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Background: A specific psychotherapy for chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), was compared to escitalopram (ESC). Methods: Sixty patients with chronic major depression were randomized to ‘CBASP' (22 sessions) or ‘ESC plus clinical management' (ESC/CM) at two treatment sites. The primary outcome measure was the score on the Montgomery-Asberg Depression Rating Scale (MADRS) after 8 weeks of acute treatment assessed by blinded raters. In the case of nonimprovement (Results: An intent-to-treat analysis revealed that clinician-rated depression scores decreased significantly after 8 and 28 weeks with no significant differences between the groups. The response rates after 28 weeks of treatment were high (CBASP: 68.4%, ESC/CM: 60.0%), and the remission rates were moderate (CBASP: 36.8%, ESC/CM: 50.0%) with neither group being superior. Nonimprovers to the initial treatment caught up with the initial improvers in terms of depression scores and response and remission rates by the end of the treatment after being augmented with the respective other condition. Conclusions: CBASP and ESC/CM appear to be equally effective treatment options for chronically depressed outpatients. For nonimprovers to the initial treatment, it is efficacious to augment with medication in the case of nonresponse to CBASP and vice versa.

Substance P (SP) is a neuropeptide which is abundant in the periphery and the central nervous system, where it is colocalized with other neurotransmitters such as serotonin or dopamine. SP has been proposed to play a role in the regulation of pain including migraine and fibromyalgia, asthma, inflammatory bowel disease, emesis, psoriasis as well as in central nervous system disorders. This review summarizes our current knowledge of the role of SP in the pathogenesis of neuropsychiatric disorders with special emphasis on affective disorders including bipolar disorders. It also reviews current treatment approaches with neurokinin 1 receptor antagonists which appear to be promising drugs for the future treatment of affective disorders.

Although lithium remains the preferred medication for bipolar disorders, new investigations suggest that only 60 to 80% of patients have a good response with a classical presentation. The antiepileptics carbamazepine and valproate are important alternatives. Several studies have shown that lithium, carbamazepine and valproate are effective in pure mania. Mixed mania and rapid cycling respond, however, well to valproate. One disadvantage of carbamazepine is its enzyme inducing property with the consequence of a decrease of plasma levels of other psychotropic medications and a worsening of psychopathology. First data indicate a good antimanic and antidepressive efficacy of the new antiepileptic drug lamotrigine.

A growing body of evidence indicates that cytokines, especially interleukin-1 beta, are involved in the regulation of sleep and wakefulness. The aim of the present pilot study was to investigate the relationship between interleukin-1 beta (IL-1 beta) and gamma-interferon (gamma-IFN) production and the regulation of sleep and wakefulness. Four healthy male volunteers were investigated. After one adaptation night, beginning at 8 a.m. in the morning, the EEG was recorded by means of a mobile long-term EEG and blood samples were drawn every 45 min for the analysis of IL-1 beta, gamma-IFN and cortisol for 24 h. For the analysis of cytokines whole blood cultures were established. After 48 h of incubation in the presence of endotoxin Salmonella typhimurium, IL-1 beta and gamma-IFN levels were measured in the culture supernatants using specific immunodetection assays. Methods of stochastic time series analysis were adopted to evaluate the biochemical data. Our results show the capability of cultured blood cells to produce cytokines upon endotoxin challenge to be at a maximum around the time of sleep onset and during the first hours of sleep, declining during the night to a minimum level in the morning hours. The opposite was observed for cortisol. The analysis of autocorrelation functions gives evidence of a 24-hour rhythm of cortisol and cytokines. The results indicate that the cytokines IL-1 beta and gamma-IFN may play a role in sleep regulation.

The centrally acting α2-adrenoceptor agonist clonidine was used to assess the sensitivity of α2-adrenergic neurotransmis-sion in man, using receptor-binding studies and clonidine-induced growth hormone response. Neither acute (2 μg/kg body weight) nor subchronic (3 days, 2 × 150 μg/kg body weight) administration of clonidine affected platelet α2-adrenoceptor number in humans as judged by 3H-yohimbine and 3H-UK-14,304 binding. The same treatment also did not modify central postsynaptic α2-adrenoceptor function in the same individuals as assessed by clonidine-induced growth hormone responses. Similarly, subchronic (3 days, 500 μg/kg body weight, i.p.) or chronic (14 days, 500 μg/kg, i.p.) administration of clonidine to mice failed to change 3H-yohimbine or 3H-UK-14,304 binding sites in membranes prepared from frontal cortex. On the other hand, in vitro experiments using mouse frontal cortex or human platelet membranes showed pronounced reduction of 3H-UK-14,304 but not of 3H-yohimbine binding sites after incubation with several adrenoceptor agonists. The data indicate that acute and subchronic clonidine treatment may not change α2-adrenoceptor sensitivity in humans or mice as assessed both at the functional and receptor level.

The agonist-stimulated increase of intracellular free-Ca2+ concentration, an indicator of the sensitivity of the inositol phospholipid second-messenger generating system, was measured in neutrophils from patients with manic-depressive disorder, and controls. Dose-response curves of the calcium response were determined by measuring the fluorescence of neutrophils loaded with fura-2 and stimulated with various concentrations of the chemotactic tripeptide formylmethionylleucylphenylalanine. EC50 values were obtained for 14 medication-free patients (5 acutely depressive, and 9 symptom free remitted patients with a history of manic-depression or recurrent major depression), 9 lithium-treated, euthymic manic-depressive patients and 10 drug-free healthy controls. The EC50 values of the untreated patients were significantly lower than in the controls. Lithium-treated patients had EC50 values significantly higher than controls. These results suggest that manic-depressive disorder is associated with an increased sensitivity of the inositol phospholipid second-messenger generating system, which is counteracted by lithium treatment.

The results of several studies on sleep EEG and dreams in patients with eating disorders are presented and compared with the data obtained in patients with a major depression. The sleep pattern, which is characteristic of depression, could not be found in the eating disorder group. Regarding the cholinergic REM induction test, the depressives displayed a pronounced shortening of REM sleep latency. However, this biological marker, indicating a cholinergic hyperactivity in depression, could not be observed in patients with eating disorders. The content analysis of laboratory-recorded dreams yielded several differences between depression and eating disorders and also, more subtle, between anorexia and bulimia.

Studies on personality traits and coping styles as determinants of interindividual differences in neuroendocrine responses to stress have not yet yielded conclusive results. In a previous investigation, strong hints to distinct interindividual differences in the susceptibility of the HPA axis of 12 male volunteers aged 27 +/- 5 years exposed to five different stress situations were found. In the present report, psychometric variables (personality traits and coping styles) assessed in the same subjects before the study were analyzed to test whether specific psychometric variables were related to the interindividual differences in the susceptibility of the HPA axis. The results revealed that interindividual differences in the frequency of cortisol responses to stress situations could not be predicted by any of the psychometric variables investigated. The question if psychological factors contribute to neuroendocrine stress response and to what degree warrants further interest. These preliminary findings suggest, however, that nonpsychological factors should be considered more seriously as determinants of interindividual differences in neuroendocrine stress responses in healthy subjects as well as in psychiatric patients.