Timing is an essential function for the survival of many living organisms. Despite its significance, it is relatively under-researched, particularly in schizophrenia. We examined neurophysiological, neuropathological, imaging and genetic studies of both healthy subjects and subjects suffering from schizophrenia in relation to time perception as measured by interval timing. We found that the data from studies in healthy populations indicate that time perception may be inter-linked with numerous other cognitive functions and share common brain networks. The same networks are implicated in the pathophysiology of schizophrenia. There is also evidence that several neurotransmitter systems, particularly the dopaminergic D2 system, are involved in interval timing. Patients with schizophrenia have been shown to suffer from a distorted sense of time, which has an impact on their cognitive function and results in both positive and negative symptoms. Therefore, genes involved in interval timing can be considered candidate genes for distorted cognition in schizophrenia. We discuss the hypothesis that time perception dysfunction is a primary cognitive dysfunction in schizophrenia.

Cognitive impairment in schizophrenia is a core feature and seems to be related mainly to dopaminergic dysfunction in the prefrontal cortex (PFC). The functional polymorphism Val158Met of the COMT (catechol-. O-methyltransferase) gene could mediate the relationship between cognition and dopamine activity in PFC. The present study tested the influence of this polymorphism on the cognitive performance of schizophrenia spectrum patients and their relatives, using some subtests of the neuropsychological battery, the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and evaluated the impact of this polymorphism on a specific prefrontal cognitive function using a cognitive neuroscience paradigm. A Group of 74 schizophrenia spectrum disorder patients, 48 relatives and 67 controls performed some subtests of the MATRICS Consensus Cognitive Battery. In addition, 40 schizophrenia spectrum disorder patients, 26 relatives and 63 controls performed the Dot Pattern Expectancy Task (DPX) to study context processing. For the neuropsychological battery, no differences in any of the cognitive domains were found according to genotype. The DPX task was sensitive to genotype effects in patients as well as in relatives. Context processing deficits in schizophrenia patients and their relatives may be mediated by COMT genotype. The influence of the COMT genotype on cognition is more relevant in specific cognitive tasks related to prefrontal function. These results should be replicated in larger samples.

Background: As marker genes for bipolar disorder (BP) and attention deficit hyperactivity disorder (ADHD) are not fully identified, we carried out a complete genome analysis to search for genes differentially expressed in ADHD and BP. Materials and methods: We recruited 39 patients (30 ADHD, 9 BP), aged 7 to 23 years. For evaluation of the psychiatric diagnosis, we used a semi-structured interview based on the K-SADS-PL (DSM-IV). RNA was extracted from peripheral blood and analyzed with the GeneChip (R) Human Genome U133-Plus 2.0 (Affymetrix). For the validation of differentially expressed genes, real-time PCR was used. Results: Hybridization and subsequent statistical analysis found 502 probe-sets with significant differences in expression in ADHD and BP patients. Of these, 82 had highly significant differences. Neuregulin (NRG1), cathepsins B and D (CTSB, CTSD) and prostaglandin-D2-synthase (FTGDS) were chosen for semi-quantitative mRNA determination. The expression of PTGDS was statistically increased in ADHD relative to BP patients (p = 0.01). We found no such differential expression with NRG1, CTSB and CTSD genes (p > 0.05). Conclusions: The gene coding for FTGDS was found to be more expressed in patients with ADHD relative to patients with BP, indicating a possible link with the differential etiology of ADHD. The experimental approach we have used is, at least in part, validated by the detection of proteins directly concerned with brain functions, and shows a possible way forward for studies of the connection between brain function genes and psychiatric disorders. Limitations: Confirmation of our findings requires a larger sample of patients with clearly-defined phenotypes. (C) 2012 Elsevier B.V. All rights reserved.

Dopamine levels in the prefrontal cortex (PFC) seem to play a crucial role in cognitive function in schizophrenia. The COMT enzyme has a functional polymorphism (val158met): val/val individuals have a higher functioning enzyme leading to lower dopamine levels in PFC and therefore to poorer cognitive performance. This genetic polymorphism could mediate the relationship between dopamine levels, cognitive functioning and neural activity of PFC. We used global neuropsychological and specific cognitive assessments and fMRI to study the influence of COMT genotype on cognition and brain function in schizophrenia spectrum disorder patients, relatives and healthy control subjects.