Patrícia Polgár

Association study of NRG1, DTNBP1, RGS4, G72/G30, and PIP5K2A with schizophrenia and symptom severity in a Hungarian sample†

Genetic association studies have yielded extensive but frequently inconclusive data about genetic risk factors for schizophrenia. Clinical and genetic heterogeneity are possible factors explaining the inconsistent findings. The objective of this study was to test the association of commonly incriminated candidate genes with two clinically divergent subgroups, non‐deficit (SZ‐ND) and deficit‐schizophrenia (SZ‐D), and symptom severity, in order to test for replication of previously reported results. A homogeneous sample of 280 schizophrenia patients and 230 healthy controls of Hungarian, Caucasian descent were genotyped for polymorphisms in schizophrenia candidate genes NRG1, DTNBP1, RGS4, G72/G30, and PIP5K2A. Patients were divided into the diagnostic subgroups of SZ‐ND and SZ‐D using the Schedule for Deficit Syndrome (SDS), and assessed clinically by the Positive and Negative Symptom Scale (PANSS). SNP8NRG241930 in NRG1 and rs1011313 in DTNBP1 were associated with SZ‐ND (P = 0.04 and 0.03, respectively). Polymorphisms in RGS4, G72/G30, and PIP5K2A were neither associated with SZ‐ND nor with SZ‐D. SNP8NRG241930 showed association with the PANSS cognitive and hostility/excitability factors, rs1011313 with the negative factor and SDS total score, and rs10917670 in RGS4 was associated with the depression factor. Although these results replicate earlier findings about the genetic background of SZ‐ND and SZ‐D only partially, our data seem to confirm previously reported association of NRG1 with schizophrenia without prominent negative symptoms. It was possible to detect associations of small‐to‐medium effect size between the investigated candidate genes and symptom severity. Such studies have the potential to unravel the possible connection between genetic and clinical heterogeneity in schizophrenia.

Are patients with schizophrenia rational maximizers? Evidence from an ultimatum game study

Schizophrenia is associated with impaired social cognition and community functioning. Social decision-making strategies of healthy controls and patients with schizophrenia were compared by using the ultimatum game (UG). In this game two players have to split a sum of money. The proposer offers a portion to the responder, who decides to either accept or reject the offer. Rejection results in no income to either of the parties. Unfair proposals are frequently rejected by nonclinical individuals, a phenomenon described as altruistic punishment. Patients and controls participated in a series of UG interactions as responders in a computerized test setting. We also tested the effect of the proposers facial expression on decision-making. Our results indicate that patients with schizophrenia accepted unfair offers at a significantly higher rate than did healthy controls. In contrast, at fair proposals, the acceptance rate was lower in patients compared with controls. At higher offers, the proposers facial expression (positive/negative) significantly influenced the acceptance rate (positive facial expression increased the likelihood of acceptance) in the control group. This effect was not observed in the patient group. These results suggest that schizophrenia patients are impaired in socioeconomic interactions requiring emotion recognition and decision-making, which may result in unstable behavioral strategies.

Associative learning in deficit and nondeficit schizophrenia.

When two stimuli are associated and treated as equivalent, generalization occurs between them (acquired equivalence). The feedback-guided learning of associations is related to the basal ganglia, whereas the medial temporal lobe participates in acquired equivalence learning. In this study, we investigated feedback-guided associative learning and acquired equivalence in deficit and nondeficit schizophrenia. Results revealed that acquired equivalence learning was similarly impaired in deficit and nondeficit patients, whereas feedback-guided associative learning was impaired only in deficit patients. Associative learning and acquired equivalence were not related to frontal lobe tests. These results suggest that the enduring negative symptoms of deficit patients may be related to decreased response to cognitive feedback and deficient basal ganglia functioning.