Oligodendroglial abnormalities in schizophrenia, mood disorders and substance abuse. Comorbidity, shared traits, or molecular phenocopies?

The evidence implicating oligodendroglia in major mental disorders has grown significantly in the past few years. Microarray analysis revealed altered expression of oligodendroglia-related genes in multiple brain regions from several, clinically diverse groups of subjects with schizophrenia (SZ) as well as subjects with bipolar disorder (BD) and major depressive disorders (MDD), alcoholics and cocaine users. In line with gene expression findings, evidence for ultrastructural changes in white matter and altered oligodendroglia in these disorders were reported in neuroimaging and neuropathological studies.

Allele C-specific methylation of the 5-HT2A receptor gene: evidence for correlation with its expression and expression of DNA methylase DNMT1.

Differential DNA methylation has been suggested to contribute to differential activity of alleles C and T and thereby to genetic associations between the C/T(102) polymorphism in the 5-HT2A receptor gene (5HT2AR) and psychiatric disorders. We surveyed methylation in two CpG sites, which are specific to allele C. The majority of allele C-specific CpG sites were methylated in human temporal cortex and peripheral leukocytes and levels of methylation varied between individuals.

Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness.

Aggressive behaviors have been reported in patients who suffer from some psychiatric disorders, and are common in methamphetamine (METH) abusers. Herein, we report that multiple (but not single) injections of METH significantly increased aggressiveness in male CD-1 mice. This increase in aggressiveness was not secondary to METH-induced hyperactivity.

Microarray analysis of postmortem temporal cortex from patients with schizophrenia.

To examine molecular mechanisms associated with schizophrenia this study measured expression of approximately 12,000 genes in the middle temporal gyrus from 12 subjects with schizophrenia and 14 matched normal controls. Among the most consistent changes in genes with robust expression were significant decreases in the expression of myelination-related genes MAG, PLLP (TM4SF11), PLP1, ERBB3 in subjects with schizophrenia. There was also altered expression of genes regulating neurodevelopment (TRAF4, Neurod1, histone deacetylase 3), a circadian pacemaker (PER1), and several other genes involved in regulation of chromatin function and signaling mechanisms.

Chronic methamphetamine increases fighting in mice.

A propensity for violent behaviors to develop in chronic methamphetamine (METH) abusers has been noted. The idea that increased aggressiveness might result from chronic METH administration was tested in mice after chronic (long-term intermittent, 8 weeks) or single exposures to the drug. A single injection of METH (6 mg/kg) did not augment fighting.

Novel putative nonprotein-coding RNA gene from 11q14 displays decreased expression in brains of patients with schizophrenia.

A modified method of differential display was employed to identify a novel gene (named PSZA11q14), the expression of which was reduced in brains from patients with schizophrenia. Decreased expression of PSZA11q14 was identified initially in Brodmann's area (BA) 21 from a small group of patients with schizophrenia (n = 4) and normal controls (n = 6) and was confirmed subsequently using independent RT-PCR assay in BA 21, 22, and 9, and in hippocampus from a larger group of patients with schizophrenia (n = 36) and controls (n = 35). PSZA11q14 is located on chromosome 11q14, an area shown previously to co-segregate with schizophrenia and related disorders in several families.

Transcription profiling reveals mitochondrial, ubiquitin and signaling systems abnormalities in postmortem brains from subjects with a history of alcohol abuse or dependence.

Alcohol abuse is a common human disorder with high rate of comorbidity with other psychiatric disorders. To identify candidate mechanisms for alcohol abuse, the expression of 12,626 genes was measured in postmortem temporal cortex from 11 subjects with a history of alcohol abuse or dependence, with or without other psychiatric diagnoses and compared pairwise with the expression in 11 nonalcoholic subjects matched for the other psychiatric diagnoses and demographics. Genes were defined to have altered expression in alcohol abuse if: 1) the gene showed decreased expression in at least 10 of 11 subjects with alcohol abuse, or showed increased expression in at least 10 of 11 subjects with this diagnosis compared to matched non-abusers (P < 0.

Mouse brain gene expression changes after acute and chronic amphetamine.

Gene expression changes are candidate mechanisms to contribute to long-term consequences of psychostimulant use. We use microarrays to examine the expression of 6340 genes in brains of mice killed 5 or 20 h following 14 day, twice-daily treatments with saline (SS), saline followed by a single 7.5 mg/kg amphetamine dose (SA), or repeated 7.

Differential expression of the "C" and "T" alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics.

A genetic association between schizophrenia and a silent C/T(102) polymorphism in the 5-HT2A receptor gene (5-HT2AR) has been previously reported; however, the mechanisms underlying this association remain unknown. Here we developed an improved quantitative assay for measurements of allele ratios, which revealed that the expression of allele "C" in the temporal cortex of normal heterozygous individuals was significantly lower than the expression of allele "T" (allele "C" to allele "T" ratio of approximately 0.8, P < 0.