E. Timuçin Oral

Cytokine levels in euthymic bipolar patients

BACKGROUND The pathophysiology of bipolar disorder is not thoroughly understood. Several studies have investigated the possible role of cytokines in psychiatric disorders, based on their role in neuro-immune modulation; however, findings in studies on bipolar disorder remain limited and contradictory, and most studies have focused on either manic or depressive episodes. These studies suggest that both manic and depressive episodes could be pro-inflammatory states. The present study aimed to determine whether there are enduring differences in cytokine levels-unrelated to the effects of medication-between euthymic bipolar patients and healthy controls. METHODS The study included 31 euthymic bipolar patients-16 medication-free (MF) and 15 on lithium monotherapy (LM) and 16 healthy volunteers in whom serum cytokine levels were measured. The 3 groups were homogenous in terms of age, gender, and ethnicity. IFN-γ, TNF-α, IL-2, IL-4, IL-5, and IL-10 levels were measured in all groups using flow cytometry. RESULTS There were no differences in cytokine levels between MF euthymic bipolar patients and healthy controls. TNF-α and IL-4 levels in LM euthymic bipolar patients were higher than in both the MF euthymic bipolar patients and controls. LIMITATIONS The small and strictly selected study sample could limit the generalizability of the findings. CONCLUSIONS Cytokine production in MF euthymic bipolar patients was similar to that in healthy controls. The present study shows that the pro-inflammatory state resolves in euthymia and that lithium had an influence on the cytokine profile, which could create a confounding factor while investigating disease- related immunopathology of bipolar disorder.

Evidence for an association between tumor necrosis factor-alpha levels and lithium response

BACKGROUND The role of inflammation in bipolar disorder has recently emerged as a potential pathophysiological mechanism. Tumor necrosis factor-alpha (TNF-α) modulation may represent a pathogenic molecular target and a biomarker for staging bipolar disorder. In this context, the possible association between lithium response and TNF-α level was examined. METHODS Sixty euthymic bipolar patients receiving lithium therapy were recruited for assessment of TNF-α level. The ALDA lithium response scale (LRS) was used to evaluate longitudinal lithium response in bipolar patients, using cut-offs of poor response, partial response and good response. TNF-α level was assessed using enzyme-linked immunosorbent assay. RESULTS There was a significant increase in TNF-α level in patients with poor lithium response compared to those with good response, also after controlling for a range of potential confounders (adjusted effect size: 0.47, p=0.011). Partial response showed a directionally similar, but attenuated and statistically inconclusive association (adjusted effect size: 0.16, p=0.326). LIMITATIONS Assessment of response was retrospective and natural course cannot be separated easily from treatment response in an observational design. Selection of additional inflammatory markers could provide for a better understanding of underlying immune changes. CONCLUSIONS This study strengthens the hypothesis that TNF-α level may mark or mediate lithium response, and that continuous immune imbalance in poor lithium responders may occasion treatment resistance. Further investigation of immune alterations in treatment-resistant bipolar patients may be productive.

Plasma concentrations of soluble cytokine receptors in euthymic bipolar patients with and without subsyndromal symptoms

BackgroundCurrent evidence suggests that high concentrations of pro-inflammatory markers are associated with bipolar disorder characterized by severe impairment during inter-episodic periods, reduced treatment response and persistent subsyndromal symptoms. We tested whether persistent subsyndromal symptoms in euthymic bipolar patients were associated with markers of an ongoing chronic pro-inflammatory process.MethodsForty-five euthymic bipolar patients (22 with subsyndromal symptoms (BD+) and 23 without subsyndromal symptoms (BD-) and 23 well controls (WC) were recruited for assessment of soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin-6 receptor (sIL-6R) and soluble interleukin-2 receptor (sIL-2R) concentrations. Soluble cytokine receptor concentrations were assessed using enzyme-linked immunosorbent assay.ResultsIn comparison to WC, sTNF-R1 concentration was higher in both BD- and BD+ (age and sex adjusted standardized β, respectively: β = 0.34, p = 0.012 and β = 0.41, p = 0.003). Similarly, compared to WC, sIL-6R concentration was higher in both BD- and BD+ (age and sex adjusted standardized β, respectively: β = 0.44, p = 0.001 and β = 0.37, p = 0.008). There was no difference between BD- and BD+ in the concentration of either sTNF-R1 or sIL-6R; plasma concentration of sIL-2R was not analyzed as 75% percent of the samples were non-detectable.ConclusionsAlthough bipolar patients present with a pro-inflammatory shift compared to well controls, subsyndromal symptoms are not associated with additive increasing effects. Longitudinal studies with larger samples are required to clarify the relationship between illness course and inflammatory markers in bipolar disorder.

Metabolic syndrome prevalence in different affective temperament profiles in bipolar-I disorder

OBJECTIVE Temperament originates in the brain structure, and individual differences are attributable to neural and physiological function differences. It has been suggested that temperament is associated with metabolic syndrome (MetS) markers, which may be partly mediated by lifestyle and socioeconomic status. Therefore, we aim to compare MetS prevalence between different affective temperamental profiles for each season in bipolar patients. METHODS Twenty-six bipolar type-I patients of a specialized outpatient mood disorder unit were evaluated for MetS according to new definition proposed by the International Diabetes Federation in the four seasons of a year. Temperament was assessed using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego - autoquestionnaire version (TEMPS-A). RESULTS The proportions of MetS were 19.2, 23.1, 34.6, and 38.5% in the summer, fall, spring, and winter, respectively. Only depressive temperament scores were higher (p = 0.002) during the winter in patients with MetS. CONCLUSION These data suggest that depressive temperament profiles may predispose an individual to the development of MetS in the winter.

A survey of verbal and physical assaults towards psychiatrists in Turkey

Background: Assaults on health professionals have been an area of burgeoning clinical and political interest in recent years. There is now a body of literature suggesting that violence towards psychiatrists is more common than to other doctors. Thus far the vast majority of research in this area has been conducted in Western European and North American clinical settings. For the first time, this study examines this issue in the context of Turkish psychiatric settings. Objective: (i) The study aims to detect the prevalence of verbal and physical assaults towards psychiatrists in Turkey. (ii) It aims to compare the experience of verbal and physical assaults according to the gender and training experience of psychiatrists. (iii) The paper intends to investigate how psychiatrists reacted to and appraised the experience of violence. Methods: A questionnaire was prepared to evaluate violence towards psychiatrists (adapted from the Overt Agression Scale). The questionaire was administered to psychiatric specialists and residents working in state hospitals, research and training hospitals, mental health hospitals and university psychiatry clinics. A response rate of 93% was achieved with 186 out of 200 psychiatrsits approached completing the study questionnaire. Results: Of all the psychiatrists who responded, 71% reported having experienced verbal or physical assaults during their professional life (verbal assaults only (19.9%), physical assaults only (2.7%) and both (48.4%)). Of these, 26% suffered injury to at least a mild degree. There was no statistically significant difference in terms of gender and workplace. In spite of the extremely high rates of aggression and violence towards psychiatrists, roughly 50% perceived these acts a normal part of their job and only 5% formally reported the violent incident. Conclusion: The majority of psychiatrists described having been victims of verbal and physical assaults although half perceived aggression and violence as a normal part of their job. Levels of reporting of violence were very low in the context of this study. Studies such as this provide evidence to inform the development of improved management of violence and may encourage psychiatrists to report violence.

Uzmanlaşmış bir merkezde izlem iki uçlu depresyon belirti sayısını ve şiddetini etkiler mi

Does follow-up in a specialized center influence symptom profile and severity of bipolar depression? Introduction: Despite bipolar patients spend up to one third of their lives in depression, the treatment of bipolar depression remains as an understudied area. Although more atypical depressive symptoms are expected to be seen in bipolar depression, ethnocultural differences and regular follow-ups can change the onset and expression of clinical symptoms. Thus, in the present study, we aimed to evaluate the symptoms of depressive bipolar patients who are followed up in a specialized mood disorder unit. Methods: The most severe depressive symptoms of 144 bipolar patients were followed up using standardized forms in a specialized mood disorder outpatient unit. Obtained data analyzed by descriptive statistics. Results: It was determined that less than 10% of depressive symptoms were severe. Feelings of guilt and low self-esteem were not detected in nearly half of the patients (45,8%); active (3,5%) or passive (15,3%) suicidal ideation was seen approximately in one-fifth of the patients. The rate of psychotic symptoms was considerably low (4,2%). Beside this, vegetative symptoms other than loss of energy and lack of concentration were not seen in more than half of the patients. Adding a mood stabilizer or titrating the levels and psychotherapeutic interventions were adequate for remission in one-third of the patients. Discussion: Although previously it was reported bipolar depressive symptoms were severe with higher suicide rates, in less than 10% of patients, depressive symptoms were severe and the rate of active suicidal ideation was 3,5% in our study. Moreover, the rate of psychotic symptoms was found 4,2%. Although occurrence of milder symptoms contradicts with the literature, this can be explained by the follow-up of the patients in a specialized unit and early intervention before symptoms get more severe. Decreased need for pharmacological intervention can also be explained by the same reason.