Postmortem studies have shown a loss of 
-aminobutyric acid (GABA)–transmitting or –secreting markers in the cingulate cortex of subjects with schizophrenia and bipolar disorder. With a double in situ hybridization of messenger RNA for glutamic acid decarboxylase (GAD67), a marker for GABA cells, and the NR2A subunit of the N-methyl-D-aspartate (NMDA) receptor, Woo et al (SEE ARTICLE) observed a preferential reduction of GABA cells expressing NMDA receptors in subjects with schizophrenia and bipolar disorder. These results support the view that NMDA-mediated excitotoxicity may play a role in GABA cell pathologic features in psychotic disorders.
It has been hypothesized that altered connectivity between frontal and temporal speech-related areas are essential in the generation of auditory hallucinations. When investigating the underlying structural interconnections in patients with schizophrenia with hallucinations using diffusion tensor imaging, Hubl et al (SEE ARTICLE) found altered organization in these white matter fiber tracts. This may lead to the previously described abnormal activation of the primary acoustical cortex, which may account for the patients' inability to distinguish self-generated thoughts from external stimulation.
The Texas Medication Project is an algorithm-driven treatment program for the self-declared persistently and seriously mentally ill in the public mental health sector. Trivedi et al (SEE ARTICLE) describe the 1-year outcomes for patients with major depressive disorder receiving algorithm-guided treatment (ALGO) compared with treatment as usual (TAU). While all patients improved during the study, the ALGO patients exhibited significantly greater reductions in symptoms and improvements in function than the TAU patients.
Pandey et al (SEE ARTICLE) studied protein kinase C (PKC), a component of phosphoinositide signaling pathway, in the postmortem brains of teenagers who committed suicide. They found that PKC activity and the protein and messenger RNA expression of PKC 
, 
, and isozymes were decreased in the prefrontal cortex and hippocampus of teenagers who committed suicide as compared with matched, nonpsychiatric control subjects, suggesting that the phosphoinositide signaling cascade may be abnormal in teenagers who kill themselves.
Nofzinger et al (SEE ARTICLE) have assessed regional cerebral metabolism during waking and rapid eye movement (REM) sleep in unmedicated patients with depression with an [18F]fluoro-2-deoxy-D-glucose positron emission tomography protocol. Statistical parametric mapping and region of interest analyses showed a greater waking to REM sleep activation of anterior paralimbic structures as well as the executive cortex in patients with depression compared with control subjects. These results suggest that altered function of limbic/anterior paralimbic and prefrontal circuits in depression are accentuated during the REM sleep state.
Mounting evidence suggests alterations in the amino acid neurotransmitter systems contribute to the pathophysiologic features of major depressive disorder (MDD). Sanacora et al (SEE ARTICLE) add to this evidence by both confirming lower -aminobutyric acid (GABA) concentrations in the cortex of MDD studies and demonstrating increased glutamate content in the same cortical region. Further examination demonstrates that GABA and glutamate levels differ between subtypes of MDD, providing initial evidence that the measures could potentially serve as clinically relevant diagnostic markers.
Pampallona et al (SEE ARTICLE) investigate the relative efficacy of antidepressant drugs alone vs antidepressant drugs combined with psychological treatment in this meta-analysis. The combined treatment was found to be superior. The article also addresses the issue of whether this benefit corresponds to a reduction in the number of nonresponders, dropouts, or both and concludes that in longer therapies the addition of psychotherapy helps to keep patients in treatment.
Pujol et al (SEE ARTICLE) used tridimensional magnetic resonance imaging and a voxel-based analysis method to map structural brain alterations in a large series of patients with obsessive-compulsive disorder. They identified areas of gray matter reduction in the insula and the medial frontal cortex that correlated with volume increases in the ventral part of the striatum. Age was related to the development of some of these changes. They also observed that specific symptom subtypes showed distinctive anatomical features. These data may help inform the biological models of obsessive-compulsive disorder.
Attention-deficit/hyperactivity disorder (ADHD) occurs more frequently than expected in prevalent cohorts with epilepsy but little is known about the time order of this association. In a case-control study in children, Hesdorffer et al (SEE ARTICLE) found that ADHD is associated with an increased risk for developing unprovoked seizures.
Foley et al (SEE ARTICLE) have confirmed in an American sample that the risk for male conduct disorder is associated with the interaction between exposure to familial adversity and monoamine oxidase A (MAO-A) genotype. There was a main effect of adversity but not MAO-A on risk for conduct disorder. Low MAO-A activity increased risk for conduct disorder only in the presence of an increasingly adverse childhood environment.
