Can the “connectomic way” provide a link between molecular neurobiology and phenomenological psychopathology? The case of schizophrenia

F. Iasevoli (1 2), F. Larøi (3 4), E.F. Buonaguro (1), E. Gebhardt (5), A. Raballo (6)

1 Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University School of Medicine Federico II, Naples, Italy; 2 Outpatient Unit on Treatment Resistant Psychosis, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University School of Medicine Federico II, Naples, Italy; 3 Department of Psychology: Cognition and Behaviour, University of Liège, Liège, Belgium; 4 Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway; 5 Neurosciences, Mental Health and Sensory Functions (NESMOS) Department, Faculty of Medicine and Psychology, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy; 6 Norwegian Centre for Mental Disorders Research (NORMENT), University of Oslo, and Diakonhjemmet Hospital, University Department of Psychiatry, Oslo, Norway


Schizophrenia is a severe and complex mental illness whose aetiology remains unknown. Moreover, changing definitions of the diagnostic criteria of schizophrenia over past decades have not contributed to any substantial progress in terms of deeper pathophysiological understanding of the disease. Nevertheless, to date, significant evidence continues to be accumulated from epidemiologic, genetic and preclinical studies that point to a number of genetic factors that play important roles in the pathophysiology of schizophrenia, especially in terms of disrupted synaptic plasticity molecular processes. Specifically, the most recent approach in human research on schizophrenia is represented by “connectomics” or the study of connectomes, which can be defined as comprehensive maps of connections within an organism’s nervous system. Indeed, it has been suggested that schizophrenic pathophysiology might rely on circuit-based dysfunctions that may represent the consequence, on a network scale, of the impairment in synaptic plasticity and neuronal connections that are increasingly found in preclinical molecular research, and that may stem from de novo and/or inherited disease-variants in target genes as well as from aberrant epigenetic mechanisms. On the other hand, circuit-based dysfunctions may underlie the defects in integration of higher-order cognitive functions that characteristically connote schizophrenia patients, and may account for aberrant self-experience which are typically described in phenomenological approaches to the disease. In this paper, we will critically explore the recent advances on molecular, genetic and neuro-imaging research in schizophrenia. Based on these data, we will emphasise the potential of the connectomic framework as an intermediate step between the biological and the phenomenological levels to capture the complexity of schizophrenia manifestations.

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