Psychiatric developments最新文献

Studies of the mode of action of antidepressant treatments and the biological basis of depression have recently concentrated on monoamine neurotransmitter receptors. This paper reviews the studies relating to alpha 2-adrenoceptors. Chronic administration of some but not all antidepressant treatments to animals alters the number and function of brain alpha 2-adrenoceptors. In man, platelet alpha 2-adrenoceptors have been widely studied as a quantifiable peripheral model of central alpha 2-adrenoceptors. The majority of studies have not identified clear differences in platelet alpha 2-adrenoceptors between drug-free depressed patients and control subjects, nor have they identified unequivocal effects of antidepressant treatments. Methodological problems and choice of radioligand may contribute to discrepancies between studies. Central alpha 2-adrenoceptor function in man has been assessed by measuring neuroendocrine and physiological responses to clonidine. Despite considerable variation in procedure, in diagnostic criteria, and in the interval since previous treatment, most studies find the growth hormone response attenuated in depressed patients. This provides the strongest evidence to date of an abnormality of alpha 2-adrenoceptors in depression. However, it seems likely that none of the measures to date adequately mirrors the function of the cortical and limbic receptors implicated in the pathophysiology of depression. It is also likely that no single neurotransmitter abnormality is common to all depressed subjects and that future studies should be aimed at the inter-relationship and dysregulation of several neurotransmitter systems.

Motor disturbance is a major disadvantage of the antipsychotic drugs currently available for the treatment of schizophrenia. Acute akathisia is a dose-related side-effect comprising a subjective awareness of inner tension and characteristic patterns of restless movement. The natural history of akathisia is unclear, and several variants of the condition are seen in older patients on maintenance antipsychotic medication. These include acute akathisia that has persisted, and tardive akathisia which tends to be associated with signs of tardive dyskinesia. Tardive akathisia and tardive dyskinesia share some pharmacological characteristics which raises the possibility that common elements of pathophysiology underlie the 2 conditions. Tardive dyskinesia, comprising oro-facial dyskinesia and choreiform trunk and limb movements, has come to symbolize the complications of long-term antipsychotic drug treatment, although the condition is often little more than a mild social handicap and is manifest in only a minority of patients receiving such treatment. This paper discusses the treatment and patient variables that may be considered as risk factors for tardive dyskinesia. Some of the inconsistencies in the relevant literature may be explained by a speculative sub-classification of tardive dyskinesia into early and late forms. The interaction of advancing age, drug treatment and the schizophrenic disease process in the development of late dyskinesia is discussed.

Nearly every category of psychotropic drug has been investigated in an attempt to find a pharmacologic treatment for obsessive compulsive disorder (OCD). This study reviews published trials from the English literature in which tricyclic antidepressants, monoamine oxidase inhibitors, neuroleptics, benzodiazepines, and other agents were employed for treatment of OCD. Weaknesses in the current methodology including diagnosis, measurement of severity and criteria for improvement have contributed to invalid conclusions about drug treatment and efficacy. It appears that OCD is an etiologically heterogeneous disorder with a complex differential diagnosis. For the clinician, a major conclusion drawn from this review is that no agent emerges as a drug of choice. Although clorimipramine, the most actively investigated agent, shows some promise, it has not been conclusively demonstrated that other, more readily available heterocyclic agents are less effective. Furthermore, when other disorders co-exist, such as panic disorder, alternative agents may prove as effective.

It has been recently proposed that positive (productive) and negative (deficit) symptoms in schizophrenia constitute distinct syndromes that carry different etiological, prognostic, and treatment implications. Inconclusive results to date may be attributable to methodological weaknesses, including problems of measurement and lack of longitudinal, dynamic, and multiphasic investigation. We describe a series of multidimensional studies on the validity and significance of this distinction, deriving from a new rating instrument and separate typological, dimensional, longitudinal, phasic, and psychopharmacological research perspectives. The data suggest that positive and negative features represent opposing polarities of psychopathology which can be reliably assessed. Various sources of syndromal validation were demonstrated, including construct and criterion-related validity and differential response to psychotropic medication. Positive and negative syndromes were equally prevalent in the acute and chronic phases of schizophrenia but stable only in the latter. The meaning of the syndromes also varied according to chronicity. In the chronic stage, a negative profile was uniquely associated with ominous genealogical, premorbid, and phenomenological signs, whereas in acute schizophrenia it carried favorable import and predicted successful outcome. The results contest a monolithic concept of the positive-negative distinction and fail to support the prevalent hypothesis of structural organic impairment underlying the negative syndrome. We instead postulate a dual-process model that distinguishes between neuroleptic responsive arousal-related (positive) and neuroleptic resistant development (negative) components in chronic schizophrenia.

We note the recent paradigm shift to sub-divide anxiety into endogenous and exogenous forms, with the former (panic disorder) being viewed as a genetically-determined metabolic disorder. We examine some of the supportive evidence and note the limitations of an exclusive biological model for panic disorder. Drug and other therapies are considered briefly and attention is drawn to the pluralistic approaches used in specialized treatment centres in Australia.

The discovery of specific behavioral effects of several neuropeptides and the expanded appreciation of a wide range of endocrine disturbances in depressive illness have recently renewed interest in the nature of the relationship between mood and endocrine changes. Major depressive disorders are a major and life-threatening complication of Cushing's syndrome, Addison's disease, hyperthyroidism, hypothyroidism and hyperprolactinemic amenorrhea. A treatment primarily directed to the physical condition may be more effective than antidepressant drugs in such organic affective syndromes. The influence of hormonal disturbances in the development of depression in Conn's disease, pheochromocytoma, parathyroid disturbances, SIADH, acromegaly, hirsutism and other endocrine diseases should be individually evaluated. Antidepressant drugs remain the most specific and readily available treatment of major depressive disorders in the setting of endocrine illness.

The relationship between epilepsy and psychiatry is reviewed. It is concluded that patients with epilepsy display more psychopathology than control populations and that patients with temporal lobe epilepsy are especially susceptible to more severe psychiatric illness. Psychosis, particularly with a schizophrenia-like presentation seems associated with dominant hemisphere pathology especially with altered function. The relationship between personality disorder and epilepsy is less clear. Affective disorder is a common clinical problem, although earlier reports of a link with the non-dominant hemisphere have not been replicated in some recent studies. The problem of cognitive decline is examined and it is concluded that many patients with epilepsy show either selective or more generalized impairments of abilities. This may be related to the effects of anticonvulsant drugs, and the possibility that carbamazepine may possess psychotropic properties is noted.

Differential vulnerabilities to acquire specific types of psychiatric disorders exist for males and females. Alcoholism, antisocial personality and completed suicide predominate in males, while depression, anxiety, eating disorders, and attempted suicide are more common in females. In this paper evidence is explored to support developmental linkages between these disorders in adults and disorders in childhood and adolescence. The findings of this review support the assumption that various disorders of children showing sex differences in prevalence rates are precursors of adult disorders with a similar sex ratio. Longitudinal studies of personality development also provide data supporting the idea that sex-related behavioral predispositions originating early in life may contribute to differences in prevalence rates at subsequent points in the life cycle. Biological and social mechanisms that help explain the nature of these vulnerabilities are explored in some detail. The biological mechanisms considered relate to the pre- and postnatal effects of androgens on the brain and hormonal mechanisms associated with sex chromosomal aberrations. The social factors considered include differences in the rearing of male and female infants, and variations in life-style. Research directions to further explore sex differences in psychiatric disorders are suggested. Such studies are important because they may lead to a better understanding of genetic-brain-behavioral relationships. Secular trends in sex-related socialization practices may also explain why changes in the incidence and age of onset of some types of psychiatric disorder are occurring.

Positron emission tomography (PET) is a brain imaging technique which safely provides quantitative, regional measurements of biochemical and physiological processes. Because of its capabilities, PET is well suited to the study of psychiatric disorders. Among psychiatric disorders, panic disorder is especially well suited for study. Since anxiety attacks can be precipitated by biological agents, blocked by anti-panic medications, and studied in a laboratory setting, PET can be used to investigate the elements necessary for the generation and treatment of anxiety attacks. Recently, we employed PET to identify several abnormalities in a sub-group of patients with panic disorder. Patients with panic disorder who were vulnerable to lactate-induced anxiety attacks had abnormal hemispheric asymmetries of parahippocampal blood flow, blood volume, and oxygen metabolism; abnormally high whole brain metabolism; and abnormal susceptibility to episodic hyperventilation. This article reviews the current concepts of panic disorder; it provides an introduction to the components, capabilities and limitations of PET; and it describes the strategy now being employed at Washington University to investigate the neurobiology of panic disorder.

Despite great efforts in clinical psychiatric research in the last decades, many simple questions still remain open. Present day clinical practice still lacks theoretically founded and generally accepted therapeutic rules, especially in the individual case. Similarly, in basic research we are far from understanding the etiopathogenetics of psychiatric illness. From summarizing some aspects of previous research strategies and results in neurobiological determinants in psychosis, future research strategies are outlined, which already have proven successful and thus should be pursued more rigorously. Not least because of general limited research capacities with respect to time and costs, future research has to proceed economically, i.e. guided by clear strategies.