Effects of atypical antipsychotics on neurocognition in euthymic bipolar patients

International audiencen.

Differential executive functioning performance by phase of bipolar disorder

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92428/1/j.1399-5618.2012.01032.x.pd

Employment outcomes in people with bipolar disorder : a systematic review

Objective: Employment outcome in bipolar disorder is an under investigated, but important area. The aim of this study was to identify the long-term employment outcomes of people with bipolar disorder. Method: A systematic review using the Medline, PsychInfo and Web of Science databases. Results: Of 1962 abstracts retrieved, 151 full text papers were read. Data were extracted from 25 papers representing a sample of 4892 people with bipolar disorder and a mean length of follow-up of 4.9 years. Seventeen studies had follow-up periods of up to 4 years and eight follow-up of 5–15 years. Most studies with samples of people with established bipolar disorder suggest approximately 40–60% of people are in employment. Studies using work functioning measures mirrored this result. Bipolar disorder appears to lead to workplace underperformance and 40–50% of people may suffer a slide in their occupational status over time. Employment levels in early bipolar disorder were higher than in more established illness. Conclusion: Bipolar disorder damages employment outcome in the longer term, but up to 60% of people may be in employment. Whilst further studies are necessary, the current evidence provides support for extending the early intervention paradigm to bipolar disorder

Study protocol – elucidating the neural correlates of functional remediation for older adults with bipolar disorder

IntroductionBeyond mood abnormalities, bipolar disorder (BD) includes cognitive impairments that worsen psychosocial functioning and quality of life. These deficits are especially severe in older adults with BD (OABD), a condition expected to represent most individuals with BD in the upcoming years. Restoring the psychosocial functioning of this population will thus soon represent a public health priority. To help tackle the problem, the Bipolar and Depressive Disorders Unit at the Hospital Clínic of Barcelona has recently adapted its Functional Remediation (FR) program to that population, calling it FROA-BD. However, while scarce previous studies localize the neural mechanisms of cognitive remediation interventions in the dorsal prefrontal cortex, the specific mechanisms are seldom unknown. In the present project, we will investigate the neural correlates of FR-OABD to understand its mechanisms better and inform for potential optimization. The aim is to investigate the brain features and changes associated with FROA-BD efficacy.MethodsThirty-two individuals with OABD in full or partial remission will undergo a magnetic resonance imaging (MRI) session before receiving FR-OABD. After completing the FR-OABD intervention, they will undergo another MRI session. The MRI sessions will include structural, diffusion-weighted imaging (DWI), functional MRI (fMRI) with working memory (n-back) and verbal learning tasks, and frontal spectroscopy. We will correlate the pre-post change in dorsolateral and dorsomedial prefrontal cortices activation during the n-back task with the change in psychosocial functioning [measured with the Functioning Assessment Short Test (FAST)]. We will also conduct exploratory whole-brain correlation analyses between baseline or pre-post changes in MRI data and other clinical and cognitive outcomes to provide more insights into the mechanisms and explore potential brain markers that may predict a better treatment response. We will also conduct separate analyses by sex.DiscussionThe results of this study may provide insights into how FROA-BD and other cognitive remediations modulate brain function and thus could optimize these interventions

Burden of rare variants in synaptic genes in patients with severe tinnitus: An exome based extreme phenotype study

Background: tinnitus is a heterogeneous condition associated with audiological and/or mental disorders. Chronic, severe tinnitus is reported in 1% of the population and it shows a relevant heritability, according to twins, adoptees and familial aggregation studies. The genetic contribution to severe tinnitus is unknown since large genomic studies include individuals with self-reported tinnitus and large heterogeneity in the phenotype. The aim of this study was to identify genes for severe tinnitus in patients with extreme phenotype. Methods: for this extreme phenotype study, we used three different cohorts with European ancestry (Spanish with Meniere disease (MD), Swedes tinnitus and European generalized epilepsy). In addition, four independent control datasets were also used for comparisons. Whole-exome sequencing was performed for the MD and epilepsy cohorts and whole-genome sequencing was carried out in Swedes with tinnitus. Findings: we found an enrichment of rare missense variants in 24 synaptic genes in a Spanish cohort, the most significant being PRUNE2, AKAP9, SORBS1, ITGAX, ANK2, KIF20B and TSC2 (p < 2E 04), when they were compared with reference datasets. This burden was replicated for ANK2 gene in a Swedish cohort with 97 tinnitus individuals, and in a subset of 34 Swedish patients with severe tinnitus for ANK2, AKAP9 and TSC2 genes (p < 2E 02). However, these associations were not significant in a third cohort of 701 generalized epilepsy individuals without tinnitus. Gene ontology (GO) and gene-set enrichment analyses revealed several pathways and biological processes involved in severe tinnitus, including membrane trafficking and cytoskeletal protein binding in neurons. Interpretation: a burden of rare variants in ANK2, AKAP9 and TSC2 is associated with severe tinnitus. ANK2, encodes a cytoskeleton scaffolding protein that coordinates the assembly of several proteins, drives axonal branching and influences connectivity in neurons

Cognitive impairment in patients with a schizoaffective disorder: a comparison with bipolar patients in euthymia

OBJECTIVES: Several studies have shown persistent neurocognitive impairment in patients with a bipolar affective disorder (BD) even in euthymia as well as in patients with a schizoaffective disorder (SAD). The aim of our study was to compare the neuropsychological performance between these two groups. Confounding variables were controlled to enhance our understanding of cognitive dysfunction in both BD and SAD. METHODS: Several domains of neurocognitive function, executive function, memory, attention, concentration and perceptuomotor function were examined in 28 euthymic SAD patients and 32 BD patients by using a neuropsychological test battery. The Hamilton Depression Rating Scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to evaluate the patients' clinical status. Data analysis was performed by using a multivariate analysis of covariance (ANCOVA/MANCOVA). RESULTS: Euthymic SAD patients showed greater cognitive impairment than euthymic BD patients in the tested domains including declarative memory and attention. Putative significant group differences concerning cognitive flexibility vanished when controlled for demographic and clinical variables. Age and medication were robust predictors to cognitive performance of both SAD and BD patients. CONCLUSIONS: Our results point out the worse cognitive outcome of SAD compared to BD patients in remission. Remarkably, the variance is higher for some of the test results between the groups than within each group, this being discussed in light of the contradictive concept of SAD

A polymorphism associated with depressive disorders differentially regulates brain derived neurotrophic factor promoter IV activity

PMCID: PMC3712170Peer reviewedPublisher PD

Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S): Psychometric properties of a brief scale for cognitive evaluation in schizophrenia

[EN] Objective: The Screen for Cognitive Impairment in Psychiatry (SCIP) is a brief scale designed for detecting cognitive deficits in several psychotic and affective disorders. This study examined the psychometric properties of the Spanish version of the SCIP in a sample of outpatients suffering schizophrenia-spectrum disorders. Methods: Psychometric properties were evaluated in a sample of 126 stable patients with schizophrenia. Men and women 18 to 55 years of age were recruited from consecutive admissions to 40 psychiatric outpatient clinics in Spain and asked to complete a series of cognitive measures at baseline, as well as three versions of the SCIP separated by one week intervals. A matched sample of 39 healthy controls was also subjected to the baseline examination. The feasibility, reliability and validity of the SCIP was examined; concurrent validity was assessed by means of a complete neuropsychological battery. Results: Average time for SCIP administration was 16.02 (SD=5.01) minutes. Test–retest reliability intra-class correlation coefficients ranged from 0.74 to 0.90, with an internal consistency Cronbach's alpha value of 0.73. The three parallel forms of SCIP were shown to be equivalent. The SCIP scales were correlated with corresponding neuropsychological instruments, with Pearson's r between 0.38 and 0.60, pb0.01. The SCIP effectively discriminated between the patient and control samples. Factor analysis revealed one significant dimension, cognitive performance, that accounted for 49.8% of the total variance. Conclusions: The Spanish version of the SCIP is a simple, brief, valid and reliable tool for detection of cognitive impairment in patients with schizophrenia by minimally trained healthcare personnel

Obstetric complications and genetic risk for schizophrenia: Differential role of antenatal and perinatal events in first episode psychosis

Background: Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors. Study Design: 405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis-Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS-SZ) and interactions between these. Results: Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case–control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS-SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe. Conclusions: We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk

Neurocognitive and Neuroimaging Predictors of Clinical Outcome in Bipolar Disorder

Historically, bipolar disorder has been conceptualized as a disease involving episodic rather than chronic dysfunction. However, increasing evidence indicates that bipolar disorder is associated with substantial inter-episode psychosocial and vocational impairment. Here we review the contributions of neurocognitive deficits and structural and functional neuroanatomic alterations to the observed functional impairments. In particular, compelling evidence now suggests that neurocognitive impairments, particularly in the areas of attention, processing speed, and memory, are associated with functional outcome. Although investigation of the neural correlates of functional disability in bipolar disorder is only in its nascent stages, preliminary evidence suggests that white matter abnormalities may be predictive of poor outcome. A better understanding of the relationship between neurocognitive and neuroimaging assays and functional outcome has the potential to improve current treatment options and provide targets for new treatment strategies in bipolar disorder