Lara G. Chepenik

The Influence of Sad Mood on Cognition

Neuroimaging has identified an overlapping network of brain regions whose activity is modulated by mood and cognition. Studies of depressed individuals have shown changes in perception, attention, memory, and executive functions. This suggests that mood has a pervasive effect on cognition. Direct evidence of the effect of sad mood on cognition is surprisingly limited, however. Published studies have generally addressed a single cognitive ability per study because the fleeting nature of laboratory-induced mood precludes extended testing, and robust findings are limited to mood effects on memory for emotional stimuli. In this study, sad mood was induced and prolonged, enabling the effects of mood to be assessed for an array of abilities, including those that share neural substrates with sad mood and those affected by depression. Sad mood affected memory for emotional words and facial emotion recognition, but not the other processes measured, with a significant nonuniformity of effect over tasks. These results are consistent with circumscribed effects of sad mood on certain emotion-related cognitive processes, but not on cognition more generally.

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 (BD). 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 BD and 40 healthy comparison participants. Fractional anisotropy (FA) measures were compared between groups with region of interest (ROI) 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 BD 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 BD that might contribute to altered interhemispheric connectivity in this disorder.

Functional connectivity between ventral prefrontal cortex and amygdala at low frequency in the resting state in bipolar disorder

Trait abnormalities in bipolar disorder (BD) within the ventral prefrontal cortex (vPFC) and the amygdala suggest dysfunction in their connectivity. This study employed low frequency resting state functional magnetic resonance imaging (LFRS-fMRI) to analyze functional connectivity between the vPFC and the amygdala in BD. LFRS-fMRI identified a negative correlation in vPFC-amygdala activity, and the magnitude of this correlation was greater in healthy participants than in subjects with BD. Additionally, whole-brain analysis revealed higher correlations between left and right vPFC in BD, as well as with ventral striatum.

Relation Between Amygdala Structure and Function in Adolescents With Bipolar Disorder

OBJECTIVE Previous study supports the presence of reduced volume and elevated response to emotional stimuli in amygdala in adolescents with bipolar disorder (BD). In the present study, structural and functional magnetic resonance imaging scans were obtained during the same neuroimaging session to examine amygdala structure-function relations in adolescents with BD. We hypothesized that amygdala volume would be inversely associated with amygdala response to emotional stimuli, such that BD participants with the smallest amygdala volumes would exhibit the highest amygdala response. METHOD Fifty-one adolescents (21 with BD I and 30 control adolescents, ages 10-18 years) underwent structural and functional magnetic resonance imaging scans. Amygdala volume (n = 49) and signal change (n = 44) during emotional face processing were compared between groups, and structure-function correlations were examined within the BD group (n = 16). RESULTS Adolescents with BD showed decreased amygdala volume (p =.009) and increased amygdala response to emotional faces (p =.043). There was no significant interaction between diagnosis and emotion type. A significant inverse association between amygdala volume and activation during emotional face processing was observed (r = -0.54, p =.029). CONCLUSIONS Decreased volume and increased response to emotional stimuli in the amygdala in adolescents with BD are consistent with previous reports. This study represents the first report, to our knowledge, of the two findings in the same adolescent BD sample and supports an amygdala structure-function relation characterized by an inverse association between volume and response to emotional stimuli. This preliminary finding requires replication and suggests a possible pathophysiological link between abnormalities in amygdala structure and response to emotional stimuli in BD.

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.

Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder.

Histological and behavioral research in bipolar disorder (BD) implicates structural abnormalities in the hippocampus. Brain-derived neurotrophic growth factor (BDNF) protein is associated with hippocampal development and plasticity, and in mood disorder pathophysiology. We tested the hypotheses that both the BDNF val66met polymorphism and BD diagnosis are associated with decreased hippocampus volume, and that individuals with BD who carry the met allele have the smallest hippocampus volumes compared to individuals without BD and val/val homozygotes. We further explored localization of morphological differences within hippocampus in BD associated with the met allele. Twenty individuals with BD and 18 healthy comparison (HC) subjects participated in high-resolution magnetic resonance imaging scans from which hippocampus volumes were defined and measured. We used linear mixed model analysis to study effects of diagnosis and BDNF genotype on hippocampus volumes. We then employed three-dimensional mapping to localize areas of change within the hippocampus associated with the BDNF met allele in BD. We found that hippocampus volumes were significantly smaller in BD compared to HC subjects, and presence of the BDNF met allele was associated with smaller hippocampus volume in both diagnostic groups. The BD subgroup who carried the BDNF met allele had the smallest hippocampus volumes, and three-dimensional mapping identified these decreases as most prominent in left anterior hippocampus. These results support effects of BD diagnosis and BDNF genotype on hippocampus structure and suggest a genetic subgroup within BD who may be most vulnerable to deficits in hippocampus and may most benefit from interventions that influence BDNF-mediated signaling.

Role of variation in the serotonin transporter protein gene (SLC6A4) in trait disturbances in the ventral anterior cingulate in bipolar disorder.

Bipolar disorder (BD) is associated with abnormalities of the ventral anterior cingulate cortex (vACC) and its connection sites, including the amygdala, which are key components of a corticolimbic neural system that subserves emotional regulation. Decreased functional connectivity from the vACC to the amygdala in healthy individuals is associated with the short ‘s’ allele—as opposed to the long ‘l’ allele—of a well-known serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4), as are features of BD. This study tests the hypothesis that the s allele influences dysfunction in the vACC–amygdala neural system in BD. A total of 30 euthymic individuals with BD (20 s carriers, 10 ll) and 48 healthy comparison (HC) participants (34 s, 14 ll) participated in an event-related functional magnetic resonance imaging scan while processing fearful, happy, or neutral faces. During fear and happy face processing, vACC activation was significantly lower in the BD compared to the HC group, and in s carriers compared to ll individuals within both the HC and BD groups, such that BD s carriers exhibited the greatest magnitude of vACC dysfunction. No significant differences were detected in amygdala activation. The findings suggest that the 5-HTTLPR s allele may contribute to a trait-related, genetically derived, neurobiological subgroup within BD characterized by prominent vACC dysfunction. Future treatment may be optimized for this BD subgroup by targeting the serotonergic system and the vACC.

Influence of Vascular Endothelial Growth Factor Variation on Human Hippocampus Morphology

BACKGROUND Morphological abnormalities in hippocampus have been implicated in neuropsychiatric disorders, including depression, schizophrenia, and dementia. Vascular endothelial growth factor (VEGF) has been demonstrated to have neurogenic effects in the hippocampus in rats. However, influence of VEGF variation on hippocampus morphology in humans has yet to be shown. Here, an integrated genetic and neuroimaging approach was used to investigate whether VEGF variation influences hippocampus morphology in humans. METHODS High-resolution magnetic resonance imaging and voxel-based morphometry were used to identify the influence of genetic variation of VEGFA [rs833068 (SNP-1), rs833070 (SNP-2), rs2146323 (SNP-3) and rs3025020 (SNP-4)] on brain morphology in 47 healthy individuals. RESULTS Variation in VEGFA SNP-2 and SNP-3 showed significant effects on hippocampus concentration. CONCLUSIONS The findings suggest that effects of VEGF in hippocampus found in rats extend to humans; further understanding of effects of VEGFA variation might have important implications in identifying individuals more vulnerable to hippocampus pathology as well as those neuropsychiatric populations most likely to benefit from VEGF-mediated interventions.

Sexually dimorphic features of vermis morphology in bipolar disorder.

OBJECTIVES The cerebellar vermis is increasingly implicated in bipolar disorder (BD). In this study, we investigated vermis morphology in BD using a quantitative volumetric analysis. METHODS Volumes for total vermis and vermis subregions V1 (lobules I-V), V2 (lobules VI-VII), and V3 (lobules VIII-X) were calculated using high-resolution structural magnetic resonance imaging obtained from 44 individuals with BD (25 females and 19 males) and 43 healthy comparison (HC) subjects (26 females and 17 males). Total vermis volumes were compared between the BD and HC groups. Potential effects of vermis subregions and clinical features were explored. RESULTS Total vermis volumes were significantly larger in the BD group than in the HC group (p = 0.02). There was a significant group-by-sex interaction (p = 0.02). Total vermis volumes were significantly larger in males with BD than HC males (p = 0.004); vermis volumes did not differ significantly between females with and without BD (p = 0.95). Subregion analyses showed a trend-level interaction between diagnosis and subregion (p = 0.07) in which subregion V1 volumes were significantly larger in BD participants (p = 0.001), with differences primarily driven by males (p = 0.001). CONCLUSIONS Our findings demonstrate increases in cerebellar vermis volumes in males with BD. These findings support the presence of structural alterations in the cerebellar vermis in BD and furthermore the influence of sex on such changes.

Olfactocentric Paralimbic Cortex Morphology in Adolescents with Bipolar Disorder.

The olfactocentric paralimbic cortex plays a critical role in the regulation of emotional and neurovegetative functions that are disrupted in core features of bipolar disorder. Adolescence is thought to be a critical period in both the maturation of the olfactocentric paralimbic cortex and in the emergence of bipolar disorder pathology. Together, these factors implicate a central role for the olfactocentric paralimbic cortex in the development of bipolar disorder and suggest that abnormalities in this cortex may be expressed by adolescence in the disorder. We tested the hypothesis that differences in olfactocentric paralimbic cortex structure are a morphological feature in adolescents with bipolar disorder. Subjects included 118 adolescents (41 with bipolar disorder and 77 healthy controls). Cortical grey matter volume differences between adolescents with and without bipolar disorder were assessed with voxel-based morphometry analyses of high-resolution structural magnetic resonance imaging scans. Compared with healthy comparison adolescents, adolescents with bipolar disorder demonstrated significant volume decreases in olfactocentric paralimbic regions, including orbitofrontal, insular and temporopolar cortices. Findings in these regions survived small volume correction (P < 0.05, corrected). Volume decreases in adolescents with bipolar disorder were also noted in inferior prefrontal and superior temporal gyri and cerebellum. The findings suggest that abnormalities in the morphology of the olfactocentric paralimbic cortex may contribute to the bipolar disorder phenotype that emerges in adolescence. The morphological development of the olfactocentric paralimbic cortex has received little study. The importance of these cortices in emotional and social development, and support for a central role for these cortices in the development of bipolar disorder, suggest that study of the development of these cortices in health and in bipolar disorder is critically needed.