The relation of integrated psychological therapy to resting state functional brain connectivity networks in patients with schizophrenia.

Functional brain dysconnectivity measured with resting state functional magnetic resonance imaging (rsfMRI) has been linked to cognitive impairment in schizophrenia. This study investigated the effects on functional brain connectivity of Integrated Psychological Therapy (IPT), a cognitive behavioral oriented group intervention program, in 31 patients with schizophrenia. Patients received IPT or an equal intensity non-specific psychological treatment in a non-randomized design. Evidence of improvement in executive and social functions, psychopathology and overall level of functioning was observed after treatment completion at six months only in the IPT treatment group and was partially sustained at one-year follow up. Independent Component Analysis and Isometric Mapping (ISOMAP), a non-linear manifold learning algorithm, were used to construct functional connectivity networks from the rsfMRI data. Functional brain dysconnectivity was observed in patients compared to a group of 17 healthy controls, both globally and specifically including the default mode (DMN) and frontoparietal network (FPN). DMN and FPN connectivity were reversed towards healthy control patterns only in the IPT treatment group and these effects were sustained at follow up for DMN but not FPN. These data suggest the use of rsfMRI as a biomarker for accessing and monitoring the therapeutic effects of cognitive remediation therapy in schizophrenia.

Cognitive impairments and psychopathological parameters in patients of the schizophrenic spectrum.

Cognitive impairment is a core feature of schizophrenia and it is considered by many researchers as one of the dimensional components of the disorder. Cognitive dysfunction occurs in 85% of schizophrenic patients and it is negatively associated with the outcome of the disorder, the psychosocial functioning of the patients, and non-compliance with treatment. Many different cognitive domains are impaired in schizophrenia, such as attention, memory, executive functions and speech. Nowadays, it is argued that apart from clinical heterogeneity of schizophrenia, there is probable heterogeneity in the accompanying neurocognitive dysfunction. Recent studies for cognitive dysfunction in schizophrenia employ computerized assessment batteries of cognitive tests, designed to assess specific cognitive impairments. Computerized cognitive testing permits for more detailed data collection (e.g. precise timing scores of responses), eliminates researcher's measurement errors and bias, assists the manipulation of data collected, and improves reliability of measurements through standardized data collection methods. The aims of the present study are: the comparison of cognitive performance of our sample of patients and that of healthy controls, on different specific cognitive tests, and the testing for possible association between patients' psychopathological symptoms and specific cognitive impairments, using the Cogtest computerized cognitive assessment battery. 71 male inpatients diagnosed with schizophrenia or other psychotic spectrum disorders (mean = 30.23 ± 7.71 years of age), admitted in a psychiatric unit of the First Department of Psychiatry, Athens University Medical School, Eginition Hospital (continuous admissions) were studied. Patients were excluded from the study if they suffered from severe neurological conditions, severe visual or hearing impairment, mental retardation, or if they abused alcohol or drugs. The patients' diagnoses were based on the semi-structured diagnostic interview "Diagnostic Interview for Psychosis" (DIP) and were clinically confirmed by two independent expert psychiatrists, according to the criteria of DSM-IVTM. Our healthy control group consisted of 20 healthy male participants (mean = 31.65 ± 5.90 years of age), who met the same inclusion criteria for the study as the patient group, as well as the same exclusion criteria from the study, having no history of psychiatric disorders. All statistical analyses were conducted using the statistical package SPSS.17. According to our results, healthy controls cognitively outperform our patient sample in all cognitive tests, with the differences between performances being statistically significant. Results concerning the association between psychotic symptoms and cognitive deficits of our patients indicated that hallucinations, highly organized delusions, persecutory delusions, agitation, catatonia and inappropriate affect did not associate with any subtype of cognitive deficit. Blunted affect associated significantly with response inhibition ("GoNoGo test", p = 0.007), and poor speech associated significantly with declarative memory of faces ("FMT test", p = 0.002). Moreover, psychomotor ability (non-dominant hand) associated significantly with generalized delusions ("TST test", p = 0.033), and with constricted affect ("TST test", p = 0.026). Furthermore, there was a tendency towards significance association between persecutory delusions and executive function ("CPT test", p = 0.053), inappropriate affect and declarative face memory ("FMT test", p = 0.056), and psychomotor ability and poor speech (p = 0.086).

Schizophrenia-related RGS4 gene variations specifically disrupt prefrontal control of saccadic eye movements.

BACKGROUND: The gene encoding the regulator of G-protein signaling subtype 4 (RGS4), located on chromosome 1q23-3, has been proposed as a possible susceptibility gene for schizophrenia and has been specifically linked to prefrontal cortical structural and functional integrity. METHOD: The effects of four core single nucleotide polymorphisms (SNPs) within the RGS4 gene on oculomotor parameters in a battery of oculomotor tasks (saccade, antisaccade, smooth eye pursuit, fixation) were investigated in a sample of 2243 young male military conscripts. RESULTS: The risk allele of RGS4SNP18 was found to be associated with two variables of antisaccade performance, increased error rate and variation in the correct antisaccade latency. By contrast, the same allele and also the risk allele of RGS4SNP4 led to an improvement in smooth eye pursuit performance (increased gain). Structural equation modeling confirmed that the combined gene variation of RGS4SNP4 and RGS4SNP18 was a significant predictor of antisaccade but not smooth eye pursuit performance. CONCLUSIONS: These results provide evidence for a specific effect of schizophrenia-related RGS4 genotype variations to prefrontal dysfunction measured by oculomotor indices of performance in normal individuals, further validating the hypothesis that RGS4 is related to prefrontal dysfunction in schizophrenia.

Stiff person syndrome: avoiding misdiagnosis.

Stiff person syndrome (SPS) is a rare neurological disorder characterised by muscular rigidity and superimposed spasms of the trunk and limbs that may be precipitated by voluntary movements and unexpected tactile, auditory or emotional stimulation. The high prevalence of autoantibodies against glutamic acid decarboxylase (antiGAD) in both serum and cerebrospinal fluid, as well as the frequent association of SPS with other autoimmune disorders, suggest an autoimmune pathogenesis. SPS is frequently misdiagnosed as axial dystonia or psychogenic movement disorder. We report a patient with SPS in order to emphasise the reasons for this common misdiagnosis.

Active eye fixation performance in 940 young men: effects of IQ, schizotypy, anxiety and depression.

A total of 940 young men performed a task in which they actively maintained fixation for 50 s in three conditions: a). on a visual target, b). on a visual target while distracting targets appeared briefly on the periphery and c). with no visual target present. The same individuals completed psychometric evaluation tests measuring IQ, schizotypy and current state-dependent psychopathology. The proportion of fixation time decreased and saccade frequency increased in condition b compared wih condition a, and sequentially in condition c compared with condition b. A trend towards a decrease in proportion of fixation time and increase in saccade frequency was found as the subjects maintained fixation during the task and this time-dependent deterioration of performance was again most pronounced in condition c, less so in condition b and absent in condition a. Psychometric test scores were significantly correlated with fixation performance in the population. Worse performance in all three fixation conditions was observed for individuals with lower IQ scores. A deterioration of fixation performance with time in condition b was correlated with disorganization characteristics of schizotypy, suggesting that these individuals had difficulty maintaining active fixation in the presence of increased inhibitory load. A connection of such a difficulty with the frontal lobes and their role in the control of voluntary inhibitory functions is discussed.