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This Month in Archives of General Psychiatry
January 2005

This Month in Archives of General Psychiatry

Arch Gen Psychiatry. 2005;62(1):13. doi:10.1001/archpsyc.62.1.13

Using an intravenous glucose tolerance test, Henderson et alArticle examined 36 nonobese patients with schizophrenia treated with clozapine, olanzapine, or risperidone. The 3 groups showed significant differences on several measures of glucose metabolism including fasting serum insulin levels, insulin sensitivity, and glucose effectiveness. For each parameter, clozapine was worse than olanzapine, which was worse than risperidone, and the clozapine and olanzapine groups displayed significant insulin resistance. Patients treated with these agents must be examined for insulin resistance and its consequences.

For about 20 years, Weissman et alArticle have studied a cohort of parents and their offspring at high and low risk for major depression. New data on the third generation find high rates of mood and anxiety disorders in the grandchildren (mean age, 12 years) with 2 generations of moderate to severe impairing major depression. This familial group may be an informative target for neuroimaging and genetic and other biological studies.

Salloum et alArticle report on the first placebo-controlled trial evaluating the efficacy of valproate in comorbid bipolar disorder and alcoholism. Acutely ill subjects with bipolar disorder and comorbid active alcohol dependence were randomized to either valproate and treatment as usual (lithium carbonate and psychotherapy) or placebo and treatment as usual in a 24-week trial. Subjects treated with valproate had a greater reduction in heavy drinking than those treated with placebo. These findings demonstrate the utility of the anticonvulsant valproate in reducing heavy drinking in comorbid bipolar disorder and alcoholism.

Pharmacogenetic evidence, linkage of GABRA6 and GABRG2 subunits with alcohol dependence (AD), and association of GABRA6, GABRB2, and GABRG2 alleles with AD make the 5q34 γ-aminobutyric acid type A (GABAA) gene cluster of particular interest in AD genetics. Radel et alArticle add to this evidence by reporting an association of 5q34 GABAA genetic variants with AD using single-point and haplotype analysis in 2 semi-isolated populations. The region with the Pro385Ser GABRA6 polymorphism was implicated in both populations.

Compulsive alcohol consumption and relapses in alcohol-dependent patients are mediated by the endogenous opiate system. The PET study from Heinz et alArticle indicates a higher μ-opioid receptor availability in the ventral striatum, a central area of the brain reward system. This was correlated with a more intense subjective craving for alcohol. Their findings demonstrate a neuronal correlate of craving in humans and may be pertinent for the further course of alcohol dependence.

Using the data from a 25-year longitudinal study of a New Zealand birth cohort, Fergusson et alArticle examined the extent to which subthreshold depression in adolescence was prognostic of later mental disorders. This analysis shows that even following adjustment for confounding factors, those with subthreshold depression had a similar prognosis to those with major depression in terms of increased risks of depression and suicidality.

Recent studies in adults suggest that enhanced carbon dioxide (CO2) sensitivity is a risk factor for panic disorder. Since children at risk for panic disorder manifest clinical symptoms of anxiety, they might also manifest CO2 hypersensitivity. Pine et alArticle examined the relationships between parental panic disorder, childhood anxiety disorders, and CO2 hypersensitivity in 142 children and adolescents. They demonstrate an association between childhood anxiety disorders and CO2 hypersensitivity. However, parental panic disorder shows a stronger association with anticipatory anxiety than with CO2 hypersensitivity.

Childhood shyness is heritable, can predate social anxiety or avoidant personality disorder, and may be associated with biased discrimination of social cues. Battaglia et alArticle recorded children’s brain potentials evoked by facial expressions of other children. Shyness was significantly higher in carriers of the SS serotonin transporter promoter polymorphism (5-HTTLPR) genotype and predicted significantly smaller N400 amplitudes in response to angry and neutral expressions. Analyses of covariance revealed a significantly smaller amplitude in subjects who were SS and S carriers compared with those who were LL carriers in response to the anger expression. SS and S carriers were also significantly less accurate in a trial of expression discrimination completed 1 year before the evoked response potential recordings.

Interviewing 3084 tribal members, Beals et alArticle estimated the mental health burden and associated help-seeking in 2 reservation communities. Alcohol disorders and posttraumatic stress disorder were more common in these American Indian populations than in other populations, using comparable methods. Substantial comorbidity between depressive and anxiety and substance disorders suggests the need for greater coordination of treatment for comorbid disorders.