The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology

Background: schizophrenia's endophenotipic profile is not only generally complex, but often varies from case to case. The perspective of trying to define specific anatomic correlates of the syndrome has led to disappointing results. In that context, neurophysiologic hypotheses (e. g. glutamatergic hypothesis) and connectivity hypotheses became prominent. Nevertheless, despite their commitment to the principle of denying 'localist' views and approaching the syndrome's endophenotype from a whole brain perspective, efforts to integrate both have not flourished at this moment in time. Objectives: This paper aims to introduce a new etiological model that integrates the glutamatergic and the WM (WM) hypotheses of schizophrenia's etiology. This model proposes to serve as a framework in order to relate to patterns of brain abnormalities from the onset of the syndrome to stages of advanced chronification. Highlights: Neurotransmitter abnormalities forego noticeable WM abnormalities. The former, chiefly represented by NMDAR hypo-function and associated molecular cascades, is related to the first signs of cell loss. This process is both directly and indirectly integrated to the underpinning of WM structural abnormalities; not only is the excess of glutamate toxic to the WM, but its disruption is associated to the expression of known genetic risk factors (e. g., NRG-1). A second level of the model develops the idea that abnormal neurotransmission within specific neural populations ('motifs') impair particular cognitive abilities, while subsequent WM structural abnormalities impair the integration of brain functions and multimodality. As a result of this two-stage dynamic, the affected individual progresses from experiencing specific cognitive and psychological deficits, to a condition of cognitive and existential fragmentation, linked to hardly reversible decreases in psychosocial functioning.

Normative Data for Healthy Middle-Aged and Elderly Performance on the Addenbrooke Cognitive Examination-Revised

Objective: To provide normative data for healthy middle-aged and elderly Brazilians' performance on the Addenbrooke Cognitive Examination-Revised (ACE-R) and to investigate the effects of age, sex, and schooling on test performance. Background: The ACE-R is a brief cognitive battery that assesses various aspects of cognition. Its 5 subdomains (Attention and Orientation, Memory, Verbal Fluency, Language, and Visuospatial Abilities) are commonly impaired in Alzheimer disease or frontotemporal dementia. Methods: We evaluated 144 cognitively healthy volunteers (50% men, 50% women) aged 50 to 93 years, with 4 to 24 years of schooling. We divided the participants into 4 age groups, each of which was then stratified into 3 groups according to years of education. We assessed all participants with the ACE-R, the Mattis Dementia Rating Scale, and the Cornell Scale for Depression in Dementia. Results: Years of education affected all ACE-R subscores. Age influenced the Verbal Fluency subscore (P < 0.001) and the ACE-R total score (P < 0.05). Sex affected the Attention and Orientation (P = 0.037) and Mini-Mental State Examination subscores (P = 0.048), but not the ACE-R total score (P > 0.05). Conclusions: The performance of healthy middle-aged and elderly individuals on the ACE-R battery is strongly influenced by education and, to a lesser extent, by age. These findings are of special relevance in countries with populations that have marked heterogeneity in educational levels.

The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder

Background. - Persistent impairment in cognitive function has been described in euthymic individuals with bipolar disorder. Collective work indicates that obesity is associated with reduced cognitive function in otherwise healthy individuals. This sub-group post-hoc analysis preliminarily explores and examines the association between overweight/obesity and cognitive function in euthymic individuals with bipolar disorder. Methods. - Euthymic adults with DSM-IV-TR-defined bipolar I or II disorder were enrolled. Subjects included in this post-hoc analysis (n = 67) were divided into two groups (normal weight, body mass index [BMI] of 18.5-24.9 kg/m(2); overweight/obese, BMI >= 25.0 kg/m(2)). Demographic and clinical information were obtained at screening. At baseline, study participants completed a comprehensive cognitive battery to assess premorbid IQ, verbal learning and memory, attention and psychomotor processing speed, executive function, general intellectual abilities, recollection and habit memory, as well as self-perceptions of cognitive failures. Results. - BMI was negatively correlated with attention and psychomotor processing speed as measured by the Digit Symbol Substitution Test (P < 0.01). Overweight and obese bipolar individuals had a significantly lower score on the Verbal Fluency Test when compared to normal weight subjects (P < 0.05). For all other measures of cognitive function, non-significant trends suggesting a negative association with BMI were observed, with the exception of measures of executive function (i.e. Trail Making Test B) and recollection memory (i.e. process-dissociation task). Conclusion. - Notwithstanding the post-hoc methodology and relatively small sample size, the results of this study suggest a possible negative effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder. Taken together, these data provide the impetus for more rigorous evaluation of the mediational role of overweight/obesity (and other medical co-morbidity) on cognitive function in psychiatric populations. (C) 2011 Elsevier Masson SAS. All rights reserved.