Association of obesity with cognitive function and brain structure in patients with major depressive disorder.

BACKGROUND: Obesity has been implicated in the pathophysiology of major depressive disorder (MDD), which prompted us to examine the possible association of obesity with cognitive function and brain structure in patients with MDD. METHODS: Three hundred and seven patients with MDD and 294 healthy participants, matched for age, sex, ethnicity (Japanese), and handedness (right) were recruited for the study. Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). Gray and white matter structures were analyzed using voxel-based morphometry and diffusion tensor imaging in a subsample of patients (n = 114) whose magnetic resonance imaging (MRI) data were obtained using a 1.5 T MRI system. RESULTS: Verbal memory, working memory, motor speed, attention, executive function, and BACS composite scores were lower for the MDD patients than for the healthy participants (p < 0.05). Among the patient group, working memory, motor speed, executive function, and BACS composite scores were lower in obese patients (body mass index ≥ 30, n = 17) than in non-obese patients (n = 290, p < 0.05, corrected). MRI determined frontal, temporal, thalamic, and hippocampal volumes, and white matter fractional anisotropy values in the internal capsule and left optic radiation were reduced in obese patients (n = 7) compared with non-obese patients (n = 107, p < 0.05, corrected). LIMITATIONS: Sample size for obese population was not very large. CONCLUSIONS: Obesity is associated with decreased cognitive function, reduced gray matter volume, and impaired white matter integrity in cognition-related brain areas in patients with MDD.

Sexually dimorphic deficits of prepulse inhibition in patients with major depressive disorder and their relationship to symptoms: A large single ethnicity study.

BACKGROUND: Sensorimotor gating deficits as measured by prepulse inhibition (PPI) of acoustic startle reflex have been repeatedly observed in patients with schizophrenia. However, studies investigating PPI in patients with major depressive disorder (MDD) are scarce, and this issue remains to be elucidated. METHODS: Subjects were 221 patients with MDD and 250 age-matched healthy comparison subjects. Depressive symptoms were assessed by the 21-item version of the Hamilton Depression Rating Scale (HAM-D21), and the scores were divided into six factors. Thirty-five trials of startle reflex to pulse alone and pulse with prepulse were measured by electromyography. Startle magnitude, habituation, and PPI were compared between patients and comparisons stratified by sex. Relationships of startle measures to symptoms and antidepressant medication were assessed. RESULTS: Male patients showed significantly reduced PPI compared to male comparisons, while no significant PPI difference was found between female patients and comparisons. HAM-D21 total score and several subscales were significantly correlated with PPI only in male patients. The effect of antidepressant medication was not significant for either male or female patients. LIMITATIONS: Possible effects of the menstrual cycle could not be excluded among female subjects. CONCLUSIONS: These findings suggest that male patients with MDD show sensorimotor gating deficits in a state-dependent manner. However, we obtained no evidence for such abnormalities in female patients with MDD.

A large single ethnicity study of prepulse inhibition in schizophrenia: Separate analysis by sex focusing on effect of symptoms.

Deficits in sensorimotor gating, as measured with prepulse inhibition (PPI), have been considered an endophenotype of schizophrenia. However, the question remains whether these deficits are related to current symptoms. This single site study aimed to explore clinical features related to the modulation of startle reflex in a large sample of Japanese patients with schizophrenia (DSM-IV). The subjects comprised 181 patients and 250 healthy controls matched for age and sex. Schizophrenia symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Startle reflex to acoustic stimuli was recorded using a startle stimulus of 115 dB and a prepulse of four different conditions (intensity: 86 dB or 90 dB; lead interval: 60 ms or 120 ms). Patients exhibited significantly reduced startle magnitude (p < 0.001), habituation (p = 0.001), and PPI (90 dB, 60 ms, p = 0.016; 90 dB, 120 ms, p = 0.001) compared with controls. Patients of both sexes exhibited significantly lower habituation and PPI (90 dB, 120 ms) compared with the same sex controls. We could not detect a significant correlation with any clinical variable in the entire patients, however, when men and women were examined separately, there was a negative correlation with the PANSS cognitive domain (ρ = -0.33, p = 0.008) in men, but not in women. Moreover, when patients were subdivided into four clusters, two clusters with high positive symptoms showed significant PPI deficits in men. Our results suggest that sensorimotor gating is impaired in schizophrenia of both sexes, and PPI deficits may be related to thought disturbance and disorganization in male patients with schizophrenia.