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.

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.

Tc-99m HMPAO brain perfusion SPECT in drug-free obsessive-compulsive patients without depression.

The aim of this study was to confirm prior results of brain-imaging studies on obsessive-compulsive disorder (OCD) in a sample of Turkish patients, as a cross-cultural study. Tc-99m HMPAO brain perfusion SPECT imaging was performed in nine drug-free OCD patients without depression and six controls. The patients' Hamilton Depression Rating Scale scores were <16. The severity of obsessive-compulsive symptoms was rated with the Yale-Brown Obsessive-Compulsive Rating Scale (YBOCS). Quantitative evaluation of regional cerebral blood flow revealed that right thalamus, left frontotemporal cortex and bilateral orbitofrontal cortex showed significant hyperperfusion in patients with OCD compared with controls. YBOCS scores did not show any correlation with hyperperfusion in regional cerebral blood flow in these areas. Results of this cross-cultural study may support orbitofrontal and thalamic dysfunction in OCD in a sample of Turkish patients.

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.