Prefrontal Function and Activation in Bipolar Disorder and Schizophrenia

Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, UK.
American Journal of Psychiatry (Impact Factor: 12.3). 04/2008; 165(3):378-84. DOI: 10.1176/appi.ajp.2007.07020365
Source: PubMed


Distinctive patterns of speech and language abnormalities are associated with bipolar disorder and schizophrenia. It is, however, unclear whether the associated patterns of neural activation are diagnosis specific. The authors sought to determine whether there are differences in language-associated prefrontal activation that discriminate bipolar disorder and schizophrenia.
Forty-two outpatients with bipolar I disorder, 27 outpatients with schizophrenia, and 37 healthy comparison subjects were recruited. Differences in blood oxygen level-dependent activity were evaluated using the Hayling Sentence Completion Test and analyzed in Statistical Parametric Mapping (SPM) 2. Differences in activation were estimated from a sentence completion versus rest contrast and from a contrast of decreasing sentence constraint. Regional activations were related to clinical variables and performance on a set shifting task and evaluated for their ability to differentiate among the three groups.
Patients with bipolar disorder showed differences in insula and dorsal prefrontal cortex activation, which differentiated them from patients with schizophrenia. Patients with bipolar disorder recruited the orbitofrontal cortex and ventral striatum to a greater extent relative to healthy comparison subjects on the parametric contrast of increasing difficulty. The gradient of ventral striatal and prefrontal activation was significantly associated with reversal errors in bipolar disorder patients.
Brain activations during the Hayling task differentiated patients with bipolar disorder from comparison subjects and patients with schizophrenia. Patients with bipolar disorder showed abnormalities in frontostriatal systems associated with performance on a set shifting task. This finding suggests that bipolar disorder patients engaged emotional brain areas more than comparison subjects while performing the Hayling task.

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Available from: Eve C Johnstone, Oct 19, 2015
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    • "Few functional magnetic resonance imaging studies investigating language networks have sought to identify cerebral biomarkers to discriminate these patient groups (McIntosh et al., 2008; Maïza et al., 2010; Whalley et al., 2012). Nevertheless, some authors have reported decreased leftward functional lateralization for language in SZ patients (Sommer et al., 2003; Dollfus et al., 2005; van Veelen et al., 2011; Sheng et al., 2013), and one previous study suggested that change in functional hemispheric lateralization for language could be a biomarker of SZ (Alary et al., 2013b). "
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    ABSTRACT: This study aimed to compare the functional and gray matter asymmetries in patients with schizophrenia (SZ), patients with bipolar disorders (BD), and healthy controls (HCs) to test whether decreased leftward functional hemispheric lateralization and gray matter volume asymmetry could mark the boundary between schizophrenia and bipolar disorder. A total of 31 right-handed SZ and 20 right-handed BD underwent a session of functional MRI with a speech listening paradigm. Participants were matched with HCs for gender, age, and education. Functional laterality indices (FLI) and gray matter volume asymmetry indices (GVAI) were computed from the individual functional language network. Correlations between the FLI and GVAI indices were also examined. SZ exhibited significantly decreased leftward functional hemispheric lateralization whereas BD did not. The GVAIs did not differ significantly between SZ and HCs or between BD and HCs. There were positive correlations between GVAIs and FLIs in all groups. Loss of laterality for language comprehension with retention of gray matter volume asymmetry indicates that gray matter loss alone will not account for the pathophysiology of schizophrenia. Impaired leftward functional hemispheric lateralization for language but not gray matter volume asymmetry can be considered a biomarker of SZ. Copyright © 2014 Elsevier B.V. All rights reserved.
    Full-text · Article · Dec 2014 · Schizophrenia Research
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    • "Differentiating bipolar disorder (BP) and schizophrenia (SCZ) is challenging, particularly with their overlap in symptomatology such as psychosis. Neuroimaging studies, including those that directly compare BP and SCZ, indicate both overlapping and disparate abnormalities between BP and SCZ; however, identification of biomarkers that clearly differentiate between the two disorders remains elusive due to complicating factors such as varying medication exposure and clinical heterogeneity (McIntosh et al., 2008a, 2008b; Arnone et al., 2009; Hamilton et al., 2009; Ellison-wright and Bullmore, 2010; Hall et al., 2010; Ongür et al., 2010; Rimol et al., 2010; Brown et al., 2011; Sui et al., 2011). "
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    ABSTRACT: In this study, we examined the morphology of the basal ganglia and thalamus in bipolar disorder (BP), schizophrenia-spectrum disorders (SCZ-S), and healthy controls (HC) with particular interest in differences related to the absence or presence of psychosis. Volumetric and shape analyses of the basal ganglia and thalamus were performed in 33 BP individuals [12 without history of psychotic features (NPBP) and 21 with history of psychotic features (PBP)], 32 SCZ-S individuals [28 with SCZ and 4 with schizoaffective disorder], and 27 HC using FreeSurfer-initiated large deformation diffeomorphic metric mapping. Significant volume differences were found in the caudate and globus pallidus, with volumes smallest in the NPBP group. Shape abnormalities showing inward deformation of superior regions of the caudate were observed in BP (and especially in NPBP) compared with HC. Shape differences were also found in the globus pallidus and putamen when comparing the BP and SCZ-S groups. No significant differences were seen in the nucleus accumbens and thalamus. In summary, structural abnormalities in the caudate and globus pallidus are present in BP and SCZ-S. Differences were more apparent in the NPBP subgroup. The findings herein highlight the potential importance of separately examining BP subgroups in neuroimaging studies.
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    • "All studies included in the imaging analyses, with exception of (McIntosh et al., 2008b) and (Lagopoulos and Malhi, 2007) provided detailed neurocognitive results. Euthymic BD patients (N ¼ 228) showed comparable performance to controls (N ¼ 277) in accuracy during the go/no-go, Stroop and SSRT (Cohen's d ¼ 0.09, 95% Confidence Interval À0.18 to 0.35, z ¼ 0.67, p ¼ 0.51, see Fig. 4) as well as in Stroop interference and stopsignal response times (Cohen's d ¼ 0.15, 95% Confidence Interval À0.38 to 0.67, z ¼ 0.55, p ¼ 0.58, see Fig. 6). "
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    ABSTRACT: Impaired response inhibition underlies symptoms and altered functioning in patients with bipolar disorders (BD). The interpretation of fMRI studies requires an accurate estimation of neurocognitive performance, for which individual studies are typically underpowered. Thus, we performed the first combined meta-analysis of fMRI activations and neurocognitive performance in studies investigating response inhibition in BD. We used signed differential mapping to combine anatomical coordinates of activation and standardized differences between means to evaluate neurocognitive performance in 30 fMRI studies of response inhibition comparing controls (n = 667) and patients with BD (n = 635). Relative to controls, BD patients underactivated the right inferior frontal gyrus (rIFG) regardless of current mood state and behavioral performance. Unique to euthymia were cortical hyperactivations (left superior temporal, right middle frontal gyri) combined with subcortical hypoactivations (basal ganglia), whereas unique to mania were subcortical hyperactivations (bilateral basal ganglia), combined with cortical hypoactivations (right inferior and medial frontal gyri). The fMRI changes in euthymia were associated with normal cognitive performance, whereas manic patients committed more errors during response inhibition. The rIFG hypoactivations were congruent with a BD trait, which may underlie the impaired response inhibition in mania. Euthymic BD subjects may compensate for the rIFG hypoactivations by hyperactivations of adjacent cortical areas, yielding comparable performance in inhibitory functions and suggesting possibilities for neuromodulation treatment of these cognitive impairments. The reversal of the activation pattern between mania and euthymia has implications for monitoring of treatment response and identification of imminent relapse.
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