Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of Alzheimer disease. A central issue in Alzheimer disease pathogenesis is the amyloid cascade hypothesis that abnormal amyloid processing and accumulation is the primary causative factor of Alzheimer disease and other associated neuropathologies are of secondary consequence. Rosenberg (SEE ARTICLE) indicates that future research directed at the prediction and prevention of Alzheimer disease will focus on genomic and proteomic analyses with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset Alzheimer disease.
Lane et al (SEE ARTICLE) studied schizophrenic inpatients with acute exacerbation who received sarcosine, D-serine, or placebo in addition to the concomitant optimal risperidone therapy. Sarcosine adjunctive treatment was superior to placebo in reducing Positive and Negative Syndrome Scale and Scale for the Assessment of Negative Symptoms scores. Cotreatment of D-serine and risperidone did not differ significantly from risperidone monotherapy. This short-term treatment study suggests that sarcosine can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia.
Cannon et al (SEE ARTICLE) evaluated the disrupted-in-schizophrenia 1 (DISC1) and translin-associated factor X (TRAX) genes on chromosome 1q42 for association with schizophrenia, neurocognitive task performance, and regional gray matter density. Two haplotypes were associated with increased risk for schizophrenia, impaired short- and long-term memory, and reduced prefrontal gray matter. Thus, particular alleles of the DISC1 and TRAX genes appear to contribute to genetic risk for schizophrenia through disruptive effects of the prefrontal cortex and other brain regions.
Davatzikos et al (SEE ARTICLE) present a morphometric magnetic resonance imaging study of schizophrenia in 148 participants, using high-dimensional shape analysis. The study identified a spatially complex pattern of reduced brain volumes in patients, particularly in gray matter structures. A high-dimensional pattern classification applied to standard magnetic resonance images yielded predictive power ranging from 81% to 85% (cross-validated), thereby highlighting the potential diagnostic value of advanced classification methods applied to structural images.
Using functional magnetic resonance imaging combined with dopaminergic probe (a 30-mg dose of oral dextroamphetamine sulfate), Tremblay et al (SEE ARTICLE) were able to visualize the neural substrates of altered reward processing in patients with major depressive disorder. The response to dextroamphetamine was associated with activation of well-defined areas of the brain including ventrolateral and orbitofrontal cortex and caudate putamen tying dopamine-related neural substrates to major depressive disorder–disturbed reward processing.
Using data from a recent randomized controlled trial, Lynch et al (SEE ARTICLE) conducted an incremental cost-effectiveness analysis of a group cognitive therapy prevention program for youth at risk for depression. They found that societal cost-effectiveness of a brief prevention program to reduce the risk of depression in offspring of parents with depression was comparable with that of accepted depression treatments and cost-effective in comparison with other health interventions commonly covered in most insurance contracts.
Sareen and colleagues (SEE ARTICLE) used a population-based, longitudinal study to demonstrate that even after adjusting for comorbidity with other mental disorders, the presence of an anxiety disorder at baseline increased the risk of subsequent-onset suicidal ideation and attempts (adjusted odds ratios of 2.32 and 3.64, respectively). The presence of an anxiety disorder in combination with a mood disorder was also associated with a higher likelihood of suicide attempts in comparison with a mood disorder alone.
Koenen et al (SEE ARTICLE) tested competing explanations for the association between posttraumatic stress disorder (PTSD) and nicotine dependence (ND) using data from the Vietnam Era Twin Registry. They found that shared genetic influences explained the majority of the association. However, there was a robust PTSD-ND association beyond that explained by genetic and other shared risk factors. Their data suggested that veterans with ND may be at increased risk of developing PTSD when exposed to trauma.
The RUPP Autism Network (SEE ARTICLE) reports that methylphenidate hydrochloride was superior to placebo in improving hyperactivity and inattention in pervasive developmental disorders but that the magnitude of response was smaller than that seen in studies involving typically developing children with attention-deficit/hyperactivity disorder. Furthermore, methylphenidate treatment led to discontinuation in 18% of treated patients because of irritability and other adverse events.
Genetic and prenatal environmental factors and prefrontal cortical function are thought to contribute to antisocial behavior. Thapar et al (SEE ARTICLE) found that a gene variant in the catechol O-methyltransferase (COMT) gene, previously linked to prefrontal cortical functioning, and birth weight predict childhood-onset antisocial behavior accompanied by attention-deficit/hyperactivity disorder. There is also significant evidence of gene x environment interaction. These findings suggest that genes can confer additional risk for psychopathology by increasing susceptibility to very early environmental factors.
