title: Association between prefrontal N-acetylaspartate and insight in psychotic disorders.
abstract: Insight is impaired in most patients with psychosis and has been associated with poorer prognosis. The exact neural basis of impaired insight is still unknown, but it may involve disrupted prefrontal neural connectivity. Numerous studies have indeed found white matter (WM) abnormalities in psychosis. The association between prefrontal WM abnormalities and insight has not been studied yet by means of proton magnetic resonance spectroscopy (1H-MRS).1H-MRS can be used to measure N-acetylaspartate (NAA), which is considered to be a marker of neuronal integrity. We measured insight with the Birchwood Insight Scale (BIS) as well as item G12 of the Positive and Negative Syndrome Scale (PANSS) in 88 patients with psychosis. Prefrontal WM concentrations of NAA and ratios of NAA to creatine (Cr) were assessed with1H-MRS. Nonparametric partial correlational analyses were conducted between NAA concentrations and insight controlling for illness duration, standardized antipsychotic dose, symptom scores, voxel grey matter content and voxel cerebrospinal fluid content. We found a significant correlation between reduced NAA/Cr ratios and poorer insight as measured with the BIS, which remained significant after additional correction for full width at half maximum, signal/noise and age. This is the first study reporting a relationship between lower prefrontal concentrations of a marker of neuronal integrity and impaired insight, providing further evidence that prefrontal pathology may play an important role in impaired insight in psychosis. This may be explained by the involvement of the prefrontal cortex in several executive and metacognitive functions, such as cognitive flexibility and perspective taking.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands. Electronic address: d.i.larabi@umcg.nl.
authors.forename: Daouia I
authors.initials: DI
authors.lastname: Larabi
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands; Lentis Psychiatric Institute, Hereweg 80, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Rob Giel Research Center, Hanzeplein 1, Groningen, The Netherlands.
authors.forename: Edith J
authors.initials: EJ
authors.lastname: Liemburg
authors.affiliation: GGZ Drenthe, Department of Psychotic Disorders, Dennenweg 9, Assen, The Netherlands; University of Groningen, Department of Psychology, Grote Kruisstraat 2/1, Groningen, The Netherlands.
authors.forename: Gerdina H M
authors.initials: GH
authors.lastname: Pijnenborg
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Sibeijn-Kuiper
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands; GGZ Drenthe, Department of Psychotic Disorders, Dennenweg 9, Assen, The Netherlands.
authors.forename: Annerieke E
authors.initials: AE
authors.lastname: de Vos
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands; Lentis Psychiatric Institute, Hereweg 80, Groningen, The Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: Bais
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands; Lentis Psychiatric Institute, Hereweg 80, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Rob Giel Research Center, Hanzeplein 1, Groningen, The Netherlands.
authors.forename: Henderikus
authors.initials: H
authors.lastname: Knegtering
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands.
authors.forename: Branislava
authors.initials: B
authors.lastname: Ćurčić-Blake
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Neuroimaging Center, Antonius Deusinglaan 2, Groningen, The Netherlands; University of Groningen, Department of Psychology, Grote Kruisstraat 2/1, Groningen, The Netherlands.
authors.forename: André
authors.initials: A
authors.lastname: Aleman
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001364:Awareness / Q000502:physiology*; D032882:Comprehension / Q000502:physiology*; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D000067489:Metacognition / Q000502:physiology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: Connectivity; Executive functions; Neuronal pathology; Proton magnetic resonance spectroscopy ((1)H-MRS); White matter