To establish phenomics-based genetic association studies in schizophrenia, a unique database was created by GRAS (Göttingen Research Association for Schizophrenia). In a first phenomics-based genetic association study, Begemann et al found 6 single-nucleotide polymorphisms in the complexin 2 gene associated with current cognition but not premorbid intelligence of schizophrenic patients. In complexin 2–null mutant mice, cognitive loss of function occurred only combined with an environmental “second hit.” As a mechanism explaining this second hit effect, single-nucleotide polymorphism rs3822674 was found to influence microRNA-498 binding.
Using Danish neonatal dried blood spots, McGrath et al compared neonatal 25 hydroxyvitamin D concentrations in 424 individuals with schizophrenia vs 424 controls matched for sex and date of birth. They found a significant relationship between neonatal vitamin D status and risk of schizophrenia. The finding raises the tantalizing prospect of the primary prevention of schizophrenia.
Guo et al report on a randomized controlled 12-month trial of 1268 patients with early-stage schizophrenia in China to examine the effectiveness of augmenting antipsychotic medication with a comprehensive, monthly psychosocial intervention. Compared with a medication-only group, patients receiving combined medication and psychosocial treatment had lower rates of treatment discontinuation and relapse and improved functioning and quality of life.
Using the large international familial schizophrenia cohort, Toulopoulou et al show that a substantial portion of the phenotypic correlation between schizophrenia and cognition is due to shared genetic influences. However, their results also suggest that the genetics of schizophrenia are not restricted to the genetic determinants of cognitive impairment.
In a multilevel longitudinal study, Zammit et al show that almost all the variance in risk of nonaffective psychoses is explained by individual-level rather than school- or area-level variation. They also observe cross-level interactions between individual- and school-level markers of ethnicity, social fragmentation, and deprivation on risk of developing psychosis, suggesting that any characteristic that defines individuals as being different from most other people in their local environment may increase psychosis risk.
Combining Swedish and Danish birth cohorts, Abel et al examined the risk for schizophrenia and other adult mental illnesses according to birth weight across the whole range and found that the risk for mental illness, not specifically schizophrenia, correlated inversely with birth weight and that there was no obvious threshold.
Fazel et al used Swedish national registers from 1973 to 2004 to determine the risk of violent crime in individuals after diagnosis with bipolar disorder compared with general population controls and their unaffected siblings and contextualized these findings by conducting a novel meta-analysis. Substance abuse comorbidity markedly increased violence risk irrespective of comparison group. However, in those without comorbidity, there was no increased risk of violent crime compared with unaffected siblings and a minimal risk increase compared with the general population.
Bigos et al found that a genetic variant in CACNA1C, which is associated with risk for bipolar disorder and schizophrenia, predicts increased hippocampal activity during emotional processing and increased prefrontal activity during executive cognition as measured by functional magnetic resonance imaging in healthy subjects. The risk single-nucleotide polymorphism also predicts increased expression of CACNA1C messenger RNA in the human brain, implicating a molecular and neural systems mechanism for the clinical genetic associations.
Hoerst et al investigated neurometabolite concentrations in the anterior cingulate cortex in patients with borderline personality disorder compared with healthy controls. A positive correlation between glutamate concentration and the self-reported Barratt impulsivity score could be demonstrated with significantly higher levels of impulsivity and glutamate in the patient group. Other borderline symptoms also correlated with anterior cingulate cortex glutamate.
Using anatomical magnetic resonance imaging, Miller et al detected volumetric increases in the lateral thalamus of children and adults with Tourette syndrome. The findings promote the thalamus as an anatomical crossroad wherein hypertrophic executive portions of cortical-subcortical circuits interact with and modulate activity in hypoplastic and hyperexcitable sensorimotor circuits. The thalamus thus may be a locus where putative compensatory systems directly modulate activity in motor pathways to attenuate the severity of tics.
Chamberlain et al used diffusion tensor imaging in conjunction with permutation cluster analysis to explore brain white matter tract integrity in trichotillomania. Compared with matched controls, people with trichotillomania exhibited reduced integrity of white matter tracts linking brain nodes involved in the monitoring, generation, and top-down suppression of habitual motor responses. These findings inform neurobiological models of trichotillomania and related obsessive-compulsive spectrum conditions.