Functioning In Bipolar Disorder Research Articles

The catechol-O-methyltransferase (COMT) Val158Met genotype modulates working memory-related dorsolateral prefrontal response and performance in bipolar disorder.

Cognitive dysfunction affects a substantial proportion of patients with bipolar disorder (BD), and genetic-imaging paradigms may aid in the elucidation of mechanisms implicated in this symptomatic domain. The Val allele of the functional Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene is associated with reduced prefrontal cortex dopamine and exaggerated working memory-related prefrontal activity. This functional magnetic resonance imaging (fMRI) study investigated for the first time whether the COMT Val158Met genotype modulates prefrontal activity during spatial working memory in BD. Sixty-four outpatients with BD in full or partial remission were stratified according to COMT Val158Met genotype (ValVal [n=13], ValMet [n=34], and MetMet [n=17]). The patients completed a spatial n-back working memory task during fMRI and the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Working Memory test outside the scanner. During high working memory load (2-back vs 1-back), Val homozygotes displayed decreased activity relative to ValMet individuals, with Met homozygotes displaying intermediate levels of activity in the right dorsolateral prefrontal cortex (dlPFC) (P=.016). Exploratory whole-brain analysis revealed a bilateral decrease in working memory-related dlPFC activity in the ValVal group vs the ValMet group which was not associated with differences in working memory performance during fMRI. Outside the MRI scanner, Val carriers performed worse in the CANTAB Spatial Working Memory task than Met homozygotes (P≤.006), with deficits being most pronounced in Val homozygotes. The association between Val allelic load, dlPFC activity and WM impairment points to a putative role of aberrant PFC dopamine tonus in the cognitive impairments in BD.

Effects of risk for bipolar disorder on brain function: A twin and family study

Bipolar disorder (BPD) is associated with altered regional brain function during the performance of cognitive tasks. The relative contribution of genetic and environmental risk factors for BPD to these changes has not yet been quantified. We sought to address this issue in a functional neuroimaging study of people who varied in their risk for BPD. Functional magnetic resonance imaging was used to study 124 subjects (29 twin and 9 sibling pairs with at least one member with BPD, and 24 healthy twin pairs) performing a working memory task. We assessed the influence of risk for BPD on regional brain function during the task in a two stage process. Firstly, we identified areas where there were group differences in activation. Secondly, we estimated the heritability and phenotypic correlation of activation and BPD using genetic modeling. BPD was associated with increased activation in the anterior cingulate, orbitofrontal, medial prefrontal, and left precentral cortices, and in the precuneus. Within these regions, activation in the orbitofrontal cortex rendered the most significant heritability estimate (h2=0.40), and was significantly correlated with BPD phenotype (rph=0.29). A moderate proportion of the genetic influences (rg=0.69) acting on both BPD and on the degree of orbitofrontal activation were shared. These findings suggest that genetic factors that confer vulnerability to BPD alter brain function in BPD.

The effect of gender on neurocognitive functioning in bipolar disorder

IntroductionBipolar disorder (BD) is frequently associated with cognitive deficits in attention, verbal memory and executive functions that have been related to various clinical characteristics of the disorder.ObjectivesHowever, few studies have examined the effect of gender on cognition despite its clinical relevance.AimsThe aim of our study was to investigate potential diagnosis-specific gender effects on visual memory/learning and executive functions in BD.MethodsCognitive performance of 60 bipolar-I patients and 30 healthy controls was evaluated by using CANTAB battery tasks targeting spatial memory (SRM), paired associative learning (PAL), executive functions (ID/ED, SOC). A multivariate analysis of covariance (MANCOVA) of neuropsychological parameters was performed with gender and diagnosis as fixed effects and age and education as covariates. Following univariate analyses of covariance (ANCOVA) were undertaken to examine the effect of gender on each neuropsychological task.ResultsBipolar patients showed significantly poorer performance in paired associative learning (PAL), set shifting (ID/ED) and planning (SOC). Moreover, a diagnosis specific gender effect was observed for cognitive functioning in BD (gender × diagnosis interaction P = 0.029). Specifically, male healthy controls outperformed healthy females in tasks of visual memory/learning but this pattern was not sustained (SRM) or was even reversed (PAL) in BD patients.ConclusionsThe present study is one of the few studies that have examined the effect of gender on neurocognitive function in BD. Our findings indicate that the gender-related variation observed in healthy subjects is disrupted in BD. Moreover, they suggest that gender may modulate the degree of frontotemporal dysregulation observed in BD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

High cognitive reserve in bipolar disorders as a moderator of neurocognitive impairment

BackgroundCognitive reserve (CR) reflects the capacity of the brain to endure neuropathology, minimize clinical manifestations and successfully complete cognitive tasks. The present study aims to determine whether high CR may constitute a moderator of cognitive functioning in bipolar disorder (BD).MethodsOne hundred and two patients with BD and 32 healthy controls were enrolled. All patients met DSM-IV criteria for I or II BD and were euthymic (YMRS ≤ 6 and HDRS ≤ 8) during a 6-month period. All participants were tested with a comprehensive neuropsychological battery, and a Cerebral Reserve Score (CRS) was estimated. Subjects with a CRS below the group median were classified as having low CR, whereas participants with a CRS above the median value were considered to have high CR.ResultsParticipants with BD with high CR displayed a better performance in measures of attention (digits forward: F = 4.554, P = 0.039); phonemic and semantic verbal fluency (FAS: F = 9.328, P = 0.004; and Animal Naming: F = 8.532, P = 0.006); and verbal memory (short cued recall of California Verbal Learning Test: F = 4.236, P = 0.046), after multivariable adjustment for potential confounders, including number of admissions and prior psychotic symptoms.ConclusionsHigh cognitive reserve may therefore be a valuable construct to explore for predicting neurocognitive performance in patients with BD regarding premorbid status.Disclosure of interestDr. I. Grande has received a Juan Rodés Contract (JR15/00012), Instituto de Salud Carlos III, Spanish Ministry of Economy and Competiveness, Barcelona, Spain and has served as a consultant for Ferrer and as a speaker for AstraZeneca, Ferrer and Janssen-Cilag.Disclosure of interestDr. I. Grande has received a Juan Rodés Contract (JR15/00012), Instituto de Salud Carlos III, Spanish Ministry of Economy and Competiveness, Barcelona, Spain and has served as a consultant for Ferrer and as a speaker for AstraZeneca, Ferrer and Janssen-Cilag.

The correlation between plasma brain-derived neurotrophic factor and cognitive function in bipolar disorder is modulated by the BDNF Val66Met polymorphism

ObjectivesBrain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of bipolar disorder (BD). The functional BDNF Val66Met polymorphism (rs6265) is associated with secretion of BDNF. The current study aimed to explore the correlation between changes of plasma BDNF and cognitive function after 12 week of treatment, considering the influence of the BDNF val66Met polymorphism. The correlation of changes of plasma BDNF with quality of life (QOL) was explored.MethodsFirst diagnosed patients with BD were recruited. Symptom severity, plasma BDNF levels were examined during weeks 0, 1, 2, 4, 8, and 12. QOL, Wisconsin Card Sorting Test (WCST) and the Conners’ Continuous Performance Test (CPT) were assessed at baseline and endpoint. The genotype of the BDNF Val66Met polymorphism was determined. The change of cognitive function and QOL measures over 12 weeks were reduced by factor analysis. Pearson's correlation was used to investigate the association between change of plasma BDNF levels with cognitive function and QOL.ResultsFive hundred and forty-one BP patients were recruited. Three hundred and fifty-five (65.6%) patients completed the 12-week follow-up. A significant negative correlation was found between changes of plasma BDNF level with factor 1 (WCST) (r = −0.25, P < 0.001). After further stratification according to subtypes of BD and the BDNF genotypes, above significant correlation was found only in those with BP-I and the BDNF Val66Met Val/Met genotype (r = −0.54, P < 0.008).ConclusionWe conclude that changes in plasma BDNF significantly correlated with changes in WCST in patients with BD; such correlation is moderated by the BDNF Val66Met polymorphism and subtype of BD.Disclosure of interestThe author has not supplied his declaration of competing interest.

Poor quality of life and functioning in bipolar disorder

BackgroundThis study explores the association of demographic and clinical features with quality of life and functioning in individuals with bipolar disorder.MethodsAdult participants (N = 482) with bipolar I or II disorder were enrolled in a comparative effectiveness study across eleven study sites and completed baseline measures of medical and psychiatric history, current mood, quality of life, and functioning. Participants with at least mildly depressive or manic/hypomanic symptomatic severity were randomized to receive lithium or quetiapine in addition to adjunctive personalized treatment for 6 months.ResultsParticipants with more severe depressive and irritability symptoms had lower quality of life and higher functional impairment. All psychiatric comorbid conditions except substance use disorder were associated with worse quality of life. On average, females had lower quality of life than males. Patients who were married, living as married, divorced, or separated had worse functional impairment compared with patients who were single or never married. A composite score of social disadvantage was associated with worse functioning and marginally associated with worse quality of life. Symptom severity did not moderate the effect of social disadvantage on quality of life or functioning.ConclusionsOur findings highlight that depression, irritability, and psychiatric comorbid conditions negatively impact quality of life and functioning in bipolar disorder. The study suggests that individuals with social disadvantage are at risk for functional impairment.Trial Registration This study is registered with ClinicalTrials.gov. Identification number: NCT01331304

The predictive role of daily cognitive stimulation on executive functions in bipolar disorder

This study aimed to estimate the predictive role of clinical and demographic variables on the three core executive functions (EF) – working memory (WM), inhibitory control (IC) and cognitive flexibility (CF) – in bipolar disorder (BD). The sample consisted of 38 patients with BD type I, 39 with BD type II, and 106 control participants with no mood disorders. Subjects completed the Hayling Test, Trail Making Test, Digit Span Backwards, Sentence Word Span Test, and Stroop Color-Word Test. Composite scores for WM, IC and CF were calculated, and their correlations with clinical and demographic variables were analyzed. Stepwise hierarchical regression models including all significant correlates, gender, and diagnosis, revealed that the frequency of reading and writing habits (FRWH), IQ and diagnosis predicted 38.1% of the variance in IC. Diagnosis and IQ predicted 24.9% of the variance in WM scores. CF was predicted by the FRWH only, which accounted for 7.6% of the variance in this construct. These results suggest that daily cognitive stimulation through reading and writing make a significant positive contribution to executive functioning in BD, even in the absence of continued education. These and other forms of routine cognitive stimulation should be further emphasized in intervention programs for BD.

Influence of cognitive reserve on neuropsychological functioning in bipolar disorder: Findings from a 5-year longitudinal study.

The present study examined the 5-year longitudinal course of cognitive functioning in a large sample of well-characterized patients with bipolar disorder (BP), compared to healthy controls (HCs), and the influence of cognitive reserve factors (e.g., education and IQ) on cognitive change over time. Participants included 159 individuals diagnosed with BP and 54 HCs recruited as part of a longitudinal naturalistic study of BP who had completed neuropsychological testing at the time of their enrollment and again 5years later. The overall relative rate of change did not differ between the BP and HC groups. In total, 46.5% of the BP group and 37% of the HC group showed evidence of decline on at least one measure over time. T-test analyses did not find differences between BP 'decliners' and 'non-decliners' in cognitive reserve variables. However, we found that higher baseline intellectual ability was associated with more stability in cognitive test scores over time for the BP group. Results of linear regression modeling revealed that lower verbal IQ and education were related to increased cognitive decline in specific domains in the BP group. This study has explored the influence of cognitive reserve on preservation of specific cognitive abilities over time in BP. The BP group did not demonstrate accelerated cognitive decline over 5years compared to the HC group. Although the trajectory of cognitive change over time was similar between BP patients and HCs, higher overall intellectual ability may be a protective factor against cognitive decline, particularly for BP patients.

The effect of premorbid intelligence on neurocognitive and psychosocial functioning in bipolar disorder

BackgroundThe aim of this study was to assess if premorbid IQ moderates the association between measures of clinical severity and neurocognitive or psychosocial functioning in euthymic patients with bipolar disorder. MethodsOne hundred and nineteen outpatients and forty healthy controls were included. The length of illness, number of previous hypo/manic and depressive episodes, episode density, and history of psychosis assessed clinical severity. Performances in verbal memory, attention, and executive functions, as well as level of psychosocial functioning were used as outcomes. ResultsThe negative relationship between number of hypo/manic episodes and performance in executive functions decreased as a function of higher values of premorbid IQ. No other influences of premorbid IQ were found in the association between clinical severity measures and neurocognitive and psychosocial functioning. ConclusionsPremorbid IQ might moderate the relationship between the number of hypo/manic episodes and executive functioning in bipolar disorder. Possible interpretations of this finding are discussed.

Treatment of Functional Impairment in Patients with Bipolar Disorder.

Traditionally, functional impairment has received little attention in bipolar disorder, despite the fact that many patients experience significant impairments in daily life. In the last decade, research has changed its focus from clinical remission to functional recovery in bipolar patients as a priority. A literature review of this topic will allow us provide an overview of the relevance of functional impairment as well as the potential factors that can predict or contribute to low functioning in bipolar disorder (BD). Treatment approaches should consider not only euthymia as a goal but also cognitive and functional improvement of patients with such a complex disorder. Functional remediation and psychoeducation among psychological interventions may help to enhance functioning. The combination of cognitive enhancers and cognitive/functional remediation programs may help in improving cognitive and functional impairments. Early interventions are essential to prevent cognitive deficits and disability.

Mental disorders, functional impairment, and nerve growth factor.

Nerve growth factor (NGF) is an important member of the neurotrophin family and its alteration has been associated with psychiatric disorders. Functionality consists of the activities that an individual can perform, as well as their social participation, which is an important factor in analyzing the carrier living conditions of subjects with psychiatric suffering. Several studies have evaluated functionality in bipolar disorder; however, no studies have evaluated the functionality in other mental disorders. There are also few studies investigating the association between functionality and the biological bases of mental disorders. This study aimed to evaluate the serum NGF levels in psychiatric patients and to verify a possible association between the serum neurotrophic levels and functionality. This was a cross-sectional study with a convenient sample obtained from the Public Mental Health Service from the south of Brazil. The final sample was composed of 286 patients enrolled from July 2013 to October 2014. Data was collected using a sociodemographic questionnaire, and the diagnosis was confirmed using the Mini International Neuropsychiatric Interview (M.I.N.I) and a Functioning Assessment Short Test. The serum NGF levels were determined using the enzyme-linked immunosorbent assay method. Statistical analyses were performed using IBM SPSS Statistic 21.0 software. NGF serum levels were increased significantly in patients with obsessive–compulsive disorder compared with patients with no obsessive–compulsive disorder (P=0.015). An increase in serum NGF levels in generalized anxiety disorder patients was observed compared with patients with no generalized anxiety disorder (P=0.047). NGF was negatively associated with autonomy (P=0.024, r=−0.136), work (P=0.040, r=−0.124), and cognition (P=0.024, r=−0.137), thereby showing that changes in serum levels of NGF are associated with functionality in mental disorders.

The correlation between plasma brain-derived neurotrophic factor and cognitive function in bipolar disorder is modulated by the BDNF Val66Met polymorphism.

We explored the effect of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) on correlation between changes in plasma BDNF levels with cognitive function and quality of life (QoL) after 12 weeks of treatment in bipolar disorder (BD). Symptom severity and plasma BDNF levels were assessed upon recruitment and during weeks 1, 2, 4, 8 and 12. QoL, the Wisconsin Card Sorting Test (WCST), and the Conners’ Continuous Performance Test (CPT) were assessed at baseline and endpoint. The BDNF Val66Met polymorphism was genotyped. Changes in cognitive function and QoL over 12 weeks were reduced using factor analysis for the evaluation of their correlations with changes in plasma BDNF. Five hundred forty-one BD patients were recruited and 65.6% of them completed the 12-week follow-up. Changes in plasma BDNF levels with factor 1 (WCST) were significantly negatively correlated (r = −0.25, p = 0.00037). After stratification of BD subtypes and BDNF genotypes, this correlation was significant only in BP-I and the Val/Met genotype (r = −0.54, p = 0.008). We concluded that changes in plasma BDNF levels significantly correlated with changes in WCST scores in BD and is moderated by the BDNF Val66Met polymorphism and the subtype of BD.

High cognitive reserve in bipolar disorders as a moderator of neurocognitive impairment

BackgroundCognitive reserve (CR) reflects the capacity of the brain to endure neuropathology, minimize clinical manifestations and successfully complete cognitive tasks. The present study aims to determine whether high CR may constitute a moderator of cognitive functioning in bipolar disorder (BD). Methods102 patients with BD and 32 healthy controls were enrolled. All patients met DSM-IV criteria for I or II BD and were euthymic (YMRS≤6 and HDRS≤8) during a 6-month period. All participants were tested with a comprehensive neuropsychological battery, and a Cerebral Reserve Score (CRS) was estimated. Subjects with a CRS below the group median were classified as having low CR, whereas participants with a CRS above the median value were considered to have high CR. ResultsParticipants with BD with high CR displayed a better performance in measures of attention (digits forward: F=4.554, p=0.039); phonemic and semantic verbal fluency (FAS: F=9.328, p=0.004; and Animal Naming: F=8.532, p=0.006); and verbal memory (short cued recall of California Verbal Learning Test: F=4.236, p=0.046), after multivariable adjustment for potential confounders, including number of admissions and prior psychotic symptoms. LimitationsThe cross-sectional design of the study does not allow the establishment of causal inferences. Additionally, the small size of the sample may have limited some results. ConclusionsHigh cognitive reserve may therefore be a valuable construct to explore for predicting neurocognitive performance in patients with BD regarding premorbid status.

Cognitive reserve lessens the burden of white matter lesions on executive functions in bipolar disorder.

The concept of cognitive reserve (CR) hypothesizes that intellectually stimulating activities provide resilience against brain pathology/disease. Whereas brain abnormalities and cognitive impairment are frequently reported in bipolar disorder (BD), it is unknown whether the impact of brain alterations can be lessened by higher CR in BD. We tested if higher CR would reduce the influence of total volumes of deep white matter hypointensities (WMH), ventricular cerebrospinal fluid (CSF), and prefrontal cortex on memory, executive, and attention/speed functions in patients with BD (n = 75). Linear regression models with interaction terms for CR and brain volumes were applied to directly test if CR reduces the influence of brain pathology on cognitive domains. CR reduced the influence of total volumes of deep WMH (β = -0.38, Q = 0.003) and ventricular CSF (β = -41, Q = 006) on executive functions. The interactions between CR and total volumes of deep WMH/ventricular CSF appear to account for executive functioning in BD. The results suggest that the concept of CR is applicable in BD. Higher reserve capacity in BD alters the relationship between brain pathology and clinical presentation.

Family functioning in bipolar disorder: Characteristics, congruity between patients and relatives, and clinical correlates.

Functional improvement has become one of the aims of the treatment of bipolar disorder. However, scant attention has been given to family functioning, even though it has a role in the illness outcome and is affected by the disorder. The aims of this study were to compare family functioning reported by euthymic patients with bipolar disorder and healthy controls; explore the level of congruence in the perception of family environment between patients with bipolar disorder and their relatives; and analyse the relationship between clinical variables and family functioning. The sample comprised 82 adult euthymic subjects with bipolar disorder, 82 family caregivers of these patients and 47 healthy controls. Participants completed the Family Environment Scale. Results showed moderate correlations and a mean pattern almost identical between relatives' and patients' reported scores in family functioning subscales. There were significant differences between patients and controls, favourable for the latter, in the subscales cohesion (p<0.005), expressiveness (p=0.002), conflict (p=0.038), intellectual-cultural orientation (p=0.001), active-recreational orientation (p<0.005), and a non-significant trend in organization (p=0.064). Significant associations were found between family environment and clinical variables of severity. These findings contribute to increasing the understanding of family functioning in bipolar disorder and highlight the importance of family work.

Toward a complex system understanding of bipolar disorder: A chaotic model of abnormal circadian activity rhythms in euthymic bipolar disorder.

In the absence of a comprehensive neural model to explain the underlying mechanisms of disturbed circadian function in bipolar disorder, mathematical modeling is a helpful tool. Here, circadian activity as a response to exogenous daily cycles is proposed to be the product of interactions between neuronal networks in cortical (cognitive processing) and subcortical (pacemaker) areas of the brain. To investigate the dynamical aspects of the link between disturbed circadian activity rhythms and abnormalities of neurotransmitter functioning in frontal areas of the brain, we developed a novel mathematical model of a chaotic system which represents fluctuations in circadian activity in bipolar disorder as changes in the model's parameters. A novel map-based chaotic system was developed to capture disturbances in circadian activity across the two extreme mood states of bipolar disorder. The model uses chaos theory to characterize interplay between neurotransmitter functions and rhythm generation; it aims to illuminate key activity phenomenology in bipolar disorder, including prolonged sleep intervals, decreased total activity and attenuated amplitude of the diurnal activity rhythm. To test our new cortical-circadian mathematical model of bipolar disorder, we utilized previously collected locomotor activity data recorded from normal subjects and bipolar patients by wrist-worn actigraphs. All control parameters in the proposed model have an important role in replicating the different aspects of circadian activity rhythm generation in the brain. The model can successfully replicate deviations in sleep/wake time intervals corresponding to manic and depressive episodes of bipolar disorder, in which one of the excitatory or inhibitory pathways is abnormally dominant. Although neuroimaging research has strongly implicated a reciprocal interaction between cortical and subcortical regions as pathogenic in bipolar disorder, this is the first model to mathematically represent this multilevel explanation of the phenomena of bipolar disorder.

Stability of facial emotion recognition performance in bipolar disorder

The aim of this study was to assess the performance in emotional processing over time in a sample of euthymic patients with bipolar disorder (BD). Performance in the facial recognition of the six basic emotions (surprise, anger, sadness, happiness, disgust, and fear) did not change during a follow-up period of almost 7 years. These preliminary results suggest that performance in facial emotion recognition might be stable over time in BD.

Thinking ahead: Executive dysfunction in bipolar disorder

Cognitive reserve (CR) reflects the capacity of the brain to endure neuropathology, minimize clinical manifestations and successfully complete cognitive tasks. The present study aims to determine whether high CR may constitute a moderator of cognitive functioning in bipolar disorder (BD).102 patients with BD and 32 healthy controls were enrolled. All patients met DSM-IV criteria for I or II BD and were euthymic (YMRS≤6 and HDRS≤8) during a 6-month period. All participants were tested with a comprehensive neuropsychological battery, and a Cerebral Reserve Score (CRS) was estimated. Subjects with a CRS below the group median were classified as having low CR, whereas participants with a CRS above the median value were considered to have high CR.Participants with BD with high CR displayed a better performance in measures of attention (digits forward: F=4.554, p=0.039); phonemic and semantic verbal fluency (FAS: F=9.328, p=0.004; and Animal Naming: F=8.532, p=0.006); and verbal memory (short cued recall of California Verbal Learning Test: F=4.236, p=0.046), after multivariable adjustment for potential confounders, including number of admissions and prior psychotic symptoms.The cross-sectional design of the study does not allow the establishment of causal inferences. Additionally, the small size of the sample may have limited some results.High cognitive reserve may therefore be a valuable construct to explore for predicting neurocognitive performance in patients with BD regarding premorbid status.

The association among smoking, HSV-1 exposure, and cognitive functioning in schizophrenia, bipolar disorder, and non-psychiatric controls

Previous investigations have found that smokers with schizophrenia demonstrate reduced performance on cognitive tasks compared to non-smokers. However previous studies have not taken into account other environmental factors associated with cognitive functioning such as exposure to Herpes Simplex Virus type 1 (HSV-1). We examined these factors in a sample consisting of individuals with schizophrenia (n=773), bipolar disorder (n=493), or controls without a psychiatric disorders (n=548). Participants were assessed on a cognitive battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and had a blood sample drawn to measure seropositivity to HSV-1. Within each group linear regression models were constructed to determine whether cigarette smoking and HSV-1 seropositivity were jointly associated with cognitive functioning after adjusting for relevant covariates. Within the schizophrenia group, the effect size of lower total cognitive score was −0.279 (p<0.0001) for individuals who were both smokers and HSV-1 seropositive and a significant effect was found in all cognitive domains. The odds of being in the highest quartile of RBANS Total score were significantly lower for smokers (OR=0.58, 95% CI 0.41, 0.82, p=0.002). Smoking was not as consistently associated with levels of cognitive functioning in the bipolar disorder or the non-psychiatric control group. While experimental studies show that nicotine transiently improves functioning on sensory gating and attention tasks known to be deficient in schizophrenia, long-term nicotine exposure via smoking appears to have an adverse effect on cognitive functioning.

Polymorphisms of BDNF and CACNA1C are not associated with cognitive functioning in bipolar disorder or healthy controls

ABSTRACTIntroduction: The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737.Methods: Regression models with five aggregated cognitive domains derived from a comprehensive test battery and IQ score were run using directly genotyped risk variants of SNPs rs6265 and rs1006737 as predictors with covariates as appropriate. Models were performed in a clinical sample of Swedish patients with BD (N = 114) and sex- and age-matched population controls (N = 104).Results: No significant associations (regardless of correction for multiple testing) between the BDNF and CACNA1C risk variants and cognitive functioning were found in either patients or controls.Conclusions: Our results do not support that the common genetic risk variants in rs6265 and rs1006737 are associated with cognitive dysfunction.