S18. STRUCTURAL COVARIANCE PREDICTORS OF CLINICAL IMPROVEMENT AT 2-YEAR FOLLOW-UP IN FIRST-EPISODE PSYCHOSIS

BACKGROUND: Neural correlates of psychotic disorders encompass multiple brain regions in multiple brain circuits, even at early stages. Previous research has characterized structural brain alterations in first-episode psychosis (FEP), but few studies have focused on the relationship between brain alterations and disease trajectories. First psychotic episodes typically evolve into a chronic course, affecting quality of life of patients and their families, with huge societal costs. Importantly, up to 80% of the patients relapse in the next five years after a first psychotic episode, with a significant risk of developing treatment resistance. Here, we investigated whether disease course may be predicted from brain structural assessments. Specifically, we measured structural covariance, a well-established approach to identify abnormal patterns of volumetric correlation across distant brain regions, which allows to incorporate network-level information to structural assessments. We performed a whole-brain structural covariance assessment of three bilateral regions form to three different cortical networks - dorsolateral prefrontal cortex (dlPFC) for the executive network, posterior cingulate cortex for the default mode network and insulae for the salience network - and subcortical structures (hippocampi, amygdalae and dorsomedial nucleus of the thalamus) that have shown to play a key role in schizophrenia. METHODS: We assessed a sample of 74 subjects from a multicenter, naturalistic, prospective and longitudinal study designed to evaluate clinical, neuropsychological, neuroimaging, biochemical, environmental and pharmacogenetic variables in first episode psychotic patients (PEPs project). Magnetic resonance imaging (MRI) scans were acquired at baseline and at 2-year follow-up, as well as clinical assessments. Psychotic symptoms were assessed using the Positive and Negative Symptom Scale (PANSS) due its widespread use in clinical studies and its reliability in assessing psychopathology across a range of patient populations. The sample was split in two groups as a function of the clinical improvement at 2-year follow-up: responders (i.e. 40% reduction in PANSS global score from baseline; n=29) and non-responders (n=45). RESULTS: Responder patients showed increase structural covariance between the left dlPFC and the left middle frontal gyrus, and between the right dlPFC and the right middle and superior gyrus, the left rectus and inferior frontal gyrus, the right hippocampus, and the vermis of the cerebellum. In addition, they showed increased structural covariance between the left anterior hippocampus and the ipsilateral middle occipital gyrus and the contralateral postcentral gyrus. Likewise, the structural covariance of right anterior hippocampus with right superior occipital gyrus and precentral gyrus was also increased in responder patients. DISCUSSION: This study shows, for the first time in the literature, that increased structural covariance at baseline within the executive network and between the hippocampi and posterior brain regions was associated with a superior treatment response at two-year follow-up. These results indicate that the integrity of structural networks should be taken into account to predict treatment outcome in FEP patients.