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To investigate epistasis within the NRG1 schizophrenia risk pathway, Nicodemus et al applied machine learning algorithms to a genetic case-control study and defined significant 2-way interactions between single-nucleotide polymorphisms within NRG1 and between NRG1 and its receptor ERBB4 and a 3-way interaction between single-nucleotide polymorphisms in NRG1, ERBB4, and AKT1. All 3 interactions were biologically validated using functional magnetic resonance imaging in an independent sample of healthy controls; carriers of risk-associated genotypes showed significantly less efficient processing in the dorsolateral prefrontal cortex during the N-back task.
In an outpatient sample (n = 289), van Tol et al reported on a generic reduction of the rostral anterior cingulate gyrus in major depressive disorder and/or frequently occurring anxiety disorders, while controlling for illness severity, selective serotonin use, and sex. Furthermore, early onset of depression was associated with subgenual prefrontal reductions.
Depressive symptoms during pregnancy have been inconsistently reported to be associated with an increased risk of preterm birth (<37 weeks' gestation), low birth weight (<2500 g), and intrauterine growth restriction (<10th percentile for gestational age). In a meta-analysis of 29 prospective studies, Grote et al observed that pregnant women with depression are at increased risk for preterm birth and low birth weight neonates, although the effect size varies by depression measurement, country location, and socioeconomic status within the United States.
Lock et al conducted a multisite randomized controlled trial of 121 adolescents with anorexia nervosa comparing family-based treatment and adolescent-focused individual therapy. Those treated with family-based treatment had greater changes in body mass index percentiles and eating-related psychopathology at the end of treatment and higher rates of full remission at follow-up.
Halmøy et al investigated the long-term consequences of maternal serotonin deficiency on offspring behavior. After identifying families with functional variants in the genes for the serotonin-synthesizing enzymes tryptophan hydroxylase 1 and tryptophan hydroxylase 2, they showed that offspring of mothers with tryptophan hydroxylase 1 mutations had 1.5 to 2.5 times higher symptom scores of attention-deficit/hyperactivity disorder than random controls or offspring of fathers carrying the corresponding mutations.
Chronis-Tuscano et al found that young children with attention-deficit/hyperactivity disorder were at greatly increased risk for depression and suicide attempts during adolescence. Among children with attention-deficit/hyperactivity disorder, girls, children with depressed mothers, and children with more symptoms of other mental disorders at 4 to 6 years of age were at greatest risk for adverse outcomes.
Barnea-Goraly et al used diffusion tensor imaging to investigate white matter structure in children with autism, their unaffected siblings, and controls. Compared with the control group, both the autism and sibling groups had widespread, significantly aberrant white matter structure in the frontal parietal and temporal lobes, including regions important for social cognition.
Denys et al used a double-blind crossover design with randomly assigned 2-week periods of active and sham stimulation to determine whether bilateral deep brain stimulation of the nucleus accumbens is an effective and safe treatment for therapy-refractory obsessive-compulsive disorder. The results suggest that stimulation of the accumbens may be an effective treatment of refractory obsessive-compulsive disorder.
Acamprosate, an approved alcoholism treatment, has an unknown mechanism of action. Animal studies suggest that it might act by dampening a hyperglutamatergic state. In this issue, Umhau et al used magnetic resonance spectroscopy to examine this hypothesis by scanning alcohol-dependent subjects on days 4 and 25 of abstinence. Measures of central glutamate increased over time in the placebo group but were markedly suppressed in acamprosate-treated subjects.
In this study, Cuijpers et al calculated the economic costs of neuroticism in a large representative sample of the Dutch general population. The per capita excess costs of neuroticism were surprisingly high. The total costs of neuroticism per million inhabitants resulting from the 25% highest scorers ($1.393 billion) were about 2.5 as high as the excess costs of common mental disorders ($585 million).
This Month in Archives of General Psychiatry. Arch Gen Psychiatry. 2010;67(10):982. doi:10.1001/archgenpsychiatry.2010.120
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