The structural brain correlates of neurological soft signs in AeSOP first-episode psychoses study

Abstract

Patients with schizophrenia and related psychoses have an excess of minor neurological abnormalities (neurological soft signs) of unclear neuropathological origin. These include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing complex motor tasks. Neurological soft signs seem not to reflect primary tract or nuclear pathology. It still has to be established whether neurological soft signs result from specific or diffuse brain structural abnormalities. Studying their anatomical correlates can provide not only a better understanding of the aetiopathogenesis of soft signs, but also of the pathophysiology of schizophrenia. Surprisingly few studies have investigated the brain correlates of neurological soft signs. In the present study, we investigated the relationship between brain structure and neurological soft signs in an epidemiologically based sample of 77 first-episode psychosis patients. We used the Neurological Evaluation Scale for neurological assessment and high-resolution MRI and voxel-based methods of image analysis to investigate brain structure. Higher rates of soft neurological signs (both motor and sensory) were associated with a reduction of grey matter volume of subcortical structures (putamen, globus pallidus and thalamus). Signs of sensory integration deficits were additionally associated with volume reduction in the cerebral cortex, including the precentral, superior and middle temporal, and lingual gyri. Neurological soft signs and their associated brain changes were independent of antipsychotic exposure. We conclude that neurological soft signs are associated with regional grey matter volume changes and that they may represent a clinical sign of the perturbed cortical-subcortical connectivity that putatively underlies psychotic disorders.

Different Effects of Typical and Atypical Antipsychotics on Grey Matter in First Episode Psychosis: the ÆSOP Study

“…Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses), carried out in three English cities, which investigated the higher rates of schizophrenia in the African-Caribbean population in the United Kingdom (Dazzan et al, 2004). Ethical approval for the study was granted by the Ethical Committee of the Institute of Psychiatry, and the participants gave written informed consent, in accordance with the Declaration of Helsinki.…”

“…These drugs (typical antipsychotics, for example, haloperidol and chlorpromazine) act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors in mesolimbic areas (Carlsson, 1978). Owing to this D2 blockade, they also induce a number of side effects, among which extrapyramidal symptoms are the most prominent (Dazzan and Murray, 2002;Dazzan et al, 2004). Recently, a new generation of antipsychotic drugs, the atypical antipsychotics, have become available (for example, clozapine, risperidone, olanzapine, and quetiapine).…”

“…We collected a complete medication history for each subject, and used highresolution MRI and voxel-based methods of image analysis. Voxel-based analysis has the major advantage of allowing the evaluation of the entire brain rather than of a few preselected regions; furthermore, it is automated, which means that it does not require the identification of anatomical boundaries nor manual tracing of the regions of interest (Dazzan et al, 2004). This study aimed: (1) to investigate whether antipsychotics have a measurable effect on brain anatomy; and if so, (2) to investigate if typical and atypical antipsychotics affect brain anatomy differently.…”

Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

“…Subjects were recruited in Southeast London as part of the AESOP study, which investigates, in three cities, the higher rates of schizophrenia in the African-Caribbean population in the UK (Dazzan et al, 2004;Dazzan et al, 2005). Ethical approval for the study was granted by the Ethical Committee of the Institute of Psychiatry, and the participants gave written informed consent, in accordance with the Declaration of Helsinki.…”

“…Furthermore, the small sample size did not allow us to evaluate any possible differences associated with specific diagnoses within psychoses. To clarify these issues, we have investigated the pituitary volume, using high-resolution MRI, in a different sample of 78 subjects at their first psychotic episode, recruited in London as part of the UK AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study (Dazzan et al, 2004;Dazzan et al, 2005). This is an epidemiologically based sample of patients at the first psychotic episode, which includes both antipsychotictreated and antipsychotic-free subjects, and both affective and nonaffective psychoses.…”