The effects of hypertension and body mass index on diffusion tensor imaging in schizophrenia.

Recently, the negative effects of hypertension and elevated body mass index on cognitive functioning in schizophrenia have been reported (Friedman et al., 2010). Data suggests that cognitive changes in hypertensive patients from the general population may be mediated, in part, by white matter damage. Therefore, we performed diffusion tensor imaging (DTI) in the same subjects studied by Friedman et al. (2010) to investigate the effects of hypertension and elevated body mass index on the fractional anisotropy (FA) of several major white matter tracts. Significant interactions between a diagnosis of schizophrenia and hypertension on FA in several white matter regions were detected. Hypertension was associated with lower FA in the schizophrenic group and higher FA in the same tracts in the non-schizophrenic subjects. These results suggest hypertension-induced compensatory mechanisms in the brains of non-schizophrenic patients with hypertension which may be impaired in persons with schizophrenia.

The effects of hypertension and body mass index on cognition in schizophrenia.

OBJECTIVE: In recent years there has been a greater appreciation of the elevated prevalence of cardiovascular risk factors in the schizophrenia population and the liability some treatments have for their development. These vascular risk factors are in turn important risk factors in the development of dementia and more subtle cognitive impairments. However, their impact on the cognitive functions of patients with schizophrenia remains underexplored. The authors investigated whether vascular risk factors influence the cognitive impairments of schizophrenia and whether their effects on cognition in schizophrenia are different from those observed in nonpsychiatric comparison subjects. METHOD: The authors compared 100 patients with schizophrenia and 53 comparison subjects on cognitive test performance in 2×2 matrices composed of individual vascular risk factors and group (schizophrenia patients and comparison subjects). RESULTS: Hypertension exerted a significant negative effect on immediate delayed and recognition memory in both groups. Patients with schizophrenia and hypertension were adversely affected in recognition memory, whereas comparison subjects were not. A body mass index above 25 was associated with negative effects on delayed memory in both groups, although the association fell short of statistical significance. CONCLUSIONS: Given that patients with schizophrenia have a higher prevalence of vascular risk factors than the general population and are undertreated for them, treatment of these risk factors may significantly improve cognitive outcome in schizophrenia.

Diffusion tensor imaging findings in first-episode and chronic schizophrenia patients.

OBJECTIVE: Comparisons of diffusion tensor imaging (DTI) data between first-episode and chronic schizophrenia patients assessed in different studies have led to the suggestion that the decreased fractional anisotropy observed in chronic schizophrenia patients is less pronounced in first-episode patients. However, such comparisons of imaging data generated across studies are susceptible to numerous confounders, which may limit the interpretation of any differences. In order to address these issues and determine whether the DTI abnormalities of chronic schizophrenia are present at illness onset, the authors conducted a DTI investigation of the largest cohort of first-episode schizophrenia patients yet reported in conjunction with a group of chronic schizophrenia patients and healthy subjects for comparison. METHOD: Fractional anisotropy data generated by diffusion tensor imaging with a 3-T Siemens Allegra head-dedicated MRI system were compared between 40 first-episode schizophrenia patients and 39 age- and gender-matched healthy comparison subjects and between 40 chronic schizophrenia patients and 40 age- and gender-matched healthy comparison subjects. The following regions of interest were assessed: forceps minor (bilaterally), forceps major (bilaterally), inferior longitudinal fasciculus (bilaterally), and the genu and splenium of the corpus callosum. RESULTS: In most regions, chronic schizophrenia patients showed significant or trend-level lower fractional anisotropy than healthy comparison subjects, whereas the first-episode schizophrenia patients showed only trend-level lower fractional anisotropy in the inferior longitudinal fasciculus. CONCLUSIONS: The cross-sectional data reported here suggest less widespread changes in white matter at illness onset in schizophrenia which progress in more chronic states. More definitive conclusions will require follow-up imaging of first-episode schizophrenia patients.

A pilot study of adjunctive atomoxetine treatment to second-generation antipsychotics for cognitive impairment in schizophrenia.

Relationships between altered prefrontal cortical dopamine, norepinephrine, and some of the cognitive impairments of schizophrenia support an approach for pharmacological remediation of cognitive symptoms through manipulations of prefrontal cortical dopamine and norepinephrine. Atomoxetine, a selective norepinephrine reuptake inhibitor, produces a widespread increase in brain norepinephrine and a secondary and selective increase in prefrontal dopamine. Given this, we evaluated atomoxetine's cognitive effects in a pilot placebo-controlled trial in patients with schizophrenia. Moreover, a functional magnetic resonance imaging investigation was undertaken to assess the neural mechanisms underlying the cognitive effects of atomoxetine. Twenty participants with schizophrenia were randomized to treatment with placebo or atomoxetine 80 mg daily for an 8-week parallel-designed treatment trial. Cognitive performance was assessed with the Brief Assessment of Cognition in Schizophrenia. No significant cognitive improvement was associated with atomoxetine treatment. However, atomoxetine treatment was associated with significantly greater increases in working memory-related activation of the left dorsolateral prefrontal and left posterior cingulate cortices. The negative results of this study conflict with the effectiveness of amphetamine in enhancing the cognitive abilities of schizophrenic patients and may be related to the differential pattern of cortical activation and deactivation produced by amphetamine.