This Month in Archives of General Psychiatry FREE

Using functional magnetic resonance imaging, Kuperberg et alArticle demonstrated that patients with chronic schizophrenia showed inappropriate increases in neural activity within the inferior prefrontal and temporal cortices to semantically associated (relative to nonassociated) words. These increases in temporal activity predicted severity of positive thought disorder. This inappropriate activity may reflect a neural correlate of the loosening of associations that has long been considered fundamental to the pathogenesis of schizophrenia.

Menzies et alArticle investigated the effects of γ-aminobutyric acid (GABA)–modulating drugs (lorazepam and flumazenil) on performance of a working memory task and related brain function in people with chronic schizophrenia compared with matched healthy volunteers. The randomized, double-blind, placebo-controlled functional magnetic resonance imaging study showed that people with schizophrenia demonstrated differential sensitivity to GABA-modulating drugs, both in terms of task performance and brain activations.

Damier et alArticle conducted a phase 2 multicenter prospective study to assess the efficacy of bilateral deep brain stimulation of the internal part of the globus pallidus to treat severe tardive dyskinesia. Six months after surgery, all 10 patients had a clear and sustained improvement of their abnormal involuntary movements. No serious psychiatric adverse effects were observed in this group of patients.

Using blood oxygen level–dependent functional magnetic resonance imaging, Benedetti et alArticle showed that successful chronotherapeutics of bipolar depression (repeated sleep deprivation and morning light treatment) resulted in changes of neural response to a moral valence decision task that paralleled the amelioration of depressive symptoms. Both clinical results and neural responses in anterior cingulate and dorsolateral prefrontal cortices were influenced by a polymorphism in the promoter for the serotonin transporter gene.

Using proton magnetic resonance spectroscopy, Hasler et alArticle found that in unmedicated patients with major depressive disorder, glutamate/glutamine and γ-aminobutyric acid concentrations were reduced in the dorsomedial/dorsal anterolateral prefrontal cortex and that the glutamate/glutamine concentration was also reduced in the ventromedial prefrontal cortex.

Using the positron emission tomography ligand trans-1,2,3,5,6,10 β-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline ([¹¹C](+)− McNeil 5652), which binds to the serotonin transporter, Oquendo et alArticle report that compared with controls, depressed patients with bipolar disorder have 16% to 26% lower binding potential in the amygdala, midbrain, anterior cingulate cortex, hippocampus, putamen, and thalamus. Binding potential is unrelated to serotonin transporter promoter (5-HTTLPR) triallelic genotype. These findings suggest that bipolar depression is associated with extensive serotonergic dysfunction.

Stewart et alArticle report findings from an obsessive-compulsive disorder (OCD) candidate gene study of oligodendrocyte lineage transcription factor 2 (OLIG2). OLIG2 is an essential regulator in the development of myelin-producing cells and is highly expressed in brain regions implicated in OCD. They report an association between OLIG2 and OCD, specifically in the absence of comorbid Tourette disorder.

In a pharmacogenomic study of attention-deficit/hyperactivity disorder, Polanczyk and colleaguesArticle demonstrate the role of the G allele in the 1291 C>G polymorphism at the adrenergic α2A receptor gene on the improvement of inattentive symptoms with methylphenidate hydrochloride. This finding provides clinical evidence for the involvement of the noradrenergic system on the modulation of methylphenidate action.

Stewart et alArticle evaluated the relative importance of depressive symptoms, anxiety symptoms, and hostility/anger in predicting 3-year progression of carotid intima-media thickness (IMT), a measure of subclinical atherosclerosis, among healthy adults. Depressive symptoms at baseline were positively associated with IMT progression, although anxiety symptoms and hostility/anger were not. The somatic-vegetative symptoms, but not the cognitive-affective symptoms, predicted IMT progression.

Wilson et alArticle found that loneliness was associated with increased risk of developing Alzheimer disease and more rapid cognitive decline in a cohort of more than 800 older persons followed up to 4 years. Loneliness did not change during the study period and was not related to Alzheimer disease pathology or cerebral infarction in those who died and underwent postmortem examination. The results suggest that loneliness is associated with increased risk of late-life dementia but not with its leading causes.

Osborn et alArticle compared mortality in 2 large UK cohorts of people with and without severe mental illnesses. Schizophrenia and bipolar affective disorder were associated with high death rates from cardiovascular diseases, but not cancer. The relative risks were particularly marked in people younger than 50 years. Smoking, antipsychotic medications, and geographical deprivation only explained part of the inequality.