Psychiatric developments最新文献

Both longitudinal and retrospective studies have inherent weaknesses. With psychiatric mortality studies as an example of longitudinal research, this article presents a study design, the ambidirectional study, that combines some of the advantages and minimizes some of the weaknesses inherent in longitudinal and retrospective studies respectively. The method involves 2 phases: first, definition of a base population some of whom proceed to encounter an event of interest (e.g. death, suicide, illness), secondly, a retrospective comparison of those emerging from the same base population with or without the event of interest. The advantages of this design are feasibility and freedom from confounding coherent effects, since cases and controls enter the study at the same point. The difficulties are those of retrospective data collection. Definition of controls, case matching and statistical methodology are discussed.

There has been little consensus in the previous literature about the prevalence of non-psychotic psychiatric disorders in pregnancy. Only a few studies have included control groups and in these studies no substantial differences in rates have been reported. There have been methodological difficulties in establishing the incidence, course and nature of neurotic disorders occurring during pregnancy. However, from the available evidence, it seems likely that such neurotic disorders are similar to those occurring at other times.

Geriatric psychiatry involves the study of the interaction of age, medical illnesses, psychopathology, and treatment responsivity. Many of these interactions are demonstrated by reviewing mania in the elderly. Studying geriatric aspects of psychiatric disorders may give clues to understanding the pathophysiology of the same disorder in younger patients. For instance, localization of lesions associated with late onset mania suggests brain areas which may be involved in the early onset form of bipolar affective disorder. Reviewing the use of lithium in the elderly patient with mania provides the opportunity to review general geriatric psychopharmacologic principles.

This paper compares two broad views of psychotherapy, the etiological and the rehabilitative. The etiological view is based on the premise that the psychotherapeutic process provides a basis for laying bare the causal link between 'deeply repressed' unconscious forces and the patient's current condition. Spence's critique of this position is based on drawing a distinction between narrative truth and historical truth, pointing out the persuasive or rhetorical power of a coherent synthesis of the material presented by the patient, regardless of its historical veracity. Michels also draws attention to this difficulty by pointing to Freud's discovery that reports from childhood were based not on fact, but on fantasies which re-emerge in the transference relationship. The proposal that the therapist provides a context more conducive to the resolution of childhood trauma implies that the trauma was fact and not fantasy. Frank has drawn the parallel between confession in a cueless vacuum with brainwashing techniques which result in the confession of non-events. Besides these difficulties, the etiological approach cannot establish the direction of supposed causality linking childhood events, repressed psychological forces and the patient's condition. The apparently consistent pattern of expectations, perceptions, behavior and 'defenses' may themselves be the effects rather than the causes of the patient's condition. The psychotherapeutic process is intrinsically incapable of deciding objectively between these possibilities. Grunbaum has emphasized this epistemological weakness in the etiological position. The author therefore proposes a more pragmatic, rehabilitative, view of the psychotherapeutic process. Psychotherapy that deals with the personal and social life of the patient may help to alter the circumstances that contribute to discomfort, or change behavior that leads to dissatisfaction, without any commitment to unproven etiological theories. In this sense, psychotherapy, like physiotherapy and rehabilitation, is non-specific and can be applied without making any assumptions regarding specific causal conditions or pathogenetic factors.

The addition of lithium salts to the treatment regime of depressed patients who have failed to respond to adequate courses of antidepressant drugs shows great promise in meeting the considerable challenge of refractory depression. Although the mechanisms whereby lithium exerts its augmentatory action have not been fully elucidated, the available evidence supports the hypothesis that lithium-induced enhancement of serotonergic neurotransmission is involved. Enhancement or stabilization of cholinergic neurotransmission, and inhibition of the phosphoinositide second messenger system may also be relevant. In view of lithium's well established efficacy as an antidepressant in its own right, it is also unclear whether a separate augmentatory mechanism needs to be invoked, rather than an additive synergistic action with concurrently administered conventional antidepressants. Several case reports suggest that lithium augmentation may be effective in otherwise extremely refractory cases of depression. Despite a number of methodological limitations, the body of evidence from open and placebo controlled clinical trials suggests strongly that a response rate to lithium augmentation of about 60 per cent may be expected. Further clinical trials are needed to clarify the characteristics of likely responders to lithium augmentation, and the use of neuroendocrine probes may be particularly useful in elucidating the neurotransmitter mechanisms involved.

The comments by Gray, Gelder, Liebowitz, Eysenck, Nurnberger, Roy and Linnoila are discussed. Most of the recommendations in the comments have already been carried out and the others are under way. Specifically, practical assessment instruments have been developed, and their psychometric properties are under investigation. Explicit criteria for systematic diagnosis of personality disorders have been developed. Longitudinal studies have been carried out to evaluate the predictive validity of the scales. Empirical tests have confirmed the predicted relationship between novelty seeking and somatic anxiety, as well as between harm avoidance and cognitive anxiety. A more detailed model of the underlying neural processes has been described. Growing evidence of norepinephrine's role in reward dependence has been reported. Finally, a more comprehensive learning model has been developed that can account for both the higher-order and the lower-order factor structure of personality in terms of specific stimulus-response characteristics. Several commentators have provided additional evidence supporting the predicted role of the monoamines in modulating personality and learning. Finally, predictions from my model about pain sensitivity, stimulus intensity modulation, and the factor structure of personality have been compared to those of Gray and Eysenck. The predictions are confirmed for my model, but not those of Gray or Eysenck.

Different brain pathways have been shown to subserve the therapeutic effects of neuroleptics and their extrapyramidal side effects. Agents which can discriminate between these pathways, therefore, might be able to produce 'atypical' clinical effects. Molindone, a novel neuroleptic of the indoleamine class, has been shown in basic paradigms to discriminate between brain dopaminergic systems by virtue of its ability to preferentially inhibit dopamine autoreceptors (DARs). Clinical studies suggest that molindone may be less likely than traditional neuroleptics to induce tardive dyskinesia and that molindone may preferentially ameliorate some negative schizophrenic symptoms. We suggest that the distinct clinical effects of molindone result from its ability to block DARs.

Recent advances in the study of the neurofibrillary tangles (NFT), neuritic plaques (NP), and cerebrovascular amyloid found in the brain of Alzheimer's disease (AD) victims have greatly expanded our understanding of the molecular biology of this disease. Paired helical filaments (PHF) are the primary intracellular filamentous deposit. They appear to be distinct from normal cytoskeletal proteins, but they do contain a significant component of a microtubule-associated protein called 'tau'. Amyloid fibrils make up the extracellular filamentous deposits in AD. Amyloid fibrils are composed of a small protein of about 43 amino acids which has been sequenced. Some investigators suggest PHF are composed of this same protein, but this remains debatable. Molecular genetic studies have shown that a gene which codes for a larger protein containing the sequence of the 'beta-amyloid protein' exists in many tissues and in many species. Interestingly, this gene is located on chromosome 21 which is also the location of the familial AD gene, but these 2 genes are distinct. Several hypotheses exist on the origin of these abnormal deposits and range from neuronal origin to synthesis outside of the CNS with transportation via the blood. The implications of these recent advances are great and include the possibility of accurate and early antemortem diagnostic tests for AD, as well as therapeutic manipulation of the synthesis, deposition, or removal of these filamentous proteins.

Epidemiological and developmental methodologies are 2 complementary approaches to the study of the relationship between adverse temperament and the development of personality and psychopathology in childhood. The association between adverse temperament and clinical disorders in childhood is now well documented in the general population. This paper argues that at least 5 epidemiological questions about child temperament need answers before investing time and energy in limited analyses of molecular interactions between temperament and specific environmental characteristics. (1) We need to know to what extent child adverse temperament really increases risk of clinical disorders; this must be expressed quantitatively and compared with the other well-documented psychosocial risk factors. (2) We need to test, in random samples, different general models of the temperament-environment interplay through the 'additive, synergistic, control of exposure to other environmental risks' paradigm. (3) Do we have evidence that adverse temperament interacts with some of the well-known psychosocial risk factors or with special areas of family functioning? (4) Does adverse temperament predispose, in the general population, to particular types of childhood disorders or is there a non-specific risk effect? (5) Are there sex differences in the risk associated with adverse temperament in the population?

The predictive value of patients' characteristics with regard to subsequent success of antidepressant therapy was investigated in a prospective study. Starting from the amine-deficiency hypotheses the sample was randomized and 30 patients were treated with maprotiline, 30 with clomipramine. Sociodemographic data, data about the immediate history of the illness and also most of the psychopathological symptoms before the start of treatment have no predictive capacity. Predictors of a subsequent response to clomipramine proved to be: positive reaction to sleep deprivation, decrease in MAO activity as a result of sleep deprivation, absence of signs of fatigue in the EEG after the first infusion, a serum concentration of at least 75 ng clomipramine/ml serum or 30 ng desmethyl-clomipramine/ml serum on the 7th day of treatment. A negative response to sleep deprivation, an increase in MAO activity as a result of sleep deprivation, the appearance of signs of fatigue (vigilance index) in the EEG after the first infusion as well as obvious autonomic symptoms before the start of treatment are indicative of a response to maprotiline. Diurnal variations of mood point rather to a general responsiveness to antidepressants without preference for a particular antidepressant. The results of this study provide theoretical reasons why unchangeable characteristics of patients, so-called 'static variables', can be of only slight predictive value. In contrast, changeable characteristics, so-called 'dynamic variables', such as reaction to sleep deprivation, EEG changes resulting from the first infusion, etc., could be of predictive value.