Cellular models to study bipolar disorder: A systematic review.

BACKGROUND: There is an emerging interest in the use of cellular models to study psychiatric disorders. We have systematically reviewed the application of cellular models to understand the biological basis of bipolar disorder (BD). METHOD: Published scientific literature in MEDLINE, PsychINFO and SCOPUS databases were identified with the following search strategy: [(Lymphoblastoid OR Lymphoblast OR Fibroblast OR Pluripotent OR Olfactory epithelium OR Olfactory mucosa) AND (Bipolar disorder OR Lithium OR Valproate OR Mania)]. Studies were included if they had used cell cultures derived from BD patients. RESULTS: There were 65 articles on lymphoblastoid cell lines, 14 articles on fibroblasts, 4 articles on olfactory neuronal epithelium (ONE) and 2 articles on neurons reprogrammed from induced pluripotent stem cell lines (IPSC). Several parameters have been studied, and the most replicated findings are abnormalities in calcium signaling, endoplasmic reticulum (ER) stress response, mitochondrial oxidative pathway, membrane ion channels, circadian system and apoptosis related genes. These, although present in basal state, seem to be accentuated in the presence of cellular stressors (e.g. oxidative stress--rotenone; ER stress--thapsigargin), and are often reversed with in-vitro lithium. CONCLUSION: Cellular modeling has proven useful in BD, and potential pathways, especially in cellular resilience related mechanisms have been identified. These findings show consistency with other study designs (genome-wide association, brain-imaging, and post-mortem brain expression). ONE cells and IPSC reprogrammed neurons represent the next generation of cell models in BD. Future studies should focus on family-based study designs and combine cell models with deep sequencing and genetic manipulations.

The efficacy of atomoxetine as adjunctive treatment for co-morbid substance use disorders and externalizing symptoms.

BACKGROUND: We examined the effect of atomoxetine supplementation in treated-as-usual patients with alcohol, tobacco and other drug dependence (ATOD) and co-morbid externalizing symptoms (ES). METHOD: Subjects were selected from a substance dependence treatment-cohort and assessed for: (a) high ES counts, (b) maximum prior period of abstinence, (c) quality of life during that period, and (d) shortest time from prior relapse to restarting treatment. Subjects were prescribed atomoxetine and followed up to their first relapse. RESULTS: Out of 262 subjects screened during the study period (March-April 2008), 18 subjects who fulfilled eligibility criteria were recruited. All subjects were male, with early onset of substance dependence to at least two substances. Atomoxetine treatment led to significant treatment benefits: ES reduction, longer abstinence, shorter turnaround time and better quality of life. CONCLUSIONS: Atomoxetine has a potential role in the treatment of early onset ATOD patients with ES, as an adjuvant to the standard treatment.

Entorhinal Cortex Volume in Antipsychotic-naïve Schizophrenia.

BACKGROUND: Entorhinal cortex (ERC), a multimodal sensory relay station for the hippocampus, is critically involved in learning, emotion, and novelty detection. One of the pathogenetic mechanistic bases in schizophrenia is proposed to involve aberrant information processing in the ERC. Several studies have looked at cytoarchitectural and morphometric changes in the ERC, but results have been inconsistent possibly due to the potential confounding effects of antipsychotic treatment. MATERIALS AND METHODS: In this study, we have examined the entorhinal cortex volume in antipsychotic-naïve schizophrenia patients (n=40; M:F=22:18) in comparison with age, sex, and handedness, matched (as a group) with healthy subjects (n=42; M:F=25:17) using a valid method. 3-Tesla MR images with 1-mm sections were used and the data was analyzed using the SPSS software. RESULTS: Female schizophrenia patients (1.25±0.22 mL) showed significant volume deficit in the right ERC in comparison with female healthy controls (1.45±0.34 mL) (F=4.9; P=0.03), after controlling for the potential confounding effects of intracranial volume. However, male patients did not differ from male controls. The left ERC volume did not differ between patients and controls. CONCLUSIONS: Consistent with the findings of a few earlier studies we found a reduction in the right ERC volume in patients. However, this was limited to women. Contextually, our study finding supports the role for ERC deficit in schizophrenia pathogenesis - perhaps mediated through aberrant novelty detection. Sex-differential observation of ERC volume deficit in schizophrenia needs further studies.