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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    • "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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    • "These data supported the hypothesis that abnormalities in fronto-limbic circuitries might be a major underpinning of suicidality independent of the associated psychopathological conditions. Patients with BD show reduced OFC activity and GM volumes (Haldane and Frangou, 2004; Konarski et al., 2008), and OFC GM has been inversely correlated with depressive symptom intensity (Nery et al., 2009). One study associated suicidality with reduced volume of anterior corpus callosum in patients affected by BD, thus supporting a role for abnormal prefrontal function in this psychopathological dimension of BD (Matsuo et al., 2010). "
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    ABSTRACT: Mood disorders are associated with the highest increase of attempted and completed suicide. Suicidality in major depressive disorder and in schizophrenia has been associated with reduced gray matter volumes in orbitofrontal cortex. Lithium reduces the suicide risk of patients with bipolar disorder (BD) to the same levels of the general population, and can increase GM volumes. We studied the effect of a positive history of attempted suicide and ongoing lithium treatment on regional GM volumes of patients affected by bipolar depression. With a correlational design, we studied 57 currently depressed inpatients with bipolar disorder: 19 with and 38 without a positive history of suicide attempts, 39 unmedicated and 18 with ongoing lithium treatment. Total and regional gray matter volumes were assessed using voxel-based morphometry. Total GM volume is inversely correlated with depression severity. A positive history of suicide attempts was associated with higher stress in early life. Suicide attempters showed reduced GM volumes in several brain areas including dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate, superior temporal cortex, parieto-occipital cortex, and basal ganglia. Long term lithium treatment was associated with increased GM volumes in the same areas where suicide was associated with decreased GM. Reduced GM volumes in critical cortical areas of suicidal patients could be a biological correlate of an impaired ability to associate choices and outcomes and to plan goal-directed behaviors based on a lifetime historical perspective, which, coupled with mood-congruent depressive cognitive distortions, could lead to more hopelessness and suicide. Lithium could exert its specific therapeutic effect on suicide by acting in the same areas.
    Journal of Affective Disorders 07/2011; 135(1-3):139-47. DOI:10.1016/j.jad.2011.07.006 · 3.38 Impact Factor
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