In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group.

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

The relationship between cognition and functioning in Bipolar Disorder: An investigation using functional imaging during working memory performance.

The psychosocial functioning of individuals suffering from bipolar disorder (BD) has a significant impact on prognosis and quality of life. The aim of this study was to assess brain functional correlates of psychosocial functioning in BD individuals during the performance of a working memory task. Sixty-two subjects (31 euthymic BD individuals and 31 matched healthy controls) underwent structural and functional magnetic resonance imaging scanning while performing the 1- and 2-back versions of the n-back task (1-back and 2-back). The Functional Assessment Short Test (FAST) and its subdomains were used to assess functioning. Whole brain analysis revealed only overall activation differences between BD patients and healthy controls, but the patients showed failure of de-activation in the medial frontal cortex. Six clusters of significant inverse correlation with the FAST scores were found in the dorsolateral prefrontal cortex, the superior parietal cortex, and temporo-occipital regions bilaterally, and in the left inferior frontal cortex. Cognitive and occupational functioning were the subdomains most significantly associated with brain activation in these clusters. The results suggest that poor psychosocial functioning in BD individuals is associated with hypoactivation in a range of cortical regions, including the fronto-parietal working memory network and inferior temporo-occipital regions.

A prospective longitudinal study searching for predictors of response to group psychoeducation in bipolar disorder.

BACKGROUND: The efficacy of adjunctive group psychoeducation in bipolar disorder has been proven although treatment response differ among individuals. The aim of this study was to characterize responders and non-responders to group psychoeducation in order to identify baseline variables that could predict treatment response. METHODS: The sample was composed of 103 medicated euthymic patients with bipolar disorder referred to 21 sessions of group psychoeducation (6 months). Sociodemographic and clinical variables, temperament, circadian rhythms, BDNF, cognitive and psychosocial functioning were collected. At the 18-month endpoint, the patients were split in two groups on the basis of having suffered any recurrence. Significant group differences were included in a logistic regression analysis. RESULTS: Ninety patients out of 103 engaged in group psychoeducation, 47 of whom (52.2%) responded to psychoeducation and 43 (47.8%) did not. Recurrences occurred more often in the follow-up, the most common being depression. Responders and non-responders differed in gender, age at diagnosis, latency of diagnosis, temperament, attention composite score and BDNF. Lower age at diagnosis of bipolar disorder, lower cyclothimic temperament scores and being male -which was associated with bipolar type I and a trend to more previous manic episodes- were significantly related to a better response to psychoeducation in the regression analysis. LIMITATIONS: No control group. CONCLUSIONS: This study identifies age at diagnosis as a significant modifiable risk factor of treatment response, highlighting the need for early identification of bipolar disorder. Existing programs should be adjusted to the characteristics of specific subpopulations in the framework of a personalized approach.

Structural abnormality in schizophrenia versus bipolar disorder: A whole brain cortical thickness, surface area, volume and gyrification analyses.

OBJECTIVES: The profiles of cortical abnormalities in schizophrenia and bipolar disorder, and how far they resemble each other, have only been studied to a limited extent. The aim of this study was to identify and compare the changes in cortical morphology associated with these pathologies. METHODS: A total of 384 subjects, including 128 patients with schizophrenia, 128 patients with bipolar disorder and 127 sex-age-matched healthy subjects, were examined using cortical surface-based morphology. Four cortical structural measures were studied: cortical volume (CV), cortical thickness (CT), surface area (SA) and gyrification index (GI). Group comparisons for each separate cortical measure were conducted. RESULTS: At a threshold of P = 0.05 corrected, both patient groups showed significant widespread CV and CT reductions in similar areas compared to healthy subjects. However, the changes in schizophrenia were more pronounced. While CV decrease in bipolar disorder was exclusively explained by cortical thinning, in schizophrenia it was driven by changes in CT and partially by SA. Reduced GI was only found in schizophrenia. The direct comparison between both disorders showed significant reductions in all measures in patients with schizophrenia. CONCLUSIONS: Cortical volume and cortical thickness deficits are shared between patients with schizophrenia and bipolar disorder, suggesting that both pathologies may be affected by similar environmental and neurodegenerative factors. However, the exclusive alteration in schizophrenia of metrics related to the geometry and curvature of the brain cortical surface (SA, GI) suggests that this group is influenced by additional neurodevelopmental and genetic factors.

Functional impairment in adult bipolar disorder with ADHD.

BACKGROUND: It is well established that patients with either bipolar disorder (BD) or attention-deficit/hyperactivity disorder (ADHD) present functional impairment even when in remission. Nevertheless, research on functional impairment with adult patients with bipolar disorder comorbid to ADHD (BD+ADHD) is very scarce. The main objective of the current report was to evaluate the overall and specific domains of functioning, in patients with BD+ADHD compared to patients with pure bipolar disorder (pBD) and healthy controls (HCs). METHOD: 162 subjects from 3 groups were compared: 63 pBD, 23 BD+ADHD and 76 HCs. All the patients with BD had been euthymic for at least 6 months and they were recruited at the Hospital Clinic of Barcelona. All the participants were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS) and the Functioning Assessment Short Test (FAST). Clinical, and sociodemographic data were also recorded. RESULTS: Clinical groups, pBD and BD+ADHD, showed lower overall functioning (p < 0.001) in each domain of the FAST scale compared to the HCs. Moreover, the Tukey post hoc test revealed that the BD+ADHD group showed a worse score than pBD in the cognitive domain of the FAST. However, after controlling for potential confounding variables, only the HDRS scores (p < 0.026) remained significant for the cognitive domain of the FAST. LIMITATIONS: The small sample size of the comorbid BD+ADHD group. CONCLUSIONS: Adult patients with BD+ADHD showed the worst scores in functioning compared with the HCs, but did not show more severe functional impairment than the pBD group except for the cognitive domain. Therefore our findings suggest that depressive symptoms in adults with BD+ADHD may negatively influence cognitive functioning. Further studies are needed to confirm our findings for the management of BD+ADHD.

Structural and Functional Brain Correlates of Cognitive Impairment in Euthymic Patients with Bipolar Disorder.

INTRODUCTION: Cognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain. METHODS: Thirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task. RESULTS: No clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls. CONCLUSIONS: Cognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function.

Restoring functioning in bipolar disorder: functional remediation.

Over the past several years, many evidence-based interventions have proven to be effective as adjunctive therapies in the treatment of bipolar disorder. Only a few, however, have addressed the issue of functional recovery in bipolar euthymic patients, which is difficult to achieve after an affective episode. The functional remediation program has been designed at the Hospital Clinic of Barcelona with the main aim of treating functional impairment in bipolar disorder. The program consists of 21 weekly group sessions and is based on a neuro-cognitive-behavioral approach. Throughout the sessions, euthymic patients are trained in the use of neurocognitive skills to be applied during their daily routines. Modeling techniques, role playing, self-instructions, verbal instructions, positive reinforcement, and metacognitive cues are some of the techniques that are used in the program. The present report aims at explaining this new intervention to improve functional outcomes in euthymic bipolar patients.

Has number of previous episodes any effect on response to group psychoeducation in bipolar patients? A 5-year follow-up post hoc analysis.

UNLABELLED: Colom F, Reinares M, Pacchiarotti I, Popovic D, Mazzarini L, Martínez-Arán A, Torrent C, Rosa A, Palomino-Otiniano R, Franco C, Bonnin CM, Vieta E. Has number of previous episodes any effect on response to group psychoeducation in bipolar patients? A 5-year follow-up post hoc analysis. OBJECTIVE: One of the main utilities of staging in bipolar disorder is enhancing the formulation of pharmacological and non-pharmacological treatment strategies. Hence, it is essential to ascertain whether the number of previous episodes influences treatment response. Hereby, we present a 5-year post hoc study on the efficacy of group psychoeducation for bipolar disorders according to the number of previous episodes. METHODS: For this subanalysis, we have compared the 5-year outcome of 120 euthymic psychoeducated versus non-psychoeducated bipolar patients according to the number of previous episodes at study entry. RESULTS: Patients with more than seven episodes at study entry did not show any significant improvement with psychoeducation according to time to recurrence. Patients with more than 14 episodes did not benefit from psychoeducation in terms of a reduction of time spent ill. Patients with 7 or 8 episodes showed a benefit in terms of fewer days spent in hypomania, depression, mixed episodes or any episodes but not mania, while patients with 9-14 episodes showed a benefit in terms of fewer days spent in hypomania and depression but not in mixed states or mania. Only patients who presented up to 6 episodes showed reduction in time spent in any episode polarity. CONCLUSION: The number of previous episodes clearly worsens response to psychoeducation, perhaps in a more subtle way than that observed with other psychological therapies. Psychoeducation should be delivered as soon as possible in the illness course, supporting the idea of early intervention.