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Background The extent and location of longitudinal morphometric changes after first-episode of psychosis (FEP) remains unclear. We investigated the progressive profile of ventricular and cortico-subcortical regions over a 3-year period in FEP patients compared with healthy controls (HC), and whether any progressive neuroanatomical changes were related to clinical factors. Methods High resolution 1.5T T1-weighted MR images were obtained from 28 FEP patients and 28 HCs shortly after presentation to services and again after 3-year follow-up. The longitudinal FreeSurfer pipeline (v.5.3.0) was used for regional volumetric and cortical reconstruction image analyses. Repeated-measures ANCOVA and vertex-wise linear regression analyses were used to compare progressive changes in relation to subcortical structures/ventricles and thickness across the cortical mantle, respectively, between groups. Partial correlations were used to determine associations of progressive neuroanatomical change with clinical and functional characteristics. Results Compared with controls, patients displayed progressively reduced volume of the caudate [F(1,51)=5.86, p=0.02, Hedges’ g=0.66], putamen [F(1,51)=6.06, p=0.02, g=0.67] and thalamus [F(1,51)=6.99, p=0.01, g=0.72], with a trend for increased lateral ventricular volume [F(1,51)=3.37, p=0.07, g=0.50] more prominent on the right [F(1, 51)=4.03, p=0.05], and significantly increased rate of cortical thinning [F(1,52)=5.11, p=0.028)] at a mean difference of 0.844% [95% CI (0.095, 1.593)] in the left lateral orbitofrontal region (LLOFR) over the 3-year period. In FEP individuals, greater reduction in putamen volume over time was associated with low cumulative antipsychotic medication dose (r=0.49, p=0.01), and increasing lateral ventricular volume over time was associated with worsening negative symptoms (r=0.41, p=0.04) and poorer global assessment of functioning (r=-0.41, p=0.04). Discussion Our results demonstrate existence of localised progressive structural disturbance in the subnetwork of the cortico-striato-thalamo-cortical circuitry after the onset of psychosis. Furthermore, increasing ventricular volume is a neuroanatomical marker of poorer clinical and functional outcome. These findings lend weight to the evidence of early progressive brain changes in psychotic disorders and thus, this knowledge could potentially contribute to the identification of imaging biomarkers for timely intervention.

Background Neurocognitive impairments are a prevalent aspect of psychosis which, on average, begin in early adolescents, with particular impairment apparent in speed of processing and nonverbal working memory in early stages (Kelleher et al., 2012). It is important to understand the impact of cognitive impairment on functional ability, particularly in early stages of illness which may assist in the development of targeted therapeutic strategies. Methods A population sample of 212 school going adolescents aged 11–13 years partook in the study, which included community-based adolescents who report experiencing psychotic symptoms but who were not clinically diagnosed. Psychotic symptoms were assessed using the psychosis section of the Schedule for Affective Disorders and Schizophrenia. Six cognitive domains were assessed using the MATRICS consensus cognitive battery. Functioning was assessed using the Children’s Global Assessment Scale. Six separate linear regression analyses were performed to test if each cognitive domain of the MATRICS battery predicted functioning. Results In the entire sample (including those who experienced psychotic experiences and those who did not) (n=211), speed of processing significantly explained 8% of the variance in functioning (F(1, 76) = 6.61, p = .0012, R-squared = 0.08.), (Beta = 0.39, p = 0.012). When the sample was subdivided into those who ever experienced auditory hallucinations (AH) (n=62) versus those that did not (n=149), speed of processing significantly predicted 18% of the variance in functioning in the group experiencing AHs (F(2, 33) = 3.82, p =0.032, R-squared = 0.18), (Beta = 0.43, p = 0.06). However, no effect was found in the group without AVs (F(1,40) = 1.19, p =0.28). No other cognitive domain predicted functioning. Discussion Speed of processing appears to be a core cognitive deficit in psychosis which impacts on functioning in young adolescents particularly in those experiencing psychotic symptoms such as auditory hallucinations, however the variance predicted by processing speed is relatively low. This research highlights the potential of speed of processing as a possible viable target for early intervention in psychotic disorders.