Relative Glucose Metabolic Rate Higher in White Matter in Patients With Schizophrenia

Department of Psychiatry, Radiology and Neuroscience, Mount Sinai School of Medicine, Mount Sinai Medical Center, New York, NY 10029-6574, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 08/2007; 164(7):1072-81. DOI: 10.1176/appi.ajp.164.7.1072
Source: PubMed


There is increasing evidence demonstrating that circuits involving the frontal lobe, striatum, temporal lobe, and cerebellum are abnormal in individuals with schizophrenia, which suggests that metabolic activity in the white matter connecting these areas should be investigated.
The authors obtained [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and matching T1-weighted magnetic resonance imaging (MRI) on 170 subjects. Participants were 103 normal volunteers and 67 unmedicated patients with schizophrenia (N=61) or schizoaffective disorder (N=6). The images were coregistered and warped to standard space for significance probability mapping.
Compared with normal volunteers, patients showed higher relative metabolic rates in the frontal white matter, corpus callosum, superior longitudinal fasciculus, and white matter core of the temporal lobe. Elevated activity in white matter was most pronounced in the center of large white matter tracts, especially the frontal parts of the brain and the internal capsule. The white matter elevation did not appear to be entirely related to changes in gray matter/white matter brain proportions, whole brain metabolic rate bias, or excess head motion in patients, but this cannot be ruled out without absolute glucose determinations. Patients also showed significantly lower relative glucose metabolism in the frontal and temporal lobes, caudate nucleus, cingulate gyrus, and mediodorsal nucleus of the thalamus relative to normal volunteers, which is consistent with earlier studies.
In comparisons of unmedicated schizophrenia patients with normal volunteers, relative metabolic increases are apparent in white matter in patients with schizophrenia as well as decreases in gray matter. Inefficiency in brain circuitry, defects in white matter leading to enhanced energy need, white matter damage, and alterations in axon packing density are among the possible explanations for these schizophrenia-related findings of relatively increased metabolism in white matter.

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    • "Compared to control participants and based on post-mortem and positron emission tomography studies, patients with schizophrenia are suspected to have higher metabolic rates in the superior longitudinal fasciculus and anterior limb of the internal capsule (40, 41) suggesting roles in the pathophysiology of the disorder. The anterior limb of the internal capsule serves as a bridge between the thalamus, cingulate, and prefrontal cortices and thus plays an important role in motivation, reward, and emotion (8). "
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    ABSTRACT: Negative symptoms occur in several major mental health disorders with undetermined mechanisms and unsatisfactory treatments; identification of their neural correlates might unveil the underlying pathophysiological basis and pinpoint the therapeutic targets. In this study, participants with major depressive disorder (n = 24), schizophrenia (n = 22), and healthy controls (n = 20) were assessed with 10 frequently used negative symptom scales followed by principal component analysis (PCA) of the scores. A linear model with the prominent components identified by PCA was then regressed on gray and white-matter volumes estimated from T1-weighted magnetic resonance imaging. In depressed patients, negative symptoms such as blunted affect, alogia, withdrawal, and cognitive impairment, assessed mostly via clinician-rated scales were inversely associated with gray matter volume in the bilateral cerebellum. In patients with schizophrenia, anhedonia, and avolition evaluated via self-rated scales inversely related to white-matter volume in the left anterior limb of internal capsule/anterior thalamic radiation and positively in the left superior longitudinal fasiculus. The pathophysiological mechanisms underlying negative symptoms might differ between depression and schizophrenia. These results also point to future negative symptom scale development primarily focused on detecting and monitoring the corresponding changes to brain structure or function.
    Frontiers in Psychiatry 08/2014; 5:116. DOI:10.3389/fpsyt.2014.00116
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    • "Taken together, we hypothesize that the fusiform gyrus in the patients with ASD may require greater activation in order to interpret to the meaning of emotional words, compared to healthy subjects. In other words, that pattern was though as cortical inefficiency during social information processing [41]. "
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    ABSTRACT: Studies of social dysfunction in patients with autism spectrum disorder (ASD) have generally focused on the perception of emotional words and facial affect. Brain imaging studies have suggested that the fusiform gyrus is associated with both the comprehension of language and face recognition. We hypothesized that patients with ASD would have decreased ability to recognize affect via emotional words and facial emoticons, relative to healthy comparison subjects. In addition, we expected that this decreased ability would be associated with altered activity of the fusiform gyrus in patients with ASD. Ten male adolescents with ASDs and ten age and sex matched healthy comparison subjects were enrolled in this case-control study. The diagnosis of autism was further evaluated with the Autism Diagnostic Observation Schedule. Brain activity was assessed using functional magnetic resonance imaging (fMRI) in response to emotional words and facial emoticon presentation. Sixty emotional words (45 pleasant words +15 unpleasant words) were extracted from a report on Korean emotional terms and their underlying dimensions. Sixty emoticon faces (45 pleasant faces +15 unpleasant faces) were extracted and modified from on-line sites. Relative to healthy comparison subjects, patients with ASD have increased activation of fusiform gyrus in response to emotional aspects of words. In contrast, patients with ASD have decreased activation of fusiform gyrus in response to facial emoticons, relative to healthy comparison subjects. We suggest that patients with ASD are more familiar with word descriptions than facial expression as depictions of emotion.
    PLoS ONE 03/2014; 9(3):e91214. DOI:10.1371/journal.pone.0091214 · 3.23 Impact Factor
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    • "We interpreted this pattern of frontostriatal hyperactivation to reflect compensatory mechanisms reflective of cortical inefficiency to respond flexibly to social targets in ASD (see also Schmitz et al. 2006). This account is consistent with patterns of increased brain activation in other forms of psychopathology during tasks requiring cognitive control (e.g., Wagner et al. 2006; Buchsbaum et al. 2007; Manoach 2003). "
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    ABSTRACT: This study investigated cognitive control of social and nonsocial information in autism using functional magnetic resonance imaging. Individuals with autism spectrum disorders (ASDs) and a neurotypical control group completed an oddball target detection task where target stimuli were either faces or nonsocial objects previously shown to be related to circumscribed interests in autism. The ASD group demonstrated relatively increased activation to social targets in right insular cortex and in left superior frontal gyrus and relatively decreased activation to nonsocial targets related to circumscribed interests in multiple frontostriatal brain regions. Findings suggest that frontostriatal recruitment during cognitive control in ASD is contingent on stimulus type, with increased activation for social stimuli and decreased activation for nonsocial stimuli related to circumscribed interests.
    Journal of Autism and Developmental Disorders 05/2013; 43(12). DOI:10.1007/s10803-013-1837-4 · 3.06 Impact Factor
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