Psychiatric developments最新文献

The history of adoption studies and their use in separating heredity from environmental influences is reviewed. The adoptee separation paradigm became possible through changing social practices which formalized adoption procedures. In the earlier past of this century, the technique was used principally to investigate the relative importance of heredity and environment in the determination of IQ. It was not until the sixties that the technique was used to study the role of heredity in psychopathology. Genetic factors in alcoholism, criminality, personality disorders, antisocial personality, somatization disorder, affective disorder, hyperactivity and schizophrenia were assessed. The review analyses the potential interactions of confounding variables in such studies and how these can be controlled, and discusses the major methodological criticisms which have been raised. Although the predominant interest has been in the use of the technique to define genetic etiological factors in psychopathology, the paradigm is equally able to delineate precisely the role of environmental factors while controlling for heredity. With about 1 per cent of populations being adopted in Western countries, the further scope for such studies continues to hold promise.

It is argued that further research to achieve more detailed diagnostic systems in many psychiatric disorders is unlikely to be productive without taking genetic effects into account. Even when this is done, for example when carrying out segregation analysis to determine a mode of genetic transmission, mental illnesses often pose specific problems that preclude accurate analysis. Because techniques in molecular biology and genetics have made it possible to study gene effects in human disease systematically it should now be possible to specify the genes that are involved. When this has been achieved then a diagnostic system based on genetic causation can develop. This will have the advantage of helping to pinpoint environmental factors more accurately. Specific strategies will need to be adopted to overcome uncertain modes of inheritance, incomplete or non-penetrance of disease alleles and disease heterogeneity. Highly speculative hypotheses can be put forward for a locus causing Alzheimer's disease on a portion of the long arm of chromosome 21. For autism it is plausible that there is a disease locus at or near the fragile X site on the X chromosome. A locus for manic depression has been very tentatively mapped using DNA markers to chromosome 11 and in a small proportion of families DNA markers have also shown some evidence for X linkage. Schizophrenia does not seem to be associated with any favoured loci. Candidate genes for schizophrenia include those encoding dopamine, other neurotransmitter receptors or enzymes and various neuropeptides such as enkephalin and beta endorphin.

A general theory of heritable personality traits and their neurobiological basis is described. Three independent dimensions of personality are defined and related to heritable variation in patterns of response to specific types of environmental stimuli: 'novelty seeking' is due to a heritable tendency toward frequent exploratory activity and intense excitement in response to novel stimuli; 'harm avoidance' is due to a heritable tendency to respond intensely to aversive stimuli and to learn to avoid punishment, novelty, and non-reward passively; and 'reward dependence' is due to a heritable tendency to respond intensely to reward and succorance and to learn to maintain rewarded behavior. Evidence suggests that variation in each dimension is strongly correlated with activity in a specific central monoaminergic pathway: novelty seeking with low basal dopaminergic activity, harm avoidance with high serotonergic activity, and reward dependence with low basal noradrenergic activity. These neurobiological dimensions interact to give rise to integrated patterns of differential responses to punishment, reward, and novelty. The combination of high novelty seeking, high reward dependence, and low harm avoidance (histrionic personality) or the combination of high harm avoidance, low reward dependence, and low novelty seeking (obsessional personality) are each associated with information-processing patterns that lead to unreliable discrimination of safe and dangerous situations and hence to chronic anxiety. In individuals with high novelty seeking, chronic anxiety is characterized by global uneasiness or alarm without specific premonitory cues, frequent bodily pains due to low pain and sensation thresholds, low sedation threshold, and slow fatigability. In contrast, in individuals with high harm avoidance, chronic anxiety is characterized by frequent anticipatory worries based on specific cues, high pain and sedation thresholds, and easy fatigability. In response to frustrative non-reward, individuals with high reward dependence are susceptible to compensatory noradrenergic hyperactivity and hence acute or recurrent states of agitated dysphoria associated with reward-seeking behaviors such as overeating and increased sexual activity. Specific predictions are made about normal personality development as well as the development and familial aggregation of anxiety, somatoform, depressive and personality disorders. These predictions are compared with available information, and recommendations are made for future research.

Compliance research is reviewed with particular reference to neuroleptic treatment of schizophrenia. Reported noncompliance rates of up to 50 per cent are likely to be an underestimate. Models of compliance and health-seeking behaviour borrowed from physical medicine are of questionable relevance to schizophrenia where perception of illness is often distorted. Factors thought to be implicated in noncompliance need to be evaluated and a theoretical model applicable to schizophrenia constructed. In the meantime there is evidence to suggest that behavioural intervention strategies may be superior to simple educational ones in the management of noncompliance. A discussion of methodological issues relating to the assessment of compliance is offered and a strategy for further research outlined.

The evidence supporting genetic factors in alcoholism comes from family studies (an alcoholic biological parent is seen in 31 per cent of alcoholics), twin studies (MZ concordance 55 per cent and 28 per cent for DZ twins), and adoption studies (alcoholism 44 per cent higher in adopted out offspring of alcoholics than controls). Once the presence or absence of a biological alcoholic parent is controlled for, rearing experiences and parental loss do not increase the risk for alcoholism. This conclusion justifies the search for genetic factors which might mediate the increased risk, particularly in groups identified as being at high risk for the development of alcoholism. The methodological assets and liabilities of the 'high risk' approach are reviewed, with reference to a detailed discussion of existing longitudinal and cross-sectional studies of high-risk populations. There is little convincing evidence that measurable personality attributes or differences in rate of ethanol breakdown contribute to alcoholism vulnerability, although high risk groups may have a unique EEG pattern in childhood, and in early adulthood decreased intensity of ethanol response, and increased acetaldehyde may be important.

Panic disorder, comprising also agoraphobia for the purpose of this review, has a prevalence of 1.2-8.4 per cent, affecting females twice as frequently as males, and has a mean age of onset of 25. It is one of the more familial diseases in Psychiatry in that 2/3 of cases have relatives affected with the same condition, and the risk to first degree relatives is approximately 3-4 times the rate of the general population. Although some family studies have suggested an overlap in the transmission of panic disorders and depression, and a common diathesis hypothesis has been proposed, depression is more common in the families of depressives, as in panic disorder in the families of probands with panic disorder. Twin studies of anxiety disorders, although limited in number, report a 30-40 per cent concordance among MZ twins, against 0-4 per cent among DZ twins, which supports a genetic predisposition. The mode of transmission is uncertain. Studies which have used the 'ancestral pairs' method (which examines the incidence of the condition in maternal versus paternal forebears, on the assumption that single locus transmission is favored by unilateral clustering, and polygenic theories are favored by a more even spread) have favored single locus transmission, although such unilateral clustering can still be accommodated within a multifactorial-polygenic hypothesis. Potential biological markers for the condition are reviewed. The observation that lactate infusion can precipitate panic attacks in predisposed individuals is well established. The association with mitral valve prolapse suggests that perhaps 38 per cent of patients presenting with symptoms of panic disorders have mitral valve prolapse on echocardiography. The possibility of an endogenous anxiety-producing agent that binds to the benzodiazepine receptor is discussed.

Since its introduction in 1934, electroconvulsive therapy has been subjected to a large number of clinical trials of varying methodological sophistication. Although doubts continue to be expressed about the efficacy of ECT, there is a remarkable degree of unanimity in the findings of trials published over a period of 50 years: improvement rates in depression of 70-80 per cent, compared with 20-30 per cent in untreated controls. The principal caveat is that ECT is not a ubiquitous treatment, even in the field of depression, and only patients with endogenous illnesses, whether unipolar or bipolar, can be expected to respond. Even among these, ECT cannot be expected to prevent the relapses in an illness whose underlying course is episodic. The published studies leave little doubt that ECT is statistically more effective than any of the antidepressant drugs, although the relative difference in outcome between the 2 forms of therapy is small, and drugs are to be preferred in mild or moderate cases. However, ECT is an effective and rapidly acting treatment for severe depressive illness, and the rapidity of the response makes its early use desirable in patients at risk of suicide, and those showing marked retardation, agitation and weight loss.

The method of clinico-pathological correlation for drawing inferences about the localization of particular cerebral functions has a long history of use, and well established theoretical limitations. Release phenomena, loss of excitatory drive, as well as non-specific tissue responses to injury may all have a bearing on observed behavioral change. Nevertheless, the consistent observation that severity of depression in stroke patients is greater for left hemispheric strokes, and greater for left frontal versus left occipital strokes is of considerable interest. Site of lesion appears to have greater explanatory power for this emotional symptom than the obvious psychological explanations in terms of loss of self-esteem and loss of function. Depression is greater for strokes in general than would be expected for equivalent loss of motor function with orthopedic etiology. Loss of cognitive function likewise is a poorer guide to severity of depression than site of lesion. On the other hand, accuracy of lesion assessment using present static anatomical methods (CAT scan), and reliability and validity of the psychopathological examination present methodological difficulties which are discussed. As newer brain imaging techniques that are sensitive to function are developed, this line of enquiry holds considerable promise for furthering our understanding of the anatomy and physiology of emotion.

Reliable concepts of borderline disorders are a prerequisite for studies of validity. Gunderson's and DSM-III's definition of Borderline personality disorder (BPD) and DSM-III's definition of Schizotypal personality disorder (SPD) fulfill these demands. The empirical evidence for descriptive, construct and predictive validity of these disorders is presented and discussed. The review concludes that BPD has descriptive validity but lacks the 2 other stronger types of validity. SPD has both descriptive and construct validity but lacks predictive validity. Various strengths and weaknesses of the empirical studies of these borderline concepts are discussed.

The abnormal performance of the DST in depressive illness has been shown to be one of the most reproducible findings in biological psychiatry. Initial claims of its very high diagnostic specificity for the diagnosis of endogenous depression have not been substantiated: an abnormal response appears to reflect a biological dysfunction that cuts across the clinically established boundaries of psychiatric nosology. This lack of diagnostic utility does not reduce its prognostic value and abnormal DST response may indicate or reflect a versatile component in psychiatric disturbance and could serve therefore to predict or monitor the effects of physical and psychological intervention. Contributory factors to abnormal DST response are explored: factors such as stress, nutrition and age are reviewed and discussed. Concepts of biogenetic (neurohumoral) and psychological (psychodynamic and psychosocial) vulnerability and initiation/promotion are invoked and an integrated hypothesis is suggested: emotional strain provokes neurohumoral and neuroendocrine changes; these changes lead to vegetative disturbances including loss of appetite and weight with subsequent nutritional deficiencies that promote/reverse their neurohumoral and neuroendocrine changes. The role of 5-hydroxytryptamine is emphasized. Supportive evidence for aspects of this hypothesis is provided including animal studies and studies of the clinical and biological correlates of abnormal DST response.