Kürşat Altınbaş

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.

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.

A multinational study to pilot the modified Hypomania Checklist (mHCL) in the assessment of mixed depression.

BACKGROUND Mixed depression is a common, dimensional phenomenon that is increasingly recognized in unipolar and bipolar disorders. We piloted a modified version of the Hypomania Checklist (mHCL-32) to assess the prevalence and clinical correlates of concurrent manic (hypo) symptoms in depressed patients. METHODS The mHCL-32, Young Mania Rating Scale (YMRS) and Hamilton Rating Scale for Depression (HAMD-24) were utilized in the assessment of unipolar (UP=61) and bipolar (BP=44) patients with an index major depressive episode confirmed by the Structured Clinical Interview for DSM-IV (SCID). Differential mHLC-32 item endorsement was compared between UP and BP. Correlation analyses assessed the association of symptom dimensions measured by mHCL-32, YMRS and HAMD-24. RESULTS There was no significant difference between mood groups in the mean mHCL-32 and YMRS scores. Individual mHLC-32 items of increased libido, quarrels, and caffeine intake were endorsed more in BP vs. UP patients. The mHCL-32 active-elevated subscale score was positively correlated with the YMRS in BP patients and negatively correlated with HAMD-24 in UP patients. Conversely, the mHCL-32 irritable-risk taking subscale score was positively correlated with HAMD-24 in BP and with YMRS in UP patients. LIMITATIONS Small sample size and cross-sectional design. CONCLUSION Modifying the HCL to screen for (hypo) manic symptoms in major depression may have utility in identifying mixed symptoms in both bipolar vs. unipolar depression. Further research is encouraged to quantify mixed symptoms with standardized assessments.

Evaluation of affective temperament and anxiety-depression levels of patients with polycystic ovary syndrome.

BACKGROUND Women with polycystic ovary syndrome (PCOS) are reported to experience depressive episodes at a higher rate than healthy controls (HC). Affective temperament features are psychiatric markers that may help to predict and identify vulnerability to depression in women with PCOS. Our aim was to evaluate the affective temperaments of women with PCOS and to investigate the association with depression and anxiety levels and laboratory variables in comparison with HC. METHODS The study included 71 women with PCOS and 50 HC. Hormonal evaluations were performed for women with PCOS. Physical examination, clinical history, Hospital Anxiety and Depression Scale (HADS) and TEMPS-A were performed for all subjects. Differences between groups were evaluated using Students t-tests and Mann-Whitney U tests. Correlations and logistic regression tests were performed. RESULTS All temperament subtype scores, except hyperthymic, and HADS anxiety, depression, and total scores were significantly higher in patients with PCOS compared to HC. A statistically significant positive correlation was found between BMI and irritable temperament, and insulin and HADS depression scores in patients with PCOS. Additionally, hirsutism score and menstrual irregularity were correlated with HADS depression, anxiety and total scores in PCOS patients. In logistic regression analysis, depression was not affected by PCOS, hirsutism score or menstrual irregularity. However, HADS anxiety score was associated with hirsutism score. CONCLUSIONS Our study is the first to evaluate the affective temperament features of women with PCOS. Consequently, establishing affective temperament properties for women with PCOS may help clinicians predict those patients with PCOS who are at risk for depressive and anxiety disorders.

Temperament characteristics in patients with panic disorder and their first-degree relatives.

AIM Panic disorder is one of the highly heritable anxiety disorders; and temperament characteristics are considered predicting liability to panic disorder. Accumulating evidence suggests temperament characteristics are intermediate phenotypes for clinical conditions. Given this background, we aimed to investigate temperament characteristics in patients with panic disorder, their first-degree relatives, and healthy controls. METHOD Study sample consisted of 60 patients with panic disorder, 37 first-degree relatives of these patients, and 37 age, gender, and education level matched healthy controls (HC). SCID-I, the Panic Agoraphobia Scale, and the State and Trait Anxiety Inventory were applied to assess clinical characteristics of the patient group. Temperament characteristics were assessed using the Temperament Evaluation of Memphis, Pisa, Paris, San Diego Autoquestionnaire (TEMPS-A). RESULTS Anxious, depressive, cyclothymic, and irritable temperament scores of patients were higher than those of HC. There was no difference between the patients and the relatives, with the exception of higher anxious temperament scores in patients. CONCLUSION Overall, our findings suggest that anxious temperament characteristic might be a trait marker for liability to panic disorder. Further research with a prospective design in a larger sample is required to confirm our findings.

Electrocardiography changes in bipolar patients during long-term lithium monotherapy

OBJECTIVE Cardiovascular side effects of lithium have been reported to occur mainly at higher-than-therapeutic serum levels. We aimed to investigate the impact of the long-term lithium use on electrocardiogram (ECG) parameters in association with the serum levels in patients with bipolar disorder (BD) and in healthy controls (HCs) serving as the reference group. METHODS The study sample consisted of 53 euthymic BD type I patients on lithium monotherapy at therapeutic serum levels (M = 0.76, S.D. = 0.14, range = 0.41-1.09 mmol/l) for at least 12 months and 45 HCs. A 12-lead surface ECG was obtained from all participants at resting state for at least half an hour for 5-min recording. Heart-rate, Pmax, Pmin, QRS interval, QT dispersion, QT dispersion ratio (QTdR) and Tpeak-to-end interval (TpTe) were measured. RESULTS Regression analyses revealed that QTdR (B = 14.17, P = .001), TpTe (B = 18.38, P < .001), Pmax (B = 17.84, P<.001) and Pmin (B = 25.10, P < .001) were increased in BD patients who were on chronic lithium treatment than in HCs after controlling for age, sex and strict Bonferroni correction for multiple testing. There were no associations between serum lithium levels and ECG parameters. CONCLUSION Our findings suggest that the use of lithium is associated with both atrial and ventricular electrical instability, even when lithium levels are in the therapeutic range.

Minor hemoglobins HbA2 and HbF associate with disease severity in bipolar disorder with a likely protective role of HbA2 against post-partum episodes

BACKGROUND There exist studies indicating that bipolar disorder (BD) associates with changes in brain blood flow. Human brain with its high demand to oxygen constitutes 2% of the total body weight, while it receives 20% of cardiac output. α and β globin chains of hemoglobin were recently found in neural tissues, yet no study has questioned blood hemoglobins in BD. METHODS A total of 120 euthymic BD patients (40 males and 80 females) were analyzed via high performance liquid chromatography (HPLC) to measure minor hemoglobin levels, which were statistically compared with disease characteristics. RESULTS Minor hemoglobins HbA2 and HbF associated positively with episode density as a measure of disease severity in BD. An increased level of HbA2 meant significantly less postpartum episodes in child bearing women. HbF levels were higher in patients with a positive family history of any psychotic disorder. Sum of HbA2 and HbF correlated with episode density with a stronger significance (p<0.001) supporting intermittent hypoxia hypothesis in BD. LIMITATIONS The study was conducted only on euthymic patients to avoid likely bigger exogenous effects such as electro-convulsive therapy and diverse drug regimes, yet larger comparative studies are needed to support our current findings. CONCLUSIONS Higher HbA2 and HbF in more severe bipolar disorder may be compensations against intermittent hypoxias in BD. HbA2 increases following myocardial angina and in mountain dwellers, which may indicate protective roles in extreme conditions. HbF increase may act more as a maladaptation or emerge via haplotypal associations of BD genes and gamma-globin locus at 11p15.5.

Screening mixed depression and bipolarity in the postpartum period at a primary health care center

INTRODUCTION Mixed depression is a clinical condition accompanied by the symptoms of (hypo)mania and is considered to be a predictor for bipolar disorder. Compared to pure major depression, mixed depression is worse in progress. There are limited data on the prevalence of mixed depression since it is a relatively new entity. Therefore, the present study aimed to investigate the prevalence of mixed depression during the postpartum period which is risky for mood disorders. METHODS The study included 63 postpartum women. The participants were administered Beck Depression Scale, Edinburgh Postnatal Depression Scale (EPDS), Mood Disorders Questionnaire (MDQ), and Modified Hypomania Symptom Checklist-32 (mHCL-32). RESULTS The MDQ scores of the women with expected depression according to the EPDS cut-off scores, were significantly higher than the women with lower EPDS scores (t=-4.968; p<0.001). The modified hypomania scores were significantly higher in the women with higher depression scores compared to the women under EPDS cut-off scores (t=-4.713; p<0.001). According to the EPDS and BDS results, 27 (42.9%) and 14 (22.2%) women needed additional clinical examination for depression, respectively. In addition, 3 (4.8%) women require additional clinical examination for bipolar disorder. The scores for the first item of MDQ were above the cut-off value in 11 (17.5%) women. According to the mHCL-32 results, 50 (79.4%) women had at least 1 symptom, 45 (71.4%) women had at least 3 symptoms, and 43 (68.3%) women had at least 5 symptoms of mixed depression. CONCLUSION Postpartum mixed depression should be promptly diagnosed by using appropriate diagnostic tools, particularly by primary health care physicians. Patients with mixed depression should be closely monitored to avoid manic switch.

Evaluation of Serum Ghrelin and Leptin Levels in Suicide Attempters

Previous studies have reported a relationship between cholesterol and leptin levels, and suicide attempts, impulsivity, and aggressive behaviors. An orexigenic hormone seems to be strongly associated with lipid metabolism and leptin levels. Therefore, we aimed to compare serum cholesterol, leptin, and ghrelin levels in 36 patients with suicide attempts and 25 healthy controls. Patients with suicide attempts had decreased leptin levels and significantly higher ghrelin levels compared to healthy controls. While the serum ghrelin level did not show any correlation with the demographic and clinical factors, leptin showed a correlation with body mass index (BMI), and cholesterol levels were correlated with the age, BMI, and number of suicide attempts in the suicidal group. The results suggest that suicide attempts seem to be related with higher serum ghrelin values, decreased leptin, and cholesterol levels.