The effects of minocycline in improving of methamphetamine withdrawal syndrome in male mice.

Methamphetamine (METH) is a potent psychostimulant drug with an increasing rate of abuse over recent years. Depressive-like behaviors are one of the major symptoms patients in the METH withdrawal period experience. There is limited evidence regarding the METH withdrawal treatment, and conventional managements are not completely effective. Furthermore, extensive promising literature supports minocycline, a well-known antibiotic with anti-oxidant, anti-inflammatory properties, to treat depressive-like behaviors. Therefore, we hypothesized that administration of minocycline might mitigate the methamphetamine (METH) induced depression in male mice. Administration of METH (2 mg/kg) to mice two times a day for 14 constitutive days was done to induce the METH-induced withdrawal syndrome model. Animals were divided into 10 groups (n = 10 in each group), and three doses of minocycline (2.5, 5 and 10 mg/kg) were daily administered to male albino mice for 10 days. Following the behavioral test, the animals were scarified, their hippocampus were dissected to measure oxidative stress parameters. Our data revealed that chronic administration of minocycline provoked antidepressant effects in behavioral tests, such as forced swim test (FST), tail suspension test (TST) and splash test. Additionally, minocycline was able to improve oxidative stresses and neuronal damage in the hippocampus and restore the body's antioxidant system by increasing glutathione (GSH) and the cellular energy (ATP) and reducing the malondialdehyde (MDA) level. According to our promising results of minocycline on targeting mitochondria and its performance, we suggest minocycline as a new therapeutic option in clinical trials of depression treatment.

White matter microstructural associates of apathy-avolition in schizophrenia.

Apathy is present at the onset in nearly half the patients with schizophrenia. Current therapies lack the efficiency to improve apathy in patients. The presence of apathy is also associated with poorer outcomes. Despite its clinical importance, the underlying mechanism of apathy in schizophrenia is unclear, but it seems frontostriatal connections play a role. In this study, we investigated whole-brain white matter microstructural properties associated with the severity of apathy-avolition in schizophrenia. We included 80 schizophrenia patients (60 Male, 20 Female) from the Mind Clinical Imaging Consortium database and associated Apathy-Avolition score of "Scale for Assessment of Negative Symptoms" with fiber integrity measures derived from diffusion-weighted imaging using Tract-Based Spatial Statistics (TBSS). We also did tractography on eight tracts, including bilateral superior longitudinal fasciculus, uncinate fasciculus, cingulum, genu and splenium of the corpus callosum. Age, gender, years of education, chlorpromazine equivalent cumulative dose, and acquisition site were inserted as covariates. We showed a widespread association between lower fiber integrity (by measures of increased mean diffusivity and decreased fractional anisotropy) and increased apathy-avolition in TBSS, which we also validated in tractography. Moreover, mean diffusivity, and not fractional anisotropy, was associated with apathy independent of disease severity. In conclusion, we propose diffuse white-matter pathology, within the corpus callosum, limbic system, and the frontostriatal circuit is involved in apathy-avolition in schizophrenia. Also, we suggest that diffuse neuroinflammatory processes may play a part in apathy-avolition, independent of disease severity.

White Matter Microstructural Properties Associated with Impaired Attention in Chronic Schizophrenia: A Multi-Center Study.

Attention as a key cognitive function is impaired in schizophrenia, interfering with the normal daily life of the patients. Previous studies on the microstructural correlates of attention in schizophrenia were limited to single fibers, did not include a control group, or did not adjust for drug dosage. In the current study, we investigated the association between microstructural properties of the white matter fibers and attention tests in 81 patients and 79 healthy controls from the Mind Clinical Imaging Consortium database. Integrity measures of superior longitudinal fasciculus, cingulum, genu, and splenium were extracted after tractography. Using an interaction model between diagnosis and microstructural properties, and adjusting for age, gender, acquisition site, education, and cumulative drug usage dose, and after correcting for family-wise error, we showed decreased integrity in the patients and a significant negative association between fractional anisotropy of the tracts and trail making test part A with a greater expected decrease in the attention per unit of decrease of integrity in the patients compared to the healthy controls. Our findings suggest that decreased integrity of the bilateral cingulum, and splenium, are independent of the cumulative drug dosage, age, gender, and site, and may underlie the impaired attention in the schizophrenia.

Structural white matter alterations in male adults with high functioning autism spectrum disorder and concurrent depressive symptoms; a diffusion tensor imaging study.

BACKGROUND: Autism spectrum disorder (ASD), a prevalent developmental condition, is associated with comorbid mood disorders, most importantly depression. Here, we explored the underlying association between brain white matter microstructural integrity, assessed by diffusion tensor imaging (DTI), and depressive symptoms, in male adults with high-functioning ASD. METHOD: To assess our main purpose, Autism Brain Imaging Data Exchange II dataset was used to acquire brain diffusion imaging from 26 adult male patients with ASD ranging from 18 to 62 years of age, and 26 age and gender-matched typically developed control subjects. Participants were evaluated for depressive symptoms manifestation by the Beck Depression Index (BDI). DWI images were preprocessed and analyzed for DTI scalers in the "ExploreDTI" toolbox. Adjusted linear regression models were used. Association between normalized BDI score and its interaction with diagnosis, as predictors, and measures of fractional anisotropy (FA) and mean diffusivity (MD) of regions of interest according to Mori atlas was assessed. RESULT: Significant lower microstructural integrity of white matter was found in association with higher BDI scores in ASD group, mainly in regions of anterior limb of internal capsule (ALIC) and corona radiata. Also, a statistically significant positive interaction between BDI and ASD was seen in FA of left ALIC. DISCUSSION: Considering similar regional brain white matter involvement with the imaging studies of depression in the typically developed population, we propose that these alterations of white matter tracts in depressive symptoms of adult ASD subjects might be, at least, similar to depression in typically developed population.