Cingulate Cortex Anatomical Abnormalities in Children and Adolescents With Bipolar Disorder

University of Udine, Udine, Friuli Venezia Giulia, Italy
American Journal of Psychiatry (Impact Factor: 12.3). 10/2005; 162(9):1637-43. DOI: 10.1176/appi.ajp.162.9.1637
Source: PubMed


In vivo imaging studies have suggested anatomical and functional abnormalities in the anterior cingulate in adults with mood disorders. This anatomical magnetic resonance imaging study examined the cingulate cortex in children and adolescents with bipolar disorder and matched healthy comparison subjects.
Sixteen patients (mean age=15.5 years, SD=3.4) with DSM-IV bipolar disorder and 21 matched healthy comparison subjects (mean age=16.9 years, SD=3.8) were studied. Three-dimensional gradient echo imaging was performed (TR=25 msec, TE=5 msec, slice thickness=1.5 mm) in a 1.5-T GE Signa magnet. Cingulate volumes were compared by using analysis of covariance, with age and intracranial volume as covariates.
The patients with bipolar disorder had significantly smaller mean volumes relative to the healthy subjects in the left anterior cingulate (mean=2.49 cm(3 [SD=0.28] versus 3.60 cm3 [SD=0.12], respectively), left posterior cingulate (2.53 cm3 [SD=0.32] versus 2.89 cm3 [SD=0.09]), and right posterior cingulate (2.19 cm3 [SD=0.13] versus 2.28 cm3 [SD=0.08]). No significant between-group difference was found for the right anterior cingulate (2.64 cm3 [SD=0.21] versus 2.71 cm3 [SD=0.10]).
The findings indicate smaller cingulate volumes in children and adolescents with bipolar disorder, suggesting that such abnormalities may be present early in the illness course.

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    • "Another VBM study reported greater GM density in the ACC of bipolar patients than in controls and lithium-treated patients showed significantly greater GM density in the right ACC than patients not-taking lithium (Bearden et al., 2007). Decreased (Atmaca et al., 2007; Chiu et al., 2008; Kaur et al., 2005; Lochhead et al., 2004; Lyoo et al., 2004) or unchanged (Biederman et al., 2008; Brambilla et al., 2002; Zimmerman et al., 2006) GM density/volume in the ACC of bipolar patients have also been reported. Although an association between GM deficits in the right ACC and the genetic risk for bipolar disorder has been reported in one high-risk design MRI study using a quantitative measure of genetic liability and computational morphometric techniques (McDonald et al., 2004), we did not replicate this finding in our sample using VBM. "
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    ABSTRACT: Bipolar disorder (BD) is a highly heritable mental illness which is associated with neuroanatomical abnormalities. Investigating healthy individuals at high genetic risk for bipolar disorder may help to identify neuroanatomical markers of risk and resilience without the confounding effects of burden of illness or medication. Structural magnetic resonance imaging scans were acquired from 30 euthymic patients with BD-I (BP), 28 healthy first degree relatives of BD-I patients (HR), and 30 healthy controls (HC). Data was analyzed using DARTEL for voxel based morphometry in SPM8. Whole-brain analysis revealed a significant main effect of group in the gray matter volume in bilateral inferior frontal gyrus, left parahippocampal gyrus, left lingual gyrus and cerebellum, posterior cingulate gyrus, and supramarginal gyrus (alphasim corrected (≤0.05 FWE)). Post-hoc t-tests showed that inferior frontal gyrus volumes were bilaterally larger both in BP and HR than in HC. BP and HR also had smaller cerebellar volume compared with HC. In addition, BP had smaller left lingual gyrus volume, whereas HR had larger left parahippocampal and supramarginal gyrus volume compared with HC. This study was cross-sectional and the sample size was not large. All bipolar patients were on medication, therefore we were not able to exclude medication effects in bipolar group in this study. Our findings suggest that increased inferior frontal gyrus and decreased cerebellar volumes might be associated with genetic predisposition for bipolar disorder. Longitudinal studies are needed to better understand the predictive and prognostic value of structural changes in these regions. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 07/2015; 186:110-118. DOI:10.1016/j.jad.2015.06.055 · 3.38 Impact Factor
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    • "Another aspect of sulcal morphology, sulcal depth, was not abnormal in the anterior cingulate sulcus in adults with first-episode psychosis and schizophrenia (Csernansky et al., 2008; Fornito et al., 2008; Rametti et al., 2010). With regard to bipolar disorder, reduced frontal cortical thickness and gyrification has been demonstrated in adult patients (McIntosh et al., 2009; Penttila et al., 2009; Foland-Ross et al., 2011; Palaniyappan et al., 2011) but findings for adolescent-onset bipolar disorder have been inconclusive (Wilke et al., 2004; Chang et al., 2005; Dickstein et al., 2005; Frazier et al., 2005; Kaur et al., 2005; Sanches et al., 2005; Adler et al., 2007; Janssen et al., 2008). Our sample differs in two important ways from previously studied adolescent-onset bipolar populations which may have influenced the results. "
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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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    • "Although cytoarchitectonic explorations of the region consistently discriminate between the anterior and posterior cingulate cortices, the boundary separating the two regions cannot be readily identified from clear proximal landmarks in an MR image, resulting in an array of approaches (summarised in Figure 3). Whilst some simply do not divide the cingulate gyrus into two at all (Convit et al. 2001; Sowell et al. 2002; Tzourio et al. 1997), the most commonly adopted landmarks for the ACC's posterior extent use sub-cortical markers such as the anterior commissure (Bremner et al. 2002; Fornito et al. 2006; Kaur et al. 2005; Nifosi et al. 2010; Paus et al. 1996; Takahashi et al. 2002; Tisserand et al. 2002; Yucel et al. 2008) which is thought to exclude the SMA (Jones et al., 2006), the most anterior or dorsal extents of the corpus callosum (Bremner et al 1998; Haznedaar et al. 1997; Ranta et al. 2009; Raz et al. 1995; Salat et al. 2001), the septum pellucidum (Noga et al. 1995) and mammillary bodies (Yamasue et al,. 2004), whilst others have selected more proximal cortical features such as where the ascending ramus of the "
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    ABSTRACT: Manual volumetric measurement of the brain's frontal lobe and its subregions from magnetic resonance images (MRIs) is an established method for researching neural correlates of clinical disorders or cognitive functions. However, there is no consensus between methods used to identify relevant boundaries of a given region of interest (ROI) on MRIs, and those used may bear little relation to each other or the underlying structural, functional and connective architecture. This presents challenges for the analysis and synthesis of such results. We therefore performed a systematic literature review to highlight variations in the anatomical boundaries used to measure frontal regions, contextualised by up-to-date evidence from histology, hodology and neuropsychology. We searched EMBASE and MEDLINE for studies in English reporting three-dimensional boundaries for manually delineating the brain's frontal lobe or sub-regional ROIs from MRIs. Exclusion criteria were: exclusive use of co-ordinate grid systems; insufficient detail to allow method replication; publication in grey literature only. Papers were assessed on quality criteria relating to bias, reproducibility and protocol rationale. There was a large degree of variability in the three-dimensional boundaries of all regions used by the 208 eligible papers. Half of the reports did not justify their rationale for boundary selection, and each paper met on average only three quarters of quality criteria. For the frontal lobe and each subregion (frontal pole, anterior cingulate, dorsolateral, inferior-lateral, and orbitofrontal) we identified reproducible methods for a biologically plausible target ROI. It is hoped that this synthesis will guide the design of future volumetric studies of cerebral structure.
    Brain Structure and Function 03/2013; 219(1). DOI:10.1007/s00429-013-0527-5 · 5.62 Impact Factor
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