Molecular Genetics and the Human Personality

I was very interested to discover what the human genome project and the rapid advances in the field of genetics have contributed to the understanding of psychiatric disorders. We are all aware of the frustrating search for the elusive genes for schizophrenia and bipolar disorder. It took years to realize that these clinical entities are complex diseases that do not follow simple Mendelian inheritance patterns, even though they cluster in families and cannot be explained by environmental factors alone. What else is known?

The editors of Molecular Genetics and the Human Personality are three Israeli professors—Jonathan Benjamin, M.D., and Robert H. Belmaker, M.D., from the Ben-Gurion University of the Negev and Richard P. Ebstein, Ph.D., from the Research Laboratory of Herzog Memorial Hospital in Jerusalem. They have assembled an impressive group of 35 psychologists, psychiatrists, and geneticists from universities around the world to write the 18 chapters that make up the book.

The authors assume that genetic factors are significant contributors to mental disorders and present recent and relevant studies that correlate genes, alleles, and gene products with normal and abnormal traits of human personality. The studies are constrained by small samples and the challenge of defining mental illness. Psychiatric disorders are genetically complex, and the associated genes act probabilistically. For example, the gene variant ALDH2Lys487 is generally associated with alcoholism, yet it is causally related only to the more precisely defined alcohol-induced flushing.

In this book we find a clear introduction to the methods used in the study of complex phenotypes, along with a review of linkage and association studies and a summary of relevant statistical methods. There is discussion of normal personality traits and criteria for personality disorders and an observation that human personality has the same multidimensional structure in a sample of psychiatric patients as in the population at large. Personality dimensions, defined by psychological tests, such as harm avoidance, self-directedness, and novelty seeking, correlate with specific disorders and predict response to drugs and psychotherapy. Roughly 50 percent of personality traits are inherited. The genetic interactions are complex and defy genetic engineering. Several candidate genes and alleles associated with personality types and behavioral abnormalities are discussed in the book. Differences in temperament among normal children are observed early and persist over time, which suggests a possible genetic basis. The evidence for genetic transmission of aggression is not very robust. There is some indication of heritability of a trait for impulsive aggression and of abnormalities in serotonin metabolism associated with aggression, but there is no evidence for genetic transmission of personality disorders.

A chapter on animal models demonstrates the usefulness of such models to our understanding of temperament and mood. Several chapters are devoted to dopamine D4 and the serotonin transporter and their relationship to personality traits, novelty seeking, and temperament in early childhood. Dopamine pathways are thought to promote exploratory and impulsive behaviors, whereas serotonergic excitations generally foster avoidance. These findings are tentative given that the gene effect is weak. A section is devoted to the social and ethical implications of research on genes and personality. It reviews misperceptions common in the lay community and cautions against premature application of genetic findings to social policy. The editors do not shy away from controversial issues; they include a chapter on the genetics of sexual orientation and one on general intelligence. A chapter on autism demonstrates the approach taken in this book: Autism, as defined by DSM-IV-TR, is a lifelong, pervasive behavioral disorder characterized by broad language deficits, poor social interactions, and ritualized, repetitive behaviors. It has an oligogenic (a few genes with marked effects) inheritance pattern, several susceptibility loci on chromosomes 7 and 15, and a concordance rate of 36 to 91 percent among monozygotic twins, in contrast with none among dizygotic twins. Some relatives of autistic children possess genetically transmitted personality and language defects similar to, but milder than, those of autism. Their syndrome, called broad autism phenotype (BAP), can serve as a model for genetic determinants of personality. People with BAP are a defined group with inherited personality traits. Unfortunately, the phenotype is complex; it is associated with a range of neuronal abnormalities rather than a single brain disorder, and its symptom categories overlap.

The penultimate chapter is a critique of the correlative-genetics-of-human-behavior approach that is endorsed in this book. For example, linkage and quantitative trait loci studies equate evidence of heredity with genetic transmission, even though animal studies demonstrate alternative, nongenetic ways of transmitting biological traits from the parent to the child, such as modification of DNA structure, differences in uterine environment, and subtle postnatal maternal behavior. Another point of contention is the tacit expectation that normal and abnormal behavior might be better understood by information on allelic variation, or that a simple gene-behavior correlation is meaningful without an understanding of the details of the intervening steps between an identified allele and behavior.

The authors of this volume are well aware of these reservations but consider that the studies they present in the book are sufficiently provocative to warrant publication.

I recommend the book to psychiatrists, social workers, and psychologists who work with patients and have become aware of the importance of innate predisposing factors to the resiliency of our patients and their ability to overcome trauma. I also recommend it to those who have an intellectual interest in the challenges of the new research and in the nature-nurture controversy.