BRAIN IMAGING research on antisocial, violent offenders is beginning to reveal potentially important functional abnormalities in these subjects. Ranging from small pilot studies of 4 cases¹ to group studies of more than 40 cases,² there is increasing evidence that poor prefrontal functioning is a characteristic of violent, antisocial persons as indicated by both positron emission tomography^3-5 and single-photon emission computed tomography.^6,7 Nevertheless, few if any of these studies control for comorbidity of substance abuse, schizophrenia-spectrum disorders, and other psychiatric comorbidity, and all have been conducted on selected samples derived from psychiatric hospitals, prisons, or forensic settings. Unlike these functional imaging findings, there have been no prior magnetic resonance imaging (MRI) studies of structural brain deficits in antisocial groups, and nothing is known about brain abnormalities in noninstitutionalized violent offenders.

While two factors are currently thought to underlie individual differences in schizotypal personality, three factors may best explain schizotypal traits. This study used confirmatory factor analysis to assess five competing models of schizotypal personality in the general population: null model, one-factor model, simple two-factor model, Kendler two-factor model, and three-factor model. The computer program LISREL was used to analyze Schizotypal Personality Questionnaire subscale scores that reflect the nine traits of schizotypal personality. The scores were obtained from (1) a sample of 822 undergraduates and (2) a replication sample of 102 subjects drawn from the community. Results indicate replicable support for a three-factor model reflecting cognitive-perceptual, interpersonal, and disorganized latent factors. Low intercorrelations between the first two factors and the lack of fit by a one-factor model are partially inconsistent with recent notions that a single vulnerability dimension underlies schizotypal personality. It is argued that future investigations should assess the correlates of all three schizotypal factors in clinical and nonclinical samples in addition to the two more traditional factors. It is hypothesized that three factors of schizophrenic symptomatology observed in recent studies may reflect an exaggeration of three analogous factors found in the general population.

Evolutionarily significant selective sweeps may result in long stretches of homozygous polymorphisms in individuals from outbred populations. We developed whole-genome homozygosity association (WGHA) methodology to characterize this phenomenon in healthy individuals and to use this genomic feature to identify genetic risk loci for schizophrenia (SCZ). Applying WGHA to 178 SCZ cases and 144 healthy controls genotyped at 500,000 markers, we found that runs of homozygosity (ROHs), ranging in size from 200 kb to 15 mb, were common in unrelated Caucasians. Properties of common ROHs in healthy subjects, including chromosomal location and presence of nonancestral haplotypes, converged with prior reports identifying regions under selective pressure. This interpretation was further supported by analysis of multiethnic HapMap samples genotyped with the same markers. ROHs were significantly more common in SCZ cases, and a set of nine ROHs significantly differentiated cases from controls. Four of these 9 “risk ROHs” contained or neighbored genes associated with SCZ ( NOS1AP , ATF2 , NSF , and PIK3C3 ). Several of these risk ROHs were very rare in healthy subjects, suggesting that recessive effects of relatively high penetrance may explain a proportion of the genetic liability for SCZ. Other risk ROHs feature haplotypes that are also common in healthy individuals, possibly indicating a source of balancing selection.

Crohn’s disease (CD)–associated variants in the LRRK2 gene for risk (N2081D) and for protection (N551K) mediate shared effects in CD and Parkinson’s disease.

Cognitive impairment in schizophrenia is frequent, involves multiple domains of information processing, and may be a core feature of the disorder.^1-4 Thus, neurocognition has come to be viewed as a key target in clinical trials.⁵ Patients with first-episode schizophrenia (FES) may be an especially important group for such studies because they have demonstrable plasticity in symptomatic response to antipsychotics, can be tested while drug naive, and do not have long histories of multiple antipsychotic drug treatment that may confound results. Furthermore, potential confounders associated with chronicity (patient role, institutionalization, interactions with aging, or disease processes) are minimized.