Biological aspects of personality disorder


A resurgence of interest in the area of personality disorder has been seen in the past 20 years. Researchers have continued along the biological line of investigation working from diverse theoretical standpoints and using increasingly sophisticated approaches. In this review these aspects are set against the background of current debate in the field and placed in their historical context.

Given that much related work has been carried out using a variety of terms such as episodic dyscontrol, impulse control and impulsive aggression, the computer-assisted search was
augmented by a manual search.

The aims of this overview are to outline current debates and
to trace the develop-ment of biological approaches in this field. In so doing, conditions mimicking per-sonality disorders will be discussed.
 

Classification of personality disorder

The standard classifications of personality disorder have undergone major revision in the past 20 years. Differences still exist between those in current use, namely the International Classification of Diseases, ninth revision (ICD-9) (World Health Organization,1978) and the Diagnostic and Statistical Manual of Mental Disorders, third edition and its later revision (DSM-III and DSM-IIIR) (American Psych-iatric Association, 1980, 1987). Changes that have been made during the development of 10th revision of the ICD (World Health Organization, 1989) have resulted in some convergence between the two systems and it has been suggested that the remaining differences are largely seman-tic (Tyrer et al, 1991). However, debate continues as to how personality and its disorders are best described.
 

Category vs dimension

The categories of abnormal personality have long been challenged. Much criticism has resulted from the poor agreement between clinicians as to what kind of personality disorder an individual has and whether or not the individual has one at all. Although DSM-III with its provision of operational definitions has led to some improvement, many continue to advocate a so called dimensional approach as an alternative (Widiger et al, 1988).

The essential difference between the two approaches lies in the questions they pose. The categorical approach asks 'Do this patient's characteristics meet the diagnostic criteria or not?', whereas the dimensional approach asks 'How much of the given characteristic does this patient display?' Perhaps the best known advocate of the dimensional approach in this country is Eysenck, who has suggested that much personality variance can be accounted for by the dimensions of extroversion-introversion (E), neuroticism-stability (N) and psychoticism-normality (P). These and other dimensions referred to below have their origins in experiments conducted from the perspective of behavioural psychology and have been described in detail elsewhere (Lewis, 1991; Siever and Davis, 1991).
 

Normal vs abnormal behaviour

The categorical and dimensional approaches are not mutually exclusive but trying to combine them poses two further questions. First, which dimensions (or behaviours) are
most relevant to personality disorder? Second, are such behaviours abnormal in themselves? Dimensional approaches tend to assume that the characteristics under consideration are present in all individuals and exaggerated in those with personality disorders.

From a slightly different perspective it has been argued that personality disorders represent attenuated forms  of frank psychiatric illness. Thus, the personality disorders in DSM-III cluster A may consti-tute part of a schizophrenia spectrum, those in cluster B an affective disorder spectrum and those in cluster C neurotic conditions. As yet the evidence seems most clear for the cluster A relationship and less clear for the other two.

Overall, the biological approaches to re-solving these and other issues of aetiology have become more sophisticated as techno-logical advances have been made. In keeping with this, the focus of attention has shifted over the last century from signs that are detectable on examination to models of CNS neurotransmitter systems.
 

Constitution and physical stigmata

One 19th century formulation of moral insanity, upheld by a number of influential authors, was that it represented a degenera-tive process arising in 'poor stock', which was handed on to successive generations, ultimately leading to extinction of the line (Lewis, 1974). Attempts were made to iden-tify and describe the outward manifesta-tions of the condition but this process was more successful in excluding other physical conditions (such as encephalitis lethargica) from the category than in establishing objective inclusion criteria (Schneider, 1958).

Subsequently, Kretschmer (1936) and Sheldon (1954) attempted to relate physical characteristics and body build to various personality types. However, this approach attracted little empirical support ('1"rimble, 1981) and is of historical rather than prac-tical interest.

The genetic aspects of personality dis-order have recently been extensively re-viewed (McGuffin and Thapar, 1992). Prob-lems of case definition hamper such work and modes of transmission are undoubtedly complex. However, these authors suggested that on balance there is reasonable evidence to support the idea of a genetic component in many categories of abnormal personality and felt that the future localization of quantitative trait loci (loci that relate to some continuously distributed character-istics) may shed some light on this area.

The role of temperament in the development of personality and personality dis-order has been reviewed in some depth by Rutter (1987). Given that the character-istics which differentiate children are not necessarily those which differentiate adults, it is difficult to establish broad clear links between specific childhood behaviours and adult personality disorders. Perhaps the strongest suggestions are those relating childhood hyperactivity to later antisocial behaviour.
 

Physical illness


Undesirable or even aggressive behaviour is not synonymous with personality disorder and the false attribution of such behaviour may lead the clinician into overlooking other important diagnoses (Lewis and Appleby, 1988). In the general hospital setting it is important that organic causes of aggressive behaviour are considered, and information obtained from the patient 5 relatives or close friends may clarify the situation greatly. In addition to a full history and examination, several points are worth considering as follows.
 

Age of the patient

The personality characteristics of those with cluster A and C diagnoses tend to be stable over time. Cluster B characteristics tend to become less pronounced in the patients' third or fourth decade (Tyrer et al, 1991). Therefore aggressive or antisocial behaviour arising after that age is less likely to be related to personality.
 

Premorbid personality

By definition the behaviours associated with personality disorder are evident in early life and persist into adulthood. Their develop-ment against the background of an unre-markable Premorbid personality may well point to either functional or organic illness.
 

Nature of the behaviour

In general, behaviour that is frankly bizarre (e.g. micturition in inappropriate places) is unlikely to represent personality dysfunc-tion, especially when it is associated with other mental state abnormalities (e.g. delu-sions or hallucinations).
 

Context of the behaviour

A pervasive nature for abnormal personality traits is assumed in the diagnosis of person-ality disorder and so behaviour that is highly specific to a given situation does not usually come under this heading.
 

Cognitive function

Disturbances in cognitive function such as disorientation and memory impairment point to an organic or conceivably a func-tional aetiology. Those with learning diffi-culties are excluded from the category of personality disorder.

The range of possible organic causes of aggressive behaviour is illustrated in Table 3 and the reader is referred to Lishman (1987) for a more detailed account. The historical relationship between personality disorder and epilepsy is complex and is dealt with separately.
 
 

Personality disorder and epilepsy

The episodic nature of the violent outbursts displayed by patients led writers to propose that epilepsy was important in the aetiology of moral insanity. Schneider later refuted this and used the term explosive personality to describe a similar group (Partridge, 1930). However, the suspicion of a link between the two persisted, and gained credence from the electroencephalographic (EEG) studies of the 1940s (Gurvitz, 1951). These and subsequent studies provided evidence of delayed cortical maturation in 'psychopaths' on the basis that slow waves particularly in the temporal region, with sudden bursts of activity) were more frequent in this group than in controls. This work was limited by numerous methodological diffi-culties and further weakened by the later finding that psychopaths were not over-represented among violent offenders with posterior temporal EEG abnormalities (Fenwick, 1981).

Attempts to relate clinical or subclinical seizure activity on the one hand and impul-sive or aggressive personality characteristics on the other have continued with the description of the episodic dyscontrol syn-drome (Bach-y-Rita et al, 1971) and the delineation of borderline personality dis-order subtypes (Andrulonis et al, 1982). The former relates to patients with histories of episodic aggression in the absence of provo-cation, who have soft neurological signs suggestive of what has been described as minimal brain damage. This remains a con-troversial formulation. Andrulonis et al (1982) reported histories of epilepsy in a small but significant subgroup of those with borderline  personality  disorder.  This diagnosis, which has attracted much atten-tion in the past 20 years (Tarnopolsky and Berelowitz, 1987), shares some of the characteristics associated with the term psychopathy.
Overall, it can be said that epilepsy is rarely the sole cause of episodic aggression, although lesions and seizures in the limbic system can lead to a lowering of impulse control and to aggression (Fenwick, 1986).
 

Epilepsy and personality

Historically, the so-called epileptic person-ality has been described using a number of adjectives (Fenton, 1981). For convenience, these can be grouped under obsessional (e.g. pedantic and circumstantial), paranoid (e.g. suspicious and touchy) and organic (e.g. concrete thinking and emotional viscosity).

Attempts to define the category have been hampered by the problems of obtaining representative samples and achieving a con-sensus on appropriate case definition.

Behavioural disturbance secondary to temporal lobe epilepsy has been more formally described as the Geschwind syn-drome (Geschwind, 1979). This constella-tion of features includes hypergraphia and hyposexuality in addition to some of the earlier characteristics.

Even if specific categories can be described, identifying the cause remains a formidable task which has to take into account such diverse factors as: age; sex; socioeconomic status; aetiology, location and chronicity of the seizure activity; stig-matization associated with the diagnosis and its impact on the individual's self-esteem; adherence to medication; interper-sonal relationships; and the effects of medication on cognitive performance and schooling. As such the exact relationship between epilepsy and personality is likely to remain unknown for some time.
 

Anatomical substrates

The search for anatomical substrates of antisocial behaviour can be traced back at least to 19th century faculty psychology. The belief that various mental faculties (including the moral faculty) could be linked to specific brain areas generated the hypo-thesis that moral insanity resulted from a lesion of that area controlling the moral faculty. A variant of this hypothesis was that the impulsive behaviour exhibited by these patients arose from an innate defi-ciency of moral inhibition secondary to a lesion in the main control centre. This was believed to be located in the frontal lobe (Burt, 1926).

German writers also favoured an organic explanation, with Kleist focusing more attention on subcortical structures. He described three aspects of self which equate with various clinical features of personality disorder, and related them to three anatomical sites. The somatopsyche or body self (governing hysterical impulses and sexual behaviour) was located in the grey matter around the third ventricle; the thymopsyche or feeling self (governing emotional lability, anxiety, lack of affect and touchiness) was related to the thalamus; and the autopsyche or character self (which was expansive, contentious, fanatical and compulsive) was ascribed to the pallido-striatum (Schneider, 1958).

The work described above in relation to epilepsy implicated the temporal lobe in the causation of antisocial behaviour. More rec-ently the mesolimbic and septal regions have been viewed as relevant in the genesis of episodic aggressive behaviour. The frontal lobe continues to attract much attention but the results of neurophysical investiga-tions of frontal lobe function have been conflicting (Zuckerman, 1991).
 

Physiological correlates

On the basis of the dimensional description outlined above, Eysenck has characterized psychopaths as displaying high levels of neuroticism and extroversion resulting from the associated variability in autonomic nervous system reactivity and arousal (as mediated by the  reticular activating system). As a consequence of this, the group should show some difficulty in learning, or more precisely in conditioning, e.g. the development of fear in response to an aver-sive stimulus. Indeed, psychopaths have been shown to exhibit lower anticipatory fear as demonstrated by lower galvanic skin responses. However, as Lewis (1991) points out in quoting Hare (1978), the nature of the aversive stimulus is important, and the appropriate  autonomic  responses  are obtained if the stimulus is changed to loss of reward.

Children with conduct disorders show an increased reactivity (measured as heart rate and skin conductance) in response to reward, which is relatively slow to fade when the stimulus is withdrawn, and a flattened response to an intense but neutral stimulus. These features distinguish this group from emotionally disordered children and con-trols. A tentative interpretation suggested that an inability to modulate arousal was evident, perhaps analogous to the high levels of sensation seeking displayed by adults with antisocial characteristics (Garralda et al, 1991).

The proposition that personality dis-orders in the DSM-IIIR cluster B are attenuated forms of affective disorders has aroused interest in a possible role for sug-gested biological markers of depression in borderline personality disorder. The dexa-methasone suppression test, the TRH/TSH (thyrotrophin-releasing hormone/thyroid-stimulating hormone) test and sleep EEGs have all been used in this group (Steiner et al, 1988). The neuroendocrine investigations are a little difficult to interpret because of the uncertain specifi-city of the tests, and the low sensitivity of the dexamethasone suppression test in particular, in this population. The blunted TSH response to TRH in some borderline patients and the shortened rapid eye move-ment latency in others may indicate an overlap with affective disorders, but definite conclusions would be premature.

Similarly, those with schizotypal per-sonality disorder may share patterns of abnormal eye tracking movements and impaired  information processing with schizophrenics (Siever and Davis, 1991). This would be in keeping with the notion of spectrum schizophrenia, such that the per-sonality disorder would be a forme fruste.
 

Biochemical approaches

Increasing evidence has accumulated in recent years to support the role of 5-hydroxytryptamine (5-HT, serotonin) in the central control of aggressive behaviour. It has been suggested that this form of behaviour includes both aggression towards others and suicide and that the association is independent of diagnostic category (van Praag, 1991). The evidence has been taken from studies in animals and humans. Many human experiments have revealed lowered values of 5-hydroxyindoleacetic acid (the main metabolite of 5-HT) in the CSF of those exhibiting a variety of aggressive behaviours. The assumption that CSF metabolite levels are an accurate reflection of central 5-HT activity has been ques-tioned (Soubrie, 1986) but overall the data seem to support the notion of reduced serotonergic activity being at least relevant to impulse aggression, particularly when postmortem and other evidence is taken into account (Coccaro, 1989).

The role of the noradrenergic system is much less clear. Although alpha2-receptor binding sites have been reported to be decreased in anxious, unmedicated border-line patients (Southwick et al, 1990), for example, the results of metabolite studies of aggressive behaviour (which is important in these patients) are as yet unconvincing (Soubrie, 1986). The use of platelet mono-amine oxidase activity as a marker remains equivocal.

One recent proposal has been that the personality dimensions of behavioural acti-vation (novelty seeking), behavioural inhibi-tion (harm avoidance) and behavioural maintenance  (reward  dependence)  are governed by the dopaminergic, serotonergic and noradrenergic systems respectively. It is suggested that these dimensions are genetic-ally determined and can be related to the more traditional categories of personality disorder (Cloninger, 1987). As yet it is too early to evaluate this hypothesis.