The association of elevated body mass index with reduced brain volumes in first-episode mania.

BACKGROUND: Compared with normal-weight patients, obese patients with bipolar I disorder (BD) suffer more manic and depressive episodes and make more suicide attempts. In the general population, obesity is associated with reduced total brain volume (TBV) and gray matter volume (GMV), but the neurobiology of obesity in BD has not been investigated. METHODS: We used magnetic resonance imaging to examine TBV, GMV, white matter volume (WMV), as well as frontal, parietal, occipital, and temporal lobe volumes, in 55 healthy subjects (17 overweight/obese and 38 normal weight) and 57 patients with BD following their first manic episode (20 overweight/obese and 37 normal weight). RESULTS: Linear regression analyses demonstrated that when other predictors of brain volume were accounted for, increased body mass index (BMI) in healthy subjects was significantly associated with decreased TBV and GMV. In contrast, increased BMI in patients with BD was significantly associated with decreased WMV and temporal lobe volume, areas of known vulnerability in early BD. CONCLUSIONS: This is the first published report to show a relationship between elevated BMI and reduced brain volumes in BD, or any psychiatric illness. Our results suggest that obesity is associated with unique neurobiological changes in BD. They further imply a possible biological mechanism underlying the association between obesity and a more severe illness course in BD.

Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats.

BACKGROUND: Perioperative beta-blockade and anemia are independent predictors of increased stroke and mortality by undefined mechanisms. This study investigated the effect of beta-blockade on cerebral tissue oxygen delivery in an experimental model of blood loss and fluid resuscitation (hemodilution). METHODS: Anesthetized rats were treated with metoprolol (3 mg x kg) or saline before undergoing hemodilution with pentastarch (1:1 blood volume exchange, 30 ml x kg). Outcomes included cardiac output, cerebral blood flow, and brain (PBrO2) and kidney (PKO2) tissue oxygen tension. Hypoxia inducible factor-1alpha (HIF-1alpha) protein levels were assessed by Western blot. Systemic catecholamines, erythropoietin, and angiotensin II levels were measured. RESULTS: Hemodilution increased heart rate, stroke volume, cardiac output (60%), and cerebral blood flow (50%), thereby maintaining PBrO2 despite an approximately 50% reduction in blood oxygen content (P < 0.05 for all). By contrast, PKO2 decreased (50%) under the same conditions (P < 0.05). Beta-blockade reduced baseline heart rate (20%) and abolished the compensatory increase in cardiac output after hemodilution (P < 0.05). This attenuated the cerebral blood flow response and reduced PBrO2 (50%), without further decreasing PKO2. Cerebral HIF-1alpha protein levels were increased in beta-blocked hemodiluted rats relative to hemodiluted controls (P < 0.05). Systemic catecholamine and erythropoietin levels increased comparably after hemodilution in both groups, whereas angiotensin II levels increased only after beta-blockade and hemodilution. CONCLUSIONS: Cerebral tissue oxygen tension is preferentially maintained during hemodilution, relative to the kidney, despite elevated systemic catecholamines. Acute beta-blockade impaired the compensatory cardiac output response to hemodilution, resulting in a reduction in cerebral tissue oxygen tension and increased expression of HIF-1alpha.

Antidepressant-associated mood elevations in bipolar II disorder compared with bipolar I disorder and major depressive disorder: a systematic review and meta-analysis.

OBJECTIVE: Antidepressant-associated manic and hypomanic episodes have been reported in bipolar I disorder but are rare in major depressive disorder (MDD). Several lines of evidence suggest that bipolar II disorder is a distinct illness from bipolar I disorder and MDD. The risk of antidepressant-associated mood elevations (AAME) in bipolar II disorder relative to bipolar I disorder and MDD is unknown. DATA SOURCES: We conducted a computer-aided MEDLINE search encompassing the dates 1949 to February 2008, using the keywords antidepressant and mania, antidepressant and hypomania, antidepressant and bipolar, fluoxetine and bipolar, fluvoxamine and bipolar, sertraline and bipolar, paroxetine and bipolar, citalopram and bipolar, escitalopram and bipolar, venlafaxine and bipolar, mirtazapine and bipolar, bupropion and bipolar, monoamine oxidase inhibitor and bipolar, phenelzine and bipolar, tranylcypromine and bipolar, tricyclic and bipolar, imipramine and bipolar, amitriptyline and bipolar, nortriptyline and bipolar, and desipramine and bipolar. STUDY SELECTION: All prospective English-language studies, including randomized, controlled trials (RCTs), open-label studies, and naturalistic treatment reports, were eligible for inclusion. We located 13 studies, including 7 RCTs, that reported rates of antidepressant-associated mood elevations in bipolar I disorder versus bipolar II disorder, and 5, including 4 RCTs, that reported rates in bipolar II disorder versus MDD. DATA EXTRACTION: Data were combined to estimate mean switch rates and subjected to meta-analysis to determine the relative risks of antidepressant-associated mood elevations in bipolar I disorder versus bipolar II disorder and in bipolar II disorder versus MDD. DATA SYNTHESIS: The mean rates of antidepressant-associated mood elevations in studies comparing bipolar I disorder and bipolar II disorder were 14.2% and 7.1%, respectively, in acute trials (less than 16 weeks), and 23.4% and 13.9%, respectively, in maintenance studies. The mean rates in reports comparing bipolar II disorder and MDD were 8.1% and 1.5%, respectively, in acute trials, and 16.5% and 6.0%, respectively, in maintenance studies. The relative risk (RR) of antidepressant-associated mood elevations was greater in bipolar I disorder than bipolar II disorder (RR = 1.78, 95% CI = 1.24 to 2.58, p = .002), and higher in bipolar II disorder than MDD (RR = 2.77, 95% CI = 1.26 to 6.09, p = .01). Mood elevations occurred almost exclusively into hypomania in MDD and bipolar II disorder, while patients with bipolar I disorder experienced manias and hypomanias with similar frequencies. CONCLUSIONS: The risk of antidepressant-associated mood elevations in bipolar II disorder is intermediate between that in bipolar I disorder and MDD.