Psychiatric developments最新文献

Techniques in molecular biology and genetics have made it possible to systematically study gene effects in human disease. The number of gene clusters specifically encoding human brain structure and function is probably about 1,600 or half of all clusters. Evolutionary effects such as linkage disequilibrium and conservation of exons (DNA encoding structural proteins) as well as the fact that there are a tractable number of gene clusters involved, tend to make it quite likely that DNA pathology or DNA variation (polymorphism) predisposing to mental illness can be detected. Genes involved in mental illness can be detected either by studying DNA obtained from blood samples (genomic DNA) directly or by the analysis of mRNA and proteins from suitable cell or tissue preparations. The study of gene expression in the human brain is still in its infancy, nevertheless there are some hints that non-poly-adenylated mRNAs may be important in brain development and certain transcribed sequences may have a specific role in gene expression of the brain. The advantage of studying genomic DNA by the use of linkage and association analysis in multiply affected families is that it will, in the end, almost certainly yield a positive result for a disease with a substantial genetic input. Analysis of gene products from tissues such as brain could in theory detect specific disease genes but the approach will also identify genes secondarily affected by the disease process. Differentiation of genes that are primarily causing mental illness from those that are secondarily affected can be carried out by using such candidate genes as linkage markers in multiply affected families.

Some of the methodological and conceptual issues relevant to behavior therapy treatment outcome studies for anxiety disorders are presented. The practice among behavioral researchers of measuring anxiety from 3 response systems (verbal, physiological and motoric-behavioral) is discussed. It is emphasized that many of the popular methods used to assess the 3 response systems have unknown or poor reliability or validity. From the point of view of treatment variables, it is noted that many behavioral treatment procedures are not reported in sufficient detail to allow replication or comparisons to be made across studies. In addition, it is argued that in order to improve the existing treatment procedures, it will be necessary for each study to assess the subjects' adherence to the treatment regimen, as well as their proficiency with any skills required to carry out the treatment plan. Finally, the importance of 'placebo' control groups is discussed in the context of identifying the specific factors in behavioral treatments which are responsible for change in the targeted symptoms. It is concluded that behavior therapy holds promise as an effective treatment for the anxiety disorders.

The nature of the relationship between 'panic disorder', agoraphobia and general anxiety disorder remains open. The aetiological theories which have tried to link them with the aid of biological and psychological concepts fail to take account of conflicting observations. 'Panic' attacks are not confined to agoraphobic and related disorders, being indistinguishable from the attacks of acute anxiety and phobic aversion manifest in a wide range of anxiety and affective disorders. There is continuity and discontinuity in the evolution of agoraphobia; those affected differ in respect of a range of premorbid features from patients with other disorders and control subjects. These variables include family history, life development, trait anxiety and other personality characteristics including introversion, neuroticism and probably emotional dependence on others. Not all the claims made on behalf of the efficacy of pharmacological treatment on the one hand and behavioural therapies on the other are substantiated. The success achieved by behavioural treatment appear to endure over some years. But the residual disabilities and defects that follow all forms of treatment and the problems posed by patient selection and high drop-out rates have received insufficient attention. Aetiological theories of agoraphobia and related conditions have been advanced along biomedical, psychological and psychodynamic lines. Some evidence supports each kind of theory. But none is wholly consistent with the findings regarding its phenomenology and evolution. Recent biological investigations have led to the formulation of hypotheses in relation to anticipatory and chronic anxiety in terms of changes in synaptic connections, enhancement of transmitter release as well as alterations in molecular configuration and regulation of gene expression. It would be premature to conclude that these findings can provide a unitary conceptual framework for the explanation of human anxiety disorders. The psychological, behavioural and psychodynamic aspects of this group of disorders should all continue to receive due attention both in clinical management and scientific investigation.

As systematic interviewing has become more widespread, it has been possible to identify significant populations of children and adolescents who meet adult criteria for depression. The difficulties associated with identifying correctly the phenomenology of major depression in children are reviewed. The significance of separation anxiety, anorexia, attention deficit and conduct disorder, as 'depressive equivalents' is discussed, although a change in mood or ability to experience pleasure appear to carry greater diagnostic weight. While the identification of mania and hence of bipolar disorder in children is more difficult, the appearance of a definite maniac syndrome in preadolescence is relatively uncommon. Data are reviewed suggesting the existence of an alternative and more common form of bipolar disorder in childhood, characterized by affective lability, irritability and explosive behavior. However, available data do not support the view that attention deficit disorder and 'emotionally unstable character disorder' are variants of bipolar syndromes.

Prior to the introduction of neuroleptics a lack of interest in complex classifications of the chronic schizophrenias was due to the lack of effective treatment. With the recognition of neuroleptic response heterogeneity, and of the hazards of long-term neuroleptic administration, interest in subtype classification such as that of Leonhard has grown. A simplification of the Leonhard scheme is presented. The first distinction drawn is between systematic or process schizophrenia and nonsystematic or episodic schizophrenia. Both groups are further subdivided according to whether the symptomatology is dominated by cognitive, affective or motor features. In the case of the systemic schizophrenias, further subdivision of the 3 major types is made on the basis of both severity and specific symptom characteristics. If such a scheme were a natural or biologically-based classification, rather than merely an artificial subdivision of schizophrenia, one might expect that similar proportions of the different subtypes would be found in independently selected samples. Preliminary data composing subtype proportions in Leonhard's original group, a population reported by Astrup, and a recently obtained international sample are presented. Some significant correlations between the samples are observed, and despite methodological short comings, the similarities in the distribution of subtypes across time and across countries give some support to Leonhard's taxonomy.

Several studies are summarized in which the relationship of high prolactin levels and self-rated anger-hostility was examined. The Symptom Questionnaire, a state measure which contains an anger-hostility scale, was included in all studies. Women with hyperprolactinemic amenorrhea were found to have higher hostility scores than amenorrheic women with normal prolactin levels. In another study, hyperprolactinemic women were found to have higher hostility scores than female family practice patients, random employees and there was a nonsignificant trend for higher hostility scores than in female nonpsychotic psychiatric outpatients. In both studies, depression and anxiety were also significantly higher. When bromocriptine, a prolactin lowering drug, was administered to hyperprolactinemic women in a double blind crossover study, there was a significant and progressive decrease of hostility, depression and anxiety while on bromocriptine, parallel with the decrease in prolactin and no change on placebo. Post-partum women who had high prolactin levels were significantly more hostile than a control group of employees and as hostile as hyperprolactinemic women. Hyperprolactinemic males were no more hostile than controls. The relationship of prolactin to post-partum aggression in mammals is briefly reviewed. The findings are inconclusive; in the three species studied, postpartum aggression is perhaps enhanced, but does not depend on high prolactin levels. There are no studies on the relationship of prolactin levels and violence in women. Hostility associated with high prolactin levels in postpartum women is perhaps a phylogenetic remnant which may have had the evolutionary advantage of protecting the young.

Individuals with early onset antisocial behavior appear to be more susceptible to serious substance abuse than those without. Individuals with deviant behavior exhibit both neuropsychological and neurophysiological deficits. With respect to alcoholism these deficits appear to antedate pathological exposure and appear to be transmissible from one generation to another. Subcortical dysfunction has been hypothesized to contribute to the behavioral disorders; however, the exact nature of the dysfunction and the contributions of genetic and environmental factors need exploration. A simple model for the association between behavior and neurochemistry is presented.

Although animal models cannot replicate human psychopathology in every detail, they should properly be conceived as experimental systems in which selected and specific questions can be investigated in ways impossible to do in humans. In considering the general kinds of animal models, distinctions must be drawn among those designed to simulate specific signs or symptoms, those designed to test a specific etiological theory, those designed to study underlying behavioral and neurobiological mechanisms, and those whose principal purpose is to permit pre-clinical drug evaluation. If, for example, drug evaluation is the first concern, the empirical validity of the model in predicting the therapeutic efficacy of drugs is primary, whereas the mechanisms responsible for inducing the syndrome, and behavioral similarity issues become secondary. The available models of depression are reviewed in the light of their specific advantages and limitations, including those induced pharmacologically, maternal and peer separation, learned helplessness, chronic stress, changes in dominance hierarchy, intra-cranial self-stimulation, conditioned motionlessness and behavioral despair models. Since multiple variables are involved in the etiology of depressions, animal models offer the possibility of evaluating their main effects and interactions in a controlled prospective manner. While caution is required in cross-species reasoning, there are nevertheless guidelines, and the continuing development of a comparative approach in Psychiatry has great potential.

The main clinical value of the EEG in psychiatry is as a non-invasive tool for the investigation of organic mental syndromes and epilepsy. Predictions that CT scanning would make the EEG redundant have not been fulfilled. Indeed, the 2 instruments complement each other, the EEG being a measure of function and the CT scan a reflection of brain structure. Both are proving useful in the investigation of dementia, providing different but complementary information about the extent and progress of the disease. Quantitative methods of EEG analysis using laboratory computers are now readily available. Significant changes in both the EEG background activity and event related potentials have been clearly demonstrated in the functional psychoses. These are not specific for any diagnostic condition. This implies that they reflect changes caused by the impact of the psychotic mental state on the individual's cognitive processes and level of arousal. The challenge for the future is to develop models of the relationship between the electrical events and underlying cognitive processes. Some progress has been made concerning the ERP changes in selective attention and in phobic disorder. The computerized EEG has a clearly established place in the investigation of drug action, by-passing the blood brain barrier and providing direct access to brain activity. Clearly this work may prove useful in the study of the effects of drug induced change on neurotransmitter systems. The EEG study of all night sleep in patients with functional psychiatric disorders has not lived up to the early expectations of workers in the field. Nevertheless the studies of insomnia and hypnotic drug effects have had valuable practical implications.