Ceren Hıdıroğlu

Executive dysfunction and cognitive subgroups in a large sample of euthymic patients with bipolar disorder

Bipolar disorder (BP), at the group level, is associated with significant but modest cognitive deficits, including executive dysfunction. Among executive functions, response inhibition deficits have been suggested to be particularly relevant to BP. However, BP is associated with significant heterogeneity in neurocognitive performance and level of functioning. Very few studies have investigated neurocognitive subgroups in BP with data-driven methods rather than arbitrarily defined criteria. Other than having relatively small sample sizes, previous studies have not taken into consideration the neurocognitive variability in healthy subjects. Five-hundred-fifty-six euthymic patients with BP and 416 healthy controls were assessed using a battery of cognitive tests and clinical measures. Neurocognitive subgroups were investigated using latent class analysis, based on executive functions. Four neurocognitive subgroups, including a good performance cluster, two moderately low-performance groups, which differ in response inhibition and reasoning abilities, and a severe impairment cluster were found. In comparison to healthy controls, BP patients were overrepresented in severe impairment cluster (27% vs 5.3%) and underrepresented in good performance cluster. BP patients with lower educational attainment and older age were significantly more likely to be members of cognitively impaired subgroups. Antipsychotic use was less common in good performance cluster. These results suggest that there is a considerable overlap of cognitive functions between BP and healthy controls. Neurocognitive differences between BP and healthy controls are driven by a subgroup of patients who have severe and global, rather than selective, cognitive deficits.

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.

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.

Response inhibition and interference control in patients with bipolar I disorder and first-degree relatives

The current study aimed to assess both response inhibition (RI) and interference control (IC) in euthymic patients with bipolar disorder (BD‐Ps) as well as asymptomatic first‐degree relatives (BD‐Rs) and healthy controls (HCs) in order to evaluate trait‐as opposed to illness‐associated features of these components.

Can Risk-Taking Be an Endophenotype for Bipolar Disorder? A Study on Patients with Bipolar Disorder Type I and Their First-Degree Relatives

Risk-taking behavior and impulsivity are core features of bipolar disorder. Whether they are part of the inherited aspect of the illness is not clear. We aimed to evaluate risk-taking behavior as a potential endophenotype for bipolar disorders, and its relationship with impulsivity and illness features. The Balloon Analogue Risk Task (BART) and Barratt Impulsiveness Scale-11 (BIS-11) were used to assess risk-taking behavior and impulsivity respectively in 30 euthymic bipolar I patients (BD), their 25 asymptomatic first-degree relatives (BD-R), and 30 healthy controls (HC). The primary BART outcome measure was the behavioral adjustment score (number of pumps after trials where the balloon did not pop minus the number of pumps after trials where the balloon popped). BD (p < .001) and BD-R (p = .001) had similar and significantly lower adjustment scores than HC. Only BD scored significantly higher on BIS-11 total (p = .01) and motor (p = .04) subscales than HC. Neither the BART, nor impulsivity scores associated with illness features. A limitation of this study is medicated patients and a heterogeneous BD-R were included. Riskiness may be a candidate endophenotype for bipolar disorder as it appears independently from illness features, presents similarly in BD and BD-R groups and differs from impulsivity.

S81. NEUROCOGNITIVE FUNCTIONING IN SCHIZOPHRENIA AND BIPOLAR DISORDER DURING THE REMISSION AND THE PSYCHOTIC STATES

Abstract Background Previous literature comparing cognitive functioning between bipolar disorder (BD) and schizophrenia (Sch), particularly focused on remitted patients with BD (i.e. euthymics) and clinically stable patients with Sch; and suggested milder cognitive impairment in BD in comparison to Sch. Acute psychotic symptoms may lead poorer cognitive functioning in both disorders. Limited evidence suggests milder deficits in psychotic mania than in acute psychosis in Sch. We aimed to compare cognitive functioning in Sch and BD during the remission and the psychotic states. Methods Several domains of cognitive functioning were compared among patients with BD who had a history of psychosis [32 with a current psychotic manic episode, 44 in euthymia for at least 6 months] and patients with Sch [41 with psychotic symptoms, 39 remitted according to Andreassen et al. criteria (2006)] in comparison to 55 healthy controls (HC). Participants performed a cognitive battery including Wisconsin Card Sorting, Rey Auditory Verbal Learning, Stroop, Auditory Consonant Trigram, Trail Making, Digit Span, Controlled Word Association, Category Fluency and Digit Symbol tests. Principal components analyses were performed to extract the ‘global cognition’ factor and for dimensionality reduction to identify neurocognitive domains among patients with BD and Sch. The optimum number of cognitive components was identified by inspecting the scree plot. Each factor score was assessed for normality by calculating tests of skewness and kurtosis. The factor scores were compared between patients with Sch and patients with BD using two-way analyses of variance (ANCOVA) adjusting for age. Pairwise comparisons with Bonferroni corrections were used for post-hoc analysis. Results Mean age, sex ratio levels of education were similar among patients with BD, patients with Sch and HCs. Principal components analyses revealed a global cognition factor that explains 52.6% of variance and a subsequent PCA revealed 5 factor domains including processing speed, verbal memory, visual memory, working memory and planning. Both patients with BD and patients with Sch have significantly poorer global cognition (p<0.001; p<0.001), processing speed (p<0.001; p<0.001); verbal memory (p<0.001; p=0.007); visual memory (p=0.033; p=0.016) and planning (p=0.011; p=0.006) than HCs. Patients with BD presented higher scores in global cognition, processing speed (p=0.010) and verbal memory (p=0.011) than patients with Sch (p<0.001). Global cognition and processing speed domains differ among groups with respect to both diagnosis [F=18.466, p<0.001; F=7.864, p=0.006] and state [F=8.910, p=0.001; F=3.958, p=0.048]. Processing speed, but not other components, displayed a significant interaction between diagnosis and state [F=14.808, p<0.001)]. Discussion Deficits in global cognition was milder in BD, than those in Sch in both the remission and the psychotic states. Although diagnosis seems to be the major factor affecting the cognitive performance, our data present significant interactions of diagnosis and state in processing speed.