Biological Psychiatry - Vol. 2

By Hugo D'Haenen; J.A. Den Boer et al. | Go to book overview

XXVI-7
Neurogenetics of Personality Disorders

Andreas Reif and Klaus-Peter Lesch


INTRODUCTION

The behavioural predisposition of an individual is commonly referred to as temperament or personality. In genetics, personality is generally defined as the characteristic manner and style of an individual's behaviour and encompasses the emotional expression, such as fearfulness, exuberance, aggressiveness, and self-restraint, as well as the vigour, temper, and persistence of the resulting behaviour (Benjamin et al., 1998; Ebstein et al., 2000). Personality disorder (PD) is an umbrella term covering a plethora of conditions characterized by a persistent pattern of abnormal behaviour, dysfunctioning in social contexts, and suffering of either the individual or the environment. Despite problems of classification, epidemiological research involving family, twin, and adoptee studies has gathered persuasive evidence that several categories of PD including antisocial, anxious/avoidant, and schizoid-schizotypal personalities are influenced by genetic factors, and that the genetic component is highly complex, polygenic, and epistatic (Coolidge et al., 2001; Eley et al., 1999; Jang et al., 1996; Kendler et al., 1991; McGuffin and Thapar, 1992; O'Connor et al., 1998; Vernon et al., 1999).

The analysis of genetic contributions to normal personality and behaviour as well as to PDs is both conceptually and methodologically difficult, so that consistent findings remain sparse. The documented heterogeneity of both genetic and environmental determinants suggests the ineffectiveness of searching for unitary causes. This vista has therefore increasingly encouraged the pursuit of dimensional and quantitative approaches to personality and behavioural genetics, in addition to the traditional strategy of studying individuals with categorically defined psychiatric entities (Plomin et al., 1994). While quantitative genetics has focused on complex, quantitatively distributed traits and their origins in naturally occurring variation caused by multiple genetic and environmental factors, molecular genetics has begun to identify specific genes for quantitative traits, called quantitative trait loci (QTLs) (Eley and Plomin, 1997). In this polygenic model, behavioural disorders are extremes of continua in which various genes interact additively or nonadditively. The QTL concept thus implies that there may not be genes for psychiatric disorders, just genes for behavioural dimensions. In line with this notion, Livesley et al. (1998) have recently suggested that personality disorders are best classified by dimensional scales and are not qualitatively distinct from normal personality traits. Underlying genes of extremes of normal personality traits may therefore contribute to a range of psychopathology including psychoses (Tien et al., 1992).

Any attempt to provide a comprehensive overview would be futile; however, an appraisal of the genetics of PDs requires the consideration of several critical caveats. This chapter therefore describes fundamental aspects of the genetics of personality and focuses on topics undergoing particularly rapid progress. Conceptual and methodological issues in the search for candidate genes of personality traits and PDs as well as for the development of mouse models of human PDs will also be reviewed.


PERSONALITY DISORDERS—A DIAGNOSTIC
DILEMMA

The diagnosis of PD is evidently not as clear-cut as is desirable. In a continuum ranging from reasonably well-characterized brain disorders with a defined genetic cause, such as Huntington's disease or fragile-X syndrome, to wider and more unspecific diagnoses such as bipolar affective or schizophrenic disorders, extreme variants of personality represent disorder entities which are the least well defined and accessible to psychobiological research. DSM-IV (American Psychiatric Association, 1994) lists the following criteria of PD: a persistent pattern of abnormal behaviour, dysfunctioning in social contexts, suffering of either the patient or the environment, and early onset in childhood or adolescence. When the first three DSM-IV criteria are inverted, (pattern of normal behaviour, functioning, and no suffering), and the last is kept, one might see this as a definition of 'normal' personality, or behaviour, as human personality is mainly what is constructed from an individual's actions. It is conceivable that the DSM-IV definition of PD covers a wide range of disorders; may be subdivided in almost infinite different ways, just as human personality; and depends not only on the patient, but also the environment. The social context is of substantial importance when the diagnosis of PD is applied; individuals functioning perfectly in some societies may fail to do so in others. Thus, we have the media stereotype of a workaholic German manager, who could be indexed as neurotic and anankastic in other socio-economic models; the temperamental stereotype of a young lady from Sicily, readily regarded as highly histrionic in Norway; and that revered eccentric English gentlemen, in DSM-IV euphemisms the archetype of a schizotype personality. Accordingly, PD, in part, lies in the eye of the beholder.

What leads to the term 'disorder', is the suffering of the individual or— as is sometimes more common in PDs – the environment. Otherwise, this 'disorder' could easily be described as 'personality variation', the outer limits of a Gaussian distribution of personality traits. Thus, the presence of PDs could be viewed as an evolutionary strategy to adapt to different environmental conditions. Dysfunctioning and abnormal behaviour might be appropriate attributes for a certain kind of personality structure in a given culture; but cultures and societies vary and, even more meaningfully, constantly change, and what was abnormal or dysfunctional yesterday might be successful and perfectly normal today. PDs therefore may be the price a given society has to pay for the flexiblity to adapt to different environments and for the variation of behaviour which helps it to maintain reproductive success and to ensure survival. Furthermore, the genes underlying behavioural traits have been shaped

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