Schizophrenia (SCZ) is a heterogeneous syndrome with a chronic course that leads to relevant psychosocial impairment. The clinical phenomenology is typically defined by “positive” symptoms such as hallucinations and delusions and “negative” symptoms such as avolition and anhedonia, that are often associated with a progressive cognitive decline. Despite intensive research on the etiopathogenetic mechanisms of this disorder, clearly defined biological markers are still lacking. On the neurophysiological level, a marked reduction of sleep spindle activity has recently been described in patients with chronic, medicated SCZ and with early-course psychotic disorders. Whether such deficit can be considered a reliable marker of or an endophenotype of the disorder remains to be cleared. The objective of my work was to accurately study the electrophysiological features of sleep spindle activity in First-Degree Relatives (FDRs) of SCZ patients and in drug-naïve subjects with First-Episode Psychosis (FEP). A high-density electroencephalogram (hd-EEG) with 256 channels was used to study a whole night of sleep in experimental subjects and in a sample of age- and gender-matched healthy control subjects. Several neurocognitive tests and clinical scales were also administered to FDR and FEP subjects in order define psychopathological status and vulnerability. None of the recruited subjects had received treatment with psychotropic medication. Among several analysed parameters of sleep macrosructure and microarchitecture, hd-EEG measurements revealed a significant reduction of Integrated Spindle Activity (ISAs) in FDR subjects. ISA was obtained by integrating the absolute amplitude values of each spindle detected at every electrode, divided by its duration. No relevant differences were observed in terms of spindle density and duration. Preliminary results from a small subgroup of drug-naïve FEP patients are also reported. The main findings of my work appear to support the view that sleep spindle deficit is an electrophyisological endophenotype of SCZ. Given the vast available knowledge on the cellular mechanisms underlying spindle activity, future perspectives include a molecular characterization in individuals who carry a known genetic vulnerability for thalamic dysfunction.

ELECTROPHYSIOLOGICAL ABNORMALITIES DURING SLEEP IN SCHIZOPHRENIA: HIGH-DENSITY EEG STUDIES IN FIRST-EPISODE PSYCHOSIS AND FIRST-DEGREE RELATIVES / A. D'agostino ; tutor: S. Sarasso ; coordinator: M. Mazzanti. - : . DIPARTIMENTO DI SCIENZE BIOMEDICHE E CLINICHE "L. SACCO", 2015 Dec 02. ((28. ciclo, Anno Accademico 2015. [10.13130/a-d-agostino_phd2015-12-02].

ELECTROPHYSIOLOGICAL ABNORMALITIES DURING SLEEP IN SCHIZOPHRENIA: HIGH-DENSITY EEG STUDIES IN FIRST-EPISODE PSYCHOSIS AND FIRST-DEGREE RELATIVES

A. D'Agostino
2015-12-02

Abstract

Schizophrenia (SCZ) is a heterogeneous syndrome with a chronic course that leads to relevant psychosocial impairment. The clinical phenomenology is typically defined by “positive” symptoms such as hallucinations and delusions and “negative” symptoms such as avolition and anhedonia, that are often associated with a progressive cognitive decline. Despite intensive research on the etiopathogenetic mechanisms of this disorder, clearly defined biological markers are still lacking. On the neurophysiological level, a marked reduction of sleep spindle activity has recently been described in patients with chronic, medicated SCZ and with early-course psychotic disorders. Whether such deficit can be considered a reliable marker of or an endophenotype of the disorder remains to be cleared. The objective of my work was to accurately study the electrophysiological features of sleep spindle activity in First-Degree Relatives (FDRs) of SCZ patients and in drug-naïve subjects with First-Episode Psychosis (FEP). A high-density electroencephalogram (hd-EEG) with 256 channels was used to study a whole night of sleep in experimental subjects and in a sample of age- and gender-matched healthy control subjects. Several neurocognitive tests and clinical scales were also administered to FDR and FEP subjects in order define psychopathological status and vulnerability. None of the recruited subjects had received treatment with psychotropic medication. Among several analysed parameters of sleep macrosructure and microarchitecture, hd-EEG measurements revealed a significant reduction of Integrated Spindle Activity (ISAs) in FDR subjects. ISA was obtained by integrating the absolute amplitude values of each spindle detected at every electrode, divided by its duration. No relevant differences were observed in terms of spindle density and duration. Preliminary results from a small subgroup of drug-naïve FEP patients are also reported. The main findings of my work appear to support the view that sleep spindle deficit is an electrophyisological endophenotype of SCZ. Given the vast available knowledge on the cellular mechanisms underlying spindle activity, future perspectives include a molecular characterization in individuals who carry a known genetic vulnerability for thalamic dysfunction.
SARASSO, SIMONE
MAZZANTI, MICHELE
schizophrenia; psychotic disorders; psychosis; cognitive deficits; first-episode psychosis; first-degree relatives; endophenotypes; sleep spindles; integrated spindle activity; thalamic reticular nucleus; high-density EEG; PV + interneurons; clinical neurophysiology
Settore BIO/09 - Fisiologia
Settore MED/25 - Psichiatria
ELECTROPHYSIOLOGICAL ABNORMALITIES DURING SLEEP IN SCHIZOPHRENIA: HIGH-DENSITY EEG STUDIES IN FIRST-EPISODE PSYCHOSIS AND FIRST-DEGREE RELATIVES / A. D'agostino ; tutor: S. Sarasso ; coordinator: M. Mazzanti. - : . DIPARTIMENTO DI SCIENZE BIOMEDICHE E CLINICHE "L. SACCO", 2015 Dec 02. ((28. ciclo, Anno Accademico 2015. [10.13130/a-d-agostino_phd2015-12-02].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/337007
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