Zeliha Tunca

Disturbance in long distance gamma coherence in bipolar disorder

The aim of this study was to investigate long distance event-related gamma (28-48 Hz) coherence in mania before and after valproate monotherapy. Gamma coherence in response to visual oddball paradigm in ten medication-free, manic patients was studied before and after six weeks of valproate monotherapy in comparison to ten controls. Inter-hemispheric F(3)-F(4), C(3)-C(4), T(3)-T(4), T(5)-T(6), P(3)-P(4), O(1)-O(2) and intra-hemispheric F(3)-P(3), F(4)-P(4), F(3)-T(5), F(4)-T(6), F(3)-O(1), F(4)-O(2), C(3)-O(1), C(2)-O(4) electrode pairs were included in the analysis. Repeated measures ANOVA revealed a significant difference between groups with regard to pre-treatment coherence values (p: 0.018). The coherence to the target stimuli at the right fronto-temporal location was significantly reduced by 35.41% in the patients compared to controls (p: 0.003). Patients showed significantly lower pre-treatment coherence values in response to non-target stimuli compared to controls at the right fronto-temporal (28.51%, p: 0.004), right fronto-occipital (23.71%, p: 0.024), and right centro-occipital (25.69%, p: 0.029) locations. After six weeks of valproate monotherapy, manic symptoms improved significantly. Post-treatment change in target and non-target coherence values was statistically non-significant. EEG coherence is a measure of functional connectivity in the brain. Event-related gamma oscillations are essential for brain electrical activity. The results show that acute mania presents right sided long distance connectivity disturbance, thus pointing to the potential importance of measuring oscillatory responses in the search for consistent neurobiological markers in such a complicated condition as bipolar disorder.

Brain oscillatory responses in patients with bipolar disorder manic episode before and after valproate treatment.

BACKGROUND GABA/Glutamatergic dysfunction and neural circuits which regulate cognitive processing are involved in the underlying pathology of bipolar disorder. Event related oscillatory neuroelectrical activity reflects integrative brain functioning, different frequency bands representing different cognitive functions. METHODS Event Related Potentials to visual odd-ball paradigm in ten manic/hypomanic medication free, DSM-IV bipolar patients were measured before and after six weeks of valproate monotherapy in comparison to ten sex and age matched healthy controls. Different frequency band responses were obtained by digital filtration of ERPs. Young mania rating scale (YMRS) was used to assess clinical response. Repeated measures ANOVA, Wilcoxon and Mann Whitney U tests were used for statistical analysis. RESULTS Patients showed significantly higher baseline occipital beta (18-30 Hz) (p: 0.014) response than healthy controls. They were devoid of the occipito-frontal alpha (8-13 Hz) dominance presented by the control group. Occipital beta response reduced significantly (p: 0.009) and became similar to controls after treatment. Post-treatment alpha responses were significantly lower than baseline in anterior temporal (p: 0.038) and occipital (p: 0.027) locations. Healthy controls displayed a significantly increased frontal alpha response at the second assessment but the patients did not. Mean YMRS score reduced significantly compared to baseline at the end of six weeks (p: 0.004). CONCLUSIONS Alpha response is the universal operator in the brain. Increased occipital beta response in mania may be compensatory to the dysfunctional alpha operation. Its reduction after valproate may be through modulation of glutamatergic and GABAergic mechanisms and indicate medications corrective effect on the underlying pathogenesis.

Diverse glial cell line-derived neurotrophic factor (GDNF) support between mania and schizophrenia: A comparative study in four major psychiatric disorders

BACKGROUND Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) have essential roles in synaptic plasticity which is involved in pathogenesis and treatment of psychiatric disorders. However, it is not clear whether they act simultaneously during illness states in major psychiatric disorders. METHODS BDNF and GDNF serum levels were measured concomitantly by enzyme-linked immunosorbent assay (ELISA) method in 171 patients diagnosed with schizophrenia (n=33), bipolar disorder-manic episode (n=39), bipolar/unipolar depression (n=64, 24/40) and obsessive-compulsive disorder (n=35) according to DSM-IV, and 78 healthy volunteers. SCID-I and SCID non-patient version were used for clinical evaluation of the patients and healthy volunteers, respectively. Correlations between the two trophic factor levels, and illness severity scores, duration of illness and medication dosages were studied across different illnesses. RESULTS While patients had equally lower BDNF levels in all diagnoses, GDNF levels were significantly higher in mania and lower in schizophrenia compared to healthy controls. BDNF levels were negatively correlated to illness severity scores in affective episodes (mania and depression). Longer duration of illness (>5 years) had an impact on lower GDNF levels in schizophrenia. BDNF levels and antipsychotic drug dosages in schizophrenia, and GDNF levels and antidepressant drug dosages in obsessive-compulsive disorder were positively correlated. CONCLUSION Our data confirmed the evidence of equally deficient neuronal support by BDNF in all major psychiatric illnesses, but suggested a diverse glial functioning between schizophrenia and mania.

Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium

OBJECTIVE Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear. METHOD BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness. RESULTS Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia. LIMITATIONS Small sample size in different episodes and drug-free patients was the limitation of thestudy. CONCLUSION Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia.

Reliability and validity of revised Turkish version of Mini Mental State Examination (rMMSE-T) in community-dwelling educated and uneducated elderly

To evaluate the reliability and validity of the revised Turkish version of Mini Mental State Examination (rMMSE‐T) in educated and uneducated community‐dwelling elderly, to re‐organize the present Turkish version of MMSE and to determine cut‐off point of the revised test.

Prevalence and risk factors of depression among community dwelling elderly

Depression in the elderly is associated with increased morbidity and mortality. The purpose of this study was to determine the prevalence and risk factors of depression among community-dwelling older population in an urban setting in Turkey. This cross-sectional study was conducted among 482 elderly individuals 65 years and over in an urban area. Cluster sampling method was used for sample size. Depression in the elderly had been diagnosed by a clinical interview and Geriatric Depression Scale. Data were collected by door-to-door survey. Chi square test was used for statistical analysis. P value, which was calculated by the results of chi square test and coefficient of phi (φ), below 0.05 was included in the analysis of logistic regression. Depression was significantly associated with female gender, being single or divorced, lower educational status, low income, unemployment, and lack of health insurance. However, logistic regression analysis revealed higher depression rates in the elderly with chronic obstructive pulmonary disease, psychiatric disease, cerebrovascular disease, low income and being dependent. Depression is common among community-dwelling older people in an urban area of Izmir, Turkey. Older adults living in community should be cautiously screened to prevent or manage depression.

Female vulnerability for thyroid function abnormality in bipolar disorder: role of lithium treatment.

Previous studies have provided evidence of subtle thyroid hormone metabolism abnormalities in patients with mood disorders. Although these studies are informative, the precise role of the hypothalamic‐pituitary‐thyroid axis in bipolar disorder, especially in women, remains unclear. We sought to further corroborate thyroid function in patients with bipolar disorder in comparison to patients with other psychiatric, as well as non‐psychiatric, diagnoses.

The relatively good prognosis of bipolar disorders in a Turkish bipolar clinic

BACKGROUND Bipolar affective disorder is considered to be a disabling illness with a relapsing and remitting course resulting in enduring psychosocial consequences. In this study, we aimed to determine the demographic and clinical characteristics of patients with bipolar illness, types of treatment at inpatient and outpatient settings and their outcome. METHOD Life charts of 61 bipolar outpatients and hospital charts of 47 manic inpatients were retrospectively evaluated regarding the demographics, course of illness and the treatment at both settings. RESULTS 82.5% of the outpatients were euthymic and 42.5% were on lithium monotherapy at the time of investigation. Psychosocial adjustment was good. High level of education and marital status affected compliance positively. In the outpatient group, 24.2% were bipolar 2 (BP-II): they differed from bipolar 1 (BP-I) patients in having a higher number of lifetime episodes. Females outnumbered males in both settings, 11 had suffered higher numbers of previous episodes, as well as longer stays in hospital. Lithium was the most commonly used agent in acute mania (78.7%); 89.4% of the inpatients received combination treatment, mainly a mood stabilizer with a neuroleptic. Adjunctive neuroleptics decreased from 82.4 to 56.7% after 1995: This resulted in longer lengths of stay in hospital. LIMITATIONS Data were collected naturalistically in a non-blind fashion. CONCLUSION Lithium is still the leading mood stabilizer of choice for the acute and maintenance phases of bipolar disorder in our patient population. We submit that family support, high levels of education as well as an in-depth follow-up represented the contributory factors in the good overall outcome.

Abnormal white matter integrity as a structural endophenotype for bipolar disorder

BACKGROUND Several lines of evidence suggest that bipolar disorder (BD) is associated with white matter (WM) pathology. Investigation of unaffected first-degree relatives of BD patients may help to distinguish structural biomarkers of genetic risk without the confounding effects of burden of illness, medication or clinical state. In the present study, we applied tract-based spatial statistics to study WM changes in patients with BD, unaffected siblings and controls. METHOD A total of 27 euthymic patients with BD type I, 20 unaffected siblings of bipolar patients and 29 healthy controls who did not have any current or past diagnosis of Axis I psychiatric disorders were enrolled in the study. RESULTS Fractional anisotropy (FA) was significantly lower in BD patients than in the control group in the corpus callosum, fornix, bilateral superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, anterior thalamic radiation, posterior thalamic radiation, cingulum, uncinate fasciculus, superior corona radiata, anterior corona radiata and left external capsule. In region-of-interest (ROI) analyses, we found that both unaffected siblings and bipolar patients had significantly reduced FA in the left posterior thalamic radiation, the left sagittal stratum, and the fornix compared with healthy controls. Average FA for unaffected siblings was intermediate between the healthy controls and bipolar patients within these ROIs. CONCLUSIONS Decreased FA in the fornix, left posterior thalamic radiation and left sagittal stratum in both bipolar patients and unaffected siblings may represent a potential structural endophenotype or a trait-based marker for BD.

Neuroanatomical correlates of genetic risk for bipolar disorder: A voxel-based morphometry study in bipolar type I patients and healthy first degree relatives.

BACKGROUND Bipolar disorder (BD) is a highly heritable mental illness which is associated with neuroanatomical abnormalities. Investigating healthy individuals at high genetic risk for bipolar disorder may help to identify neuroanatomical markers of risk and resilience without the confounding effects of burden of illness or medication. METHODS Structural magnetic resonance imaging scans were acquired from 30 euthymic patients with BD-I (BP), 28 healthy first degree relatives of BD-I patients (HR), and 30 healthy controls (HC). Data was analyzed using DARTEL for voxel based morphometry in SPM8. RESULTS Whole-brain analysis revealed a significant main effect of group in the gray matter volume in bilateral inferior frontal gyrus, left parahippocampal gyrus, left lingual gyrus and cerebellum, posterior cingulate gyrus, and supramarginal gyrus (alphasim corrected (≤0.05 FWE)). Post-hoc t-tests showed that inferior frontal gyrus volumes were bilaterally larger both in BP and HR than in HC. BP and HR also had smaller cerebellar volume compared with HC. In addition, BP had smaller left lingual gyrus volume, whereas HR had larger left parahippocampal and supramarginal gyrus volume compared with HC. LIMITATIONS This study was cross-sectional and the sample size was not large. All bipolar patients were on medication, therefore we were not able to exclude medication effects in bipolar group in this study. CONCLUSIONS Our findings suggest that increased inferior frontal gyrus and decreased cerebellar volumes might be associated with genetic predisposition for bipolar disorder. Longitudinal studies are needed to better understand the predictive and prognostic value of structural changes in these regions.