Anatomic Abnormalities of the Anterior Cingulate Cortex Before Psychosis Onset: An MRI Study of Ultra-High-Risk Individuals

Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne, Carlton South, Victoria, Australia.
Biological psychiatry (Impact Factor: 10.26). 11/2008; 64(9):758-65. DOI: 10.1016/j.biopsych.2008.05.032
Source: PubMed


Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a sample of individuals at ultra-high-risk (UHR) for psychosis.
Participants underwent baseline magnetic resonance imaging and were followed-up over 12-24 months to ascertain diagnostic outcomes. Baseline ACC morphometry was then compared between UHR individuals who developed psychosis (UHR-P; n = 35), those who did not (UHR-NP; n = 35), and healthy control subjects (n = 33).
Relative to control subjects, UHR-P individuals displayed bilateral thinning of a rostral paralimbic ACC region that was negatively correlated with negative symptoms, whereas UHR-NP individuals displayed a relative thickening of dorsal and rostral limbic areas that was correlated with anxiety ratings. Baseline ACC differences between the two UHR groups predicted time to psychosis onset, independently of symptomatology. Subdiagnostic comparisons revealed that changes in the UHR-P group were driven by individuals subsequently diagnosed with a schizophrenia spectrum psychosis.
These findings indicate that anatomic abnormalities of the ACC precede psychosis onset and that baseline ACC differences distinguish between UHR individuals who do and do not subsequently develop frank psychosis. They also indicate that prepsychotic changes are relatively specific to individuals who develop a schizophrenia spectrum disorder, suggesting they may represent a diagnostically specific risk marker.

Download full-text


Available from: Murat Yucel,
  • Source
    • "In comparison, blurring in cortical thickness analysis occurs in a topographically correct manner along the cortical surface. Research of this kind has demonstrated that individuals at CHR of psychosis who later transition show accelerated thinning in middle frontal cortex (Cannon et al., 2015), anterior cingulate (Fornito et al., 2008; Ziermans et al., 2012), superior temporal cortices and insula as compared to healthy controls (Ziermans et al., 2012), and that cortical thickness in temporal and insular regions allows quantitative prediction of symptom progression in this population (Tognin et al., 2013). Studies in people with schizophrenia have also revealed widespread thinning in frontal and temporal cortical loci (Kuperberg et al., 2003; Narr et al., 2005a; Narr et al., 2005b; Venkatasubramanian et al., 2008; Schultz et al., 2010a; Schultz et al., 2010b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Meta-cognition is compromised in people with schizophrenia and people at clinical high risk (CHR) of psychosis. In the current work in a CHR sample, we hypothesized that meta-cognitive functions would correlate with cortical thickness in five brain regions implicated in the pathogenesis of psychosis: inferior and middle frontal cortices, anterior cingulate cortex, superior temporal cortex and insula. Secondly, we hypothesized that similar neural systems would underlie different meta-cognitive functions. Narratives were gathered for 29 youth at CHR of psychosis using a semi-structured interview. Four meta-cognitive functions within the narratives were measured with the Meta-cognition Assessment Scale and regressed on cortical thickness from our a priori regions of interest using FreeSurfer. Mapping statistics from our a priori regions of interest revealed that meta-cognition functions were associated with cortical thickness in inferior and middle frontal gyri, superior temporal cortex and insula. The distribution of cortical thickness was partially similar across the four MAS items. Results confirm our hypothesis that cortical thickness is significantly associated with meta-cognition in brain regions that consistently show gray matter reductions across the schizophrenia spectrum. Evidence for thickness covariation in a variety of regions suggests partial dependence in the neural architecture underlying various meta-cognitive functions in CHR. Copyright © 2015. Published by Elsevier Ireland Ltd.
    07/2015; 233(3). DOI:10.1016/j.pscychresns.2015.07.010
    • "Crow (1995) similarly proposed that psychosis arose as a consequence of hemispheric specialisation and the evolution of language. Indeed, numerous imaging studies, including our own (e.g., Bartholomeusz et al., 2013; Lavoie et al., 2014), show that social brain regions, as well as regions devoted to speech or communication (i.e., Broca's area, Wernicke's area) and cognitive control (i.e., DLPFC), are structurally abnormal in established schizophrenia, first episode psychosis and individuals at ultra-high risk of psychosis (Pantelis et al., 2007; Fornito et al., 2008, 2009; Takahashi et al., 2009a, 2009b, 2010; Jung et al., 2010; Mechelli et al., 2011). Schizophrenia studies correlating brain structural abnormalities with poor social cognitive performance particularly implicate regions of the medial and lateral PFC, temporal lobes and amygdala (Fujiwara et al., 2007; Namiki et al., 2007; Yamada et al., 2007; Bertrand et al., 2008; Miyata et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Impairments in social cognition and poor social functioning are core features of schizophrenia-spectrum disorders. In recent years, there has been a move towards developing new treatment strategies that specifically target social cognitive and social behavioural deficits. Oxytocin (OXT) is one such strategy that has gained increasing attention. There is a strong rationale for studying OXT in psychosis, from both an evolutionary perspective and neurodevelopmental-cognitive model of schizophrenia. Thus, the aim of this review was to critique and examine the observational and clinical oxytocin trial literature in schizophrenia-spectrum disorders. A handful of clinical trials suggest that OXT treatment may be beneficial for remediating social cognitive impairments, psychiatric symptoms, and improving social outcomes. However, inconsistencies exist in this literature, which may be explained by individual differences in the underlying neural response to OXT treatment and/or variation in the oxytocin and oxytocin receptor genes. Therefore, we additionally reviewed the evidence for structural and functional neural intermediate phenotypes in humans that link genetic variants to social behaviour/thinking, and discuss the implications of such interactions in the context of dysfunctional brain networks in schizophrenia. Factors that pose challenges for future OXT clinical research include the impact of age, sex, and ancestry, task-specific effects, bioavailability and pharmacokinetics, as well as neurotransmitter and drug interactions. While initial findings from OXT single dose/clinical trial studies are promising, more interdisciplinary research in both healthy and psychiatric populations is needed before determining whether OXT is a viable treatment option/adjunct for addressing poor illness outcomes in psychotic disorders. Copyright © 2015. Published by Elsevier B.V.
    Schizophrenia Research 06/2015; DOI:10.1016/j.schres.2015.06.007 · 3.92 Impact Factor
  • Source
    • "Neuroimaging studies using magnetic resonance imaging (MRI) have indicated that ARMS showed brain alterations in the prefrontal (Borgwardt et al., 2006; Borgwardt et al., 2008; Koutsouleris et al., 2009; Mechelli et al., 2011; Wood et al., 2010), cingulate (Fornito et al., 2008; Koutsouleris et al., 2009), superior (Takahashi et al., 2009; Takahashi et al., 2010) and medial temporal (Borgwardt et al., 2007b; Tognin et al., 2014), insular (Smieskova et al., 2010) and cerebellar regions when compared to healthy controls. Furthermore, ARMS individuals with subsequent transition to psychosis showed volumetric reductions in the prefrontal, insular and cingulate cortex compared to those without transition (Smieskova et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Individuals with at-risk mental state for psychosis (ARMS) often suffer from depressive and anxiety symptoms, which are clinically similar to the negative symptomatology described for psychosis. Thus, many ARMS individuals are already being treated with antidepressant medication. To investigate clinical and structural differences between psychosis high-risk individuals with or without antidepressants. We compared ARMS individuals currently receiving antidepressants (ARMS-AD; n = 18), ARMS individuals not receiving antidepressants (ARMS-nonAD; n = 31) and healthy subjects (HC; n = 24), in terms of brain structure abnormalities, using voxel-based morphometry. We also performed region of interest analysis for the hippocampus, anterior cingulate cortex, amygdala and precuneus. The ARMS-AD had higher 'depression' and lower 'motor hyperactivity' scores than the ARMS-nonAD. Compared to HC, there was significantly less GMV in the middle frontal gyrus in the whole ARMS cohort and in the superior frontal gyrus in the ARMS-AD subgroup. Compared to ARMS-nonAD, the ARMS-AD group showed more gray matter volume (GMV) in the left superior parietal lobe, but less GMV in the left hippocampus and the right precuneus. We found a significant negative correlation between attenuated negative symptoms and hippocampal volume in the whole ARMS cohort. Reduced GMV in the hippocampus and precuneus is associated with short-term antidepressant medication and more severe depressive symptoms. Hippocampal volume is further negatively correlated with attenuated negative psychotic symptoms. Longitudinal studies are needed to distinguish whether hippocampal volume deficits in the ARMS are related to attenuated negative psychotic symptoms or to antidepressant action.
    Clinical neuroimaging 04/2015; 22. DOI:10.1016/j.nicl.2015.04.016 · 2.53 Impact Factor
Show more