As this issue of the Annals goes to press, the rock and roll pioneer Phil Spector goes to jail, likely for the rest of his life, convicted of the close range handgun murder of Lana Clarkson, a B-movie actress whose credits include Barbarian Queen and Amazon Women on the Moon. Spector was a musical innovator but may have been more famous as an eccentric (Figure 1).. It has long been suspected that these two characteristics may be linked, and recent genetic studies have begun to identify molecular candidates that could in part explain this fascinating association.
Figure 1. Phil Spector in a recent court appearance. Photo credit Associated Press/Damian Dovarganes.
In the early 1960s, Spector created the “wall of sound”, an early rock and roll innovation that brought together, in the words of his biographer, “armies of guitars and keyboards and bass and drums, celestial sleighbells, and voices keening like angels…elevating the themes of teenage love and heartbreak to the epic proportions of Wagnerian opera” (1). Spector was also a major driving force behind the mature work of the Beatles, and of John Lennon’s solo career. Although it could be argued that Spector’s special skill was low art indeed – he even referred to his work as “little symphonies for the kids” – the raw power of his musical confections helped to define the spirit and yearnings of a generation.
Sadly, by age 30 Spector’s creative energy seems to have dissipated, and over the subsequent decades he became known less for musical genius than for famously reclusive and increasingly bizarre behavior. He had a flair for the dramatic – eye catching even by the permissive standards of the Los Angeles arts scene. He lived a baronial lifestyle in a hilltop castle perched atop a lower-middle class suburb, appeared in public surrounded by a color-coordinated Fellini-esque entourage, and at social events had an unfortunate penchant for discharging firearms into the air. Spector admitted that that he suffered from bouts of severe depression, a “bipolar personality” and “devils inside that fight me” (1), He attributed these symptoms to hereditary causes; his parents may have been first cousins, his father committed suicide, and his only sibling (a sister) had spent time in mental institutions. There were reports that several weeks before the shooting Spector had stopped taking an unknown “schizophrenia” medication that he had used for many years.
The nature of musical creativity, and its confluence with mental illness, has been a subject that has fascinated many. Among classical composers, Bruckner, Handel, Ives, Klemperer, Mahler, Mussorgsky, Rachmaninoff, Ravel, Rossini , Shumann, and Tchaikovsky are often mentioned. The list of popular artists is even longer, including Berlin, Coward, Foster, Mingus, Parker, and Porter, not to mention many, many rock and roll legends. Thus Phil Spector certainly has plenty of company at the intersection of musicality and emotional disturbances. The association is also not unique to music, and may generally hold for creative activity in many different areas of endeavor (2); in one classic study, writers were the most prone to psychiatric disease (3). Schizophrenia does not seem to track with creativity – the visions and delusions of this malady may be too disorganized to be useful to the creative process (4). By contrast, affective disorders, including bipolar disease, appear to be prevalent in all types of creative people (including successful scientists). Interestingly, creativity flowers most when the psychiatric symptoms with affective disorders remit, suggesting that the psychiatric symptoms themselves do not directly confer to the owner any creative advantage.
As technologies to decipher human genetic variation advance to new levels of precision, opportunities are at hand to begin to identify genes and pathways for many complex traits –including creative behaviors. Perhaps the intersection of musicality and mental illness involve common molecules that could contribute to both processes.
Musical ability is a complex trait, with varying contributions of both inherited factors and environment at work in different individuals. A study published this past month in PLOS One indicates that a vasopressin receptor gene, arginine vasopressin receptor 1a (AVPR1a), could be one such factor (5). A pair of two locus haplotypes (AVPR1a RS1 and RS3), each consisting of two microsattelites in the promoter region influencing expression of AVPR1a, were associated with a variety of musical skills related to interest, perception and production. A component of this haplotype (RS3 allele 4, or 334) has also been related, in individual studies, to ruthlessness, a lack of altruism, divorce, and autistic behaviors (6-8). Not surprisingly, a test for this variant is commercially available from a Canadian firm, Genesis BioLabs, whose website says it better than this column ever could:
Genetics may not be a guaranteed indicator of human behavior and motivation [genetics is only one half of the nature vs. nurture debate] but genes don’t lie. Before you make a lifetime commitment, have your fiancée tested. Order a Bonding Gene Test : $99 You will receive 1 mouth swab and collection tube per test, in a return package, along with specific instructions on how to collect the samples. Ask your significant other, business partner and/or elected representative to get these genetic tests done as soon as possible. This is for informational purposes only and is not a medical diagnosis. Consult with your doctor.
Phil Spector’s attorneys might have missed an opportunity by not testing for this variant. They could have argued, in the words of Genesis BioLabs, that “genes don’t lie” and Spector was also a victim – of his DNA. Or perhaps they did test for AVPR1a but the results indicated that his genotype promoted altruism rather than aggression. And if he was a heterozygote for both ruthlessness and altruism variants, in the absence of data one could argue either side of the aisle. Fortunately, given the profoundly poor operational characteristics of such tests, e.g. their limited specificity and sensitivity, the courts have wisely refused to admit DNA studies into legal arguments of culpability. The “my genes made me do it” argument simply does not fly. We’ve recently discussed the problems with genetic testing for complex traits and conditions in these pages (9). For behavioral disorders in particular, most predisposing genetic variants reported thus far may not withstand replication – for example, the association between serotonin transporter genes and depression has recently been questioned (10) – and for all claims a healthy dose of skepticism is warranted until these are rigorously validated. The courts are beginning to openthe door to a wider array of genetic testing as evidence, for example in cases involving medical-legal issues related to childhood perinatal and developmental disorders. Here, the courts may agree to DNA testing to diagnose genetic etiologies that could explain a psychomotor delay, exculpating health care providers from responsibility.
On another note, the full genome sequence of Neanderthal DNA is expected to be published later this year, derived from 38,000 year old recovered samples. Preliminary findings, presented in February by Svante Paabo representing an international consortium, have already whetted the appetite of geneticists worldwide. We already know that critical variants of the language associated gene FoxP2 (specifically two exon 7 coding variants at position 911 and 977) sequenced from Neanderthals are identical to those present in modern humans, suggesting that our primate relatives may have had the capacity for speech (11). Also, sequences of the melanocorticin 1 receptor (MC1R) indicate that at least some Neanderthals had light skin and hair color, similar to humans; this trait evolved separately in Neanderthals and humans (12), and its selective advantage in a European environment may have been in both cases to improve UV absorption for vitamin D synthesis (Figure 2). Neanderthals appear not to have genetically admixed with our ancestors, disappointing news for movie producers everywhere. The musical ability of our Neanderthal cousins must remain unknowable for the foreseeable future, but on a more positive note we can certainly anticipate AVPR1a sequence data in the weeks ahead.
Figure 2. Computer based reconstruction of a Neanderthal child by Christoph P.E. Zollikofer and colleagues, Anthropological Institute, University of Zürich. http://www.ifi.uzh.ch/staff/zolli/CAP/Main_face.htm
Stephen L. Hauser and S. Claiborne Johnston, Editors.
References
1. Brown M. Tearing down the wall of sound. The rise and fall of Phil Spector. Vintage Books, New York, 2008.
2. Post, F. Creativity and psychopathology: A study of 291 world-famous men. British Journal of Psychiatry 165:22, 1994.
3. Trimble MR. The soul in the brain: the cerebral basis of language, art, and belief. Johns Hopkins University Press, Baltimore MD, 2007.
4. Andreasen, N. Creativity and mental illness: Prevalence rates in writers and their first degree relatives. American Journal Psychiatry 144: 288, 1987.
5. Ukkola LT et al. Musical aptitude is associated with AVPR1A-haplotypes. PLOS One 4:e5534, 2009.
6. Walum H et al. Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans. PNAS 105: 14153, 2008
7. Donaldson ZR and Young LJ. Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322: 900, 2008.
8. Holden C. Parsing the genetics of behavior. . Science 322: 892, 2008.
9. Hauser SL, Johnston SC. Personalized genetic scans: with gifts like these…Ann Neurol 65:A7, 2009.
10. Risch N et al. Interaction between the serotonin transporter gene (5HTTLPR), stressful life events, and risk of depression. A meta-analysis. JAMA 301:2462, 2009
11. Krause J et al. The derived FOXP2 variant of modern humans was shared with Neanderthals. Curr Biol 17:1909, 2007
12. Lalueza-Fox C et al. A melanocortin 1 receptor allele suggests varying pigmentation among neanderthals. Science 318: 1453, 2007.
Filed under: Message From the Editor | Tagged: AVPR1a, AVPR1a RS1, Complex Genetics, DNA, locus haplotypes, Mental Illness, Music, Phil Spector, RS3
