General Summary

A Midei and J Licinio UCLA, Los Angeles, CA, USA

Molecular Psychiatry (2005) 10, 227–228. doi:10.1038/sj.mp.4001651

SCIENTIFIC CORRESPONDENCE evidence for association between a gene that maps to 15q, called dyslexia susceptibility 1 candidate 1 Tree pollen peaks are associated with increased (DYX1C1 or EKN1). However, the findings in each nonviolent suicide in women study are somewhat contradictory. The authors TT Postolache, JW Stiller, R Herrell, MA Goldstein, examined the critical markers from the previous SS Shreeram, R Zebrak, CM Thrower, J Volkov, studies in an attempt to replicate either study. The MJ No, I Volkov, KJ Rohan, J Redditt, M Parmar, data provided no support for association, and when F Mohyuddin, C Olsen, M Moca, LH Tonelli, considered in the context of the existing evidence, the K Merikangas, HD Komarow authors concluded that DYX1C1 is unlikely to be a susceptibility gene for DD. Postolache et al. hypothesized that seasonal environ- mental factors, which cause inflammation and cyto- kine release, such as infection and allergy, contribute TEN YEARS OF MOLECULAR PSYCHIATRY to the highly replicated but poorly explained seasonal peaks of suicide. In a large US-wide epidemiological Brain–immune interactions and disease susceptibility study, the authors reported a greater rate of nonviolent A Marques-Deak, G Cizza, E Sternberg suicides during and after high tree-pollen periods. This finding is consistent with the previously Many studies have established the routes by which reported association between allergy and depression the immune and central nervous systems (CNS) in women but not in men. communicate. This network of connections permits a bidirectional regulation of the immune and Absence of psychosis may influence linkage results CNS systems, playing an important role in suscep- for bipolar disorder tibility and resistance to autoimmune, inflammatory, N Park, R Cheng, SH Juo, J Liu, JE Loth, J Endicott, infectious, and allergic diseases. This review focused TC Gilliam, M Baron on the regulation of the immune system via the neuroendocrine system, and underscored the link Genome-wide linkage analysis was carried out in between neuroendocrine dysregulation and develop- pedigrees with bipolar disorder (BP). The analysis ment of major depressive disorders, autoimmune focused on BP with no psychotic features (nonpsy- diseases, and osteoporosis. chotic BP). Support for linkage was observed on chromosomes 1p35, 3p14, 3q13, 6q24, and 8q24. Reelin glycoprotein: structure, biology and roles in These regions differ from those implicated in a health and disease previous study, which focused on BP with psychosis SH Fatemi (psychotic BP). The results suggest that some psychotic and nonpsychotic varieties of BP may be governed Reelin glycoprotein is a secretory serine protease, by different susceptibility loci. with dual roles in the mammalian brain: embryologi- cally, it guides neurons and radial glial cells to their No support for association between Dyslexia Suscep- corrected positions in the developing brain; in adult tibility 1 Candidate 1 and developmental dyslexia brain, Reelin is involved in a signaling pathway, NA Cope, G Hill, M van den Bree, D Harold, which underlies neurotransmission, memory forma- V Moskvina, EK Green, MJ Owen, J Williams, tion, and synaptic plasticity. Disruption of the Reelin MC O’Donovan signaling pathway by mutations and selective hyper- methylation of the Reelin gene promoter or following Several candidate chromosomal regions have been various pre- or postnatal insults may lead to cognitive identified for developmental dyslexia (DD) including deficits present in neuropsychiatric disorders like chromosome 15q. Recently, two groups have provided autism or schizophrenia. General Summary 228 Obsessive-compulsive disorder phenotypes: implica- Wisconsin Card Sorting, Digit Span backward, and tions for genetic studies Trail Making tests, as well as MRI frontal brain EC Miguel, JF Leckman, S Rauch, MC do Rosario- volumes and PET frontal cerebral blood flow. Campos, AG Hounie, MT Mercadante, P Chacon, Although the complex genetics and phenotypic DL Pauls heterogeneity of schizophrenia remain as major obstacles toward elucidating its underlying neuro- This review proposed several different approaches to biology, integrating multimodal investigational ap- understand the complexity of the OCD phenotype proaches from cognitive neurosciences and molecular including: (1) narrowing the phenotype to identify genetics can help address these challenges in schizo- categorically defined more homogeneous and mutu- phrenia research. ally exclusive subtypes of OCD; (2) considering OC symp- tom dimensions as quantitative components of the Influenza A virus infection causes alterations in more complex OCD phenotype; and (3) broadening expression of synaptic regulatory genes combined the phenotype to include other etiologically related with changes in cognitive and emotional behaviors conditions. A combined dimensional approach in mice within distinctive subgroups was proposed as most S Beraki, F Aronsson, H Karlsson, SO O¨gren, effective in helping to identify the heritable compo- K Kristensson nents of OCD. Viral infections have been suggested to be responsible for a number of complex human disorders including ORIGINAL RESEARCH ARTICLES schizophrenia. In the present study, influenza A virus was injected into the brains of C57BL/6 mice. Long Inhibition of System A-mediated glycine transport in after this nonlethal infection had been cleared these cortical synaptosomes by therapeutic concentrations animals exhibited disturbances in cognitive and of clozapine: implications for mechanisms of action emotional functions. These were accompanied by DC Javitt, L Duncan, A Balla, H Sershen alterations in the transcriptional activity of genes involved in synaptic transmission as compared to Clozapine is an atypical antipsychotic with particular control mice. Thus, infections targeting the brain may efficacy in schizophrenia. This study investigated the cause persistent changes in gene expression com- possibility that clozapine may produce its unique bined with behavioral disturbances. effects by blocking brain glycine reuptake, thereby stimulating N-methyl-D-aspartate (NMDA) receptor- Transcriptional profiling reveals evidence for dependent neurotransmission. Two glycine transport signaling and oligodendroglial abnormalities in the processes were identified in brain synaptosomes, temporal cortex from patients with major depressive corresponding to the properties of the glycine type I disorder (9GLYT1) and system A (SNAT2) transporters, respec- C Aston, L Jiang, BP Sokolov tively. Clozapine significantly inhibited glycine transport via the system A-mediated system, suggesting that it may significantly regulate glycine levels in vivo. Microarray analysis revealed significant changes in expression of genes involved in neurodevelopment, signal transduction, and cell communication in Catechol-O-methyl transferase Val158Met gene temporal cortex from patients with major depression. polymorphism in schizophrenia: working memory, Among these, the expression of multiple oligoden- frontal lobe MRI morphology and frontal cerebral droglia- and axonal growth/synaptic function-related blood flow genes was altered. These findings indicate that major B-C Ho, TH Wassink, DS O’Leary, VC Sheffield, depression is associated with altered cell commu- NC Andreasen nication and signal transduction mechanisms that contribute to abnormalities in oligodendroglia and The authors failed to find significant genotype effects synaptic function. The data also suggest that major on a wide range of frontal lobe-related measures: depression shares common oligodendroglial abnorm- working memory/executive functions assessed using alities with schizophrenia and bipolar disorder.

Molecular Psychiatry