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.

Nightmares and suicide risk in psychiatric patients: The roles of hopelessness and male depressive symptoms.

Although nightmares have been shown to increase the risk for suicide, less is known about the mechanisms underlying this relationship. In order to address this gap and guided by the hopelessness theory of suicide risk, we examined hopelessness and male depressive symptoms as risk factors for suicide while considering the frequency of and impairment due to nightmares. Data were collected from 172 psychiatrically hospitalized, adult patients (91 women, 81 men) with an average age of 39.15 (SD = 13.48) years. Patients were administered self-report measures of nightmare frequency/impairment, hopelessness, and male depressive symptoms, as well as undergoing a fully structured diagnostic clinical interview to determine diagnoses and suicide risk. Compared to patients with yearly or no nightmares, those with monthly or weekly nightmares reported nightmares reported higher levels of hopelessness, male depressive symptoms, and suicide risk. Male depressive symptoms significantly mediated the relation between hopelessness and suicide risk in patients who reported monthly to weekly nightmares, but not in those who reported yearly or no nightmares. Moreover, impairment due to nightmares was significantly and positively associated with male depression, but not hopelessness or suicide risk. The results also provide evidence and further understanding about possible mechanisms of emerging suicide.

Genetic association analysis of serotonin and signal transduction pathways in suicide attempters from an Italian sample of psychiatric patients.

Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments. Genomic DNA was isolated from peripheral white blood cell samples and polymorphisms were genotyped by pyrosequencing technology. Although no differences were observed between allele and genotype frequencies for all polymorphisms and suicide attempt (SA), a polygenic risk score was detected for three genes HTR2A (A-1438G), TPH1 and TPH2 increasing the prediction of SA risk (Thresh=0.43, p=0.038, R2=0.053). Moreover some nominal associations were obtained after gender and phenotypic dissection stratification (TEMPS-A, TEMPs-H, GSMD, SHSS, GAF, CGI) for SLC6A4 (5-HTTLPR), HTR1A (C-1019G), HTR2A (A-1438G), TPH1 (A799C) and GNB3 (C825T) genes, that were lost after Bonferroni correction. This is a first evidence that specific additive combinations of genes could increase the prediction of SA risk and that gender and phenotypic dissection could influence the association of the genes with SA. This could represent a further study also for future meta-analyses on larger samples.

Development of Hiccup in Male Patients Hospitalized in a Psychiatric Ward: Is it Specifically Related to the Aripiprazole-Benzodiazepine Combination?

OBJECTIVES: The aim of this study was to identify hiccup cases among patients hospitalized in a psychiatric ward and focus on their treatment, so to establish intervention risk. METHODS: We reviewed records of 354 consecutively admitted patients during the year 2013 to identify hiccup cases. RESULTS: Hiccup occurred in 7 patients on both aripiprazole and benzodiazepines and in one on delorazepam. No patient on aripiprazole alone developed hiccup. No patient on drugs other than aripiprazole or benzodiazepines developed hiccup. The symptom subsided in 3 cases upon discontinuing aripiprazole and in 5 cases after discontinuing the benzodiazepine (including the case on delorazepam alone); in 2 cases of persistent hiccup, the symptom resolved after adding the calcium channel blocker, pregabalin. All patients developing hiccup were male. There was a 70-fold increase in the risk for developing hiccup in the aripiprazole/benzodiazepine intake condition versus all other conditions, and it further increased if limiting to the male sex. LIMITATIONS: The retrospective nature of the study was its limitation. CONCLUSIONS: Hospitalized psychiatric patients on both aripiprazole and benzodiazepines may be at significant risk of hiccup. This clinical awareness could lead to antipsychotic and/or benzodiazepine discontinuation or switch or to the addition of calcium channel blocker inhibitors.

Associations among depression, suicidal behavior, and quality of life in patients with human immunodeficiency virus.

AIM: To investigate the potential associations among major depression, quality of life, and suicidal behavior in human immunodeficiency virus (HIV) patients. METHODS: A detailed MEDLINE search was carried out to identify all articles and book chapters in English published from January 1995 to January 2015. RESULTS: Based on the main findings, the prevalence of major depressive disorder (MDD) ranged from 14.0% to 27.2%. Furthermore, the prevalence of suicidal ideation varied from 13.6% to 31.0% whereas, attempted suicides were reported to range from 3.9% to 32.7%. Interestingly, various associated risk factors for both depression and suicide were identified in HIV patients. Finally, consistent associations were reported among MDD, suicidal ideation, and poor quality of life in individuals living with HIV. CONCLUSION: Although additional studies are needed to elucidate this complex association, our results suggest the importance of early detection of both MDD and suicidality in patients living with HIV.

Factors associated with hopelessness in epileptic patients.

AIM: To investigate factors related to hopelessness in a sample of epileptic patients, including measures of depression and quality of life (QOL). METHODS: Sixty-nine participants were administered the following psychometric instruments: Beck Depression Inventory-II, Beck Hopelessness Scale (BHS), and QOL in Epilepsy (QOLIE)-89. Patients were dichotomized into two categories: those affected by epilepsy with generalized tonic-clonic seizures vs those having epilepsy with partial seizures. RESULTS: The groups differed on the QOLIE Role Limitation/Emotional dimension. Patients with generalized seizures reported more limitations in common social/role activities related to emotional problems than patients with other types of epilepsy (89.57 ± 25.49 vs 72.86 ± 36.38; t 63 = -2.16; P < 0.05). All of the respondents reported moderate to severe depression, and 21.7% of patients with generalized seizures and 28.6% of patients with other diagnoses had BHS total scores ≥ 9 indicating a higher suicidal risk. The study did not control for years of the illness. CONCLUSION: Patients with generalized seizures reported more limitations in common social/role activities related to emotional problems compared to patients with other types of seizures. Patients at increased suicide risk as evaluated by the BHS were older than those who had a lower suicidal risk. Future studies are required to further investigate the impact of hopelessness on the outcome of epileptic patients.

Suicide risk in dialysis: review of current literature.

BACKGROUND: Studies have shown that patients with end-stage kidney disease (ESKD) are at risk of experiencing suicidal ideation and suicide attempt. STUDY DESIGN: The aim of the present review was to investigate whether there was a relationship between dialysis and suicide. A careful systematic review of the literature was conducted to determine the potential association between dialysis and suicide. SELECTION CRITERIA FOR STUDIES: Abstracts that did not explicitly mention suicide and dialysis were excluded. We identified as specific fields of interest in the analysis of dialysis or ESRD and suicidal behavior. RESULTS: A total of 26 articles from peer-reviewed journals were considered and the most relevant articles (N = 13) were selected for this review. OUTCOMES: It has been posited that suicidal ideation, occurring in dialysis, may arise from co-morbid depression and psychiatric symptoms are frequent in patients who underwent dialysis. LIMITATIONS: The present review should be considered in the light of some limitations. We did not carry out a meta-analysis because data from most of the studies did not permit it. Samples included different measurements and different outcomes, and they assessed patients at different time points. CONCLUSIONS: The available data suggest that the risk of self-harm may be higher than expected in dialysis patients especially in those who suffer by depression and anxiety. Moreover, although the majority of deaths among dialysis patients is preceded by withdrawal from treatment, suicide remains a separate phenomenon.

Do stroke patients have an increased risk of developing suicidal ideation or dying by suicide? An overview of the current literature.

Stroke is a leading cause of death that affects 15 million people worldwide each year. Increasing evidence suggests that stroke confers substantial risk for suicide and following a stroke, patients frequently develop poststroke depression, which is a well-established risk factor for suicide. In this overview of the current literature, we examined the association between suffering a stroke and subsequent risk for suicide and suicidal ideation. We performed a careful MedLine, Excerpta Medica, PsycLit, PsycInfo, and Index Medicus search to identify all articles and book chapters in English. We initially selected 31 articles published between 1990 and 2011; however, only 16 studies were included in this review. All articles identified stroke as a significant risk factor for suicide, especially among depressed patients, providing further support for poststroke depression and suicidality. The results also indicated that there were differences between patients who developed acute-onset suicidal plans and those who reported delayed-onset plans, which occurred more frequently. Many of the stroke patients who died by suicide suffered from depression prior to their death, suggesting that being diagnosed with a mood disorder contributes to an increased risk of suicide in this population. Suffering from a stroke increases the risk of dying by suicide and developing suicidal ideation, particularly in young adults and women. The factors found to confer the most risk for suicidality were depression, previous mood disorder, prior history of stroke, and cognitive impairment.

Prolactin and thyroid hormone levels are associated with suicide attempts in psychiatric patients.

The aim of this study is to evaluate biological factors associated with recent suicidal attempts in a naturalistic sample. A total of 439 patients suffering from major depression disorder (MDD), bipolar disorder (BD) and psychotic disorders (schizophrenia, schizoaffective disorder and psychosis not otherwise specified), who were consecutively assessed in the Emergency Department of an Italian Hospital (January 2008-December 2009), were included. In the whole sample, suicide attempters and non-attempters differed with regard to free triiodothyronine (FT3) and prolactin values only. A univariate general linear model indicated significant effects of sex (F(1;379)=9.29; P=0.002), suicidal status (F(1;379)=4.49; P=0.04) and the interaction between sex and suicidal status (F(1;379)=5.17; P=0.02) on prolactin levels. A multinomial logistic regression model indicated that suicidal attempters were 2.27 times (odds ratio (OR)=0.44; 95% confidence interval (95%CI): 0.23/0.82; P=0.01) less likely to have higher FT3 values than non-attempters; while prolactin values failed to reach statistical significance (OR=0.99; 95%CI: 0.98/1.00; P=0.051). Both prolactin and thyroid hormones may be involved in a complex compensatory mechanism to correct reduced central serotonin activity. Further studies may help in understanding how these findings can be used by clinicians in assessing suicide risk.

Suicidal behavior in bipolar disorder: epidemiology, characteristics and major risk factors.

BACKGROUND: Suicide is one of the leading causes of death and a major public health problem worldwide, and the majority of suicide attempters and completers suffer from some major affective disorder at the time of their death, which, in the majority of cases is unrecognized, under- or misdiagnosed and untreated. METHODS: Based on a systematic literature search, the authors give a detailed and critical overview of established risk factors of suicide in bipolar disorder. RESULTS: Among affective disorders, bipolar disorder carries the highest risk of suicide, yet not all bipolar patients commit or even attempt suicide during their illness. While the general suicide risk factors also apply for bipolar disorders, there are several disease-specific risk factors as well which should be taken into account when evaluating suicide risk in case of patients. CONCLUSION: It is crucial to identify suicide risk factors in bipolar disorder to be able to differentiate those patients within this already increased-risk illness group who are at especially high risk and therefore to allow for better prediction and prevention of suicidal acts.

Car accidents as a method of suicide: a comprehensive overview.

The research literature provides evidence on the possible link between single-car accident drivers and suicidal intent, and some scholars have stressed the role of unconscious suicidal motivations in some single-car accidents. This paper review relevant literature on the topic and sheds light on neglected factors that may play a central role in reducing the number of deaths due to car accidents. We performed careful PubMed, and PsycInfo searches to identify all papers and book chapters in English during the period 1955-2011. Our overview of the literature indicates that above 2% of the traffic accidents are suicide behaviors. However, the phenomenon may be underreported, considering that suicides by car accidents may be reported as accidental in the national statistics. On the other hand, the association between accident-pronesses and unconscious self-destructive impulses is an issue that is difficult to solve.

How does subjective experience of pain relate to psychopathology among psychiatric patients?

OBJECTIVE: The study aimed to investigate to what extent general psychopathology is associated with subjective experience of pain in psychiatric outpatients without comorbidity with severe physical diagnosis and whether there are any differences in the experience of pain between genders or diagnoses. METHOD: Participants were 575 consecutive outpatients affected by mood disorder or anxiety disorder. Patients completed the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) and the Symptom Checklist 90-Revised. RESULTS: Women had higher mean scores on the Global Severity Index (1.52±0.76 vs. 1.33±0.79), higher perception of negative responses from others (1.84±1.59 vs. 1.46±1.35) and higher perception of pain severity (3.31±1.73 vs. 2.88±1.63) than men. They also reported higher mean scores on the WHYMPI's General Activity (2.14±0.98 vs. 1.93±0.95) and Household Chores (3.64±1.75 vs. 2.27±1.58) and lower mean scores on the Outdoor Work (1.24±1.26 vs. 1.87±1.51) dimension than men. Higher pain severity, more negative responses from others and higher household chores are predictors of higher psychopathology, while the general level of activity may be considered as a protective factor. CONCLUSIONS: Pain and its subjective experience play a central role in psychiatric disorders, and it is a great burden for patients and caregivers. Clinicians should pay more attention to recognize and adequately treat painful symptoms in patients with anxiety and depressive disorder.

The role of microRNAs in synaptic plasticity, major affective disorders and suicidal behavior.

Major affective disorders are common widespread conditions associated with multiple psychosocial impairments and suicidal risk in the general population. At least 3-4% of all depressive individuals die by suicide. At a molecular level, affective disorders and suicidal behavior are recently associated with disturbances in structural and synaptic plasticity. A recent hypothesis suggested that small non-coding RNAs (ncRNAs), in particular microRNAs (miRNAs), play a critical role in the translational regulation at the synapse. We performed a selective overview of the current literature on miRNAs putative subcellular localization and sites of action in mature neurons analyzing their role in neurogenesis, synaptic plasticity, pathological stress changes, major affective disorders and suicidal behavior. miRNAs have played a fundamental role in the evolution of brain functions. The perturbation of some intracellular mechanisms as well as impaired assembly, localization, and translational regulation of specific RNA binding proteins may affect learning and memory, presumably contributing to the pathogenesis of major affective disorders and perhaps suicidal behavior. Also, miRNA dys-regulation has also been linked to several neuropsychiatric diseases. However, further evidence are needed in order to directly clarify the role of miRNAs in major affective disorders and suicidal behavior.