Clinical usefulness of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) scale in patients with type I bipolar disorder

Background: The relevance of persistent cognitive deficits to the pathogenesis and prognosis of bipolar disorders (BD) is understudied, and its translation into clinical practice has been limited by the absence of brief methods assessing cognitive status in Psychiatry. This investigation assessed the psychometric properties of the Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) for the detection of cognitive impairment in BD. Methods: After short training, psychiatrists at 40 outpatient clinics administered the SCIP three times over two weeks to a total of 76 consecutive type I BD admissions. Experienced psychologists also administered a comprehensive battery of standard neuropsychological instruments to clinical sample and 45 healthy control subjects. Results: Feasibility was supported by a brief administration time (approximately 15 minutes) and minimal scoring errors. The reliability of the SCIP was confirmed by good equivalence of forms, acceptable stability (ICC range 0.59 to 0.87) and adequate internal consistency (Chronbach's alpha of 0.74). Construct validity was granted by extraction of a single factor (accounting 52% of the variance), acceptable correlations with conventional neuropsychological instruments, and a clear differentiation between bipolar I and normal samples. Efficiency was also provided by the adequate sensitivity and specificity. Limitations: The sample size is not very large. The SCIP and the neurocognitive battery do not cover all potentially relevant cognitive domains. Also, sensitivity to change remains unexplored. Conclusion: With minimal training, physicians obtained a reliable and valid estimate of cognitive impairment in approximately 15 minutes from an application of the SCIP to type I BD patients.

Clinical usefulness of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) scale in patients with type I bipolar disorder

Background: The relevance of persistent cognitive deficits to the pathogenesis and prognosis of bipolar disorders (BD) is understudied, and its translation into clinical practice has been limited by the absence of brief methods assessing cognitive status in Psychiatry. This investigation assessed the psychometric properties of the Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) for the detection of cognitive impairment in BD. Methods: After short training, psychiatrists at 40 outpatient clinics administered the SCIP three times over two weeks to a total of 76 consecutive type I BD admissions. Experienced psychologists also administered a comprehensive battery of standard neuropsychological instruments to clinical sample and 45 healthy control subjects. Results: Feasibility was supported by a brief administration time (approximately 15 minutes) and minimal scoring errors. The reliability of the SCIP was confirmed by good equivalence of forms, acceptable stability (ICC range 0.59 to 0.87) and adequate internal consistency (Chronbach's alpha of 0.74). Construct validity was granted by extraction of a single factor (accounting 52% of the variance), acceptable correlations with conventional neuropsychological instruments, and a clear differentiation between bipolar I and normal samples. Efficiency was also provided by the adequate sensitivity and specificity. Limitations: The sample size is not very large. The SCIP and the neurocognitive battery do not cover all potentially relevant cognitive domains. Also, sensitivity to change remains unexplored. Conclusion: With minimal training, physicians obtained a reliable and valid estimate of cognitive impairment in approximately 15 minutes from an application of the SCIP to type I BD patients.

Prenatal and perinatal risk factors for bipolar disorder

Bipolar disorder (BPD) is a severe mental disorder associated with considerable morbidity and mortality. Prenatal insults have been shown to be associated with later development of mental disorders and there is a growing interest in the potential role of prenatal and perinatal risk factors in the development of BPD. The aims of this thesis were to describe the overall study design of the Finnish Prenatal Study of Bipolar Disorders (FIPS-B) and demographic characteristics of the sample. Furthermore, it was aimed to examine the association of parental age, parental age difference, perinatal complications and maternal smoking during pregnancy with BPD. This thesis is based on FIPS-B, a nested case-control study using several nationwide registers. The cases included all people born in Finland between January 1st 1983 and December 31st 1998 and diagnosed with BPD according to the Finnish Hospital Discharge Register (FHDR) before December 31st 2008. Controls for this study were people who were without BPD, schizophrenia or diagnoses related to these disorders, identified from the Population Register Centre (PRC), and matched two-fold to the cases on sex, date of birth (+/- 30 days), and residence in Finland on the first day of diagnosis of the matched case. Conditional logistic regression models were used to examine the association between risk factors and BPD. This study included 1887 BPD cases and 3774 matched controls. The mean age at diagnosis was 19.3 years and females accounted for 68% of the cases. Mothers with the lowest educational level had the highest odds of having BPD in offspring. Being born in Eastern and Southern region of Finland increased the odds of having BPD later in life. A U-shaped distribution of odds ratio was observed between paternal age and BPD in the unadjusted analysis. Maternal age and parental age difference was not associated with BPD. Birth by planned caesarean section was associated with increased odd of BPD. Smoking during pregnancy was not associated with BPD in the adjusted analyses. Region of birth and maternal educational level were associated with BPD. Both young and old father’s age was associated with BPD. Most perinatal complications and maternal smoking during pregnancy were not associated with BPD. The findings of this thesis, considered together with previous literature, suggest that the pre- and perinatal risk factor profile varies among different psychiatric disorders.

Group cognitive behavior therapy for bipolar disorder can improve the quality of life

Bipolar disorder (BD) can have an impact on psychosocial functioning and quality of life (QoL). Several studies have shown that structured psychotherapy in conjunction with pharmacotherapy may modify the course of some disorders; however, few studies have investigated the results of group cognitive behavior therapy (G-CBT) for BD. Our objective was to evaluate the effectiveness of 14 sessions of G-CBT for BD patients, comparing this intervention plus pharmacotherapy to treatment as usual (TAU; only pharmacotherapy). Forty-one patients with BD I and II participated in this study and were randomly allocated to each group (G-CBT: N = 27; TAU: N = 14). Thirty-seven participants completed the treatment (women: N = 66.67%; mean age = 41.5 years). QoL and mood symptoms were assessed in all participants. Scores changed significantly by the end of treatment in favor of the G-CBT group. The G-CBT group presented significantly better QoL in seven of the eight sub-items assessed with the Medical Outcomes Survey SF-36 scale. At the end of treatment, the G-CBT group exhibited lower scores for mania (not statistically significant) and depression (statistically significant) as well as a reduction in the frequency and duration of mood episodes (P < 0.01). The group variable was significant for the reduction of depression scores over time. This clinical change may explain the improvement in six of the eight subscales of QoL (P < 0.05). The G-CBT group showed better QoL in absolute values in all aspects and significant improvements in nearly all subscales. These results were not observed in the TAU control group.

Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

History of eating disorder in mothers of children with early onset eating disorder or disturbance

The literature suggests that there is significant familial aggregation of eating disorders. A specific association has also been reported between childhood feeding problems and maternal eating disorder. This study investigates whether subgroups of children with early onset eating disturbance are distinguished by maternal eating disorder history. The mothers of 66 children with either anorexia nervosa (AN), food avoidance emotional disorder (FAED) or selective eating (SE) were interviewed to ascertain eating disorder history. Seventeen per cent of mothers reported a history of eating disorder, compared with 3%–5% reported for community samples. A history of eating disorder was reported by 5.9% of mothers of children with SE, 12.9% of mothers of children with AN and 33.3% of mothers of children with FAED. The findings, based on this small sample, suggest that children with FAED are especially likely to have grown up in a dysfunctional food environment.

Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder

In the rodent forebrain GABAergic neurons are generated from progenitor cells that express the transcription factors Dlx1 and Dlx2. The Rap-1 guanine nucleotide exchange factor, MR-GEF, is turned on by many of these developing GABAergic neurons. Expression of both Dlx1/2 and MR-GEF is retained in both adult mouse and human forebrain where, in human, decreased Dlx1 expression has been associated with psychosis. Using in situ hybridization studies we show that MR-GEF expression is significantly down-regulated in the forebrain of Dlx1/2 double mutant mice suggesting that MR-GEF and Dlx1/2 form part of a common signalling pathway during GABAergic neuronal development. We therefore compared MR-GEF expression by in situ hybridization in individuals with major psychiatric disorders (schizophrenia, bipolar disorder, major depression) and control individuals. We observed a significant positive correlation between layers II and IV of the dorso-lateral prefrontal cortex (DLPFC) in the percentage of MR-GEF expressing neurons in individuals with bipolar disorder, but not in individuals with schizophrenia, major depressive disorder or in controls. Since MR-GEF encodes a Rap1 GEF able to activate G-protein signalling, we suggest that changes in MR-GEF expression could potentially influence neurotransmission.

Functional and Structural Connectivity Between the Perigenual Anterior Cingulate and Amygdala in Bipolar Disorder

Objective: Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions in BD. Methods: Thirty-three individuals with BD and 31 healthy comparison subjects (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results: Functional connectivity was decreased between the pACC and amygdala in the BD group compared with HC group, during the processing of fearful and happy faces (p < .005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter, including the region of the uncinate fasciculus, was identified (p < .005). Conclusion: This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.

Abnormal Corpus Callosum Integrity in Bipolar Disorder: A Diffusion Tensor Imaging Study

Objective: Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in bipolar disorder (BID). In this study, we used complementary diffusion tensor imaging methods to study the structural integrity of the CC and localization of potential abnormalities in BD. Methods: Subjects included 33 participants with BID and 40 healthy comparison participants. Fractional anisotropy (FA) measures were compared between groups with region of interest (ROD methods to investigate the anterior, middle, and posterior CC and voxel-based methods to further localize abnormalities. Results: In ROI-based analyses, FA was significantly decreased in the anterior and middle CC in the BID group (p <.05). Voxel-based analyses similarly localized group differences to the genu, rostral body, and anterior midbody of CC (p <.05, corrected). Conclusion: The findings demonstrate abnormalities in the structural integrity of the anterior CC in BID that might contribute to altered interhemispheric connectivity in this disorder.

Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging

Background Convergent evidence implicates white matter abnormalities in bipolar disorder. The cingulum is an important candidate structure for study in bipolar disorder as it provides substantial white matter connections within the corticolimbic neural system that subserves emotional regulation involved in the disorder. Aims To test the hypothesis that bipolar disorder is associated with abnormal white matter integrity in the cingulum. Method Fractional anisotropy in the anterior and posterior cingulum was compared between 42 participants with bipolar disorder and 42 healthy participants using diffusion tensor imaging. Results Fractional anisotropy was significantly decreased in the anterior cingulum in the bipolar disorder group compared with the healthy group (P=0.003); however, fractional anisotropy in the posterior cingulum did not differ significantly between groups. Conclusions Our findings demonstrate abnormalities in the structural integrity of the anterior cingulum in bipolar disorder. They extend evidence that supports involvement of the neural system comprising the anterior cingulate cortex and its corticolimbic gray matter connection sites in bipolar disorder to implicate abnormalities in the white matter connections within the system provided by the cingulum.