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Progressive Brain Changes in Children and Adolescents With First-Episode Psychosis
Celso Arango, MD, PhD;
Marta Rapado-Castro, PhD;
Santiago Reig, PhD;
Josefina Castro-Fornieles, MD, PhD;
Ana González-Pinto, MD, PhD;
Soraya Otero, MD, PhD;
Inmaculada Baeza, MD, PhD;
Carmen Moreno, MD;
Montserrat Graell, MD;
Joost Janssen, PhD;
Mara Parellada, MD, PhD;
Dolores Moreno, MD, PhD;
Nuria Bargalló, MD, PhD;
Manuel Desco, MD, PhD
Arch Gen Psychiatry. 2012;69(1):16-26. doi:10.1001/archgenpsychiatry.2011.150
Context Progressive loss of brain gray matter (GM) has been reported in childhood-onset schizophrenia; however, it is uncertain whether these changes are shared by pediatric patients with different psychoses.
Objective To examine the progression of brain changes in first-episode early-onset psychosis and their relationship to diagnosis and prognosis at 2-year follow-up.
Design Prospective, multicenter, naturalistic, 2-year follow-up study.
Setting Six child and adolescent psychiatric units in Spain.
Participants A total of 110 patients and 98 healthy controls were recruited between March 1, 2003, and November 31, 2005. Magnetic resonance imaging of the brain was performed for 61 patients with schizophrenia (n = 25), bipolar disorder (n = 16), or other psychoses (n = 20) and 70 controls (both at baseline and after 2 years of follow-up). Mean age at baseline was 15.5 years (patients) and 15.3 years (controls).
Main Outcome Measures The GM and cerebrospinal fluid (CSF) volumes in the total brain and frontal, parietal, and temporal lobes.
Results Compared with controls, patients with schizophrenia showed greater GM volume loss in the frontal lobe during the 2-year follow-up (left: –3.3 vs –0.6 cm3, P = .004; right: –3.7 vs –0.8 cm3, P = .005) and left frontal CSF volume increase (left: 6.7 vs 2.4 cm3, P = .006). In addition to frontal volume, changes for total GM (–37.1 vs –14.5 cm3, P = .001) and left parietal GM (–4.3 vs –2.2 cm3, P = .04) were significantly different in schizophrenic patients compared with controls. No significant differences emerged for patients with bipolar disease. Greater left frontal GM volume loss was related to more weeks of hospitalization, whereas severity of negative symptoms correlated with CSF increase in patients with schizophrenia.
Conclusions Patients with schizophrenia or other psychoses showed greater loss of GM volume and increase of CSF in the frontal lobe relative to controls. Progressive changes were more evident in patients with schizophrenia than those with bipolar disorder. These changes in specific brain volumes after onset of psychotic symptoms may be related to markers of poorer prognosis.
Author Affiliations: Department of Child and Adolescent Psychiatry (Drs Arango, Rapado-Castro, C. Moreno, Parellada, and D. Moreno), Medical Imaging Laboratory, Hospital General Universitario Gregorio Marañón, CIBERSAM (Drs Reig, Janssen, and Desco), Bioengineering and Aerospatial Engineering, University Carlos III of Madrid (Dr Desco), and Psychiatry and Psychology Section, Hospital Infantil, Universitario Niño Jesús, CIBERSAM (Dr Graell), Madrid, Spain; Image Diagnostic Center (Dr Bargalló), Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Hospital Clinic de Barcelona, Institut dInvestigacions Biomèdiques August Pi Sunyer, CIBERSAM (Drs Castro-Fornieles and Baeza), Barcelona, Spain; Stanley Institute International Mood-Disorders Research Center, Hospital Santiago Apóstol de Vitoria, CIBERSAM, Vitoria, Spain (Dr González-Pinto); and Child Psychiatry Unit, Hospital Universitario Marqués de Valdecilla, CIBERSAM, Santander, Spain (Dr Otero).
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