Dr. Grossi's Blog
The connection between creativity and bipolarity has been widely debated for years but was publicized by Kay Jamison Redfield (herself a bipolar patient who is responsive to lithium) in the book Touched with Fire. A number of creative people in contemporary American society are known to be bipolar. They include Jackson Pollock, Kurt Cobain, Rosemary Clooney, Ernest Hemingway, Jane Pauley, Ozzy Osburn, Margot Kidder, Carrie Fisher, Russell Brand, and many others.
I thought it would be revealing to examine this idea in a historical personage who was a creative poet, natural scientist, and politician/statesman who wrote voluminously about feelings and mental status over a lifetime. I am referring to Johann Wolfgang von Goethe who lived from 1749 to 1832. He was active in poetry, drama, natural science, and politics. His long poem, Faust, is one of the half dozen greatest long poems ever written. He wrote numerous other poems and the novel The Sorrows of Young Werther. He also wrote about the morphology of plants and animals in the book Theory of Colours. He was also active in political life, serving as Privy Councilor in the German duchy of Saxe-Weimar.
Goethe's family seems devoid of mood disorders, except for his sister who had two postpartum depressions and died shortly after the second one. Goethe's first depressive episode occurred when he was 14, following the termination of a love relationship and was characterized by withdrawal, anorexia, and indications of suicidal intentions. He then ruminated about being physically ill. Several years later he began his studies at Leipzig, where he confessed to his sister in a number of letters that he was often depressed, felt worthless, joyless, and doubted his abilities and talents. On his return to Frankfurt at 19, he wrote of lacking drive, feelings of numbness, and lack of joy in anything which again followed the failure of a love relationship. Indeed, during the next six years he had a number of failed relationships and depressive episodes. In 1775, when he was 25, he took office at the court at Weimar where he performed many political and administrative tasks which he performed well and these accomplishments considerably enhanced his self-esteem. Indeed, for about 10 years while performing these political duties he was free of depressive episodes. Only in 1786, prior to his trip to Italy, did another depression strike which he later expressed in the play Torquato Tasso. Goethe, alias Tasso, a depressed self-destructive poet overcomes his depression through communication and artistic creation. I believe a good literary case can be made that Werner, Tasso, and Faust are self-perceptions and represent his effort to concretize his moods and more importantly his efforts to overcome those aspects of himself that he rejected through creative production which he called his "household remedy".
After he returned from Italy and after the successful development of a love relationship in 1788, he had a long period of mental stability and coincidentally was unproductive as a poet. In 1798 he once again became depressed and it was then that he again began to write Faust, his monumental tragedy. The depression gradually remitted, but he was again depressed in 1802 and began work on a play about the French Revolution and his depression gradually lifted. Subsequently he returned to work with the privy council and scientific inquiry. In 1805 his very close friend, the poet Schiller, died and he became depressed again and used the same remedy, creative production, which eventuated in the completion of the first part of Faust. His wife died in 1816 and in 1823 he became involved in a love relationship with a nineteen-year-old girl who rejected him. Subsequently he became depressed again and, as in prior times, he became poetically active and produced the Marienbader Elegie which is part of a trilogy that revolves around depression and suicidality. Subsequently he remained very active in literary and creative ways. He continued to work on his own story, Faust, until the end of his life in 1832.
From a diagnostic standpoint, it is likely that Goethe suffered from a bipolar II disorder. There are several soft signs of this disorder including the postpartum depressions of his sister, the early onset of his depression, the many recurrences of his depression, prominent suicidality throughout his life, as well as accelerated thinking and increased literary productivity when he would emerge from depressive episodes. These are conclusions from his written letters, poems, and plays and as such are as limited as any hermeneutic analysis would be.
Until 1997 the family of compounds collectively known as amphetamines were thought to have been synthesized in Berlin in 1887 (about the same time as valproic acid was synthesized as an organic solvent in France), but A.B. Clements et al. found mescaline, nicotine, and methamphetamine in a species of the Texas acacia bushes (Acacia rigidula). Amphetamines are potent agents that produce their effects by increasing the levels of biogenic amines (dopamine, norepinephrine, and serotonin) in the synapse. Amphetamine binds to all monoamine transporters, but its main behavioral effect is the result of its binding to and blocking the dopamine transporter (DAT). It also enhances the reverse transport of amphetamine from the cell interior to the synapse or extracellular space. It also adversely affects the vesicular storage of dopamine in the cell thus allowing it to accumulate in the cytoplasm. Finally, it inhibits monoamine oxidase A and B (MAO-A and MAO-B) and this results in less breakdown and an accumulation of dopamine in the cell.
The major value of amphetamine is in the treatment of ADHD, although they have a role in narcolepsy (less in the last 12 years) and excessive daytime sleepiness resulting from other drugs, obesity (mostly in the 1950s), or from particular circumstances (military, long haul trucking, student cramming). In the late 1930s, a pediatrician in London who cared for institutionalized, disruptive children was seeking a remedy for the headache which followed the X-ray procedure known as pneumoencephalogram in which air is introduced into the spinal column and when sitting it makes its way to the ventricles in the brain. This allows xrays to be taken and because the air is darker than the surrounding brain a judgment can be made regarding any shift in the brain. Usually after such a procedure the patient experiences a severe headache. What occurred, however, was startling. The patients became much less disruptive, distracted, oppositional and hyperactive. This paved the way for their usage in what became labeled ADHD in the late 1970s. In earlier years it was known as minimal brain dysfunction or hyperactivity of children. I should note that the reinforcing properties of amphetamine were noted in the 1930s and in the following approximate 30 years the drugs were regulated by many countries and they are classified as Schedule II under the Convention of Psychotropic Substances.
What are the effects on the central nervous system (CNS)? Amphetamine crosses the blood-brain barrier and thus quickly reaches the primary sites of action. Behavioral effects include wakefulness, anorexia, hyperactivity, often elation or euphoria, and a generally very pleasant and activated feeling. Adverse effects can include moodiness, aggravation of mood instability, cardiac effects (tachycardia especially) gastrointestinal upset, insomnia, jitters, occasional headache, occasional tics, proneness to crying. Very rarely an amphetamine psychosis may develop. Generally, any of these adverse effects diminish and disappear shortly after discontinuation of the drug. Are there any long-term consequences of amphetamine treatment? The answer is probably not or minimal in comparison to the benefits. Their effects on growth are controversial but the recent consensus is that evidence for growth changes stemming from treatment are lacking. If there were an effect it would undoubtedly be mediated by lower caloric intake and this can usually be easily remedied.
A very rare adverse effect is the development of an amphetamine psychosis. High doses can produce psychotic behavior and thinking indistinguishable from schizophrenia in healthy individuals. Hallucinations, delusions, paranoid thinking, etc. can be present. The current illicit amphetamine epidemic is increasing the incidence of this problem because of the high doses used on the street as well as an element of adverse selection. KeKiten et.al. corrected for prior history of psychotic disorder and still found a prevalence rate of three times the general population. In humans who experience flashbacks, spontaneous recurrence of amphetamine-induced psychosis, there is a concomitant increased plasma norepinephrine and 3-methoxytyramine which are metabolites of DA from the PFC.
And yet, when one considers the relative benefits and liabilities of treatment with amphetamine, the benefits seem to outweigh the risks. While we have not discussed the animal studies with amphetamine or the post mortem studies of amphetamine abusers, it is noteworthy that the elevated risk for substance abuse in individuals with ADHD can be reduced when treatment is initiated during childhood but not adolescence. Accompanying this is a reduction in structural brain pathology. Specifically, unmedicated ADHD children demonstrated smaller brain white matter volume than medicated children, suggesting that stimulant treatment may normalize brain white matter volume.
ADHD is an illness that revolves around disturbances in attention, hyperactivity, and impulsiveness. It comes in inattentive, hyperactive, and combined types. I do not plan to discuss the criteria further here as they are readily available on many sites including two that the reader can access from the home page of this site by clicking on recommended links.
I would like to talk about how the pathology of the disorder is understood. Irrelevant and extraneous signal inputs to the prefrontal cortex (PFC) are considered too strong to be ignored while at the same time the signal inputs from what should be attended to are too low to be noticed. In children who have ADHD, dopamine (DA) and/or norepinephrine (NE) are thought to be low, which in turn causes deficient activity at the pyramidal neurons. This results in high noise and low signals. From a clinical standpoint, this produces hyperactivity, impulsivity, and inattention in children and mostly inattention in adults.
Treatment of these symptoms most often involves prescription of stimulants (amphetamine molecule or methylphenidate molecule) which theoretically should increase input signal strength by increasing NE activity and reducing extraneous input signals by increasing DA actions. S. Vijayraghavan et.al. have shown that pyramidal neurons process information in an inverted U curve. Therefore low signals can be augmented by NE and high extraneous input can be decreased by DA.
What explains prominent inattention in adults that we see in the office? Often these individuals are under enormous stress of various sorts including financial, marital, business, family, health, etc. In these individuals, it is hypothesized that the NE and DA levels in the PFC are too high and the inattention is again accounted for by the information processing by the pyramidal neurons in the PFC. In this case, stimulants will probably make the situation worse or at best produce little effect. In those cases of chronic stress the levels of DA and NE are lowered and in the event of co-morbid ADHD the risk of substance abuse and anxiety disorders is increased. These are subtle differences that the clinician must appreciate to achieve best results.