Cortical Development Alterations and the “At-Risk Mental State” for Schizophrenia
Abnormal glutamatergic transmission may occur before psychosis and may be associated with changes in cortical volume. Stone et al. (pages 533–539) studied brain glutamate and glutamine levels in people with an at-risk mental state (ARMS) using magnetic resonance spectroscopy. They found increased glutamine in anterior cingulate and reduced glutamate in left thalamus compared to controls. In the ARMS subjects, lower levels of glutamate in thalamus were associated with lower gray matter in medial temporal cortex and insula.
Using diffusion tensor imaging, Karlsgodt et al. (pages 562–569) found that individuals at ultra-high risk for developing schizophrenia demonstrated changes in white matter integrity in the main connection between the frontal and parietal lobes. In addition, high-risk subjects failed to show the same age-related increase in white matter integrity in temporal regions as healthy subjects, indicating an altered developmental trajectory. White matter integrity measured at baseline predicted changes in functional outcome at 15 months follow up.
Dolan and Fullam (pages 570–577) provide evidence that violent patients with schizophrenia and high psychopathy scores exhibit reduced neural responses to facial expressions of fear, as measured by blood oxygen level-dependent (BOLD) responses in the amygdala, when compared to violent patients with schizophrenia alone. This gives further insight into the possible neurocognitive mechanisms that may mediate the risk for violence and antisocial behavior in this particular clinical population.
Cognitive Dysfunctions and Aging in Schizophrenia
Sambataro et al. (pages 540–548) studied the effect of the Val158Met polymorphism in the gene for the dopamine-metabolizing catechol-O-methyltransferase (COMT) enzyme on brain circuitry across adulthood using a functional magnetic resonance imaging (fMRI) working memory paradigm. Their findings suggest that it modulates both the activity and functional connectivity of brain regions within working memory networks and that the effect on connectivity is exaggerated with increasing age, contributing to the variability in age-related decline in executive cognition.
Elderly schizophrenia patients develop cognitive impairment but etiology is unclear. Using a novel technique allowing accurate localization of gray matter changes, Frisoni et al. (pages 578–585) mapped cortical gray matter anomalies in elderly schizophrenia compared to Alzheimer's patients. Despite similar global cognitive deterioration, total gray matter loss in schizophrenia patients was 20 to 30% lower than in Alzheimer's.
Cognitive Rehabilitation and Functional Capacity in Schizophrenia
Schizophrenia may be related to decreased brain-derived neurotrophic factor (BDNF) functioning, which plays an important role in brain development and neuroplasticity. Vinogradov et al. (pages 549–553) found that schizophrenia outpatients had lower than normal serum BDNF levels, but after 10 weeks of a specialized computerized cognitive training program, they increased their serum BDNF to normal levels, while participants who played only computer games showed no change. Increased BDNF was significantly associated with improved quality of life.
Leeson et al. (pages 586–593) examined whether patients with schizophrenia are able to learn by experience and adapt to a changing environment. Patients were able to learn basic rules and apply them to new circumstances, but displayed an inability to modify responses to negative feedback. This was consistent over the first 6 years of illness and was related to symptoms of disorganization. Complex problem solving was related to IQ.
Kumari et al. (pages 594–602) report that, within the working memory neural network, pre-therapy dorsolateral prefrontal cortex (DLPFC) activity and its connectivity with the cerebellum predict responsiveness to cognitive behavior therapy (CBT) for psychosis in schizophrenia. This effect may be mediated by the PFC-cerebellum contributions to executive processes facilitating effective CBT within a psychotherapeutic context. The results may imply that addressing cognitive deficits associated with DLPFC in schizophrenia would maximize benefit from CBT.
L-DOPA-Induced Dyskinesia: Roles of ΔFosB and D1 Receptor
Involuntary movements, or dyskinesia, represent a debilitating side effect of L-DOPA therapy, a dopamine replacement, in patients with Parkinson Disease (PD). In a macaque model of PD, Berton et al. (pages 554–561) used intracerebral application of recombinant viruses to assess the role of ΔFosB protein in the development of dyskinesia, and to block its activity. The results establish a mechanism of dyskinesia induction and provide a potential strategy to oppose its development of this debilitating side effect.
Genetic inactivation of either the dopamine D1 or D2 receptor was used to define the involvement of these receptor subtypes in development of L-DOPA-induced dyskinesia and associated molecular changes in hemiparkinsonian mice. Darmopil et al. (pages 603–613) demonstrate that the dopamine D1 receptor is critical for the development of L-DOPA-induced dyskinesia in mice and in the underlying molecular changes in the denervated striatum, and that the D2 receptor has little or no involvement.
Genetic Variability Modulates Sensorimotor Gating
Quednow et al. (pages 614–620) have confirmed that the well-known sensorimotor gating deficits of schizophrenia patients depend on 5-HT2A receptor and COMT genotype. Sensorimotor gating is thought to regulate sensory input by filtering out irrelevant or distracting stimuli in order to prevent sensory information overflow. The present finding is essential for establishing the credibility of the association of the 5-HT2A receptor and COMT genotypes and sensorimotor gating.
© 2009 Published by Elsevier Inc. All rights reserved.