Prevalence and risk factors for recurrence of depression five years after short term psychodynamic therapy.

BACKGROUND: Follow-up research concerning the efficacy of treatment for depression is scarce and varies widely in clinical and methodological terms. Aim was to conduct a five-year follow-up study of recurrence of depression after short supportive Psychodynamic Treatment (PDT) alone or in combination with pharmacotherapy. METHODS: Patients who had been treated five years previously for major depressive disorder in a randomised control trial comparing short supportive PDT alone or in combination with pharmacotherapy, were traced. Patients who completed treatment were included. Recurrent episodes in the past five years were identified using CIDI. Severity of symptoms after five years was measured with the Hamilton Rating Scale for Depression and sub-scales Depression, Anxiety and Somatisation of the self-report Symptom Checklist 90. RESULTS: 52 (37%) patients of the original sample were localised. 42% had suffered from one or more recurrences during the follow-up period. There was no significant difference between the group who had received psychotherapy and the group who had received combined therapy during the acute phase. Young women and patients with more residual depressive symptoms and less somatic symptoms directly after treatment, were more at risk for recurrence. LIMITATIONS: Relatively small study population. Furthermore it was not known if patients received other treatment during the follow-up period. CONCLUSIONS: The long-term efficacy of PDT (with or without antidepressants) seemed to be comparable with other psychotherapies for depression. But the high recurrence rate urges us to shift the focus of depression treatment to improving long-term outcome and to the prevention of recurrence, in particular for young women and patients with residual symptoms of depression.

Cytoskeletal alterations in the human tuberal hypothalamus related to argyrophilic grain disease.

The tuberal region of the human hypothalamus was examined for cytoskeletal changes related to argyrophilic grain disease (AGD). Hypothalamic sections of eight individuals afflicted with AGD and eight controls were cut serially in the frontal plane at 100 microm. The presence of argyrophilic AGD-related pathology was demonstrated utilizing the modified Gallyas silver iodide technique. Tau-positive cytoskeletal changes were stained by the phosphorylation-dependent antibody AT8. A characteristic pattern of tau-positive cytoskeletal alterations was revealed in the tuberal hypothalamus of AGD cases, while controls were devoid of such changes. The lateral tuberal nucleus was found to be particularly susceptible to AGD, demonstrating numerous tau-positive grains and neuronal cell bodies. Similar alterations were present to a moderate degree in the ventromedial nucleus. A previously unreported, conspicuous accumulation of tau-positive oligodendrocytes (coiled bodies) and interfascicular thread-like fibers was detected in the column of the fornix. Only sparse argyrophilic changes were noted in consecutive silver-stained sections, comprised mainly of accumulations of spindle-shaped grains within the lateral tuberal nucleus. Remarkably, a pronounced expression of AGD-related alterations was seen in the absence of hypothalamic changes related to other tau-positive cytoskeletal disorders, such as Alzheimer's disease. The present findings support the concept that AGD is a distinct neurodegenerative entity afflicting not only cortical but also subcortical predilection sites of the human brain.

Cytoskeletal alterations in the aged human neurohypophysis.

The hypophyses of 24 individuals, aged 79-89 years (mean age 83.5+/-3.3 years), were investigated for cytoskeletal changes associated with abnormally phosphorylated tau protein using the monoclonal antibodies AT8, PHF-1 and Alz-50. A previously unreported pattern of cytoskeletal changes was identified in the neurohypophysis consisting of axon-like fibers and large swellings resembling Herring bodies. The density of the cytoskeletal lesions was subject to notable variation among individuals. Marked neurohypophyseal alterations were also noted in cases even devoid of Alzheimer's disease-related cytoskeletal pathology in neocortical areas. Fully developed Alzheimer's disease is thus not a prerequisite for the presence of advanced neurohypophyseal alterations. In conclusion, the aged human neurohypophysis is revealed as a potential focus of abnormal cytoskeletal changes which may impair the neuroendocrine function of the hypothalamo-neurohypophyseal system.

Fosinoprilate prolongs the action potential: reduction of iK and enhancement of the L-type calcium current in guinea pig ventricular myocytes.

OBJECTIVE: The aim was to study the effect of fosinoprilate, a new ACE inhibitor, on the action potential and plateau currents of cardiac muscle. METHODS: Whole cell patch technique was used to record action potentials (n = 6), the L-type iCa (iCaL; n = 5), in some cases (n = 4) also using Cs+ loaded pipettes; with 5 mM Co2+, the time dependent K+ current (IK) underlying delayed rectification was analysed in guinea pig ventricular myocytes (n = 3). RESULTS: Fosinoprilate prolonged the 50% repolarisation (APD50) from 440(SEM 50) ms to 485(48) ms (0.1 microM), to 525(46) ms (0.3 microM), to 632(58) ms (1 microM), and to 702(69) ms (3.0 microM). The APD90 was delayed from 510(63) ms to 540(45) ms (0.1 microM), to 583(42) ms (0.3 microM), to 702(62) ms (1.0 microM), and to 765(72) ms (3.0 microM). Higher concentrations (10-100 microM) caused early afterdepolarisations, very long action potentials, and irregular oscillations. ICaL was enhanced by up to 183%, showing a Kd of 0.2 microM; in contrast to the steady state activation (d infinity), the inactivation curve f infinity was shifted in the depolarising direction, considerably enlarging the Ca2+ window. Slow inactivation time course was unchanged, whereas the fast time constant (tau f) was accelerated. Fosinoprilate reduced the outward current during depolarising clamps from 1.7(0.2) nA to 1.41(0.11) nA with a 0.1 microM dose, and to 0.54(0.14) nA with a 1.0 microM dose; the tails were decreased from 0.39(0.03) nA to 0.27(0.03) nA with 0.1 microM and to 0.13(0.02) nA with 1.0 microM. Kinetics of IK were unaltered. Computer simulations based on these data using the OXSOFT-HEART program mimicked the results rather closely. CONCLUSIONS: The results suggest that fosinoprilate prolongs the plateau due to a partial block of iK and an extension of the Ca2+ window by 10 mV, causing a class III antiarrhythmic effect. High concentrations further open the Ca2+ window resulting in early afterdepolarisations and plateau oscillations and may cause an inward transport of Ca2+ ions by the Na-Ca exchange.