices, it would recognize novelty but tend to withdraw from it (Figure 2). This neurological association of novelty and withdrawal stems from the fact that in dangerous and unfamiliar environments, curiosity and creative experimentation may be disadvantageous. Therefore, to generate systematic patterns from novel stimuli, right hemisphere novelty recognition must combine with left hemisphere approach behaviour. Subjects with high creativity have greater bilateral activation than subjects with low creativity.45

Frontotemporal Interactions

Frontotemporal interactions greatly affect creative drive. Because the frontal lobes generate actions, frontal lesions tend to produce apathy and depression. Frontal and temporal lobe connections, like left and right hemisphere connections, are mutually inhibitory (Figure 1). Thus temporal lobe lesions, by disinhibiting the frontal lobe, can increase motivation and cause aggressive or manic behaviour.

Frontal premotor and motor areas are important for generating creative actions and ideas.4547 Temporal areas, because of their function in recognizing linguistic and social meaning,48 have more role in assigning meaningfulness to those ideas. The temporal lobes are particularly important in recognizing novelty, just as the frontal lobes are important for producing complex patterned actions49 (Figure 2).

The frontal and temporal lobes' mutual inhibition affects how lesions to these areas alter verbal fluency and linguistic idea generation. Patients with temporal lobe lesions, such as Wernicke aphasia, have decreased speech comprehension, but increased talkativeness and motor activity, in part because they are less inhibited by consciousness of their mistakes. By contrast, patients with frontal lobe lesions, such as Broca aphasia, speak and move less. Their relatively preserved comprehension contributes to the dearth of their speech by making them painfully aware of, and inhibited by, their errors.

The mutual inhibition between frontal language production and temporal language reception has a parallel in the mutually inhibitory effects of idea generation and of assessing what one has produced. It may explain why brainstorming, during which critical judgment is temporarily muted, generates more creative ideas.50 When musicians improvise, for instance, they deactivate their right temporoparietal junction.41 However, brainstorming alone is not enough for creativity. The production of ideas must alternate with critical refinement of the ideas.

Mere attribution of idea production to the frontal lobe and interpretation to the temporal lobe oversimplifies their complicated interactions. Epileptic patients with hypergraphia are more likely to have contralateral right temporal lobe hypometabolism, suggesting an important role for mutual inhibition between the temporal lobes.51

The orbitofrontal cortex, for instance, plays a role in risk assessment that adds emotional meaning to stimuli. In that respect, orbitofrontal cortex functions are more like temporal lobe cortex than like dorsolateral prefrontal cortex. Thus, while dysfunction of dorsolateral prefrontal cortex can impair working memory and cause depressive symptoms, orbitofrontal dysfunction can decrease hypersensitivity to risk and improve depression.52 Such changes most likely have opposing effects on creativity.

Midbrain Inputs

The midbrain drives creative motivation via neurons that send DA, 5-HT, and NE to the cortex. Midbrain inputs interact with the contributions of hemispheric and frontotemporal influences on creativity (Figure 1).

Dopamine. DA is important for motivation and imagination, including reward-based drives and curiosity. When looking for pharmacological similarities among the illnesses associated with increased creativity, the strongest evidence points to DA.46-53 DA underlies the excessive goal-directed activity of patients with mania, disinhibition from Parkinson disease medications, and substance abuse. Dopaminergic inputs are heterogeneous, and most strongly innervate the frontal regions involved in motivated action.54 Consequently, DA drives us to act more than to consider the meaning and risk of our actions. This parallels the tension between idea production and reflection that was described above.

DA also enhances mental imagery including hallucinations, and the vivid metaphors that often underlie creative art and scientific insight.55 Because DA improves working memory via Dl receptors, it facilitates mental associations.56 Alleles of DA-related genes vary with variations in noveltyseeking behaviour and with creativity.57 DA lowers Ll (the likelihood that subjects will recognize, rather than screen out, novel phenomena), and LI is associated with creativity.14 Bilateral chronic DBS near the DA-rich nucleus accumbens can occasionally increase creative behaviour as a side effect.58�5"

Serotonin. Some 5-HT-related genes are associated with altered creativity.57�60 Although 5-HT, like DA, regulates motivation, it seems to decrease withdrawal from aversive stimuli, not increase approach to positive stimuli." When decreasing aversiveness decreases stress, 5-HT may indirectly increase pleasure and curiosity. However, 5-HT's effect on motivation sometimes decreases approach motivation as well as avoidance motivation.62 This occurs because 5-HT can inhibit dopaminergic activation.63 Serotonergic drugs can inhibit goal-directed behaviour, including sex, pleasurable exercise, and curiosity.64

Norepinephrine .NE increases activation to both positive and negative stimuli. This activation obeys the Yerkes-Dodson law: above an optimum activation level, task performance decreases, and the optimum level is lower for more difficult cognitive tasks. NE makes responses more stereotypic, and decreases the probability of cognitive shifts between different solutions to problems.65 Blocking adrenergic beta receptors increases creative flexibility.66 NE's effect of making stressed subjects respond more rigidly is reminiscent of the right hemisphere's conjunction of novelty behaviour and avoidance. In difficult environments, it may be safer, on average, for a person not to take creative risks.

Neuronal A rchitecture

Preliminary data suggest that creative brains have more interneuronal connections.67 Greater connectivity could foster divergent thinking by integrating more diverse sensory inputs, memories, ideas, and actions. Support for this proposal comes from the analysis of synesthesia, the phenomenon by which some people experience a sensation in one modality when presented with another modality. Coloured hearing, in which a speech sound also produces visualization of a colour, is the most common example. Even people without vivid synesthesia perceive high-pitched sounds as bright and low-pitched sounds as dark. Functional imaging studies show that subjects with synesthesia activate larger regions of the cerebral cortex than nonsynesthetes, and have greater white matter connectivity.68 Synesthetes are more likely to be creative, and to have mood disorders.6971

Genes

The link between creativity and brain illness has been proposed as one reason why such illnesses are not quickly bred out of populations.72 Some illnesses associated with increased creativity, such as BD, have high heritability as well as clear triggers from environmental trauma. Alleles associated with such environmental sensitivity have traditionally been considered vulnerability genes.

Newer data, however, suggests that the same alleles might better be termed plasticity genes, because they also help their carriers benefit more than noncarriers from enriched or permissive environments.73 On this model, creative people may be susceptible to brain disorders for the same reason that race cars break down on rough roads more than pickup trucks. On smooth roads, the race cars' highly tuned, responsive engines allow them to speed past pickups. This proposal implies that tolerant environments rather than dangerous ones foster creativity, and parallels recent evolutionary arguments that relaxed selection pressure fosters diversity.74 Abundance, not necessity, may be the mother of invention.

Treatment Implications

Any treatment's benefit to creativity must be weighed against the risk of destabilizing a patient's overall mental health. Current studies and the practice patterns of expert clinicians can point toward therapeutic approaches, although not yet to definitive ones. The clearest and most general recommendation is that, all other things being equal, stimulating medicines are more helpful than sedating ones.35

A ntidepressants

Selective Serotonin Reuptake Inhibitors. By decreasing depression, ADs can increase creative productivity. However, SSRIs lower not only aversive motivations, such as fear and shame, but sometimes also appetitive motivations, such as libido and curiosity. This can cause SSRI-induced apathy syndrome.75

SSRIs' ability to lower avoidance motivation makes them useful treatments for interpersonal hypersensitivity and social fears. Indifference to others' opinions is associated with creativity,76 another example of the inverse relation between creative production and judgment. SSRIs might, by fostering this indifference, be helpful influences on creative output. For instance, SSRIs could make scientists worry less about the social and interpersonal consequences of abandoning their mentors' model of the world. However, reducing interpersonal sensitivity might be less helpful for novelists who need to stay exquisitely aware of social nuance.

Alternatives to SSRIs. If a patient reports decreased motivation or creativity while taking an SSRI or an SNRI, especially if the problem increases when the drug's dose increases, then it is reasonable to consider alternatives. Cognitive-behavioural therapy is one modality that is unlikely to harm creative motivation. ADs with DA agonism, such as bupropion, may preserve or even raise goal-directed motivation.77 Adding bupropion to SSRl therapy can treat SSRI-induced apathy syndrome even if the SSRI is continued.78 Lamotrigine is an alternative to conventional ADs in patients whose depression may be on the bipolar spectrum. Mirtazapine's effects on motivation may be relatively benign. It increases DA release in prefrontal cortex, and tends to preserve goal-directed drives such as libido. The motivational effects of SNRIs, tricyclic ADs, and monoamine oxidase inhibitors are less clear-cut.

Anxiolytics

AD Anxiolytics. For pharmacologic treatment of anxiety, SSRI or SNRI ADs are typically the first choice. Patients who report decreased motivation or creativity after starting one of these may benefit from the changes described above. Many clinicians hesitate to prescribe bupropion to anxious patients, because they fear that its activating effect during the loading period will worsen the anxiety. However, controlled trials show that bupropion can be a good anxiolytic.7''80

Beta-adrenergic Drugs. Beta-blockers such as propranolol can help creative performance anxiety, and may have modest creativity benefits after acute administration.66 Although there are case reports of propranolol causing depression and decreased libido, larger trials show no statistically significant increase in risk.81

Benzodiazepines. Raising arousal raises creativity,3' but BDZs lower arousal. Many creative patients with anxiety, who seek the cognitive arousal needed for their work, end up in the counterproductive cycle of using BDZs or alcohol in the evening to calm down, and then drinking coffee throughout the day to wake up.82 BDZs also mildly hinder the encoding of new memories, even at low doses.83

Alcohol. Patients often believe alcohol can help their creativity by relieving anxiety or removing inhibitions, and may prefer it to prescription anxiolytics because it feels more familiar. However, patients' perception that a substance increases creativity is not always reliable. Absinthe, for instance, was particularly popular among 1 9th-century French writers, despite its high concentration of methanol.

Clinicians should discuss with their patients the evidence that alcohol can lower creativity.18 Even after hearing the evidence, though, many patients believe that the research does not apply to them, that their work really does improve with alcohol. It is important to explain to such patients the way alcohol can falsely elevate their opinion of their work.84 While decreased self-criticism may well be helpful to creativity, there are safer ways than alcohol to achieve it. Recent studies show that even moderate alcohol use is associated with brain atrophy despite its cardioprotective effect.85

Dopaminergic Drugs

Antagonists. When patient creativity is important, clinicians should be cautious in prescribing neuroleptics and the many antinausea agents that are DA antagonists. Considering creativity alone, lithium and the anticonvulsant drugs are safer mood stabilizers than neuroleptics are. There are, nonetheless, many situations when it is necessary to prescribe dopamine antagonists to creative patients, especially in acute settings. For instance, a psychotic physicist may be much more productive on haloperidol when no longer delusional. Less sedating neuroleptics, and the atypical antipsychotics with the least DA antagonism, may lower motivation and creativity less than typical antipsychotics.86

Agonists. Creative motivation, like motivation in general, increases in some patients taking dopaminergic agents.29�87 Motivation may be strongest with chronic administration of the less sedating agonists, less sedating DA agonists seem preferable, and D3 receptor binding may be important.88 Unfortunately, DA agonists can also cause impulse control problems, gambling addiction, compulsive spending, hypersexuality, and hallucinations. In addition, when agonists boost creativity, the new work often occurs in a field unrelated to the patient's original interests.

Stimulants. Dextroamphetamine, methylphenidate, and newer agents, such as modafinil, block DA reuptake and also have noradrenergic effects. Although some patients with ADHD feel stimulants inhibit their creativity, controlled trials do not support this.21 While stimulants can help cognition in subjects with low working memory, they can mildly impair those with high working memory.89

Mood Stabilizers and Anticonvulsants

Lithium can help creativity by making patients with BD less ill.90 Once mood is controlled, however, lithium may decrease associational productivity and idiosyncrasy." Anticonvulsant mood stabilizers are less well studied. Anticonvulsants do not suppress hypergraphic writing in patients with temporal lobe epilepsy,22 which suggests that they have a relatively benign effect on creative motivation. In one study, perceived creativity improved when patients were switched from lithium to valproate.92

Possible Anatomically Targeted Approaches

One group has argued that TMS of the anterior temporal lobe improves drawing and mathematical fluency.93 Two case studies show improved artistic or intellectual creativity after DBS near the nucleus accumbens.58�59 Although these results are intriguing, they are at present well removed from clinical relevance. The techniques are expensive and cumbersome, DBS requires invasive surgery, and TMS effects are so transient that the creative work has to be done during the magnet stimulation.

Environmental and Psychotherapeutic Interventions

Noninvasive interventions are no doubt powerful - creativity can be spurred or inhibited by a change of environment or words of praise from a mentor. However, there have been few scientific studies of these effects.

Psychotherapy. No controlled trials assess any form of psychotherapy's effects on creativity. Art therapy would seem the school of psychotherapy most directly related to creativity. Art therapy's primary goal, though, is typically not creative works that are useful to others, but self-expression, to help patients understand and vent their emotions. The few studies that address art therapy's efficacy look at its ability to improve coping skills, or physical health, rather than its benefit to the patient's creativity. The psychoanalytic literature has addressed the subject of creativity more extensively than other branches of psychiatry, but at the level of case study and theory.

Sleep and Exercise. Sleep deprivation lowers creativity, a fact relevant not only to patients but also to their physicians on call.94�95 REM sleep enhances creativity and stimulates associative networks.96 Regular exercise enhances creativity,97 through a mechanism that appears independent of its effects on mood.98

Cognitive Training and Education. In both science and the arts, traditional education has been the longest-used technique in imparting creative skill. Education can confer creative motivation as well as skill, especially when it produces emotion-rich relationships with inspiring role models.99 Behavioural interventions such as education seem safer, if slower, than drugs as creativity enhancers. Even education, though, is not free of unexpected side effects: every year, many students who go to college to become writers end up as stockbrokers.

Conclusion

Creativity requires brains with adequate capacity for goaloriented motivation, novelty seeking, flexible associative networks, and lower inhibition. Creativity's link to illness stems from the fact that most novel ideas are bad ones and, in dangerous environments, unhealthy ones. Creative solutions usually require many failed experiments first. The novelty-seeking and unusual behaviours that confer vulnerability to environmental stressors may underlie inventiveness in tolerant surroundings. One way to separate illness from creativity, then, is to place patients in more enriched or supportive environments. Although that is often not possible, we should not ignore the situations where it is.

Typically, however, medical therapy is essential for patients with creativity-related illnesses. Because current understanding of the brain mechanisms that underlie creativity is incomplete, many of the treatment implications discussed above are based on inferences from basic research, rather than on clinical trials. We cannot, however, dismiss the medical preservation of creativity as too intractable a problem to discuss, as many patients' livelihoods and emotional well-being depend on it. Direct effects of these medications on creativity should be tested explicitly in large-scale controlled clinical trials, and that will never happen without more focused discussion of the subject.

Acknowledgements

The author reports no conflicts of interest. The Canadian Psychiatric Association proudly supports the In Review series by providing an honorarium to the authors.

[Sidebar]

R�sum� : Maladie c�r�brale et cr�ativit� : m�canismes et risques du traitement

Les maladies du cerveau et leur traitement peuvent aider la cr�ativit� ou lui nuire de mani�res qui fa�onnent la qualit� de vie. Une pulsion cr�atrice accrue est souvent associ�e au trouble bipolaire, � la d�pression, � la psychose, � l'�pilepsie du lobe temporal, � la d�mence frontotemporale, aux traitements de la maladie de Parkinson, et � l'autisme. La cr�ativit� d�pend de la motivation d'approche ax�e sur les buts des syst�mes dopaminergiques du m�senc�phale. La motivation d'�vitement par la peur est moins utile � la cr�ativit�. Lorsque la serotonine et la noradrenaline diminuent la motivation et le comportement flexible, elles peuvent inhiber la cr�ativit�. La lat�ralisation h�misph�rique et les connexions frontotemporales doivent interagir pour cr�er de nouvelles id�es et des sch�mas conceptuels. Le cerveau droit et le lobe temporal conjuguent leurs aptitudes � d�tecter la nouveaut�, tandis que le cerveau gauche et le lobe frontal favorisent la motivation d'approche et produisent plus facilement des nouveaux mod�les d'action � partir des nouvelles perceptions. Les g�nes et les ph�notypes qui augmentent la plasticit� et la cr�ativit� dans des environnements tol�rants, o� la pression de s�lection est rel�ch�e, peuvent apporter un risque dans des environnements rigoureux. Peu d'articles abordent en substance ce sujet important mais charg�. Les antid�presseurs (AD) qui inhibent la motivation par la peur, comme les inhibiteurs s�lectifs du recaptage de la serotonine, inhibent parfois �galement la motivation ax�e sur les buts. Les AD qui stimulent la motivation ax�e sur les buts, comme le bupropion, peuvent rem�dier � cet effet. Les benzodiazepines et l'alcool peuvent �tre contreproductifs. Bien que les agonistes dopaminergiques stimulent parfois la cr�ativit�, ils peuvent en m�me temps d�sinhiber le comportement de fa�on inappropri�e. Les antagonistes de la dopamine peuvent supprimer la motivation cr�atrice; et les psychor�gulateurs que sont le lithium et les anticonvulsivants peuvent aussi le faire mais � un moindre degr�. L'exercice physique et le sommeil paradoxal peuvent aider la cr�ativit�. La th�rapie par l'art et la psychoth�rapie ne sont pas bien �tudi�es. Pr�server la motivation cr�atrice peut aider la cr�ativit� et d'autres aspects du bien-�tre de tous les patients, pas seulement des artistes ou des chercheurs.

[Reference]

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[Author Affiliation]

Alice W Flaherty, MD, PhD'

[Author Affiliation]

Manuscript received February 2010, revised, and accepted July 2010.

1 Assistant Professor, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Address for correspondence: DrAW Flaherty, WACC 729B, MGH, 15 Parkman Street, Boston, MA 021 14; aflaherty@partners.org