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It has been argued that unipolar major depressive disorder (MDD) and bipolar disorder (BD) exist on a continuous spectrum, given their overlapping symptomatology and genetic diatheses. The Bipolarity Index (BI) is a scale that considers bipolarity as a continuous construct and was developed to assess confidence in bipolar diagnosis. Here we investigated whether BI scores correlate with gray matter volume (GMV) in a sample of unmedicated unipolar and bipolar depressed individuals.158 subjects (139 with MDD, 19 with BD) in a major depressive episode at time of scan were assigned BI scores. T1-weighted Magnetic Resonance Imaging scans were obtained and processed with Voxel-Based Morphometry using SPM12 (CAT12 toolbox) to assess GMV. Regression was performed at the voxel level to identify clusters of voxels whose GMV was associated with BI score, (p0.001, family-wise error-corrected cluster-level p0.05), with age, sex and total intracranial volume as covariates.GMV was inversely correlated with BI score in four clusters located in left lateral occipital cortex, bilateral angular gyri and right frontal pole. Clusters were no longer significant after controlling for diagnosis. GMV was not correlated with BI score within the MDD cohort alone.Incomplete clinical data required use of a modified BI scale.BI scores were inversely correlated with GMV in unmedicated subjects with MDD and BD, but these correlations appeared driven by categorical diagnosis. Future work will examine other imaging modalities and focus on elements of the BI scale most likely to be related to brain structure and function.

In this study, the potential antidepressant-like effects of pioglitazone and the possible involvement of peroxisome proliferator-activated receptor gamma (PPARγ) and nitric oxide system in antidepressant effects of pioglitazone were determined using forced swimming test (FST) in mice. Method After assessment of locomotor activity in open-field test, mice were forced to swim individually and the immobility time of the last 4 min was evaluated. Pioglitazone was administered orally with doses (5, 10, 20 and 30 mg/kg) 2 and 4 h before FST. To assess the involvement of PPARγ in the possible antidepressant effect of pioglitazone, GW9662, a PPARγ antagonist (2 mg/kg) was administered before pioglitazone (20 mg/kg). For determination of possible role of nitric oxide pathway in this effect, a non-specific NOS inhibitor, Nω-nitro- l -arginine methyl ester ( l -NAME, 10 mg/kg, i.p.), a specific iNOS inhibitor, aminoguanidine (50 mg/kg, i.p.), or a NO precursor, l -arginine (750 mg/kg, i.p.) was co-administered with pioglitazone, either 2 or 4 h before FST. Results The immobility time significantly decreased after pioglitazone administration (20 and 30 mg/kg). GW-9662 significantly reversed antidepressant effect of pioglitazone administered 2 and 4 h prior to FST. Co-administration of non-effective doses of pioglitazone and l -NAME revealed antidepressant-like effect in FST; while, co-administration of non-effective doses of aminoguanidine and pioglitazone did not affect the immobility time. l -Arginine also reversed the antidepressant-like effect of pioglitazone. Conclusion The antidepressant-like effect of pioglitazone on mice in the FST is mediated at least in part through PPARγ receptors and nitric oxide pathway.

Heroin is commonly abused as a recreational drug and results in huge social, economical, individual, and public health hazards. Heroin affects many organs in abusers' bodies. The most well studied effects of heroin on the brain are dependence and tolerance after extended use. However, heroin also has some less commonly reported effects on the brain. For example, ischemic cerebrovascular accident following heroin use is an infrequent consequence of heroin abuse and is primarily related to impurities in the drug preparation. Another rare consequence of heroin abuse is toxic leukoencephalopathy. Although this is usually associated with heroin inhalation, its precise etiology is not clear. Here, we review existing cases for these two uncommon pathologies as well as suggested mechanisms for them, including mitochondrial impairment.

Many peripheral diseases are associated with a decline in cognitive function. In this regard, there have been reports of patients with inflammatory bowel disease and an otherwise unexplained memory impairment. We sought to assess the memory performance of mice with colitis. We also investigated the roles of N-methyl d-aspartate (NMDA) receptors and nitric oxide (NO) as possible mediators of colitis-induced amnesia. To induce colitis, male NMRI mice were intrarectally injected with a solution containing dinitrobenzene sulfonic acid (DNBS; 4 mg in 100 μl) under anesthesia. Three days after intrarectal DNBS instillation, spatial recognition and associative memories were assessed by the Y-maze and passive avoidance tasks, respectively. The NMDA antagonists, MK-801 and memantine, and the inducible NO synthase (iNOS) inhibitor, aminoguanidine, were injected intraperitoneally 45 min before the Y-maze task. Induction of colitis by DNBS impaired spatial recognition memory in the Y-maze task but had no effect on step through latencies in the passive avoidance test. Colitis-induced amnesia was reversed by administering specific doses of MK-801 and memantine (30 μg/kg and 1 mg/kg, respectively) suggesting dysregulated NMDA receptor activation as an underlying mechanism. No effect was seen with lower and higher doses of these drugs, resulting in a bell-shaped dose response curve. Colitis-induced amnesia was also inhibited by aminoguanidine (50 mg/kg), implicating a role for iNOS activation and neuroinflammation in this phenomenon. DNBS-induced colitis impairs memory through NMDA receptor overstimulation and NO overproduction.

Introduction Addiction imposes a large medical, social and economic burden on societies. Currently, there is no effective treatment for addiction. Our struggle to decipher the different mechanisms involved in addiction requires a proper understanding of the brain regions which promote this devastating behavior. Previous studies have shown a pivotal role for insula in cigarette smoking. In this study we investigated the change in opium consumption after CVA. Methods This study took place in three referral academic hospitals affiliated to Tehran University of Medical Sciences. Patients who suffered a CVA and were addicted to opium were recruited during their hospitalization or visit to the neurology clinic in this study. Age, sex and the route and mean amount of opium use of each patient before CVA and 1, 3 and 6 months post-CVA was asked using a questionnaire. The patients were divided into three groups based on the location of brain ischemia (insula, basal ganglia and non-insula non-basal ganglia group). Results Seventy five percent of the patients with ischemia of the insula changed the route or amount of opium use after CVA and 37.5% of them stopped opium use after CVA. These values were significantly higher than patients with non-insula nonbasal ganglia ischemia (p values 0.005 and 0.03 for change in route or amount and stopping opium use, respectively). This was not true in patients with ischemia of the basal ganglia. Younger patients were more likely to change the route or amount of opium use and stop opium use after CVA (p values 0.002 and 0.026, respectively). Discussion The results of the present study indicate a possible role for the insula in opium addiction, especially in younger individuals.

Previously, we showed that pioglitazone exerts its antidepressant-like effect through peroxisome proliferator-activated receptor gamma receptors and demonstrated the possible involvement of calcium-dependent nitric oxide synthase inhibitors. Based upon the in vitro results, pioglitazone reduces N-methyl-D-aspartate (NMDA)-mediated calcium currents in hippocampal neurons.In this study, we evaluated the involvement of the NMDA receptor (NMDAR) on the antidepressant-like effect of pioglitazone in the forced swimming test (FST) in mice.After the assessment of locomotor activity in the open-field test, mice were forced to swim individually and the immobility time of the last 4 min was evaluated. Pioglitazone was administered orally with doses of 5, 10, and 20 mg/kg 4 h before FST. To assess the involvement of NMDARs in the possible antidepressant-like effect of pioglitazone, a selective glutamate receptor agonist, NMDA (75 mg/kg, intraperitoneally [i.p.] or 20 ng/mouse, intracerebroventricularly [i.c.v.]), was administered before pioglitazone (20 mg/kg). To further determine a possible role of NMDARs in this effect, a noncompetitive antagonist of the NMDA, MK-801 (0.05 mg/kg, i.p. or 100 ng/mouse, i.c.v.), was coadministered with pioglitazone (10 mg/kg) 4 h prior to FST.Pioglitazone (20 mg/kg) administered 4 h prior to FST significantly reduced the immobility time. Coadministration of the noneffective doses of pioglitazone and MK-801 revealed an antidepressant-like effect in FST. Moreover, NMDA significantly reversed the antidepressant-like effect of pioglitazone administered 4 h prior to FST.The antidepressant-like effect of pioglitazone in the FST is mediated partly through NMDAR signaling. This study provides a new approach for the treatment of depression.