Dataset Information

Behavioral and Neural Sustained Attention Deficits in Bipolar Disorder and Familial Risk of Bipolar Disorder.

ABSTRACT: BACKGROUND:Few neuroimaging studies compare individuals affected with bipolar disorder (BP), at high familial risk of BP, and at low risk to identify endophenotypes for BP. None have examined variability in attention, despite promising behavioral work in this area. We used functional magnetic resonance imaging (fMRI) methods uniquely powered to compare the neural correlates of attention variability in these three groups. METHODS:The present study examined 8- to 25-year-old individuals (n = 106) who completed an fMRI attention task: 24 with BP, 29 at risk based on a first-degree relative with BP, and 53 healthy, low-risk individuals. Group differences in intrasubject variability in reaction time were examined, and a sophisticated fMRI analytic approach was used to quantify precisely trialwise associations between reaction time and brain activity. The latter has not been examined previously in BP or risk of BP. RESULTS:Relative to healthy individuals, those with BP or at risk for BP exhibited increased reaction time variability (F2,102 = 4.26, p = .02, ?p2 = .08). Importantly, we identified blunted relationships between trialwise variation in reaction time and brain activity in the inferior and middle frontal gyri, precuneus, cingulate cortex, caudate, and postcentral gyrus (all regions: p < .001, ?p2 > .06) in both at-risk and BP individuals compared with healthy, low-risk individuals. This blunting partially mediated group differences in reaction time variability (? = .010, 95% confidence interval 0.002 to 0.020, Sobel Z = 2.08, p = .038). CONCLUSIONS:Blunting in key frontal, cingulate, and striatal areas was evident in unaffected, at-risk individuals and in euthymic BP patients. Elucidating such novel neural endophenotypes can facilitate new approaches to BP prediction, diagnosis, and prevention.

SUBMITTER: Pagliaccio D

PROVIDER: S-EPMC5354995 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Behavioral and Neural Sustained Attention Deficits in Bipolar Disorder and Familial Risk of Bipolar Disorder.

Pagliaccio David D Wiggins Jillian Lee JL Adleman Nancy E NE Harkins Elizabeth E Curhan Alexa A Towbin Kenneth E KE Brotman Melissa A MA Pine Daniel S DS Leibenluft Ellen E

Biological psychiatry 20160916 9

<h4>Background</h4>Few neuroimaging studies compare individuals affected with bipolar disorder (BP), at high familial risk of BP, and at low risk to identify endophenotypes for BP. None have examined variability in attention, despite promising behavioral work in this area. We used functional magnetic resonance imaging (fMRI) methods uniquely powered to compare the neural correlates of attention variability in these three groups.<h4>Methods</h4>The present study examined 8- to 25-year-old individ ...[more]

PMID: 27837919

Similar Datasets

Project description:OBJECTIVE:Disruptive mood dysregulation disorder (DMDD), characterized by severe irritability, and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid. This is the first study to characterize neural and behavioral similarities and differences in attentional functioning across these disorders. METHOD:Twenty-seven healthy volunteers, 31 patients with DMDD, and 25 patients with ADHD (8 to 18 years old) completed a functional magnetic resonance imaging attention task. Group differences in intra-subject variability in reaction time (RT) were examined. The present functional magnetic resonance imaging analytic approach precisely quantified trial-wise associations between RT and brain activity. RESULTS:Group differences manifested in the relation between RT and brain activity (all regions: p < .01, F > 2.54, partial eta-squared [?p2] > 0.06). Patients with DMDD showed specific alterations in the right paracentral lobule, superior parietal lobule, fusiform gyrus, and cerebellar culmen. In contrast, patients with DMDD and those with ADHD exhibited blunted compensatory increases in activity on long RT trials. In addition, youth with DMDD exhibited increased activity in the postcentral gyrus, medial frontal gyrus, and cerebellar tonsil and declive (all regions: p < .05, F > 2.46, ?p2 > 0.06). Groups in the imaging sample did not differ significantly in intra-subject variability in RT (F2,79 = 2.664, p = .076, ?p2 = 0.063), although intra-subject variability in RT was significantly increased in youth with DMDD and ADHD when including those not meeting strict motion and accuracy criteria for imaging analysis (F2,96 = 4.283, p = .017, ?p2 = 0.083). CONCLUSION:Patients with DMDD exhibited specific alterations in the relation between pre-stimulus brain activity and RT. Patients with DMDD and those with ADHD exhibited similar blunting of compensatory neural activity in frontal, parietal, and other regions. In addition, patients with DMDD showed increased RT variability compared with healthy youth. This work is the first to identify common and unique behavioral and neural signatures of DMDD and ADHD.

Project description:Complex disorders, such as bipolar disorder (BD), likely result from the influence of both common and rare susceptibility alleles. While common variation has been widely studied, rare variant discovery has only recently become feasible with next-generation sequencing.To utilize a combined family-based and case-control approach to exome sequencing in BD using multiplex families as an initial discovery strategy, followed by association testing in a large case-control meta-analysis.We performed exome sequencing of 36 affected members with BD from 8 multiplex families and tested rare, segregating variants in 3 independent case-control samples consisting of 3541 BD cases and 4774 controls.We used penalized logistic regression and 1-sided gene-burden analyses to test for association of rare, segregating damaging variants with BD. Permutation-based analyses were performed to test for overall enrichment with previously identified gene sets.We found 84 rare (frequency <1%), segregating variants that were bioinformatically predicted to be damaging. These variants were found in 82 genes that were enriched for gene sets previously identified in de novo studies of autism (19 observed vs. 10.9 expected, P?=?.0066) and schizophrenia (11 observed vs. 5.1 expected, P?=?.0062) and for targets of the fragile X mental retardation protein (FMRP) pathway (10 observed vs. 4.4 expected, P?=?.0076). The case-control meta-analyses yielded 19 genes that were nominally associated with BD based either on individual variants or a gene-burden approach. Although no gene was individually significant after correction for multiple testing, this group of genes continued to show evidence for significant enrichment of de novo autism genes (6 observed vs 2.6 expected, P?=?.028).Our results are consistent with the presence of prominent locus and allelic heterogeneity in BD and suggest that very large samples will be required to definitively identify individual rare variants or genes conferring risk for this disorder. However, we also identify significant associations with gene sets composed of previously discovered de novo variants in autism and schizophrenia, as well as targets of the FRMP pathway, providing preliminary support for the overlap of potential autism and schizophrenia risk genes with rare, segregating variants in families with BD.

Dataset Information

Behavioral and Neural Sustained Attention Deficits in Bipolar Disorder and Familial Risk of Bipolar Disorder.

Publications

Behavioral and Neural Sustained Attention Deficits in Bipolar Disorder and Familial Risk of Bipolar Disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure