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Postmortem studies have shown a loss of γ-aminobutyric acid (GABA)–transmittingor –secreting markers in the cingulate cortex of subjects with schizophreniaand bipolar disorder. With a double in situ hybridization of messenger RNAfor glutamic acid decarboxylase (GAD67), a marker for GABA cells,and the NR2A subunit of the N-methyl-D-aspartate (NMDA) receptor, Woo et al Article observed a preferential reduction of GABA cells expressingNMDA receptors in subjects with schizophrenia and bipolar disorder. Theseresults support the view that NMDA-mediated excitotoxicity may play a rolein GABA cell pathologic features in psychotic disorders.
It has been hypothesized that altered connectivity between frontal andtemporal speech-related areas are essential in the generation of auditoryhallucinations. When investigating the underlying structural interconnectionsin patients with schizophrenia with hallucinations using diffusion tensorimaging, Hubl et al Article foundaltered organization in these white matter fiber tracts. This may lead tothe previously described abnormal activation of the primary acoustical cortex,which may account for the patients' inability to distinguish self-generatedthoughts from external stimulation.
The Texas Medication Project is an algorithm-driven treatment programfor the self-declared persistently and seriously mentally ill in the publicmental health sector. Trivedi et al Article describethe 1-year outcomes for patients with major depressive disorder receivingalgorithm-guided treatment (ALGO) compared with treatment as usual (TAU).While all patients improved during the study, the ALGO patients exhibitedsignificantly greater reductions in symptoms and improvements in functionthan the TAU patients.
Pandey et al Article studiedprotein kinase C (PKC), a component of phosphoinositide signaling pathway,in the postmortem brains of teenagers who committed suicide. They found thatPKC activity and the protein and messenger RNA expression of PKC α, β,and γ isozymes were decreased in the prefrontal cortex and hippocampusof teenagers who committed suicide as compared with matched, nonpsychiatriccontrol subjects, suggesting that the phosphoinositide signaling cascade maybe abnormal in teenagers who kill themselves.
Nofzinger et al Article haveassessed regional cerebral metabolism during waking and rapid eye movement(REM) sleep in unmedicated patients with depression with an [18F]fluoro-2-deoxy-D-glucosepositron emission tomography protocol. Statistical parametric mapping andregion of interest analyses showed a greater waking to REM sleep activationof anterior paralimbic structures as well as the executive cortex in patientswith depression compared with control subjects. These results suggest thataltered function of limbic/anterior paralimbic and prefrontal circuits indepression are accentuated during the REM sleep state.
Mounting evidence suggests alterations in the amino acid neurotransmittersystems contribute to the pathophysiologic features of major depressive disorder(MDD). Sanacora et al Article addto this evidence by both confirming lower γ-aminobutyric acid (GABA)concentrations in the cortex of MDD studies and demonstrating increased glutamatecontent in the same cortical region. Further examination demonstrates thatGABA and glutamate levels differ between subtypes of MDD, providing initialevidence that the measures could potentially serve as clinically relevantdiagnostic markers.
Pampallona et al Article investigatethe relative efficacy of antidepressant drugs alone vs antidepressant drugscombined with psychological treatment in this meta-analysis. The combinedtreatment was found to be superior. The article also addresses the issue ofwhether this benefit corresponds to a reduction in the number of nonresponders,dropouts, or both and concludes that in longer therapies the addition of psychotherapyhelps to keep patients in treatment.
Pujol et al Article usedtridimensional magnetic resonance imaging and a voxel-based analysis methodto map structural brain alterations in a large series of patients with obsessive-compulsivedisorder. They identified areas of gray matter reduction in the insula andthe medial frontal cortex that correlated with volume increases in the ventralpart of the striatum. Age was related to the development of some of thesechanges. They also observed that specific symptom subtypes showed distinctiveanatomical features. These data may help inform the biological models of obsessive-compulsivedisorder.
Attention-deficit/hyperactivity disorder (ADHD) occurs more frequentlythan expected in prevalent cohorts with epilepsy but little is known aboutthe time order of this association. In a case-control study in children, Hesdorffer et al Article found thatADHD is associated with an increased risk for developing unprovoked seizures.
Foley et al Article haveconfirmed in an American sample that the risk for male conduct disorder isassociated with the interaction between exposure to familial adversity andmonoamine oxidase A (MAO-A) genotype. There was a main effect of adversitybut not MAO-A on risk for conduct disorder. Low MAO-A activity increased riskfor conduct disorder only in the presence of an increasingly adverse childhoodenvironment.
This Month in Archives of General Psychiatry. Arch Gen Psychiatry. 2004;61(7):645. doi:10.1001/archpsyc.61.7.645