Golberstein and Busch discuss the implications of the June 2012 Supreme Court ruling related to the Affordable Care Act for individuals with mental health disorders. The Affordable Care Act promises to improve care and financial protection for individuals with mental illness. However, in states that choose not to expand Medicaid, many fewer individuals with mental illness will benefit.
Aberg et al conducted a meta-analysis of 18 genome-wide association studies for schizophrenia and integrated results with 6 other databases that showed significant informativeness. They then performed a replication study that, after quality control, comprised 8107 single-nucleotide polymorphisms and 6298 independent individuals from 1811 nuclear families. Replication results showed a highly significant enrichment of single-nucleotide polymorphisms, with small P values. These results included some of the most robust schizophrenia findings as well as more novel genes and pathways.
Timms et al used next-generation sequencing guided by linkage analysis to identify disease-causing mutations in large multiplex families with schizophrenia. In all 5 pedigrees, they discovered rare protein-altering mutations in 1 of 3 genes involved with the N-methyl-D-aspartate receptor, thereby uncovering new genes associated with risk for developing schizophrenia and suggesting novel therapeutic targets.
Kandaswamy et al identified a Kozak sequence mutation in the GRM3 gene that was associated with bipolar disorder with an odds ratio of 4.20. Laboratory tests found that the Kozak sequence mutation changed a transcription factor binding site and had a strong effect on gene transcription and protein translation. The GRM3 gene encodes the metabotropic glutamate receptor 3 neuroreceptor, which is the target of several drugs that have not yet been studied in clinical trials of bipolar affective disorder.
Kendler et al conducted analyses of the presence or absence of individual criteria for major depression in 7500 members of adult twin pairs. The results indicated that the DSM-IV syndrome of major depression does not reflect a single dimension of genetic liability. Rather, these criteria reflect 3 underlying dimensions that index genetic risk for cognitive/psychomotor, mood, and neurovegetative symptoms.
Milad et al examined fear extinction in a functional magnetic resonance imaging study of 21 patients with obsessive-compulsive disorder (OCD) and 21 healthy participants. They found that fear extinction and its neural substrates were impaired in patients with OCD. This study also yielded some surprising negative correlations between fear extinction deficits and OCD symptom severity that suggest that other factors, in addition to fear extinction deficiency, likely contribute to the psychopathology of OCD.
Beucke et al used resting-state functional magnetic resonance imaging and a data-driven method to determine brain connectivity alterations in patients with obsessive-compulsive disorder. Results revealed abnormally high connectivity of the orbitofrontal cortex and the basal ganglia, consistent with neurobiological models of the disease. However, these regions were characterized by greater connectivity with distant cortical areas outside of traditional corticostriatal circuitry, which provides novel implications for the functional neuroanatomy of the disorder.
Somoza et al report on a multisite US trial (N = 186) using vigabatrin to treat cocaine dependence. Patients complied well with study requirements (of the 76% who completed the 12 weeks of treatment, 89% provided data needed to document abstinence during weeks 11 and 12). The 2 groups showed no differences in abstinence. Although 85% took vigabatrin via pill count, post hoc analysis suggested that up to 50% had missed doses.
A functional magnetic resonance imaging study by Decety et al designed to examine patterns of brain activation in response to empathy-laden stimuli in incarcerated individuals with psychopathy found significantly less activation in the ventromedial prefrontal cortex, lateral orbitofrontal cortex, and periaqueductal gray relative to incarcerated controls but showed greater activation in the insula.
In This Issue of JAMA Psychiatry. JAMA Psychiatry. 2013;70(6):563. doi:10.1001/jamapsychiatry.2013.67