The domain-variant indirect association between electrophysiological response to reward and ADHD presentations is moderated by dopaminergic polymorphisms.

BACKGROUND: Understanding the etiopathogenesis of attention-deficit/hyperactivity disorder (ADHD) may necessitate decomposition of the heterogeneous clinical phenotype into more homogeneous intermediate phenotypes. Reinforcement sensitivity is a promising candidate, but the exact nature of the ADHD-reward relation - including how, for whom, and to which ADHD dimensions atypicalities in reward processing are relevant - is equivocal. METHODS: Aims were to examine, in a carefully phenotyped sample of adolescents (N = 305; Mage = 15.30 years, SD = 1.07; 39.7% girls), whether functional dopaminergic polymorphisms implicated in both reward processing and ADHD (1) are differentially associated with event-related potentials (ERPs) of reward anticipation at distinct levels of ADHD risk (nno risk = 174, nat-risk = 131, ndiagnosed = 83); and (2) moderate the indirect effect of dispositional affectivity on the association between ERPs and ADHD domains. RESULTS: In adolescents at-risk for or with ADHD, carrying a hypodopaminergic allele was associated with enhanced ERPs of attention allocation to cue and attenuated ERPs of anticipatory attention to feedback. No associations were observed in adolescents not at-risk for or without ADHD. Controlling for age and sex, both the negative indirect effect of positive affectivity (PA) on the association between ERPs and inattention and the positive indirect effect of PA on the association between ERPs and hyperactivity/impulsivity were supported only for those with high activity dopamine transporter (DAT) alleles. CONCLUSIONS: Reward and affective processing are promising intermediate phenotypes relevant to disentangling ADHD developmental pathways. Consistent with developmental multifinality, through the successive effects of reward anticipation and positive affectivity, functional dopaminergic variants may confer protection against inattention or risk for hyperactivity/impulsivity.

Expanding the range of ZNF804A variants conferring risk of psychosis.

A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).

Executive function in deficit schizophrenia: what do the dimensions of the Wisconsin Card Sorting Test tell us?

Neuropsychological characterization of the schizophrenia deficit syndrome is an unresolved issue. The initial assumption was that patients with deficit syndrome show more definitive impairments on tests sensitive for frontal and parietal functions compared with nondeficit patients,but recent studies failed to confirm this assumption. The fundamental question is whether a more refined delineation of executive dysfunctions is able to yield differences between deficit and nondeficit patients. To investigate this question, we implemented a factor analytic approach to explore potential differences between deficit and nondeficit patients using the Wisconsin Card Sorting Test (WCST). Our paper presents an exploratory factor analysis of the WCST on schizophrenia patients and healthy samples, and a comparison among deficit, non-deficit patients with schizophrenia and control samples using the identified factors. A total of 154 patients with schizophrenia fulfilling the criteria for the deficit syndrome, 121 nondeficit patients, and 130 healthy controls were compared. Factor analysis of the WCST variables using the principal component method resulted in a two-factor solution. Comparison of the diagnostic groups on each of the factors revealed that deficit schizophrenia patients suffer from a more severe degree of impairment on the 'General executive function' factor than nondeficit schizophrenia patients. To our knowledge this is the first study that compared patients with the deficit and non-deficit forms of schizophrenia using WCST factor analytic techniques. Our results provide an insight into the cognitive profile of schizophrenia patients with regard to WCST, which could serve as a framework for future clinical and research endeavors.