[Show abstract][Hide abstract] ABSTRACT: Corticolimbic circuitry has been implicated in generalized social anxiety disorder (gSAD) by several neuroimaging symptom provocation studies. However, there are limited data regarding resting state or treatment effects on regional cerebral metabolic rate of glucose uptake (rCMRglu). Given evidence for anxiolytic effects conferred by tiagabine, a gamma-aminobutyric acid (GABA) reuptake inhibitor, the present [(18)F] fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) study sought to (1) compare resting rCMRglu between healthy control (HC) and pretreatment gSAD cohorts, (2) examine pre- to post-tiagabine treatment rCMRglu changes in gSAD, and (3) determine rCMRglu predictors of tiagabine treatment response. Fifteen unmedicated individuals with gSAD and ten HCs underwent a baseline (pretreatment) resting-state (18)FDG-PET scan. Twelve of the gSAD individuals completed an open, 6-week, flexible dose trial of tiagabine, and underwent a second (posttreatment) resting-state (18)FDG-PET scan. Compared to the HC subjects, individuals with gSAD demonstrated less pretreatment rCMRglu within the anterior cingulate cortex and ventral medial prefrontal cortex (vmPFC) at baseline. Following tiagabine treatment, vmPFC rCMRglu increased significantly in the gSAD group. Further, the magnitude of treatment response was inversely correlated with pretreatment rCMRglu within vmPFC. Taken together the present findings converge with neuroimaging findings from studies of social cognition in healthy individuals and symptom provocation in gSAD to support a role for the vmPFC in the pathophysiology of gSAD. Given the pharmacological profile of tiagabine, these findings suggest that its therapeutic effects in gSAD may be mediated by GABAergic modulation within the vmPFC.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2008; 34(2):390-8. DOI:10.1038/npp.2008.69 · 7.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Impulsivity and anxiety, common features of bipolar disorder (BD), are each associated with a number of negative outcomes in BD. The relationship between anxiety and impulsivity, however, has not been a focus of study in BD. In this paper, we present data regarding the association between anxiety and impulsivity as measured by the Barratt impulsiveness scale (BIS-11) in 114 outpatients with BD. Results revealed that patients with a comorbid anxiety disorder displayed significantly higher levels of impulsivity relative to patients without an anxiety disorder. Moreover, a broad range of anxiety-related symptom domains was associated with greater impulsivity. Exploratory analyses also revealed that baseline anxiety symptoms were associated with elevated impulsivity at 9-month follow-up, although these relationships were less robust after covariate adjustment. These data demonstrate that anxiety is positively associated with impulsivity in patients with BD. Further studies are needed to elucidate the implications of and reasons for this association.
[Show abstract][Hide abstract] ABSTRACT: Recent technological advances offer an opportunity to further elucidate the complex cytokine network in Major Depressive Disorder (MDD). Twenty cytokines were simultaneously assessed in 49 individuals with MDD and 49 age and gender matched controls. Multiple pro-inflammatory and two anti-inflammatory cytokines were significantly elevated in the MDD sample, including an antidepressant naïve subset. These data support a generalized chronic inflammatory state in MDD, and implicate additional cytokines and chemokines previously linked to cardiovascular disease.
European Neuropsychopharmacology 04/2008; 18(3):230-3. DOI:10.1016/j.euroneuro.2007.06.004 · 4.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the relationship of sleep disturbance with complicated grief (CG) in patients with bipolar disorder (BD).
Adults with DSM-IV BD were asked if they ever experienced significant loss and, if so, completed the Inventory of Complicated Grief. Subjective sleep disturbance was assessed with the Pittsburgh Sleep Quality Index (PSQI). The association of CG with sleep disturbance was assessed in univariate t-tests, and in multivariate analyses controlling for the presence of anxiety disorder comorbidity and current bipolar recovery status.
Individuals with CG had significantly higher mean PSQI scores (10.9 versus 7.9, p = 0.003) than those without CG. Further, within the group of BD participants who had experienced a significant loss, those with CG had significantly poorer sleep (p = 0.01). CG remained significantly associated with greater sleep impairment after adjustment for comorbid anxiety disorder and bipolar mood state. This additive impairment in sleep with CG comorbidity was evident for four of the PSQI component scales: sleep quality, sleep duration, sleep efficiency and sleep disturbance.
Our data indicate a significant association of CG with poor sleep in individuals with BD. Disturbed sleep may be a mechanism by which CG increases the burden of illness in BD.
[Show abstract][Hide abstract] ABSTRACT: Individuals with bipolar disorder are at increased risk for suicide attempts and completion. Although anxiety may be a modifiable suicide risk factor among bipolar patients, anxiety disorder comorbidity has not been highlighted as critical in identification of high-risk individuals nor has its treatment been integrated into suicide prevention strategies. In this study, ancillary to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 120 outpatients with bipolar disorder completed detailed assessment of suicidal ideation and behaviors. We examined the association of current and lifetime comorbid anxiety disorders with suicidal ideation and behaviors univariately and with adjustment for potential confounders in regression models. Lifetime anxiety disorders were associated with a more than doubling of the odds of a past suicide attempt, and current anxiety comorbidity was associated with a more than doubling of the odds of current suicidal ideation. Individuals with current anxiety disorders had more severe suicidal ideation, a greater belief suicide would provide relief, and a higher expectancy of future suicidal behaviors. However, some of these associations appeared to be better accounted for by measures of bipolar severity including an earlier age at bipolar onset and a lack of current bipolar recovery. Comorbid anxiety disorders may play a role in characteristics of bipolar disorder that then elevate risk for suicidal ideation and attempts. While further research is needed to establish the precise nature of these associations, our data support that the presence of comorbid anxiety disorders in individuals with bipolar disorder should trigger careful clinical assessment of suicide risk.
Journal of Psychiatric Research 04/2007; 41(3-4):255-64. DOI:10.1016/j.jpsychires.2006.08.004 · 3.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prior studies suggest an association between anxiety comorbidity and suicidal ideation and behaviors in bipolar disorder. However, the nature of this association remains unclear.
We examined a range of anxiety symptoms, including panic, phobic avoidance, anxiety sensitivity, worry and fear of negative evaluation, in 98 patients with bipolar disorder. We predicted that each anxiety dimension would be linked to greater suicidal ideation and behavior as measured by Linehan's Suicide Behaviors Questionnaire (SBQ), greater depressive rumination, and poorer emotional processing and expression.
Each anxiety dimension except fear of negative evaluation was associated with greater SBQ score, greater rumination, and lower levels of emotional processing in univariate analyses. Depressive rumination was a significant predictor of higher SBQ scores in a stepwise multivariate model controlling for age, gender, bipolar subtype, and bipolar recovery status; the association between the anxiety symptom dimensions and SBQ score was found to be redundant with depressive rumination. Emotional processing emerged as protective against suicidal ideation and behaviors in men only, while emotional expression was a significant predictor of lower SBQ scores for women and for the full sample; however, emotional expression was not significantly correlated with anxiety symptoms. Confirmatory analyses examining only those in recovery or recovered (n=68) indicated that the link between rumination and suicidality was not explained by depression.
Interpretation is limited by the cross-sectional study design.
These findings indicate that increased ruminations may mediate the association between anxiety and suicidal ideation/behavior. In men, lower emotional processing may also play a role in this relationship.