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.

Discourse and bipolar disorder: Narrative therapy on northeast Brazil

Background: The expression 'bipolar disorder' refers to any of several psychological disorders of mood that alternate episodes of depression and mania. Also called manic depression or manic-depressive illness, it is a relatively common but unknown pathology that brings some stigmas for patients and provokes deleterious effects for their lives. This research aimed to comprehend actions, behaviors and emotions involved with bipolar disorder, through narratives of patient's personal and familiar histories. Methods: We surveyed 30 patients from a psychiatric service located in Aparecida, Paraiba, Brazil. Selected patients had bipolar disorder according to DSM-IV. For data collection, we used non-structured interview, approaching specific aspects related to bipolar disorder. Quantitative and qualitative analysis were done and Hamilton Rating Scale for Depression (HAMD) was used. Results: Most of patients presented depressive actions associated with moderate euphoria. 11 of them related familiar history of psychopathology. Mania and hippomania were prevalent on male gender, while psychotic symptoms overlay ate female. Conclusion: Patients lack a translation of behavioral and temperamental processes to minimize harm caused to their lives.

Impact of sunlight on the age of onset of bipolar disorder

Bauer M, Glenn T, Alda M, Andreassen OA, Ardau R, Bellivier F, Berk M, Bjella TD, Bossini L, Del Zompo M, Dodd S, Fagiolini A, Frye MA, Gonzalez-Pinto A, Henry C, Kapczinski F, Kliwicki S, Konig B, Kunz M, Lafer B, Lopez-Jaramillo C, Manchia M, Marsh W, Martinez-Cengotitabengoa M, Melle I, Morken G, Munoz R, Nery FG, ODonovan C, Pfennig A, Quiroz D, Rasgon N, Reif A, Rybakowski J, Sagduyu K, Simhandl C, Torrent C, Vieta E, Zetin M, Whybrow PC. Impact of sunlight on the age of onset of bipolar disorder. Bipolar Disord 2012: 14: 654663. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objective: Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. Method: Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. Results: The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= -4.724, 95% CI: -8.124 to -1.323, p = 0.006), controlling for each countrys median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. Conclusion: The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder.

Impact of comorbid migraine on the clinical course of bipolar disorder

Background: Recent evidence suggests an association between migraine and bipolar disorder (BD), although the impact of this association in the clinical course of BD is relatively unknown. Objective: This study aimed to compare 2 groups of individuals with BD (with vs without comorbid migraine) and evaluate differences in severity of clinical course. Methods: Three hundred thirty-nine adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition defined bipolar or II disorder were enrolled and divided into 2 groups: with and without comorbid migraine. Demographic and clinical data were obtained using standardized interviews. Results: Patients with comorbid migraines had more mood episodes, especially those with depressive polarity. In addition, comorbid migraine was associated with a higher prevalence of psychiatric and general medical comorbidities. Differences between the 2 groups in number of lifetime hospitalizations for depression/mania, rates of rapid cycling, and history of suicide attempts were not observed after Bonferroni correction. Conclusions: Comorbid migraine seems to be associated with poor outcomes in BD. Additional studies should be conducted to investigate shared vulnerabilities and pathophysiologic mechanisms as well as treatment optimization of both illnesses. (C) 2012 Elsevier Inc. All rights reserved.

Burden of maternal bipolar disorder on at-risk offspring: A controlled study on family planning and maternal care

Introduction: Bipolar disorder (BD) is a highly incapacitating disease typically associated with high rates of familial dysfunction. Despite recent literature suggesting that maternal care is an important environmental factor in the development of behavioral disorders, it is unclear how much maternal care is dysfunctional in BD subjects. Objective: The objective of this study was to characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared to healthy controls with (PD) and without (NPD) other psychiatric diagnoses. Materials and methods: Thirty-four BD mothers and 106 controls underwent an interview about family planning and maternal care, obstetrical complications, and mother-child interactions. K-SADS-PL questions about violence exposure were used to ascertain domestic violence and physical/sexual abuse. Results: BD mothers were less likely to have stable unions (45.5%; p < 0.01) or to live with the biological father of their children (33.3%; p < 0.01), but had higher educational level and higher rates of social security use/retirement. They also had fewer children and used less contraceptive methods than controls. Children of BD women had higher rates of neonatal anoxia, and reported more physical abuse (16.1%; p = 0.02) than offspring of NPD mothers. Due to BD mothers' symptoms, 33.3% of offspring suffered physical and/or psychological abuse. Limitations: Post hoc analysis, and the use of questions as a surrogate of symptoms as opposed to validated instruments. Conclusion: This is one of few reports confirming that maternal care given by BD women is dysfunctional. BD psychopathology can lead to poor maternal care and both should be considered important environmental risk factors in BD, suggesting that BD psychoeducation should include maternal care orientation. (C) 2012 Elsevier B.V. All rights reserved.

The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls

Introduction: Impairments in facial emotion recognition (PER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the alpha 1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Material and methods: Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a PER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. Results: The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Limitations: Sample size. Conclusion: The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology. (C) 2012 Elsevier B.V. All rights reserved.

Suicide attempts are associated with worse quality of life in patients with bipolar disorder type I

Background: The association between suicidal behavior and quality of life (QoL) in bipolar disorder (BD) is poorly understood. Worse QoL has been associated with suicide attempts and suicidal ideation in schizophrenic patients, but this relationship has not been investigated in BD. This study tested whether a history of suicide attempts was associated with poor QoL in a well-characterized sample of patients with BD, as has been observed in other psychiatric disorders and in the general population. Methods: One hundred eight patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition BD type I (44 with previous suicide attempts, 64 without previous suicide attempts) were studied. Quality of life was assessed using the World Health Organization's Quality of Life Instrument Short Version. Depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale-17 items and the Young Mania Rating Scale. Results: Patients with BD and previous suicide attempts had significantly lower scores in all the 4 domains of the World Health Organization's Quality of Life Instrument Short Version scale than did patients with BD but no previous suicide attempts (physical domain P=.001; psychological domain P <.0001; social domain P=.001, and environmental domain P=.039). In the euthymic subgroup (n=70), patients with previous suicide attempts had significantly lower scores only in the psychological and social domains (P=.020 and P=.004). Limitations: This was a cross-sectional study, and no causal associations can be assumed. Conclusions: Patients with BD and a history of previous suicide attempts seem to have a worse QoL than did patients who never attempted suicide. Poorer QoL might be a marker of poor copying skills and inadequate social support and be a risk factor for suicidal behavior in BD. Alternatively, poorer QoL and suicidal behavior might be different expressions of more severe BD. (C) 2012 Elsevier Inc. All rights reserved.

New structural brain imaging endophenotype in bipolar disorder

Neuroimaging studies suggest anterior-limbic structural brain abnormalities in patients with bipolar disorder (BD), but few studies have shown these abnormalities in unaffected but genetically liable family members. In this study, we report morphometric correlates of genetic risk for BD using voxel-based morphometry. In 35 BD type I (BD-I) patients, 20 unaffected first-degree relatives (UAR) of BD patients and 40 healthy control subjects underwent 3 T magnetic resonance scanner imaging. Preprocessing of images used DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) for voxel-based morphometry in SPM8 (Wellcome Department of Imaging Neuroscience, London, UK). The whole-brain analysis revealed that the gray matter (GM) volumes of the left anterior insula and right inferior frontal gyrus showed a significant main effect of diagnosis. Multiple comparison analysis showed that the BD-I patients and the UAR subjects had smaller left anterior insular GM volumes compared with the healthy subjects, the BD-I patients had smaller right inferior frontal gyrus compared with the healthy subjects. For white matter (WM) volumes, there was a significant main effect of diagnosis for medial frontal gyrus. The UAR subjects had smaller right medial frontal WM volumes compared with the healthy subjects. These findings suggest that morphometric brain abnormalities of the anterior-limbic neural substrate are associated with family history of BD, which may give insight into the pathophysiology of BD, and be a potential candidate as a morphological endophenotype of BD. Molecular Psychiatry (2012) 17, 412-420; doi: 10.1038/mp.2011.3; published online 15 February 2011

The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder

Background. - Persistent impairment in cognitive function has been described in euthymic individuals with bipolar disorder. Collective work indicates that obesity is associated with reduced cognitive function in otherwise healthy individuals. This sub-group post-hoc analysis preliminarily explores and examines the association between overweight/obesity and cognitive function in euthymic individuals with bipolar disorder. Methods. - Euthymic adults with DSM-IV-TR-defined bipolar I or II disorder were enrolled. Subjects included in this post-hoc analysis (n = 67) were divided into two groups (normal weight, body mass index [BMI] of 18.5-24.9 kg/m(2); overweight/obese, BMI >= 25.0 kg/m(2)). Demographic and clinical information were obtained at screening. At baseline, study participants completed a comprehensive cognitive battery to assess premorbid IQ, verbal learning and memory, attention and psychomotor processing speed, executive function, general intellectual abilities, recollection and habit memory, as well as self-perceptions of cognitive failures. Results. - BMI was negatively correlated with attention and psychomotor processing speed as measured by the Digit Symbol Substitution Test (P < 0.01). Overweight and obese bipolar individuals had a significantly lower score on the Verbal Fluency Test when compared to normal weight subjects (P < 0.05). For all other measures of cognitive function, non-significant trends suggesting a negative association with BMI were observed, with the exception of measures of executive function (i.e. Trail Making Test B) and recollection memory (i.e. process-dissociation task). Conclusion. - Notwithstanding the post-hoc methodology and relatively small sample size, the results of this study suggest a possible negative effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder. Taken together, these data provide the impetus for more rigorous evaluation of the mediational role of overweight/obesity (and other medical co-morbidity) on cognitive function in psychiatric populations. (C) 2011 Elsevier Masson SAS. All rights reserved.

A Sib-Pair analysis of impulsivity in bipolar disorder type I

OBJECTIVE: The aim of this study was to compare impulsivity among patients with bipolar disorder, their siblings, and healthy controls in order to examine whether impulsivity in bipolar disorder is related to genetic liability for the illness. METHODS: Using the Barratt Impulsiveness Scale, we assessed 204 subjects: 67 euthymic outpatients with bipolar disorder type I, 67 siblings without bipolar disorder, and 70 healthy controls. RESULTS: Impulsivity scores were higher among patients with bipolar disorder than among healthy controls. Siblings showed higher motor impulsivity scores than did healthy controls. CONCLUSIONS: Our results suggest that motor impulsivity may be a vulnerability marker for bipolar disorder. Our data may contribute to further improve preventive strategies in subjects at high risk for bipolar disorder.