Differences in Kynurenine Metabolism During Depressive, Manic, and Euthymic Phases of Bipolar Affective Disorder.

BACKGROUND & OBJECTIVE: The kynurenine pathway is involved in inflammatory diseases. Alterations of this pathway were shown in psychiatric entities as well. The aim of this study was to determine whether specific changes in kynurenine metabolism are associated with current mood symptoms in bipolar disorder. METHODS: Sum scores of the Hamilton Depression Scale, Beck Depression Inventory, and Young Mania Rating Scale were collected from 156 bipolar individuals to build groups of depressive, manic and euthymic subjects according to predefined cut-off scores. Severity of current mood symptoms was correlated with activities of the enzymes kynurenine 3-monooxygenase (ratio of 3-hydroxykynurenine/ kynurenine), kynurenine aminotransferase (ratio of kynurenic acid/ kynurenine) and kynureninase (ratio of 3-hydroxyanthranilic acid/ 3-hydroxykynurenine), proxied by ratios of serum concentrations. RESULTS: Individuals with manic symptoms showed a shift towards higher kynurenine 3-monooxygenase activity (χ2 = 7.14, Df = 2, p = .028), compared to euthymic as well as depressed individuals. There were no differences between groups regarding activity of kynurenine aminotransferase and kynureninase. Within the group of depressed patients, Hamilton Depression Scale and kynurenine aminotransferase showed a significant negative correlation (r = -0.41, p = .036), displaying lower metabolism in the direction of kynurenic acid. DISCUSSION: Depression severity in bipolar disorder seems to be associated with a decreased synthesis of putative neuroprotective kynurenic acid. Furthermore, higher kynurenine 3-monooxygenase activity in currently manic individuals indicates an increased inflammatory state within bipolar disorder with more severe inflammation during manic episodes. The underlying pathophysiological mechanisms of the different affective episodes could represent parallel mechanisms rather than opposed processes.

Huntington's disease: present treatments and future therapeutic modalities.

Huntington's disease (HD) is a devastating neuropsychiatric disorder for which therapeutic interventions have been rather fruitless to date, except in a slight symptomatic relief. Even the discovery of the gene related to HD in 1993 has not effectively advanced treatments. This article is essentially a review of available double-blind, placebo-controlled trials of therapy for this condition which also includes relevant open label trials. Unfortunately, HD research has tended to concentrate on the motor aspects of the disorder, whereas the major problems are behavioural (e.g. dementia, depression, psychosis), and the chorea is often least relevant in terms of management. We conclude that there is definitely poor evidence in management of HD. The analysis of the 24 best studies fails to result in a treatment recommendation of clinical relevance. Based on data of open-label studies, or even case reports, we recommend riluzole, olanzapine and amantadine for the treatment of the movement disorders associated with HD, selective serotonin reuptake inhibitors and mirtazapine for the treatment of depression, and atypical antipsychotic drugs for HD psychosis and behavioural problems. Moreover, adjuvant psychotherapy, physiotherapy and speech therapy should be applied to supply the optimal management. Finally, some cellular mechanisms are discussed in this paper because they are essential for future neuroprotective modalities, such as minocycline, unsaturated fatty acids or riluzole.

Posttraumatic stress disorder and health-related quality of life in long-term survivors of acute respiratory distress syndrome.

OBJECTIVE: Intensive care often means exposure to physical and psychological stress, with long-lasting emotional sequelae for most patients. Psychiatric morbidity and negative effects on health-related quality of life were assessed in long-term survivors of acute respiratory distress syndrome. METHOD: Forty-six long-term survivors were enrolled in a psychiatric follow-up study. All patients had received standard, protocol-driven treatment during intensive care. The median follow-up time was 8 years after treatment. DSM-IV was used for psychiatric diagnosis. Psychological tests were performed to measure posttraumatic stress symptoms; depression; state anxiety; somatization; symptoms regarding concentration, attention, and short-term memory; social support; and health-related quality of life. RESULTS: At time of discharge, 20 of the patients suffered from posttraumatic stress disorder (PTSD) and four from sub-PTSD. At follow-up, 11 patients continued to suffer from PTSD and eight from sub-PTSD. The patients with PTSD demonstrated a pronounced tendency for somatization and state anxiety. Among the groups with PTSD, sub-PTSD, and no PTSD, there were no statistically significant differences regarding social support and symptoms of cognitive dysfunction. Those with PTSD showed major impairments in some dimensions of health-related quality of life, whereas those without PTSD had scores that were in the range of the general population. Except for duration of stay on the intensive care unit, neither age, gender, sociodemographic variables, premorbid psychopathology, nor initial severity of illness discriminated between the groups. CONCLUSIONS: Long-term survivors of acute respiratory distress syndrome seem to face a major risk of PTSD and major impairments in health-related quality of life in the long term.