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Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia.
A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest.
The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms.
We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.
Despite consistently high discontinuation rates due to withdrawal of consent (WOC) and insufficient therapeutic effect (ITE) in schizophrenia trials, insight into the underlying factors contributing to poor satisfaction with treatment and dropout is limited. A better understanding of these factors could help to improve trial design and completion rates.
Using data from 1,136 trial participants with schizophrenia or schizoaffective disorder, we explored associations between predictor variables with (1) dropout due to WOC and ITE and (2) satisfaction with treatment among patients and investigators by means of hierarchic multiple regression analyses.
ITE was associated with poor clinical improvement, poor investigator satisfaction with treatment, and poor patient insight into their own disease, whereas WOC only showed a meaningful association with poor patient satisfaction with treatment. Investigator satisfaction with treatment appeared most strongly associated with Positive and Negative Syndrome Scale (PANSS) positive factor endpoint scores, whereas patient satisfaction with treatment was best predicted by the endpoint score on the PANSS emotional distress factor. The occurrence of severe side effects showed no meaningful association to satisfaction with treatment among investigators and patients, and neither did a patient’s experienced psychopathology, nor their self-rating of functional impairment.
Whereas trial discontinuation due to ITE is associated with poor treatment effectiveness, a patient’s decision to withdraw from an antipsychotic trial remains unpredictable and may occur even when the investigator observes a global clinical improvement and is satisfied with the treatment.
The time required in completing the 26 items of neurological examinations in the standard Neurological Evaluation Scale (NES) may limit its utility in pragmatic clinical situations. We propose the Short Neurological Evaluation Scale (S-NES) for use in busy clinical settings, and in research.
Using confirmatory factor analyses, we identified 12 items of neurological examination showing significant overlap with previously reported theoretical and empirical categories of neurological soft signs (NSS) in schizophrenia. This provided justification for the development of a shorter version of the NES based on the empirically identified NSS. In the present study, we relied on existing data to present an initial validation of the S-NES against the referent standard 26-item NES. We determined sensitivity, specificity, and likelihood ratios. Posterior-test probability was estimated using a Bayesian nomogram plot.
Using data derived from 84 unmedicated or minimally treated patients with first-episode schizophrenia, 12 empirically determined items of neurological examinations showed high agreement with the 26 items in the standard NES battery (sensitivity=96.3%, specificity=100%, and posterior-test probability=100%).
Within limitations of validity estimates derived from existing data, the present results suggest that the design of the S-NES based on empirically identified 12 items of neurological examination is a logical step. If successful, the S-NES will be useful for rapid screening of NSS in busy clinical settings, and also in research.
The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with frontostriatal dysfunction. While frontostriatal systems play a key role in behavioral inhibition, there are to our knowledge no fMRI studies investigating the potential impact of HIV on systems involved during the inhibition of voluntary movement. A total of 17 combined antiretroviral therapy (cART) naïve HIV+ participants as well as 18 age, gender, ethnic, education matched healthy controls performed a modified version of the stop-signal paradigm. This paradigm assessed behavior as well as functional brain activity associated with motor execution, reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing before stopping). HIV+ participants showed significantly slower responses during motor execution compared to healthy controls, whereas they had normal proactive response slowing. Putamen hypoactivation was evident in the HIV+ participants based on successful stopping, indicating subcortical dysfunction during reactive inhibition. HIV+ participants showed normal cortical functioning during proactive inhibition. Our data provide evidence that HIV infection is associated with subcortical dysfunction during reactive inhibition, accompanied by relatively normal higher cortical functioning during proactive inhibition. This suggests that HIV infection may primarily involve basic striatal-mediated control processes in cART naïve participants. (JINS, 2015, 21, 722–731)
South Africa is a country of great fascination to those interested in the origins, development and behaviour of humankind. For example, recent fossil discoveries appear to confirm Darwin's hunch that Africa – and perhaps southern Africa – was the cradle of humankind. Caves in the Sterkfontein Valley near Johannesburg have produced abundant scientific information on the evolution of modern man over the past 3.5 million years. This is of interest not only from a historical point of view but also in terms of modern science. With the significant advances in medical genetics in general, and psychiatric genetics in particular, there has been a growing interest in homogeneous populations with novel gene pools. South Africa is a rich source of homogeneous populations with an apparently common ancestry.
A possible association between disordered water homeostasis and cerebral ventricular size in patients with schizophrenia was investigated.
In a cross-sectional study of hospitalised patients, cerebral ventricular size was measured in 16 schizophrenic patients with disordered water homeostasis and 16 matched schizophrenic controls by magnetic resonance imaging.
Ventricle to brain ratio, third ventricular index, bicaudate index and bifrontal index tended to be greater in those with schizophrenia with disordered water homeostasis, although differences were significant only for the bifrontal index (P<0.05). Strong negative correlations were found between ventricular size and performance on neuropsychological testing in the disordered water homeostasis group.
These results provide evidence for an association between structural brain abnormality and disordered water homeostasis in a subset of schizophrenic patients.