Iasevoli, F., Laroøi, F., Buonaguro, E.F., Gebhardt, E., Raballo, A.
Can the "connectomic way" provide a link between molecular neurobiology and phenomenological psychopathology? the case of schizophrenia
(2015) Journal of Psychopathology, 21 (4), pp. 323-331. 
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84983156593&partnerID=40&md5=d23d9171687379a678553b70abfb5e44

AFFILIATIONS: Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University School of Medicine Federico II, Naples, Italy; 
Outpatient Unit on Treatment Resistant Psychosis, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University School of Medicine Federico II, Naples, Italy; 
Department of Psychology: Cognition and Behaviour, University of Liège, Liège, Belgium; 
Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway; 
Neurosciences, Mental Health and Sensory Functions (NESMOS) Department, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy; 
Norwegian Centre for Mental Disorders Research (NORMENT), University of Oslo, Diakonhjemmet Hospital, PB 85 Vinderen, Oslo, Norway
ABSTRACT: Schizophrenia is a severe and complex mental illness whose aetiology remains unknoIasewn. 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.
CORRESPONDENCE ADDRESS: Raballo, A.; Norwegian Centre for Mental Disorders Research (NORMENT), University of Oslo, Diakonhjemmet Hospital, PB 85 Vinderen, Norway; email: andrea.raballo@medisin.uio.no
DOCUMENT TYPE: Article

SCOPUS news

Prog Neuropsychopharmacol Biol Psychiatry. 2016 May 10;70:24-38. doi: 10.1016/j.pnpbp.2016.04.015. [Epub ahead of print]

Switching antipsychotics: Imaging the differential effect on the topography of postsynaptic density transcripts in antipsychotic-naïve vs. antipsychotic-exposed rats.

de Bartolomeis A1, Marmo F2, Buonaguro EF2, Latte G2, Tomasetti C2, Iasevoli F2.

• 1Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, School of Medicine, University "Federico II", Naples, Italy. Electronic address: adebarto@unina.it.
• 2Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, School of Medicine, University "Federico II", Naples, Italy.

Abstract

The postsynaptic density (PSD) has been regarded as a functional switchboard at the crossroads of a dopamine-glutamate interaction, and it is putatively involved in the pathophysiology of psychosis. Indeed, it has been demonstrated that antipsychotics may modulate several PSD transcripts, such as PSD-95, Shank, and Homer. Despite switching antipsychotics is a frequent strategy to counteract lack of efficacy and/or side effect onset in clinical practice, no information is available on the effects of sequential treatments with different antipsychotics on PSD molecules. The aim of this study was to evaluate whether a previous exposure to a typical antipsychotic and a switch to an atypical one may affect the expression of PSD transcripts, in order to evaluate potential neurobiological correlates of this common clinical practice, with specific regards to putative synaptic plasticity processes. We treated male Sprague-Dawley rats intraperitoneally for 15days with haloperidol or vehicle, then from the sixteenth day we switched the animals to amisulpride or continued to treat them with vehicle or haloperidol for 15 additional days. In this way we got six first treatment/second treatment groups: vehicle/vehicle, vehicle/haloperidol, vehicle/amisulpride, haloperidol/vehicle, haloperidol/haloperidol, haloperidol/amisulpride. In this paradigm, we evaluated the expression of brain transcripts belonging to relevant and interacting PSD proteins, both of the Immediate-Early Gene (Homer1a, Arc) and the constitutive classes (Homer1b/c and PSD-95). The major finding was the differential effect of amisulpride on gene transcripts when administered in naïve vs. antipsychotic-pretreated rats, with modifications of the ratio between Homer1a/Homer1b transcripts and differential effects in cortex and striatum. These results suggest that the neurobiological effects on PSD transcripts of amisulpride, and possibly of other antipsychotics, may be greatly affected by prior antipsychotic treatments and may impact significantly on the switching procedure.

Copyright © 2016 Elsevier Inc. All rights reserved.

KEYWORDS:

Amisulpride; Haloperidol; Homer; Treatment resistant schizophrenia