Progressive disability and prefrontal shrinkage in schizophrenia patients with poor outcome: A 3-year longitudinal study.
Schizophrenia is a severe disabling disorder with heterogeneous illness courses. In this longitudinal study we characterized schizophrenia patients with poor and good outcome (POS, GOS), using functional and imaging metrics. Patients were defined in accordance to Keefe's criteria (i.e. Kraepelinian and non-Kraepelinian patients).



35 POS patients, 35 GOS patients and 76 healthy controls (H) underwent clinical, functioning and magnetic resonance imaging (MRI) assessments twice over three years of follow-up. Information on psychopathology, treatment, disability (using the World Health Organization Disability Assessment Scale II, WHO-DAS-2) and prefrontal morphology was collected. Dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) were manually traced.



At baseline, subjects with POS showed significantly decreased right dorsolateral prefrontal cortex (DLPFC) white matter volumes (WM) compared to healthy controls and GOS patients (POS VS HC, p<0.001; POS vs GOS, p=0.03), with shrinkage of left DLPFC WM volumes at follow up (t=2.66, p=0.01). Also, POS patients had higher disability in respect to GOS subjects both at baseline and after 3years at the WHO-DAS-2 (p<0.05).



Our study supports the hypothesis that POS is characterized by progressive deficits in brain structure and in "real-life" functioning. These are particularly notable in the DLPFC.
UOC Psychiatry, Policlinico G.B. Rossi, Azienda Ospedaliera-Universitaria Integrata, Verona, Italy.
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Dusi
UOC Psychiatry, Policlinico G.B. Rossi, Azienda Ospedaliera-Universitaria Integrata, Verona, Italy.
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Bellani
Section of Clinical Psychology, University of Verona, Verona, Italy.
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Perlini
Section of Psychiatry, University of Verona, Verona, Italy.
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Squarcina
Section of Psychiatry, University of Verona, Verona, Italy.
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Marinelli
Department of Developmental Psychology and Socialization, University of Padova, Padova, Italy.
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Finos
Department of Neurosciences and Mental Health, Psychiatric Clinic, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Altamura
Section of Psychiatry, University of Verona, Verona, Italy.
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Ruggeri
Department of Neurosciences and Mental Health, Psychiatric Clinic, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; Department of Psychiatry and Behavioural Sciences, University of Texas Health Science Center at Houston, TX, USA. Electronic address: paolo.brambilla1@unimi.it.
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Brambilla
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D012720:Severity of Illness Index; D055815:Young Adult
D014150:Antipsychotic Agents
Disability; Dorsolateral prefrontal cortex; Follow-up; Magnetic resonance; Orbitofrontal cortex; Prefrontal cortex; Psychosis