Galantamine-ER For Cognitive Dysfunction In Bipolar Disorder and Correlation with Hippocampal Neuronal Viability: A Proof-of-Concept Study

Background: Many subjects with bipolar disorder experience significant cognitive dysfunction, even when euthymic, but few studies assess biological correlates of or treatment strategies for cognitive dysfunction.
Method: Nineteen subjects with bipolar disorder in remission, who reported subjective cognitive deficits, were treated with open-label galantamine-ER 8–24 mg/day for 4 months. Ten healthy volunteers matched for age and gender were also assessed. Mood and subjective cognitive questionnaires were administered monthly. At the beginning and the end of the trial all subjects were administered neuropsychological tests, including tests of attention (Conners CPT) and episodic memory (CVLT). Bipolar subjects underwent proton magnetic resonance spectroscopy (1H-MRS) measurements before and after treatment, healthy volunteers completed baseline 1H-MRS. We acquired 1H-MRS data at 4.0 T from voxels centered on the left and right hippocampus to measure hippocampal N -acetyl aspartate (NAA, a measure of neuronal viability) and choline containing compounds (Cho, a marker of lipid metabolism and membrane turn-over).
Results: Compared to healthy volunteers, bipolar subjects had higher baseline subjective cognitive deficits and lower scores on objective tests of attention (Conner's CPT) and verbal episodic memory (CVLT). After treatment, bipolar subjects experienced significant improvement of subjective cognitive scores and on objective tests of attention (Conner's CPT) and verbal episodic memory (CVLT). In the left hippocampus NAA increased and choline (Cho) decreased in bipolar subjects during treatment.
Conclusion: Bipolar subjects had cognitive dysfunction; treatment with Galantamine-ER was associated with improved cognition and with increases in neuronal viability and normalization of lipid membrane metabolism in the left hippocampus.
This study was registered on ClinicalTrials.gov (NCT00181636).     

Bipolar depression: relationship between episode length and antidepressant treatment

BACKGROUND: The role of antidepressant medications in bipolar depression remains controversial, mainly due to a lack of research in this area. In this study the authors examined the episode length in bipolar depression and the relationship between antidepressant therapy and episode length. METHOD: A retrospective chart review of 165 subjects identified 50 (30%) with bipolar illness who experienced a major depressive episode between 1 January 1998 and 15 December 2000. Data gathered utilized a structured instrument completed by the clinician at each visit. This instrument includes modified SCID mood modules as well as continuous ratings for each associated symptom of depression and mood elevation. Survival analysis was employed to calculate the median length of the depressive episodes for the entire group. Further survival analysis compared the episode length for subjects treated with antidepressants during the depression (N = 33) with those who did not receive antidepressants (N = 17). The rate of switch into elevated mood states was compared for the two groups. RESULTS: The survival analysis for the entire sample demonstrated 25%, 50% and 75% probability of recovery at 33 (S.E. 8.7), 66 (S.E. 17.9) and 215 (S.E. 109.9) days, respectively. Comparing those who received (N = 33) and those who did not receive (N = 17) antidepressants during the episode did not reveal any difference in the length of the depressive episode. Switch rates were not significantly different between those receiving antidepressants and those not taking these medications (15.2% v. 17.6%, respectively). CONCLUSIONS: Over the past 20 years little progress has been made in reducing the length of depressive episodes in those with bipolar illness. This is despite increasing pharmacological options available for treating depression. Clinicians treating bipolar depression should discuss with their patients the likelihood that the episode will last between 2-3 months. Our results also suggest that antidepressant treatment may not reduce the length of depressive episodes, neither did it appear to contribute to affective switch in our sample.     

Reward processing in trichotillomania and skin picking disorder

Brain Imaging and Behavior - Trichotillomania (hair pulling disorder) and skin picking disorder are common and often debilitating mental health conditions, grouped under the umbrella term of body...     

Extreme attributions predict transition from depression to mania or hypomania in bipolar disorder

Background

Relatively little is known about psychological predictors of the onset of mania among individuals with bipolar disorder, particularly during episodes of depression. In the present study we investigated attributional style as a predictor of onset of hypomanic, manic or mixed episodes among bipolar adults receiving psychosocial treatment for depression. We hypothesized that “extreme” (i.e., excessively pessimistic or optimistic) attributions would predict a greater likelihood of developing an episode of mood elevation.

Method

Outpatients with DSM-IV bipolar I or II disorder (N = 105) enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomly allocated to one of three types of intensive psychotherapy for depression or a brief psychoeducational intervention. Patients completed a measure of attributional style at baseline and were followed prospectively for up to one year. All analyses were by intent to treat.

Results

Logistic regressions and Cox proportional hazards models indicated that extreme (both positively- and negatively-valenced) attributions predicted a higher likelihood of (and shorter time until) transition from depression to a (hypo)manic or mixed episode (ps < .04), independent of the effects of manic or depressive symptom severity at baseline. Extreme attributions were also retrospectively associated with more lifetime episodes of (hypo)mania and depression (ps < .05).

Conclusions

Evaluating extreme attributions may help clinicians to identify patients who are at risk for experiencing a more severe course of bipolar illness, and who may benefit from treatments that introduce greater cognitive flexibility.     

Illness burden and medical comorbidity in the Systematic Treatment Enhancement Program for Bipolar Disorder

Magalhães PV, Kapczinski F, Nierenberg AA, Deckersbach T, Weisinger D, Dodd S, Berk M. Illness burden and medical comorbidity in the Systematic Treatment Enhancement Program for Bipolar Disorder. Objective: Coexisting chronic medical conditions are common in bipolar disorder. Here, we report the prevalence and correlates of medical comorbidity in patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD). We were particularly interested in associations between variables reflecting illness chronicity and burden with comorbid medical conditions. Method: We used intake data from the open‐label component of the STEP‐BD. History of medical comorbidity was obtained from the affective disorders evaluation, and its presence was the outcome of interest. The sample size in analyses varied from 3399 to 3534. We used multiple Poisson regression to obtain prevalence ratios. Results: The prevalence of any medical comorbidity in the sample was 58.8%. In addition to demographic variable, several clinical characteristics were associated with the frequency of medical comorbidity. Having more than 10 previous mood episodes, childhood onset, smoking, lifetime comorbidity with anxiety, and substance use disorders were independently associated with having a medical comorbidity in the final multivariate model. Conclusion: The results presented here reveal strong associations between variables related to illness chronicity and medical burden in bipolar disorder. This lends further support to recent multidimensional models incorporating medical morbidity as a core feature of bipolar disorder.     

Randomized trial of behavior therapy for adults with tourette syndrome

CONTEXT Tics in Tourette syndrome begin in childhood, peak in early adolescence, and often decrease by early adulthood. However, some adult patients continue to have impairing tics. Medications for tics are often effective but can cause adverse effects. Behavior therapy may offer an alternative but has not been examined in a large-scale controlled trial in adults. OBJECTIVE To test the efficacy of a comprehensive behavioral intervention for tics in adults with Tourette syndrome of at least moderate severity. DESIGN A randomized controlled trial with posttreatment evaluations at 3 and 6 months for positive responders. SETTING Three outpatient research clinics. PATIENTS Patients (N?=?122; 78 males; age range, 16-69 years) with Tourette syndrome or chronic tic disorder were recruited between December 27, 2005, and May 21, 2009. INTERVENTIONS Patients received 8 sessions of comprehensive behavioral intervention for tics or 8 sessions of supportive treatment for 10 weeks. Patients with a positive response were given 3 monthly booster sessions. MAIN OUTCOME MEASURES Total tic score on the Yale Global Tic Severity Scale and the Clinical Global Impression-Improvement scale rated by a clinician masked to treatment assignment. RESULTS Behavior therapy was associated with a significantly greater mean (SD) decrease on the Yale Global Tic Severity Scale (24.0?[6.47] to 17.8?[7.32]) from baseline to end point compared with the control treatment (21.8?[6.59] to 19.3?[7.40]) (P?<?.001; effect size?=?0.57). Twenty-four of 63 patients (38.1%) were rated as much improved or very much improved on the Clinical Global Impression-Improvement scale compared with 4 of 63 (6.4%) in the control group (P?<?.001). Attrition was 13.9%, with no difference across groups. Patients receiving behavior therapy who were available for assessment at 6 months after treatment showed continued benefit. CONCLUSION Comprehensive behavior therapy is a safe and effective intervention for adults with Tourette syndrome. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00231985.     

Gray matter volumes in obsessive-compulsive disorder before and after fluoxetine or cognitive-behavior therapy: a randomized clinical trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n=38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n=36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n=26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n=13), whereas no significant GM volume changes were observed in CBT-treated patients (n=13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action.