John M. Hawkins

MRI Analysis of the Cerebellum in Bipolar Disorder: A Pilot Study

Since qualitative CT studies have suggested decreased cerebellar size in patients with bipolar disorder, we performed a quantitative analysis of the cerebellum in patients with bipolar disorder to determine whether high-resolution, thin slice magnetic resonance imaging (MRI) morphometry would reveal similar results. Bipolar patients hospitalized for a first manic episode (n = 16), bipolar patients with prior manic episodes hospitalized for a manic episode (n = 14), and normal volunteers (n = 15) matched for age, sex, race, and education were recruited and anatomic brain scans were acquired using a Picker 1.5 Tesla MRI scanner. Right and left cerebellar hemisphere volumes and vermal areas V1 (lobules I-V), V2 (lobules VI-VII), and V3 (lobules VIII-X) were measured. ANCOVA comparing each ROI, adjusting for race, sex, age, total cerebral volume, and substance abuse duration, revealed a significant group effect for vermal V3 area. Specifically, V3 area was significantly smaller in multiple-episode patients than in first-episode patients or healthy volunteers. Number of previous episodes of depression may contribute to this finding. These results suggest that cerebellar vermal atrophy may be a later neurodegenerative event in patients with bipolar disorder who have had multiple affective episodes. The confounding effects of medications are considered.

Outcome and comorbidity in first- compared with multiple-episode mania.

The aim of this study was to examine the outcome and comorbidity of patients with bipolar disorder presenting with first-episode as compared with multiple-episode mania. Based on studies from the prepharmacological era and the sensitization model of bipolar disorder, we hypothesized that compared with multiple-episode mania, first-episode mania would be associated with better outcome, milder severity, and less psychiatric comorbidity. Seventy-one hospitalized patients, age 12 years and older and meeting DSM-III-R criteria for bipolar disorder, were recruited over a 1-year period. Thirty-four (48%) first-episode and 37 (56%) multiple-episode patients were compared regarding demographics, phenomenology, comorbidity, family history, and short-term course. Compared with multiple-episode mania, first-episode mania was associated with significantly shorter hospitalization and a higher rate of comorbid impulse control disorders. These data provide indirect support for the sensitization model of bipolar disorder.

Twelve-month outcome of patients with DSM-III-R schizoaffective disorder: comparisons to matched patients with bipolar disorder.

Schizoaffective disorder is a relatively common illness with an uncertain relationship with bipolar disorder. The publication of DSM-III-R in 1987 operationalized the diagnosis of schizoaffective disorder, separating it from psychotic bipolar disorder by the presence of persistent psychosis in the absence of affective symptoms. Since that time, there have been few prospective outcome studies comparing schizoaffective and bipolar disorders. The authors recruited 27 hospitalized patients with schizoaffective disorder and compared their 12-month outcome to 27 sex-, age-, socioeconomic status- and race-matched hospitalized bipolar patients. The schizoaffective patients were significantly less likely to achieve syndromic recovery than the bipolar patients, although neither group achieved high rates of symptomatic or functional recovery. As expected, the schizoaffective patients were more likely to exhibit persistent psychosis, with or without affective symptoms, throughout the follow-up interval. These data provide clinical support of the predictive value of the DSM-III-R criteria for schizoaffective disorder in a naturalistic outcome setting.

Adjunctive lisdexamfetamine in bipolar depression: a preliminary randomized, placebo-controlled trial.

This study evaluated the efficacy and tolerability of lisdexamfetamine (LDX) in the treatment of bipolar depression. Twenty-five outpatients with bipolar I or II disorder and syndromal depression despite at least 4 weeks of stable mood stabilizer and/or antipsychotic therapy were randomized to receive LDX (N=11) or placebo (N=14) in an 8-week, prospective, parallel-group, double-blind study. In the primary longitudinal analysis, LDX and placebo produced similar rates of improvement in depressive symptoms as assessed by the Montgomery–Asberg Depression Scale. However, LDX was associated with a statistically significantly greater rate of improvement in self-reported depressive symptoms and daytime sleepiness, and with greater reductions in fasting levels of low-density lipoprotein and total cholesterol. In the secondary baseline-to-endpoint analysis, LDX was associated with statistically significant improvements in self-reported measures of depression, daytime sleepiness, fatigue, and binge eating, as well as with improvements in fasting levels of triglycerides and low-density lipoprotein and total cholesterol. LDX was well tolerated and was not associated with any serious adverse events, but there was one case of suspected misuse. The small sample size (because of premature study termination by the funding sponsor) may have limited the detection of important drug–placebo differences. Larger studies on the use of psychostimulants for treatment of bipolar depression seem warranted.

A naturalistic, multi-site study of repetitive transcranial magnetic stimulation therapy for depression

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) was approved in 2008 in the United States, and there are relatively few studies describing its use in regular clinical practice since approval. METHODS From April 2011 to October 2014, ten sites within the National Network of Depression Centers (NNDC) provided data on 62 evaluable patients with a depressive episode. Treatment was determined naturalistically. Response was assessed by the Quick Inventory of Depressive Symptoms, Self-Report (QIDS-SR) as the primary outcome, and the Patient Health Questionnaire-9 (PHQ-9) and the clinician-rated Clinical Global Impression (CGI) as secondary depression measures. RESULTS Enrolled patients exhibited significant treatment resistance, with 70.2% reporting more than 4 prior depressive episodes. Most patients received treatment with standard parameters (10Hz over the left dorsolateral prefrontal cortex), although 22.6% of the patients received 1 or 5Hz stimulation at some point. Over 6 weeks of treatment, response and remission rates were 29.4% and 5.9%, respectively, for the QIDS-SR; 39.2% and 15.7%, respectively, for the PHQ-9; and 50.9% and 17.9%, respectively, for the CGI. Moderator analyses revealed no effect of prior depressive episodes, history of ECT or gender, although early life stress predicted a better response to rTMS therapy. LIMITATIONS The study was an open-label, registry trial, with relatively coarse clinical data, reflecting practice only in academic, depression-specialty centers. Because of the relatively small size and heterogeneity of the sample, type 2 errors are possible and positive findings are in need of replication. CONCLUSION rTMS demonstrates effectiveness in clinical practice within the NNDC, although remission rates appear slightly lower in comparison with other recent naturalistic studies.