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.
We hypothesize that time perception and executive functions are interrelated and share neuroanatomical basis, and that fluctuations in levels of cognitive effort play a role in mediating that relation. The main goal of this study was to identify brain structures activated both by increases in cognitive activity and during time perception tasks.
? Several studies have described volumetric brain abnormalities in first-episode psychosis. The extent to which these differ in patients with schizophrenia and affective psychoses, or are related to subsequent clinical outcome, is unclear. We examined volumetric magnetic resonance imaging (MRI) abnormalities in young patients with a first episode of psychosis, and compared these volumetric abnormalities in patients with schizophrenia versus affective psychosis. We then assessed whether baseline MRI abnormalities in the entire sample predicted subsequent clinical outcome.
Both schizophrenia and bipolar disorder have been associated with progressive changes in grey matter (GM) volume. However, the temporal trajectories of these changes are poorly understood. The aim of this study was to assess longitudinal changes in grey matter volume subsequent to the first episode of schizophrenia and of affective psychoses. Adolescent patients with a first episode psychosis (n=26) were scanned twice using magnetic resonance imaging, at first presentation and after a 3-year follow-up period. An age-matched group of healthy volunteers (n=17) was scanned at the same time points. Within-group and between-group changes in regional grey matter volume were examined using voxel-based morphometry. There were significant group by time interactions (p(FDRcorr)<0.05) in the frontal, temporal, parietal, cerebellar cortex, and in the thalamus, mainly reflecting longitudinal reductions in the controls but not in the patients. Subdivision of the patient group revealed that there were similar longitudinal reductions in patients with affective psychoses as in the controls but no volumetric changes in patients with schizophrenia. Psychosis with onset in adolescence or early adulthood may be associated with a delay or a loss of longitudinal reductions in regional grey matter volume that normally occur at this stage of development. These changes may be specific to schizophrenia.
The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of "schizophrenia" or "other psychosis" showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents.
With the double objective of searching for a physiological brain circuit concerned with time estimation and establishing whether this circuit is dysfunctional in schizophrenia patients, we carried out an activation likelihood estimate (ALE) meta-analysis of published functional neuroimaging studies. Our results reproduce the previous finding of a neurophysiological cortico-cerebellar-thalamic circuit related with time estimation in healthy individuals. In schizophrenia patients, the analysis indicates significantly lower activation of most right hemisphere regions of the circuit, suggesting that it may be subject to a pattern of disconnectivity. The ALE-meta-analysis approach is useful and further studies could elucidate how the timing circuit is connected with other cognitive tasks.
We studied relative cortical blood flow (relCBF) patterns associated to correct performance (CP) and perseverative error (PE) during Wisconsin Card Sorting Test (WCST) execution, in controls and patients with schizophrenia.
In multicenter MRI studies, pooling of volumetric data requires a prior evaluation of compatibility between the different machines used. We tested the compatibility of five different scanners (2 General Electric Signa, 2 Siemens Symphony, and a Philips Gyroscan) at five different sites by repeating the scans of five volunteers at each of the sites. Using a semiautomatic method based on the Talairach atlas, and SPM algorithms for tissue segmentation (multimodal T1 and T2, or T1-only), we obtained volume measurements of the main brain lobes (frontal, parietal, occipital, temporal) and for each tissue type. Our results suggest that pooling of multisite data adds small error for whole brain measurements, intersite coefficient of variation (CV) ranging from 1.8 to 5.2%, respectively, for GM and CSF. However, in the occipital lobe, intersite CV can be as high as 11.7% for WM and 17.3% for CSF. Compared with the intersite, intrasite CV values were always much lower. Whenever possible, T1 and T2 tissue segmentation methods should be used because they yield more consistent volume measurements between sites than T1-only, especially when some of the scans were obtained with different sequence parameters and pixel size from those of the other sites. Our study shows that highest compatibility among scanners would be obtained using equipments of the same manufacturer and also image acquisition parameters as similar as possible. After validation, data from a specific ROI or scanner showing values markedly different from the other sites might be excluded from the analysis.
There are reports of significant association between obstetric complications (OC) and childhood psychosis. Authors conducted a case-control study of 102 children and adolescents with a first episode psychosis (FEP) and 94 healthy controls (HC), using the obstetric complications scale (OCS) and their medical records, to examine the risk of FPE. Patients were recruited from child and adolescent psychiatry units at six university hospitals and controls from publicly-funded schools of similar characteristics and from the same geographic areas. A logistic regression was performed to quantify the risk of psychosis in childhood and adolescence, based on OC, adjusting for potential confounding factors like socio economic status (SES) and family psychiatric history (FPH). OC appeared more frequently in the records of patients. Significant differences between patients and controls were found in Prenatal OC (15.7% vs. 5.3%, P < 0.05) and among them, bleeding in pregnancy showed the greatest difference between groups (12.7% vs. 2.1%, P < 0.01). In the logistic regression, bleeding in pregnancy showed a crude odds ratio (OR) of 6.7 (95%CI = 1.4-30.6) and 5.1 (CI 95% = 1.0-24.9) adjusted for SES and FPH. Therefore, bleeding in pregnancy is a likely risk factor for early-onset psychosis.
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.
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.
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