A consistent procedure was used in interviewing patients, and the information elicited was recorded in a standard format. Each patient was interviewed within 48 hours of admission. Prior to the completion of the interview schedule, a full descriptive history of each patient was taken, hospital notes scrutinized, and, if appropriate, any further sources of information sought. Documentation referring to earlier hospitalization was compiled from diverse sources, even as far back as 1929 in one case. Following the collection of clinical items, patients were asked to complete the self-rating scales in random order. Each item was completed for severity for the period covering the previous month, and over 70 clinical state items were recorded. No attempt at diagnostic categorization was made, the aim being to rate each item independently and diminish any "halo" effect. The in­terview and collection of clinical information lasted an average of 2 hours, ranging from 1 to 3 1/2 hours. At an interval of 1 year after the index episode information, an outcome was systematically collected, but is not reported here.

Several lines of evidence indicate that the GABA/benzodiazepine receptor complex is coupled to a chloride ionophore (24). Thus electrophysiological studies have demonstrated that GABA produces its inhibitory effect on neurotransmis­sion by enhancing the flux of chloride ions across its specific channel on the nerve membrane (22). Recently it has been shown that using the synaptoneurosomes, a novel sub­cellular brain membrane preparation, it is possible to study the membrane per
meability to chloride ions by measuring the changes in chloride efflux induced by different drugs acting at the level of the GABA/benzodiazepine receptor / СП ionophore complex (31). Hence, by using this biochemical technique, we eval­uated the effect of foot-shock stress on 36 C1 efflux from cerebral cortex synap-toneurosomes of handling-habituated and naive rats. As shown in Table 4 foot-shock stress decreased 36 C1 efflux from synapto-neurosomes of handling-habituated rats, but failed to modify the 36 СГ exchange from the membranes of naive rats. The presence in the dilution buffer of pentobarbital, a drug that facilitates the chloride transport by increasing the opening time of the GAB A receptor-coupled chloride channel (21,34) reversed the stress-induced decrease of 36 С l efflux from synaptoneurosomes of handling-habituated rats. Moreover, pentobarbital also stimulated 36 Cl efflux from cerebral cortex synaptoneurosomes of naive rats. Thus the function of the СГ channel coupled to the GABA/benzodiazepine receptors is decreased by foot-shock stress. This finding is in line with our previous results showing that foot-shock stress markedly decreases the density of low affinity GABA receptors in the cerebral cortex of handling-habituated rats. (more…)

We studied the segregation pattern of MDI and HLA antigens combined in eight families, whose probands were diagnosed as having Major Affective Dis­orders, Recurrent, according to DSM-III (1), not taking into account the polarity of the disease. We investigated the first- and second-degree relatives of each proband with the Family Study Method using the same diagnostic criteria; for third- and fourth-degree relatives, as well as second-degree, when a personal interview was not possible, we used the Family History Method. All the probands and some of their first- and second-degree relatives were typed for their HLA structure, blind of their clinical diagnosis. For untyped subjects their HLA patterns were reconstructed when enough information allowed. To verify the hypothesis of a linkage between MDI and HLA, we applied the LIPED model (7). Parameters describing the MDI susceptibility locus were de­rived by the application of the multiple threshold models of transmission to a large sample of subjects and then experimentally tested (10). The result was a dominant SML with a reduced penetrance for the heterozygotes (q = 0.013, f(AA) = 0/0,f(Aa) = 0.923/0.926,f/(aa) = 1/1). Gene frequencies for HLA antigens were derived by a control population.
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In an adoption study performed at the Department of Child Psychiatry, Umea University, it was demonstrated that the biological parents of adoptees with neurotic-reactive depression did not differ significantly from the biological parents of control adoptees in regard to the prevalence of total psychiatric morbidity (Table 6) (7). After a subdivision of the psychiatric morbidity in the biological relatives of adoptees without psychiatric illness and those with neurotic-reactive depression, no certain relationship was found between any specific affective disorder in the biological parents and the disorders in the adoptees (Table 7) (7).

If we were to take an oblique factor through the depression cluster, scores of items on this factor should give us an intensive measure of depression, and likewise a factor through the anxiety cluster should give us an intensive measure of anxiety. The HDS approximates to the depression cluster and appears to be a good extensive measure of severity, but is clearly slightly askew and could be improved upon. It is fairly evident that the HAS could certainly be improved upon as it tends toward the center area. Somewhat surprisingly, the EPI-N and the 16 PF (Q4) appear to be reasonably good measures of anxiety. The numbers of items forming these clusters are variable; nonetheless, they tend to remain stable in the factor space formed by the first two components. We can, however, decide that a smaller rather than greater number of these items could more conveniently describe these clusters and might be a better measure of them. A series of Principal Component Analyses with a decreasing variety of items was undertaken. Each item was assessed visually so that only those that achieved the widest separation across the first and second factor plot and those that also showed contiguity within the separate clusters of anxiety and depressive features were included. It was electively decided to restrict the included items to current mental state and ignore biographical, personality, and other features for purposes of designing purely descriptive psychopathological scales of anxiety and depression; that is, in order to develop descriptive and intensity measures of anxiety and depression, symptom ratings alone were concentrated on in the sequential analysis with the object of deriving the most widely separated items that also remained stable in the factor space. This analysis led eventually to the selection of 26 items as the best replicable descriptive items of the depression and anxiety clusters. These clusters are shown in Fig. 3. This provides some explanation for the difficulties in interpretation posed by the intercorrelations in the literature. It would appear from these analyses that the BDI and ZDS poorly reflect depression in a descriptive sense. They more definitively correlate with the clinical anxiety items. Although they may be of value for rating mood change over time (7), they would appear to be functioning as extensive and not intensive measures of depression or mood in general. It is quite possible, therefore, for them to be sensitive to changes in mood yet not reflect specifically any depressive component. The HAS does not approximate to the center of the anxiety cluster and appears to be a less accurate measure of anxiety than is its counterpart, the HDS, of depression. These two factors are here designated as factor D (depression) and factor A (anxiety) for simplicity. One of the main objectives of this study was to design new rating scales. In this study the actual factor-derived scores of patients are frequently used rather than manipulating numerical scales scores. For application elsewhere, specific scores must be applied to the items comprising each scale. These scales correlate slightly negatively with each other in this population. In other populations selected by different criteria and subject to different selection processes, they might well be independent or positively correlated with each other. Having found these new dimensions that give an accurate mathematical representation of these clusters, we can now see how well the existing scales correlate with these dimensions. Table 6 shows the relative magnitudes of the correlations of the new dimensions or scales compared with the HDS and HAS. This measure of extensive severity is simply the extensive measure of mood referred to earlier, i.e., scores on the general factor. The new anxiety scale and the new depression scale have reason­ably good correlations with this general dimension of mood disorder. The new depression scale correlation is as good as the HDS. The correlations between the two Hamilton scales is 0.55. The new anxiety scale has a high correlation with the HAS and likewise the new depression scale has a high correlation with the HDS, yet their correlations are of a magnitude of -0.19. They are therefore more or less independent, far more so than the existing Hamilton scales. The
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