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This Month in Archives of General Psychiatry
February 2011

This Month in Archives of General Psychiatry

Arch Gen Psychiatry. 2011;68(2):122-123. doi:10.1001/archgenpsychiatry.2010.195

Using repeated magnetic resonance scans to assess brain volume trajectories in 211 patients with first-episode schizophrenia, Ho et al Article found that brain tissue volume reductions were associated with more antipsychotic treatment. Consistent with controlled animal studies, these findings implicate antipsychotics as a contributing factor for longitudinal brain volume decrement in schizophrenia. Although schizophrenic patients benefit from antipsychotics and their continued use remains necessary, clinicians may need to reassess the risks and benefits of high-dose and off-label antipsychotic treatment.

Associations between a common environmental risk factor (cannabis use) and a rare psychiatric disorder (schizophrenia) arguably only make sense if the existence of vulnerable subgroups can be demonstrated. The Genetic Risk and Outcome of Psychosis (GROUP) Article consortium used a family-based design, based on a national sample of 1100 sibling pairs, to uncover, and replicate, evidence that genetic risk for schizophrenia may be expressed in part as sensitivity to the psychotomimetic effect of cannabis.

The molecular genetic variation underlying sensitivity to cannabis in the same family-based sample using a large set of a priori candidate polymorphisms was also examined by van Winkel and the Genetic Risk and Outcome of Psychosis (GROUP) Article consortium. Across different approaches and samples, it was shown that genetic variation in AKT1 moderated both short-term psychotomimetic effects of cannabis in healthy siblings, as well as risk for psychotic disorder, implicating the AKT1/GSK-3 signaling pathway in sensitivity to the psychosis-inducing effects of cannabis.

Neuropeptide Y (NPY) is a ubiquitous neurotransmitter implicated in stress resilience. Mickey et al Article demonstrated that individuals with a low-expression NPY genetic variant exhibited greater responses to negative stimuli within key medial frontal circuits and experienced more negative emotions during a stress challenge. Furthermore, the low-expression variant was overrepresented among patients with major depressive disorder. The findings implicate low-expression NPY variants in the pathophysiology of affective disorders.

In a prospective multisite (n = 4) study on mental health courts (MHCs) with treatment and control groups, Steadman et al Article found that the MHC sample had a lower annualized rearrest rate, fewer post–18-month arrests, and fewer post–18-month incarceration days than the control group. They also found that MHCs meet the objectives of lowering posttreatment arrest rates and days of incarceration. Clinical and criminal justice factors are associated with better public safety outcomes for MHC participants.

North et al Article conducted structured interviews of 697 directly exposed survivors of 10 disasters to diagnose predisaster and postdisaster alcohol use disorder. Postdisaster alcohol disorders were present in 19%, but only 0.3% of the sample developed an incident postdisaster alcohol diagnosis in the first few postdisaster months. Findings suggest that survivors in recovery when disaster strikes and those who drink to cope with disaster-related emotions represent groups with increased risk for postdisaster alcohol problems.

Using a representative sample of 9- to 17-year-old twins, Lahey et al Article found that genetic influences are mostly nonspecifically shared by 11 dimensions of psychopathology. This suggests that pleiotropy is the principal mode of genetic risk transmission for common forms of child and adolescent psychopathology and implies that the broad term psychopathology has biological reality. In contrast, environmental influences are mostly unique to each dimension, indicating that they serve to differentiate dimensions of psychopathology.

Kales et al Article examined the impact of the various warnings, including the 2005 Food and Drug Administration black box warning on atypical and conventional antipsychotic use, using national Veterans Affairs data. The use of atypical antipsychotics began to decline significantly in 2003 and the Food and Drug Administration advisory was temporally associated with a significant acceleration in the decline.

Using magnetic resonance imaging and diffusion tensor tractography, Voineskos et al Article examined the interaction of the brain-derived neurotrophic factor (BDNF) Val66Met variant with age in relation to neuroimaging measures and cognitive performance. The BDNF Val66Met variant interacted with age to predict (1) cortical thickness (prominently at the entorhinal cortex and inferior temporal gyrus), (2) fractional anisotropy of white matter tracts prominently at white matter tracts connecting to the medial temporal lobe (left cingulum bundle and left inferior longitudinal fasciculus), and (3) episodic memory performance. For each of these findings, the pattern was similar: Met allele carriers in early adult life and Val/Val individuals in late life were susceptible. Therefore, the BDNF gene confers risk in an age-dependent manner on the brain structures and cognitive functions that are consistent with the neural circuitry vulnerable in the earliest stages of Alzheimer disease.

Recent genome-wide association studies have implicated 3 putative susceptibility loci for Alzheimer disease, CLU, CR1, and PICALM. Schjeide et al Article investigated these genes in a large collection of independent family-based and case-control data sets, and all 3 loci were confirmed to show significant association with Alzheimer disease risk. Furthermore, they identified a significant correlation between cerebrospinal fluid biomarker levels and the risk allele in the PICALM gene.

Kim et al Article found that persons with Alzheimer disease are highly unlikely to be capable of providing their own consent to high-risk research, such as sham control surgical studies; however, they found that the majority of such persons may still be capable of appointing a trusted surrogate to make research decisions for them.