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: 9.47). 11/2008; 64(9):758-65. DOI: 10.1016/j.biopsych.2008.05.032
Source: PubMed

ABSTRACT 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.

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Available from: Murat Yucel, Aug 02, 2015
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    • "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). "
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    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.
    04/2015; 22. DOI:10.1016/j.nicl.2015.04.016
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    • "Such finding would be consistent with a neurodevelopmental hypothesis of schizophrenia, which posits that the illness is related to abnormal brain development, with various neurological , cognitive, and behavioral difficulties being present long before illness onset (Marenco and Weinberger, 2000). Indeed, studies of longitudinal brain changes in early-onset psychosis support the concept of schizophrenia spectrum illnesses as a progressive neurodevelopmental disorders with both early and late developmental abnormalities (see Arango et al., 2008), and several studies have demonstrated structural brain volume differences even before the onset of psychotic symptoms (Johnstone et al., 2005; Fornito et al., 2008; Lawrie et al., 2008). Studies involving patients with first episode schizophrenia have also found evidence of multiple neurocognive deficits, including attention, processing speed, working memory, verbal and non-verbal memory, general cognitive ability, language, executive, visuo-spatial, motor skills and areas of social cognition, other than emotion identification (for review, see Mesholam-Gately et al., 2009). "
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    ABSTRACT: Patients with chronic schizophrenia are characterized by deficits in identifying facial expressions of emotion, and these deficits relate to impaired social and occupational function. It is not yet known if these deficits are trait-like and present at the onset of psychosis, preceding a subsequent diagnosis of schizophrenia. Our objective was to systematically review and analyze the extant literature to assess if there is a consistent profile of emotion identification problems in early-onset and first-episode psychosis.
    Schizophrenia Research 08/2014; 159(1). DOI:10.1016/j.schres.2014.07.049
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    • "A recent study (van Haren et al., 2011) also showed a normal mean cortical thickness. Besides, cortical thickness reduction was absent on the cingulate gyrus in chronic (Calabrese et al., 2008) and FE cases with schizophrenia (Fornito et al., 2008). Such variable results may be explained by some degree of biological heterogeneity in schizophrenia, in addition to the differences derived from assessment with the use of diverse methods. "
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    ABSTRACT: Cortical thickness may be useful as a treatment response predictor in first-episode (FE) patients with schizophre-nia, although this possibility has been scarcely assessed. In this study we assessed the possible relation between cortical thickness in regions of interest selected because of previously reported structural alterations in schizo-phrenia and clinical and cognitive changes after two years of treatment with risperidone or clozapine in 31 neuroleptic-naïve FE patients with schizophrenia (16 of them treated with clozapine and 15 with risperidone). Using the last-observation-carried-forward (LOCF), a larger improvement in positive, negative and total symp-toms was predicted by the amount of baseline cortical thinning in the right prefrontal cortex (pars orbitalis). After two years of treatment, cognitive status was reassessed in the 17 patients (11 on clozapine) who had not dropped out. Working memory improvement after reassessment was associated with a greater baseline cortical thinning in the left prefrontal cortex (pars orbitalis), and verbal memory improvement with a greater baseline cortical thinning in the left pars triangularis. Significant but weak cortical thickness decrease from baseline to follow-up was observed in patients in comparison to controls (left pars triangularis and opercularis, and left cau-dal middle frontal areas). These results may support a positive predictive role for cortical thinning in the frontal region with regard to clinical and cognitive improvement with clozapine and risperidone in FE patients with schizophrenia.
    Schizophrenia Research 08/2014; 158(1-3). DOI:10.1016/j.schres.2014.06.042
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