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.

Thalamic hypoperfusion and disrupted cerebral blood flow networks in idiopathic generalized epilepsy: Arterial spin labeling and graph theoretical analysis.

PURPOSE: The aim of this study was to investigate interictal cerebral blood flow (CBF) distributions and graph theoretical networks in idiopathic generalized epilepsy (IGE) using arterial spin labeling (ASL) imaging and anatomical covariance methods of graph theoretical analysis. MATERIAL AND METHODS: We recruited 19 patients with IGE and 19 age-/gender-matched healthy controls. Their CBF images were obtained by pseudo-continuous ASL imaging and compared using statistical parametric mapping 8 software (SPM8) and Graph Analysis Toolbox (GAT). RESULTS: The ASL imaging could detect interictal hypoperfusion in the thalamus, upper midbrain, and left cerebellum in IGE. Additionally, the graph theoretical analyses revealed characteristic findings of the CBF network of IGE, including significantly reduced resilience to attacks and changes of regional clustering especially in the bilateral temporo-occipital areas and lateral frontal lobes. There was no significance in the comparisons of network metrics. CONCLUSION: These findings could contribute to a better understanding of the pathophysiology of IGE.

Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study.

OBJECTIVE: l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. METHODS: Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS). RESULTS: HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration. CONCLUSION: Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.

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.

Abnormalities of cerebral blood flow in multiple sclerosis: a pseudocontinuous arterial spin labeling MRI study.

Arterial spin labeling (ASL) is a noninvasive technique that can measure cerebral blood flow (CBF). To our knowledge, there is no study that examined regional CBF of multiple sclerosis (MS) patients by using this technique. The present study assessed the relationship between clinical presentations and functional imaging data in MS using pseudocontinuous arterial spin labeling (pCASL). Twenty-seven patients with MS and 24 healthy volunteers underwent magnetic resonance imaging and pCASL to assess CBF. Differences in CBF between the two groups and the relationships of CBF values with the T2-hyperintense volume were evaluated. Compared to the healthy volunteers, reduced CBF was found in the bilateral thalami and right frontal region of the MS patients. The volume of the T2-hyperintense lesion was negatively correlated with regional CBF in some areas, such as both thalami. Our results suggest that demyelinated lesions in MS mainly have a remote effect on the thalamus and that the measurement of CBF using ASL could be an objective marker for monitoring disease activity in MS.

Laterality and aging of thalamic subregions measured by diffusion tensor imaging.

Thalamic nuclei are comprised of fibers connecting associated cortical regions, and abnormalities of the thalamus are correlated with abnormalities in cognition and behavior. Some previous studies showed the laterality of the whole thalamus and the regional differences among thalamic nuclei. This led us to assess regional characteristics in five major subregions of both sides of the thalamus using diffusion-tensor imaging. Statistically significant lateralities and regional differences were found among the thalamic subregions. Age has a significant correlation with diffusion-tensor imaging metrics where their projection areas are thought to be vulnerable to normal aging. Our results confirmed that the thalamic subregions behave independently, and their respective microstructures warrant further investigations.