Tryptophan and Kynurenine Metabolites: Are They Related to Depression?

BACKGROUND: Some previous studies found decreased concentrations of L-tryptophan (TRY) and increased L-kynurenine (KYN), or its metabolites, in the body fluids of subjects with major depressive disorder (MDD), sometimes in association with suicidal behavior. Such changes might indicate a shift of TRY away from serotonin production, possibly via the effects of inflammatory peptides which activate indoleamine-2,3-dioxygenase. However, these findings have been inconsistent and require replication. METHODS: We used sensitive liquid-chromatography mass spectrometry methods to assay plasma concentrations of TRY, 5-hydroxyindoleacetic acid (5-HIAA), and KYN and its metabolites (anthranilic acid and xanthurenic acid). We compared 49 hospitalized, depressed subjects diagnosed with MDD (n = 37) or bipolar disorder (BD, n = 12), with (n = 22) or without (n = 27) previous suicide attempts, to 78 healthy, ambulatory controls of similar age and sex (total n = 127). FINDINGS: Contrary to expectation, TRY plasma concentrations were higher, KYN plasma concentrations were lower, and their ratio much higher in depressed subjects, with no relationship to suicidal history. Concentrations of 5-HIAA and the kynurenine metabolites did not differ between depressed and healthy subjects. CONCLUSIONS: These findings are opposite to expectations and not consistent with a hypothesized increased conversion from TRY to KYN in depressed subjects. In addition, we found no evidence of altered production of serotonin as 5-HIAA concentration was unchanged. None of the observed changes was associated with a history of suicide attempt.

Bisexuality and suicide: a systematic review of the current literature.

INTRODUCTION: Many studies of lesbian, gay, and bisexual youth have demonstrated that individuals reporting a bisexual orientation have a particularly high risk of suicidal behavior and substance abuse. It has been also suggested that bisexual individuals (both men and women) have higher rates of depression and anxiety compared with homosexual and heterosexual groups. AIM: The aim of the present article was to determine whether or not an association between bisexuality and suicidal behavior exists and to analyze risk factors for suicidal behavior in bisexual individuals. MAIN OUTCOME MEASURES: The combined search strategies yielded a total of 339 records screened from PubMed, Scopus, and Web of Knowledge. Duplicate articles, articles that were not in English, and those that did not analyze bisexuality separately from homosexuality were excluded. A quality assessment was performed for each study included. METHODS: A careful systematic review of the literature was conducted investigating the potential bisexuality-suicidal behavior link. A total of 77 articles from peer-reviewed journals were considered, and the most relevant (N=19) were selected for this review. RESULTS: Individuals reporting a bisexual orientation had an increased risk of suicide attempts and ideation compared with their homosexual and heterosexual peers. Risk factors included related victimization, peer judgments, and family rejection. Bisexual individuals also reported higher rates of mental illness and substance abuse. CONCLUSIONS: Bisexual individuals may experience more psychological distress and mental health problems than individuals who identify with a homosexual or heterosexual orientation. Clinicians should consider the potential for suicidal behaviors in bisexual individuals and be alert for increased mental health problems and poor social integration.

Hypothalamic pituitary adrenal axis and prolactin abnormalities in suicidal behavior.

Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity measured with the dexamethasone suppression test and the dexamethesone/CRH test may have some predictive power for suicidal behavior in patients with mood disorders. Increased prolactin (PRL) levels may be related both to physiological and pathological conditions. HPA-axis abnormalities and increased levels of PRL may coexist, and common neuroendocrine changes may activate both HPA axis and PRL release. HPA-axis hyperactivity is presumably present in a large subpopulation of depressed subjects. Suicidal behavior is considered to be a form of inward-directed aggression, and aggressive behavior has been connected to high androgen levels. However, lower plasma total testosterone levels have also been reported in subjects with depression and higher suicidality. Lipid/immune dysregulations, the increased ratio of blood fatty acids, and increased PRL levels may each be associated with the increased production of pro-inflammatory cytokines, which have been reported in patients with major depression and patients engaging in suicidal behavior. Although no studies have been done to determine whether ante-mortem physical stress may be detected by raised post-mortem PRL, this would be of great interest for physicians.

Mood disorders medications: predictors of nonadherence - review of the current literature.

Studies have shown that there are several factors that predict nonadherence among patients with mood disorders. The aim of the present review is to identify the predictors of nonadherence among these patients. A careful review of the literature was conducted investigating several potential predictors of nonadherence among patients with mood disorders. A total of 217 relevant articles from peer-reviewed journals were considered, and articles that met our inclusion criteria (n = 54) were selected for this review. The authors identified several predictors of nonadherence among patients with mood disorders including younger age (below 40 years old), comorbidity with substance use and personality disorders, patients' beliefs, poor insight, illness severity, treatment-related side effects, specific features of the disease and a poor therapeutic alliance. Substance use disorder and illness severity are significant predictors of nonadherence especially in patients with bipolar disorder; whereas, treatment side effects are of primary importance for depressive disorder. The authors could not carry out a meta-analysis given that the studies considered in this review assessed patients at different time points and included different measurements of nonadherence. Moreover, articles cited in this review may reflect the authors' choice, and the authors did not investigate the adherence to a specific class of drugs commonly used in the management of mood disorders. Given the high social, clinical and economic impact of nonadherence among patients who are affected by mood disorders, it is critical to recognize patients at high risk of nonadherence in order to inform future strategies to examine and improve adherence to treatment. Further research is needed to clarify this issue.