Structural abnormalities in language circuits in genetic high-risk subjects and schizophrenia patients.

Schizophrenia is a severe psychiatric disorder with a strong genetic predisposition. Structural and functional brain deficits throughout the cerebral cortex, particularly in the language-processing associated brain regions, are consistently reported. Recently, increasing evidence from magnetic resonance imaging (MRI) studies suggests that healthy relatives of schizophrenia patients also show structural brain abnormalities in cortical gray matter (GM) volume and thickness, suggesting that this may be associated with an unexpressed genetic liability for the disorder. Unfortunately, the findings are not consistent, which may be caused by different age ranges of the cohorts studied. In the present study, we examined the voxel-based whole brain cortical thickness, area, GM volume densities, and regional cortical thickness-related laterality indices in 14 bilateral regions of interest (ROIs) from known language-processing circuits in 20 schizophrenia patients, 21 young non-psychotic subjects with heightened genetic risk for schizophrenia at the peak ages for development of the disorder, and 48 matched controls. The results showed widespread significant reductions in cortical thickness, cortical GM volume density, and scattered decreases in cortical surface area in the schizophrenia patients compared with those in the high-risk subjects and normal controls. Moreover, the genetic high-risk subjects showed significantly increased regional cortical thickness in 7 of the 14 ROIs in the language-processing pathway when compared with controls. They also had increased GM volume density in scattered regions associated with language-processing when compared with the normal controls. Laterality analyses showed that the spatial distribution of abnormal cortical thickness in the schizophrenia patients, as well as in the high-risk subjects, contributes to a decrease of the normal left-greater-than-right anatomical asymmetry in the inferior orbital frontal area, and a increased left-greater-than-right pattern in the inferior parietal and occipital regions. Together with the existing findings in the literature, the results of the present study suggest that developmental disruption of the anatomical differentiation of the hemispheres provides a basis for understanding the language impairment and symptoms of psychosis, and that these may arise because of abnormal left-right hemispherical communications that interrupt the normal flow of information processing. The early structural deficits in language-processing circuits may precede the appearance of psychotic symptoms and may be an indicator of an increased risk of developing schizophrenia.

Art therapy for Parkinson's disease.

OBJECTIVE: To explore the potential rehabilitative effect of art therapy and its underlying mechanisms in Parkinson's disease (PD). METHODS: Observational study of eighteen patients with PD, followed in a prospective, open-label, exploratory trial. Before and after twenty sessions of art therapy, PD patients were assessed with the UPDRS, Pegboard Test, Timed Up and Go Test (TUG), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale and PROMIS-Self-Efficacy, Montreal Cognitive Assessment, Rey-Osterrieth Complex Figure Test (RCFT), Benton Visual Recognition Test (BVRT), Navon Test, Visual Search, and Stop Signal Task. Eye movements were recorded during the BVRT. Resting-state functional MRI (rs-fMRI) was also performed to assess functional connectivity (FC) changes within the dorsal attention (DAN), executive control (ECN), fronto-occipital (FOC), salience (SAL), primary and secondary visual (V1, V2) brain networks. We also tested fourteen age-matched healthy controls at baseline. RESULTS: At baseline, PD patients showed abnormal visual-cognitive functions and eye movements. Analyses of rs-fMRI showed increased functional connectivity within DAN and ECN in patients compared to controls. Following art therapy, performance improved on Navon test, eye tracking, and UPDRS scores. Rs-fMRI analysis revealed significantly increased FC levels in brain regions within V1 and V2 networks. INTERPRETATION: Art therapy improves overall visual-cognitive skills and visual exploration strategies as well as general motor function in patients with PD. The changes in brain connectivity highlight a functional reorganization of visual networks.

A DTI study of white matter microstructure in individuals at high genetic risk for schizophrenia.

Structural brain developmental anomalies, particularly those in frontotemporal white matter pathways, may have a genetic component and place people at increased risk for schizophrenia. The current study employed Diffusion Tensor Imaging (DTI) to measure fractional anisotropy (FA) as a quantitative indicator of white matter integrity. We examined twenty-two participants at high genetic risk for schizophrenia (HR), 23 people with schizophrenia (most of whom were family members of those at HR) and 37 non-psychiatric controls for comparison. In those at HR, reduced FA was observed in the cingulate and angular gyri bilaterally. In a few regions, FA was higher in HR participants than in comparison participants. These regional variations in FA might reflect differences in white matter development from comparison participants. Our data provide some evidence that abnormal white matter integrity may be detectable before the onset of a psychotic illness, although longitudinal studies are necessary to determine whether these individuals at genetic risk with abnormal FA will develop illness and whether these changes are associated with the genetic risk for the disorder.

Telomerase levels in schizophrenia: a preliminary study.

We previously demonstrated that telomere length was markedly reduced in peripheral blood lymphocytes from individuals with schizophrenia. Since reduced telomere length can be caused by decreased telomerase activity, we quantitated basal telomerase activity in peripheral blood lymphocytes derived from individuals with schizophrenia (n=53), unaffected relatives (n=31) and unrelated controls (n=59). Telomerase activity varied greatly among individuals, suggesting that this enzymatic activity is affected by various factors. We observed a nominally significant decrease in telomerase activity among individuals with schizophrenia compared to unaffected individuals (unaffected relatives and unrelated controls). Further studies are needed to investigate the role of telomerase in schizophrenia.

An fMRI study of language processing in people at high genetic risk for schizophrenia.

BACKGROUND: Abnormalities in language processing and the related brain structures have been reported in people with schizophrenia. It has been proposed that the brain pathways for language processing are anomalous in these individuals and form the underlying basis for the positive symptoms of the illness. If language pathway abnormalities can be detected early in people at high-risk for schizophrenia prior to the onset of symptoms, early treatment can ensue. METHODS: Fifteen young adults at high genetic risk for developing schizophrenia were compared with 15 of their siblings with schizophrenia or schizoaffective disorder and 15 age and sex matched individuals at low risk for schizophrenia using a visual lexical decision task during fMRI. The data were analyzed by contrasting activation obtained during a real word-pseudoword discrimination task to activation obtained during a nonlinguistic discrimination task, and the differential activations were examined. RESULTS: Patterns of brain activation while reading and discriminating between real and pseudowords differed across groups, with more bilateral activation in schizophrenia patients and their high-risk siblings than controls. In control subjects discrimination of words from psuedowords significantly activated Brodmann's area 44 more strongly than when non-linguistic symbols were discriminated. However, high-risk subjects and their siblings with schizophrenia activated this region similarly for both language and non-language tasks. CONCLUSIONS: Normal individuals can be distinguished from subjects at high genetic risk for schizophrenia and patients with schizophrenia by their more lateralized and stronger activation of Brodmann's area 44 to word compared with symbol discrimination tasks. Thus, evaluation of language processing by fMRI may be a valuable tool for use in the prediction of individual risk for developing schizophrenia.

A preliminary DTI study showing no brain structural change associated with adolescent cannabis use.

Analyses were performed on brain MRI scans from individuals who were frequent cannabis users (N = 10; 9 males, 1 female, mean age 21.1 +/- 2.9, range: 18-27) in adolescence and similar age and sex matched young adults who never used cannabis (N = 10; 9 males, 1 female, mean age of 23.0 +/- 4.4, range: 17-30). Cerebral atrophy and white matter integrity were determined using diffusion tensor imaging (DTI) to quantify the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA). Whole brain volumes, lateral ventricular volumes, and gray matter volumes of the amygdala-hippocampal complex, superior temporal gyrus, and entire temporal lobes (excluding the amygdala-hippocampal complex) were also measured. While differences existed between groups, no pattern consistent with evidence of cerebral atrophy or loss of white matter integrity was detected. It is concluded that frequent cannabis use is unlikely to be neurotoxic to the normal developing adolescent brain.

Understanding structural brain changes in schizophrenia.

Schizophrenia is a chronic progressive disorder that has at its origin structural brain changes in both white and gray matter. It is likely that these changes begin prior to the onset of clinical symptoms in cortical regions, particularly those concerned with language processing. Later, they can be detected by progressive ventricular enlargement. Current magnetic resonance imaging (MRI) technology can provide a valuable tool for detecting early changes in cortical atrophy and anomalous language processing, which may be predictive of who will develop schizophrenia.

Subcortical structure alterations impact language processing in individuals with schizophrenia and those at high genetic risk.

OBJECTIVE: Cortical structural and functional anomalies have been found to associate with language impairments in both schizophrenia patients and genetic high risk individuals for developing schizophrenia. However, subcortical structures that contribute to language processing haven't been well studied in this population, and thus became the main objective of this study. METHOD: We examined structural MRI data from 20 patients with schizophrenia, 21 individuals at genetic high risk, and 48 controls. Surface shape and volume differences of 6 subcortical structures that are involved in language processing, including nuclei pallidum, putamen, caudate, amygdala, thalamus, and hippocampus from both hemispheres, were compared between groups. Performance scores of language-associated cognitive tests were obtained to identify relationships of subcortical structures to language-related behaviors. RESULTS: Significantly reduced volumes of both the left and right side caudate nuclei, thalami and right side amygdala were shown in patients when compared with controls. Very interestingly, the high risk group demonstrated significantly increased correlations between volumes of left side pallidum nucleus and bilateral thalami and language-related cognitive test scores when compared to controls. CONCLUSIONS: This study furthers our understanding of subcortical structural alterations in schizophrenia and high risk individuals, and suggests the contribution of subcortical structures to the language impairments that may serve as an early sign for impending development of schizophrenia.

Anxiety as a primary predictor of functional impairment after acquired brain injury: a brief report.

OBJECTIVE: Cognitive and emotional symptoms are primary causes of long-term functional impairment after acquired brain injury (ABI). Although the occurrence of post-ABI emotional difficulties is well-documented, most investigators have focused on the impact of depression on functioning after ABI, with few examining the role of anxiety. Knowledge of the latter's impact is essential for optimal treatment planning in neurorehabilitation settings. The purpose of the present study is therefore to examine the predictive relationships between cognition, anxiety, and functional impairment in an ABI sample. METHOD: Multiple regression analyses were conducted with a sample of 54 outpatients with ABI. Predictors selected from an archival data set included standardized neuropsychological measures and Beck Anxiety Inventory scores. Dependent variables were caregiver ratings of functional impairments in the Affective/Behavioral, Cognitive, and Physical/Dependency domains. RESULTS: Anxiety predicted a significant proportion of the variance in caregiver-assessed real-life affective/behavioral and cognitive functioning. In contrast, objective neuropsychological test scores did not contribute to the variance in functional impairment. Neither anxiety nor neuropsychological test scores significantly predicted impairment in everyday physical/dependency function. CONCLUSION: These findings support the role of anxiety in influencing functional outcome post-ABI and suggest the necessity of addressing symptoms of anxiety as an essential component of treatment in outpatient neurorehabilitation.

Unique topology of language processing brain network: a systems-level biomarker of schizophrenia.

OBJECTIVE: Schizophrenia is a severe and heritable brain disorder. Language impairment has been hypothesized to spur its onset and underlie the characteristic symptoms. In this study, we investigate whether altered topological pattern of the language processing brain network exists and could be a potential biomarker of schizophrenia. We hypothesized that both patients with schizophrenia and the genetic high risk population would show significantly weakened efficiencies of the network hubs for normal language processing, especially at left inferior frontal and bilateral temporal lobes. METHOD: Language task-based fMRI data from 21 patients with schizophrenia, 22 genetic high risk subjects and 36 controls were analyzed. Graph theoretic and post hoc analyses of the fMRI data, and correlations between the functional network features and scores of language tests were carried out. RESULTS: Compared to controls, patients with schizophrenia and the high risk subjects showed significantly weakened network hubs in left inferior frontal and right fusiform gyri. A unique topology of super active and intercommunicating network hubs at left fusiform gyrus and right inferior/middle frontal gyri, which were associated with the behavioral language impairment was found in the patient group, compared to the high risk and control groups. CONCLUSIONS: Aberrant systems-level topology of language processing network, especially significantly weakened network hubs in left inferior frontal and right fusiform gyri, may serve as a candidate biomarker of schizophrenia. Supported by existing findings, the hyperactive left fusiform gyrus communicating with right frontal lobe might be the key neurophysiological component causing hallucinations in schizophrenia. These findings provided a new systems-level diagnostic target for the disorder.

Preliminary neuropsychological findings in individuals at high genetic risk for schizophrenia.

AIMS: An understanding of baseline cognitive function in individuals at high genetic risk for schizophrenia could provide important information about the neurodevelopmental course of the illness and assist with early detection. In an effort to identify potential markers for the illness, this study investigates domains of neuropsychological functioning in a sample of young individuals at risk for developing schizophrenia. METHODS: Twenty-two individuals with schizophrenia, 16 participants at high risk and 31 controls participated in comprehensive cognitive assessments. RESULTS: Results support reports of a trend for high-risk participants to score intermediate to the other groups on a general cognitive battery, as well as evidencing deficits in specific skills like visual memory. The pattern appears to exist independently of and prior to the onset of prodromal symptoms. CONCLUSIONS: These findings support the hypothesis that a common cognitive pattern exists across individuals with genetic risk that may later develop into a clear psychotic illness. Further longitudinal investigation with larger cohorts is crucial to understanding these findings.