Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder.

CONTEXT: Although differences in clinical characteristics exist between major depressive disorder (MDD) and bipolar disorder (BD), consistent structural brain abnormalities that distinguish the disorders have not been identified. OBJECTIVES: To investigate structural brain changes in MDD using meta-analysis of primary studies; assess the effects of medication, demographic, and clinical variables; and compare the findings with those of a meta-analysis of studies on BD. DATA SOURCES: The MEDLINE, EMBASE, and PsycINFO databases were searched for studies from January 1, 1980, to February 2, 2010. STUDY SELECTION: Two hundred twenty-five studies that used magnetic resonance imaging or x-ray computed tomography to compare brain structure in patients with MDD with that of controls were included in an online database, and 143 that measured common brain structures were selected for meta-analysis. DATA EXTRACTION: Twenty-five variables, including demographic and clinical data, were extracted from each study, when available. For the meta-analysis, mean structure size and standard deviation were extracted for continuous variables, and the proportion of patients and controls with an abnormality in brain structure was extracted for categorical variables. DATA SYNTHESIS: Compared with the structure of a healthy brain, MDD was associated with lateral ventricle enlargement; larger cerebrospinal fluid volume; and smaller volumes of the basal ganglia, thalamus, hippocampus, frontal lobe, orbitofrontal cortex, and gyrus rectus. Patients during depressive episodes had significantly smaller hippocampal volume than patients during remission. Compared with BD patients, those with MDD had reduced rates of deep white matter hyperintensities, increased corpus callosum cross-sectional area, and smaller hippocampus and basal ganglia. Both disorders were associated with increased lateral ventricle volume and increased rates of subcortical gray matter hyperintensities compared with healthy controls. CONCLUSIONS: The meta-analyses revealed structural brain abnormalities in MDD that are distinct from those observed in BD. These findings may aid investigators attempting to discriminate mood disorders using structural magnetic resonance imaging data.

Metabolic alterations in medication-free patients with bipolar disorder: a 3T CSF-corrected magnetic resonance spectroscopic imaging study.

The objective of this study was to determine whether cerebrospinal fluid(CSF)-corrected concentrations of N-acetylaspartate are lower in several brain regions of drug- and medication-free subjects with bipolar disorder as compared with matched healthy controls. Bipolar subjects (n=21) and age- and sex-matched healthy control (n=21) were studied using proton magnetic resonance spectroscopic imaging on a 3T magnetic resonance (MR) scanner. Spectra were quantified using the LCModel, and metabolite values were CSF-corrected to yield metabolite concentrations. Fourteen regions of interest and five metabolite concentrations in each subject were selected for statistical analysis. We found that bipolar subjects had significantly decreased N-acetylaspartate concentrations in both caudate heads and the left lentiform nucleus. Choline and creatine in the head of the right caudate were also significantly decreased in bipolar subjects. Significantly increased myo-inositol was found in the left caudate head in bipolar subjects. Bipolar subjects showed significantly decreased glutamate/glutamine concentrations in the frontal white matter bilaterally and in the right lentiform nucleus. No differences were found for other metabolites examined. These preliminary findings suggest decreased neuronal density or viability in the basal ganglia and neurometabolic abnormalities in the frontal lobes of subjects with bipolar disorder.

Biogenic amines in seasonal affective disorder: effects of light therapy.

Wintertime measures of central and peripheral monoamine neurotransmitter system activity in 17 medication-free depressed patients with seasonal affective disorder (SAD) were compared with those in eight healthy volunteers. Mean cerebrospinal fluid (CSF) concentrations of the principal metabolites of norepinephrine (NE), serotonin, and dopamine did not differ between the two groups, nor did mean basal or orthostatically stimulated plasma NE levels. Patients' pretreatment depression ratings were inversely correlated with resting plasma NE concentrations. Fourteen SAD patients were clear responders to 2 weeks of full-spectrum bright light treatment. Neither the transmitter measures nor their interrelatedness was affected significantly by phototherapy.

CSF cortisol in patients with depression, mania, or anorexia nervosa and in normal subjects.

The authors studied CSF cortisol in 30 depressed patients, 10 manic patients, 21 women with anorexia nervosa, and 22 normal control subjects. All patients were also rated on a global severity scale for mania or depression. Results indicated higher CSF cortisol levels in all three patient groups than in the control group. Only the depressed group had a significant positive correlation between CSF cortisol and severity ratings. The authors recommend further research into the hypothalamic mechanisms associated with cortisol secretion and regulation.