Article

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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    • "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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    • "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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    • "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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