Distinct effects of duration of untreated psychosis on brain cortical activities in different treatment phases of schizophrenia: A multi-channel near-infrared spectroscopy study

BACKGROUND Duration of untreated psychosis (DUP) has been shown to be associated with both poor short-term and long-term outcomes in schizophrenia. Even so, few studies have used functional neuroimaging to investigate DUP in schizophrenia. In the present study, we used near-infrared spectroscopy (NIRS) to investigate the influence of DUP on brain functions during a verbal fluency test (VFT) in patients with schizophrenia. METHODS A total of 62 patients with schizophrenia were included. They were categorized into either short treatment (≤6months, n=33) or long treatment (>6months, n=29) groups based on their duration of treatment. Hemodynamic changes over the frontotemporal regions during a VFT were measured using multi-channel NIRS. We examined the associations between DUP and hemodynamic changes in each group to explore if there were different effects of DUP on brain cortical activity at different treatment durations. RESULTS In the long treatment group, we found significant associations between a longer DUP and decreased cortical activity approximately at the left inferior frontal gyrus, left middle frontal gyrus, left postcentral gyrus, right precentral gyrus, bilateral superior temporal gyrus, and bilateral middle temporal gyrus, whereas no associations between DUP and brain cortical activity were observed in the short treatment group. CONCLUSIONS Our results indicated that longer DUP may be associated with decreased level of cortical activities over the frontotemporal regions in the long-term. Early detection and intervention of psychosis that shortens DUP might help to improve the long-term outcomes in patients with schizophrenia.

[1]  Archana K. Singh,et al.  Exploring the false discovery rate in multichannel NIRS , 2006, NeuroImage.

[2]  R. Kikinis,et al.  Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia. , 2003, The American journal of psychiatry.

[3]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[4]  Makoto Ito,et al.  Multichannel near-infrared spectroscopy in depression and schizophrenia: cognitive brain activation study , 2004, Biological Psychiatry.

[5]  F. Jöbsis.  Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. , 1977, Science.

[6]  D. Boas,et al.  Non-invasive neuroimaging using near-infrared light , 2002, Biological Psychiatry.

[7]  Y. Hirayasu,et al.  Influence of duration of untreated psychosis on auditory P300 in drug‐naive and first‐episode schizophrenia , 2005, Psychiatry and clinical neurosciences.

[8]  Masato Fukuda,et al.  Reduced frontopolar activation during verbal fluency task in schizophrenia: A multi-channel near-infrared spectroscopy study , 2008, Schizophrenia Research.

[9]  Eve C. Johnstone,et al.  Structural Gray Matter Differences between First-Episode Schizophrenics and Normal Controls Using Voxel-Based Morphometry , 2002, NeuroImage.

[10]  S. Borgwardt,et al.  Duration of untreated psychosis and cognitive functioning , 2013, Schizophrenia Research.

[11]  Katja Hagen,et al.  Aging-related cortical reorganization of verbal fluency processing: a functional near-infrared spectroscopy study , 2013, Neurobiology of Aging.

[12]  H. Yamasue,et al.  A multimodal approach to investigate biomarkers for psychosis in a clinical setting: The integrative neuroimaging studies in schizophrenia targeting for early intervention and prevention (IN-STEP) project , 2013, Schizophrenia Research.

[13]  E. O'callaghan,et al.  Outcome studies in schizophrenia , 1999, Irish Journal of Psychological Medicine.

[14]  C. Pantelis,et al.  Prediction of functional outcome 18 months after a first psychotic episode: a proton magnetic resonance spectroscopy study. , 2006, Archives of general psychiatry.

[15]  Nancy C. Andreasen,et al.  Reduced thalamic volume in first-episode non-affective psychosis: Correlations with clinical variables, symptomatology and cognitive functioning , 2007, NeuroImage.

[16]  Masato Fukuda,et al.  Association between sigma-1 receptor gene polymorphism and prefrontal hemodynamic response induced by cognitive activation in schizophrenia , 2009, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[17]  J G Csernansky,et al.  Lack of association between duration of untreated illness and severity of cognitive and structural brain deficits at the first episode of schizophrenia. , 2000, The American journal of psychiatry.

[18]  J. Lieberman,et al.  Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. , 2005, The American journal of psychiatry.

[19]  Marco Ferrari,et al.  A brief review on the history of human functional near-infrared spectroscopy (fNIRS) development and fields of application , 2012, NeuroImage.

[20]  Stephan Arndt,et al.  Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia. , 2003, The American journal of psychiatry.

[21]  T. Rangaswamy,et al.  Duration of Untreated Psychosis and Treatment Outcome in Schizophrenia Patients Untreated for Many Years , 2004, The Australian and New Zealand journal of psychiatry.

[22]  J. Walecki,et al.  Duration of untreated psychosis and proton magnetic resonance spectroscopy (1H-MRS) findings in first-episode schizophrenia. , 2009, Medical science monitor : international medical journal of experimental and clinical research.

[23]  J. Addington,et al.  Duration of untreated psychosis: impact on 2-year outcome , 2004, Psychological Medicine.

[24]  R. Kikinis,et al.  Middle and inferior temporal gyrus gray matter volume abnormalities in first-episode schizophrenia: an MRI study. , 2006, The American journal of psychiatry.

[25]  K. Gaynor,et al.  Cognitive deterioration and duration of untreated psychosis , 2009, Early intervention in psychiatry.

[26]  A. Malla,et al.  Changes in cognitive functioning following comprehensive treatment for first episode patients with schizophrenia spectrum disorders , 2002, Psychiatry Research.

[27]  M. Compton,et al.  Family history of psychosis negatively impacts age at onset, negative symptoms, and duration of untreated illness and psychosis in first-episode psychosis patients , 2012, Psychiatry Research.

[28]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[29]  Peter B. Jones,et al.  Association between duration of untreated psychosis and brain morphology in schizophrenia within the Northern Finland 1966 Birth Cohort , 2010, Schizophrenia Research.

[30]  E. Chen,et al.  Impacts of duration of untreated psychosis on cognition and negative symptoms in first-episode schizophrenia: a 3-year prospective follow-up study , 2012, Psychological Medicine.

[31]  Peter B. Jones,et al.  Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. , 2005, Archives of general psychiatry.

[32]  V. Peralta,et al.  Duration of untreated negative and positive symptoms of psychosis and cognitive impairment in first episode psychosis , 2012, Schizophrenia Research.

[33]  T. McGlashan,et al.  Is active psychosis neurotoxic? , 2005, Schizophrenia bulletin.

[34]  Beng-Choon Ho,et al.  Hippocampus volume and treatment delays in first-episode schizophrenia. , 2005, The American journal of psychiatry.

[35]  Julie Kreyenbuhl,et al.  Practice guideline for the treatment of patients with schizophrenia , 1997 .

[36]  Masako Okamoto,et al.  Virtual spatial registration of stand-alone fNIRS data to MNI space , 2007, NeuroImage.

[37]  T. McGlashan.  A selective review of recent North American long-term followup studies of schizophrenia. , 1988, Schizophrenia bulletin.

[38]  Eileen M. Joyce,et al.  The Relationship Between IQ, Memory, Executive Function, and Processing Speed in Recent-Onset Psychosis: 1-Year Stability and Clinical Outcome , 2008, Schizophrenia bulletin.

[39]  J. O. Johannessen,et al.  The course of neurocognitive functioning in first-episode psychosis and its relation to premorbid adjustment, duration of untreated psychosis, and relapse , 2007, Schizophrenia Research.

[40]  Y. Kawasaki,et al.  Volume reduction of the left planum temporale gray matter associated with long duration of untreated psychosis in schizophrenia: A preliminary report , 2007, Psychiatry Research: Neuroimaging.

[41]  P. McGorry,et al.  Duration of untreated psychosis and cognitive deterioration in first-episode schizophrenia , 2002, Schizophrenia Research.

[42]  S. Hutton,et al.  Duration of untreated psychosis and social function: 1-year follow-up study of first-episode schizophrenia , 2008, The British journal of psychiatry : the journal of mental science.

[43]  Jennifer T. Crinion,et al.  Anterior temporal lobe connectivity correlates with functional outcome after aphasic stroke , 2009, Brain : a journal of neurology.

[44]  K. Kasai,et al.  Estimation of premorbid IQ in individuals with Alzheimer’s disease using Japanese ideographic script (Kanji) compound words: Japanese version of National Adult Reading Test , 2006, Psychiatry and clinical neurosciences.

[45]  R. Kahn,et al.  Correlates of cognitive impairment in first episode schizophrenia: The EUFEST study , 2009, Schizophrenia Research.

[46]  Peter B. Jones,et al.  Duration of untreated psychosis and neuropsychological function in first episode psychosis , 2007, Schizophrenia Research.

[47]  T. Sharma,et al.  Features of structural brain abnormality detected in first-episode psychosis. , 2000, The American journal of psychiatry.

[48]  John A. Sweeney,et al.  Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible? , 1998, Journal of psychiatric research.

[49]  M. Lepage,et al.  Duration of untreated psychosis is associated with orbital–frontal grey matter volume reductions in first episode psychosis , 2011, Schizophrenia Research.

[50]  Masato Fukuda,et al.  Different hemodynamic response patterns in the prefrontal cortical sub-regions according to the clinical stages of psychosis , 2011, Schizophrenia Research.

[51]  M. Lambert,et al.  Impact of duration of untreated psychosis on pre-treatment, baseline, and outcome characteristics in an epidemiological first-episode psychosis cohort. , 2008, Journal of psychiatric research.

[52]  Tyrone D. Cannon,et al.  Regional brain morphology and duration of illness in never-medicated first-episode patients with schizophrenia , 2003, Schizophrenia Research.

[53]  Peter B. Jones,et al.  Determining the chronology and components of psychosis onset: The Nottingham Onset Schedule (NOS) , 2005, Schizophrenia Research.

[54]  D. Charney,et al.  Discovering the neural basis of human social anxiety: a diagnostic and therapeutic imperative. , 2004, The American journal of psychiatry.

[55]  Arthur W. Toga,et al.  Construction of a 3D probabilistic atlas of human cortical structures , 2008, NeuroImage.

[56]  J. Waddington,et al.  Longitudinal assessment of psychopathological domains over late-stage schizophrenia in relation to duration of initially untreated psychosis: 3-year prospective study in a long-term inpatient population , 2004, Psychiatry Research.

[57]  Masato Fukuda,et al.  Neuroimaging-aided differential diagnosis of the depressive state , 2014, NeuroImage.

[58]  M. Mimura,et al.  Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. , 2014, Schizophrenia bulletin.

[59]  R. Hoffman,et al.  Parallel distributed processing and the emergence of schizophrenic symptoms. , 1993, Schizophrenia bulletin.

[60]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[61]  A. Malhotra,et al.  Lack of an inverse relationship between duration of untreated psychosis and cognitive function in first episode schizophrenia , 2009, Schizophrenia Research.

[62]  Masato Fukuda,et al.  Association between Catechol-O-Methyltrasferase Val108/158Met Genotype and Prefrontal Hemodynamic Response in Schizophrenia , 2009, PloS one.

[63]  R J Wyatt,et al.  Neuroleptics and the natural course of schizophrenia. , 1991, Schizophrenia bulletin.

[64]  Hiroki Sato,et al.  A NIRS–fMRI investigation of prefrontal cortex activity during a working memory task , 2013, NeuroImage.

[65]  T. Robbins,et al.  Executive dysfunction in first-episode schizophrenia and relationship to duration of untreated psychosis: The West London Study , 2002, British Journal of Psychiatry.

[66]  Benedicto Crespo-Facorro,et al.  Caudate nucleus volume and its clinical and cognitive correlations in first episode schizophrenia , 2007, Schizophrenia Research.

[67]  Robin M. Murray,et al.  Gray matter abnormalities associated with duration of untreated psychosis , 2006, Schizophrenia Research.