Pan European Collaboration on Antipsychotic Naïve Schizophrenia II (PECANSII)

The study is a prospective 2 year multimodal follow-up study of initially antipsychotic-naïve first-episode psychotic patients involving a standardized intervention with monotherapy with aripiprazole during the first 6 weeks. Patients and matched healthy controls will be examined after 6 weeks, 6 months and 2 years. They will be examined with MR-scannings, neurocognitive tests, EEG, and PET-scannings.

The study is a prospective 2 year multimodal follow-up study of initially antipsychotic-naïve first-episode psychotic patients involving a standardized intervention with monotherapy with aripiprazole during the first 6 weeks. Patients and matched healthy controls will be examined at baseline and after 6 weeks, 6 months and 2 years. Levels of glutamate and gamma-aminobutyric acid (GABA) are measured by proton magnetic resonance spectroscopy (1H-MRS) in the anterior cingulate cortex ACC and thalamus. Presynaptic Dopamine level is measured with Positron Emission Tomography Computed Tomography (PET/CT)-scanning using 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-DOPA). Disturbances of the reward system is measured with functional magnetic resonance imaging (fMRI) . Regional cerebral blood flow and activity in the same regions are measured with Pseudo-continuous arterial spin labelling (pCASL). The default mode network, functional and structural connectivity in the associated macro circuits are measured with resting state fMRI, EEG, and diffusion tensor imaging. Structural brain changes (in grey and white matter) are measured with MRI. Cognitive functions are measured with a neuropsychological test battery, and early information processing with event related EEG and electromyography (EMG) (psychophysiological examinations). Further patients psychopathology will be rated.

Neurocognition (measured with BACS (Brief Assessment of Cognition in Schizophrenia) and CANTAB (Cambridge Neuropsychological Test Automated Battery)

Neurocognition is measured with BACS (Brief Assessment of Cognition in Schizophrenia) and CANTAB (Cambridge Neuropsychological Test Automated Battery)

Prepulse inhibition of the startle reflex and reduced P50 suppression ( measured with event related EEG and EMG)

Disturbances in early information processing in form of impaired sensory filtering as measured with event related EEG and EMG

Inclusion Criteria Patients: Fulfilling the diagnostic criteria of schizophrenia or schizoaffective disorder according to ICD-10 (International Classification of Diseases version 10) or DSM-IV/V (Diagnostic and Statistical Manual version 4 /5) Age 18-45 years Never treated with antipsychotic compounds or central nervous system (CNS) stimulants Legally competent Inclusion criteria controls: Matching patients on age (+/- 2 years), sex and parental socioeconomic status Age 18-45 years No psychiatric or physical disease Exclusion Criteria patients: Substance abuse on a daily basis during the last 3 month or patients fulfilling the criteria of ongoing substance abuse due to ICD-10/DSM-IV/V Treatment with antidepressant during the last 30 days Head injury with more than 5 minutes of unconsciousness Patients involuntarily admitted or treated Components of metal implanted by operation Pacemaker Pregnancy Severe physical illness Exclusion criteria controls First degree relatives with psychiatric disease Substance abuse during the last 3 month or positive screening of drugs in urine-sample Head injury with more than 5 minutes of unconsciousness Components of metal implanted by operation Pacemaker Pregnancy Severe physical illness

Capital Mental Health Services, Center for Neuropsykiatrisk Skizofreniforskning, CNSR & Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS

Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Centre Glostrup

Bojesen KB, Broberg BV, Fagerlund B, Jessen K, Thomas MB, Sigvard A, Tangmose K, Nielsen MO, Andersen GS, Larsson HBW, Edden RAE, Rostrup E, Glenthoj BY. Associations Between Cognitive Function and Levels of Glutamatergic Metabolites and Gamma-Aminobutyric Acid in Antipsychotic-Naive Patients With Schizophrenia or Psychosis. Biol Psychiatry. 2021 Feb 1;89(3):278-287. doi: 10.1016/j.biopsych.2020.06.027. Epub 2020 Jul 10.

Jessen K, Mandl RCW, Fagerlund B, Bojesen KB, Raghava JM, Obaid HG, Jensen MB, Johansen LB, Nielsen MO, Pantelis C, Rostrup E, Glenthoj BY, Ebdrup BH. Patterns of Cortical Structures and Cognition in Antipsychotic-Naive Patients With First-Episode Schizophrenia: A Partial Least Squares Correlation Analysis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 May;4(5):444-453. doi: 10.1016/j.bpsc.2018.09.006. Epub 2018 Sep 25.