Several Authors proposed a dimensional approach to the reduction of schizophrenia heterogeneity. Initially, delusions, hallucination and disorganization were included in the positive dimension of psychosis. However, factor-analytic studies supported the existence of two separate clusters for the positive dimension: reality distortion, including hallucinations and delusions, and disorganization, including disorganized language and behavior, inappropriate affect and some features of cognitive impairment. These clusters emerged as separate domains of psychopathology, with distinct impacts on the outcome of schizophrenia and separate neuropsychological and brain imaging correlates.

This symposium will present recent electrophysiological and brain imaging findings supporting the neurobiological heterogeneity of reality distortion and disorganization in psychosis. Associations of these dimensions (and their constituent features) with indices of functional brain alterations in subjects at high risk for psychosis, as well as in those with first-episode or chronic schizophrenia will be reviewed.

A reduced amplitude of the auditory mismatch negativity (MMN), an ERP component thought to reflect updating of the stimulus context, is associated with positive symptoms (including auditory hallucinations) in chronic schizophrenia patients. It is unclear, however, whether the association between positive symptoms and MMN reductions can be observed in the early phase of the illness. We report that positive symptoms are associated with reductions of mismatch negativity elicited by both stimulus-change and pattern paradigms in early phase psychosis patients. This suggests that a link between positive symptom severity and brain functional alterations is present already in the earliest stages of the illness.

In subjects with schizophrenia (SCZ), the disorganization factor was found to be a strong predictor of real-life functioning. “Conceptual disorganization” (P2), “Difficulty in abstract thinking” (N5) and “Poor attention” (G11) are considered core aspects of the disorganization factor, as assessed by PANSS. The overlap of these items with neurocognitive functions is debated, and should be further investigated.

Within the Italian Network for Research on Psychoses study, electrophysiological and neurocognitive correlates of the disorganization factor and its component items were investigated.

In 145 chronic SCZ and 69 healthy controls, spectral amplitude (SAmp) differences and correlations with psychopathology and MATRICS Consensus Cognitive Battery (MCCB) scores were explored by RAGU.

A negative correlation between Alpha1 and the disorganization factor was observed in SCZ. At the item level, only ‘Difficulty in abstract thinking’ showed this correlation. MCCB neurocognitive composite score was associated with ‘Conceptual disorganization’ and ‘Difficulty in abstract thinking’ but not with Alpha1 SAmp.

Our findings suggest an heterogeneity of the disorganization dimension and a partial overlap with neurocognitive domains. The N5, “difficulties in abstract thinking”, had a unique association with alpha1 SAmp, which is thought to be involved in the formation of conceptual maps.

Formal thought disorders (FTD) are a core symptom in schizophrenia. We focus on distinguishable state cerebral blood flow (rCBF) patterns and white matter (WM) microstructure associated with FTD dimensions. We assessed FTD dimensions and imaging on a 3T MRI scanner. Positive FTD were associated with perfusion within brain regions relevant for language production, while negative FTD were associated with perfusion of semantic processing regions and fractional anisotropy in left hemispheric language system. Perfusion within the left supramarginal gyrus was associated with social functioning after 6 months. Distinguishable associations with FTD dimensions point to distinct underlying pathophysiology.

Abnormal salience processing has been found in people at ultra-high risk (UHR) for psychosis. In our study, using fMRI, we assessed the relationship between changes in the clinical features of 23 UHR and longitudinal changes in Ventral Striatum (VS) activation elicited during the Salience Attribution task. In UHR, we observed that the amelioration of abnormal beliefs over the follow-up period is linked to a longitudinal increase in VS activation during adaptive reward prediction.

Our results indicate a relationship between clinical outcome and longitudinal changes in ventral striatum during salience processing in UHR.