Orbitofrontal cortex gray matter volumes in bipolar disorder patients: A region-of-interest MRI study

Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Bipolar Disorders (Impact Factor: 4.97). 04/2009; 11(2):145-53. DOI: 10.1111/j.1399-5618.2009.00662.x
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Functional and postmortem studies suggest that the orbitofrontal cortex (OFC) is involved in the pathophysiology of bipolar disorder (BD). This anatomical magnetic resonance imaging (MRI) study examined whether BD patients have smaller OFC gray matter volumes compared to healthy comparison subjects (HC).
Twenty-eight BD patients were compared to 28 age- and gender-matched HC. Subjects underwent a 1.5T MRI with 3D spoiled gradient recalled acquisition. Total OFC and medial and lateral subdivisions were manually traced by a blinded examiner. Images were segmented and gray matter volumes were calculated using an automated method.
Analysis of covariance, with intracranial volume as covariate, showed that BD patients and HC did not differ in gray matter volumes of total OFC or its subdivisions. However, total OFC gray matter volume was significantly smaller in depressed patients (n = 10) compared to euthymic patients (n = 18). Moreover, total OFC gray matter volumes were inversely correlated with depressive symptom intensity, as assessed by the Hamilton Depression Rating Scale. OFC gray matter volumes were not related to lithium treatment, age at disease onset, number of episodes, or family history of mood disorders.
Our results suggest that abnormal OFC gray matter volumes are not a pervasive characteristic of BD, but may be associated with specific clinical features of the disorder.

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Available from: Paolo Brambilla, May 18, 2015
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    • "This finding is in agreement with research on UHR psychosis, which shows that volumetric changes in prefrontal regions are related to genetic susceptibility, whereas volumetric changes in the parietal and temporal regions are related to the transition stage into psychotic disorder (the stage in which attenuated psychotic symptoms are manifested) (Lawrie et al., 1999; Pantelis et al., 2003). This finding also coincides with morphometric studies reporting that the structural abnormalities in unaffected relatives of BP proband were relatively restricted to the prefrontal cortex, whereas the widespread volumetric changes identified in pediatric BP extended to the temporal, occipital and parietal cortexes and the amygdala, some of which were associated with symptoms (Chang et al., 2005; Frazier et al., 2005; Hajek et al., 2013; Matsuo et al., 2012; Nery et al., 2009). The increased GM volumes observed in the UHR offspring are unlikely to be protective factors because the selected age range for the offspring represents the most at-risk time for the onset of full-blown BP. "
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    ABSTRACT: Background: Validating the high-risk (HR) and ultra-high-risk (UHR) stages of bipolar disorder (BP) may help enable early intervention strategies. Methods: We followed up with 44 offspring of parents with BP, subdividing into the HR and UHR categories. The offspring were aged 8-28 years and were free of any current DSM-IV diagnoses. Our multilevel, integrative approach encompassed gray matter (GM) volumes, brain network connectivity, neuropsychological performance, and clinical outcomes. Findings: Compared with the healthy controls (HCs) (n = 33), the HR offspring (n = 26) showed GM volume reductions in the right orbitofrontal cortex. Compared with the HR offspring, the UHR offspring (n = 18) exhibited increased GM volumes in four regions. Both the HR and UHR offspring displayed abnormalities in the inferior occipital cortex regarding the measures of degree and centrality, reflecting the connections and roles of the region, respectively. In the UHR versus the HR offspring, the UHR offspring exhibited upwards-shifted small world topologies that reflect high clustering and efficiency in the brain networks. Compared with the HCs, the UHR offspring had significantly lower assortativity, which was suggestive of vulnerability. Finally, processing speed, visual-spatial, and general function were impaired in the UHR offspring but not in the HR offspring. Interpretation: The abnormalities observed in the HR offspring appear to be inherited, whereas those associated with the UHR offspring represent stage-specific changes predisposing them to developing the disorder.
    10/2015; 2(8):917-26. DOI:10.1016/j.ebiom.2015.06.027
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    • "There were even two studies reporting an absence of progressive brain changes in patients over the first 2–3 years of follow-up (James et al., 2002; James et al., 2004). Discrepant volumetric findings in young people may be at least partly attributable to different factors and conditions that moderate the detected pattern of structural brain changes, i.e., 1) differences in sex proportion (Lenroot et al., 2007; Janssen et al., 2012), 2) age at onset (Vita et al., 2012), 3) duration of illness (Haijma et al., 2013), 4) duration of follow-up (Vita et al., 2012; Haijma et al., 2013), 5) brain regions of interest (ROIs) under study (Arango et al., 2008), 6) use of voxelbased morphometry (VBM) versus ROI-based approaches (Giuliani et al., 2005), 7) exposure to lithium or antipsychotic treatment (Navari and Dazzan, 2009; Ho et al., 2011; Hafeman et al., 2012; Fusar-Poli et al., 2013; Haijma et al., 2013), 8) symptom presentation and severity (DeLisi et al., 1998; Strakowski et al., 2002; Nery et al., 2009; Arango et al., 2012), and 9) diagnostic heterogeneity (Arango et al., 2008; Arango et al., 2012). Childhood-onset schizophrenia (COS) is defined as schizophrenia with onset prior to age 13 years. "
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    ABSTRACT: Studies on longitudinal brain volume changes in patients with early-onset psychosis (EOP) are particularly valuable for understanding the neurobiological basis of brain abnormalities associated with psychosis. However, findings have not been consistent across studies in this population. We aimed to conduct a meta-analysis on progressive brain volume changes in children and adolescents with EOP. A systematic literature search of magnetic resonance imaging (MRI) studies comparing longitudinal brain volume changes in children and adolescents with EOP and healthy controls was conducted. The annualized rates of relative change in brain volume by region of interest (ROI) were used as raw data for the meta-analysis. The effect of age, sex, duration of illness, and specific diagnosis on volume change was also evaluated. Five original studies with 156 EOP patients (mean age at baseline MRI in the five studies ranged from 13.3 to 16.6years, 67.31% males) and 163 age- and sex-matched healthy controls, with a mean duration of follow-up of 2.46years (range 2.02-3.40), were included. Frontal gray matter (GM) was the only region in which significant differences in volume change over time were found between patients and controls (Hedges' g -0.435, 95% confidence interval (CI): -0.678 to -0.193, p<0.001). Younger age at baseline MRI was associated with greater loss of temporal GM volume over time in patients as compared with controls (p=0.005). Within patients, a diagnosis of schizophrenia was related to greater occipital GM volume loss over time (p=0.001). Compared with healthy individuals, EOP patients show greater progressive frontal GM loss over the first few years after illness onset. Age at baseline MRI and diagnosis of schizophrenia appear to be significant moderators of particular specific brain volume changes. Copyright © 2014 Elsevier B.V. All rights reserved.
    Schizophrenia Research 12/2014; DOI:10.1016/j.schres.2014.12.022 · 3.92 Impact Factor
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    • "Second, all patients were inpatients at the time of their first psychotic episode. Prior studies have used mixed samples of inand out-patients and patients, allowing for the possibility that different degrees of illness severity and different mood states at intake modulate brain morphology (Nery et al., 2009). In the current study, all of the patients were on anti-psychotic medication at the time of scan acquisition and four of patients with a follow-up diagnosis of bipolar disorder had treatment with lithium at the time of scan acquisition. "
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    ABSTRACT: Introduction: Recent evidence points to overlapping decreases in cortical thickness and gyrification in the frontal lobe of patients with adult-onset schizophrenia and bipolar disorder with psychotic symptoms, but it is not clear if these findings generalize to patients with a disease onset during adolescence and what may be the mechanisms underlying a decrease in gyrification. Method: This study analyzed cortical morphology using surface-based morphometry in 92 subjects (age range 11-18 years, 52 healthy controls and 40 adolescents with early-onset first-episode psychosis diagnosed with schizophrenia (n=20) or bipolar disorder with psychotic symptoms (n=20) based on a two year clinical follow up). Average lobar cortical thickness, surface area, gyrification index (GI) and sulcal width were compared between groups, and the relationship between the GI and sulcal width was assessed in the patient group. Results: Both patients groups showed decreased cortical thickness and increased sulcal width in the frontal cortex when compared to healthy controls. The schizophrenia subgroup also had increased sulcal width in all other lobes. In the frontal cortex of the combined patient group sulcal width was negatively correlated (r=-0.58, p<0.001) with the GI. Conclusions: In adolescents with schizophrenia and bipolar disorder with psychotic symptoms there is cortical thinning, decreased GI and increased sulcal width of the frontal cortex present at the time of the first psychotic episode. Decreased frontal GI is associated with the widening of the frontal sulci which may reduce sulcal surface area. These results suggest that abnormal growth (or more pronounced shrinkage during adolescence) of the frontal cortex represents a shared endophenotype for psychosis.
    Schizophrenia Research 07/2014; 158(1-3). DOI:10.1016/j.schres.2014.06.040 · 3.92 Impact Factor
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