Progressive Brain Changes in Children and Adolescents With First-Episode Psychosis | Adolescent Medicine | JAMA Psychiatry | JAMA Network
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1.
Hulshoff Pol HE, Kahn RS. What happens after the first episode? a review of progressive brain changes in chronically ill patients with schizophrenia.  Schizophr Bull. 2008;34(2):354-36618283048PubMedGoogle ScholarCrossref
2.
Ho BC, Andreasen NC, Nopoulos P, Arndt S, Magnotta V, Flaum M. Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia.  Arch Gen Psychiatry. 2003;60(6):585-59412796222PubMedGoogle ScholarCrossref
3.
Cahn W, van Haren NE, Hulshoff Pol HE, Schnack HG, Caspers E, Laponder DA, Kahn RS. Brain volume changes in the first year of illness and 5-year outcome of schizophrenia.  Br J Psychiatry. 2006;189:381-38217012664PubMedGoogle ScholarCrossref
4.
van Haren NE, Cahn W, Hulshoff Pol HE, Kahn RS. Schizophrenia as a progressive brain disease.  Eur Psychiatry. 2008;23(4):245-25418513927PubMedGoogle ScholarCrossref
5.
van Haren NE, Hulshoff Pol HE, Schnack HG, Cahn W, Mandl RC, Collins DL, Evans AC, Kahn RS. Focal gray matter changes in schizophrenia across the course of the illness.  Neuropsychopharmacology. 2007;32(10):2057-206617327887PubMedGoogle ScholarCrossref
6.
van Haren NE, Hulshoff Pol HE, Schnack HG, Cahn W, Brans R, Carati I, Rais M, Kahn RS. Progressive brain volume loss in schizophrenia over the course of the illness.  Biol Psychiatry. 2008;63(1):106-11317599810PubMedGoogle ScholarCrossref
7.
van Haren NE, Cahn W, Hulshoff Pol HE, Schnack HG, Caspers E, Lemstra A, Sitskoorn MM, Wiersma D, van den Bosch RJ, Dingemans PM, Schene AH, Kahn RS. Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-center MRI study.  Schizophr Res. 2003;64(1):41-5214511800PubMedGoogle ScholarCrossref
8.
Gogtay N, Sporn A, Clasen LS, Nugent TF III, Greenstein D, Nicolson R, Giedd JN, Lenane M, Gochman P, Evans A, Rapoport JL. Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses.  Arch Gen Psychiatry. 2004;61(1):17-2214706940PubMedGoogle ScholarCrossref
9.
Rapoport JL, Giedd J, Kumra S, Jacobsen L, Smith A, Lee P, Nelson J, Hamburger S. Childhood-onset schizophrenia: progressive ventricular change during adolescence.  Arch Gen Psychiatry. 1997;54(10):897-9039337768PubMedGoogle ScholarCrossref
10.
Rapoport JL, Giedd JN, Blumenthal J, Hamburger S, Jeffries N, Fernandez T, Nicolson R, Bedwell J, Lenane M, Zijdenbos A, Paus T, Evans A. Progressive cortical change during adolescence in childhood-onset schizophrenia: a longitudinal magnetic resonance imaging study.  Arch Gen Psychiatry. 1999;56(7):649-65410401513PubMedGoogle ScholarCrossref
11.
Sporn AL, Greenstein DK, Gogtay N, Jeffries NO, Lenane M, Gochman P, Clasen LS, Blumenthal J, Giedd JN, Rapoport JL. Progressive brain volume loss during adolescence in childhood-onset schizophrenia.  Am J Psychiatry. 2003;160(12):2181-218914638588PubMedGoogle ScholarCrossref
12.
Thompson PM, Vidal C, Giedd JN, Gochman P, Blumenthal J, Nicolson R, Toga AW, Rapoport JL. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia.  Proc Natl Acad Sci U S A. 2001;98(20):11650-1165511573002PubMedGoogle ScholarCrossref
13.
Vidal CN, Rapoport JL, Hayashi KM, Geaga JA, Sui YH, McLemore LE, Alaghband Y, Giedd JN, Gochman P, Blumenthal J, Gogtay N, Nicolson R, Toga AW, Thompson PM. Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia.  Arch Gen Psychiatry. 2006;63(1):25-3416389194PubMedGoogle ScholarCrossref
14.
Häfner H, Nowotny B, Löffler W, an der Heiden W, Maurer K. When and how does schizophrenia produce social deficits?  Eur Arch Psychiatry Clin Neurosci. 1995;246(1):17-288773215PubMedGoogle ScholarCrossref
15.
Huber G. The heterogeneous course of schizophrenia.  Schizophr Res. 1997;28(2-3):177-1859468352PubMedGoogle ScholarCrossref
16.
Fraguas D, de Castro MJ, Medina O, Parellada M, Moreno D, Graell M, Merchán-Naranjo J, Arango C. Does diagnostic classification of early-onset psychosis change over follow-up?  Child Psychiatry Hum Dev. 2008;39(2):137-14517665305PubMedGoogle ScholarCrossref
17.
James AC, James S, Smith DM, Javaloyes A. Cerebellar, prefrontal cortex, and thalamic volumes over two time points in adolescent-onset schizophrenia.  Am J Psychiatry. 2004;161(6):1023-102915169690PubMedGoogle ScholarCrossref
18.
James ACD, Javaloyes A, James S, Smith DM. Evidence for non-progressive changes in adolescent-onset schizophrenia: follow-up magnetic resonance imaging study.  Br J Psychiatry. 2002;180:339-34411925357PubMedGoogle ScholarCrossref
19.
Arango C, McMahon RP, Lefkowitz DM, Pearlson G, Kirkpatrick B, Buchanan RW. Patterns of cranial, brain and sulcal CSF volumes in male and female deficit and nondeficit patients with schizophrenia.  Psychiatry Res. 2008;162(2):91-10018201875PubMedGoogle ScholarCrossref
20.
Bakalar JL, Greenstein DK, Clasen L, Tossell JW, Miller R, Evans AC, Mattai AA, Rapoport JL, Gogtay N. General absence of abnormal cortical asymmetry in childhood-onset schizophrenia: a longitudinal study.  Schizophr Res. 2009;115(1):12-1619734017PubMedGoogle ScholarCrossref
21.
Douaud G, Mackay C, Andersson J, James S, Quested D, Ray MK, Connell J, Roberts N, Crow TJ, Matthews PM, Smith S, James A. Schizophrenia delays and alters maturation of the brain in adolescence.  Brain. 2009;132(pt 9):2437-244819477963PubMedGoogle ScholarCrossref
22.
Reig S, Moreno C, Moreno D, Burdalo M, Janssen J, Parellada M, Zabala A, Desco M, Arango C. Progression of brain volume changes in adolescent-onset psychosis.  Schizophr Bull. 2009;35(1):233-24318222929PubMedGoogle ScholarCrossref
23.
Gogtay N, Ordonez A, Herman DH, Hayashi KM, Greenstein D, Vaituzis C, Lenane M, Clasen L, Sharp W, Giedd JN, Jung D, Nugent TF III, Toga AW, Leibenluft E, Thompson PM, Rapoport JL. Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness.  J Child Psychol Psychiatry. 2007;48(9):852-86217714370PubMedGoogle ScholarCrossref
24.
Castro-Fornieles J, Parellada M, Gonzalez-Pinto A, Moreno D, Graell M, Baeza I, Otero S, Soutullo CA, Crespo-Facorro B, Ruiz-Sancho A, Desco M, Rojas-Corrales O, Patiño A, Carrasco-Marin E, Arango C.CAFEPS Group.  The child and adolescent first-episode psychosis study (CAFEPS): design and baseline results.  Schizophr Res. 2007;91(1-3):226-23717267179PubMedGoogle ScholarCrossref
25.
Lenroot RK, Giedd JN. Brain development in children and adolescents: insights from anatomical magnetic resonance imaging.  Neurosci Biobehav Rev. 2006;30(6):718-72916887188PubMedGoogle ScholarCrossref
26.
Reig S, Parellada M, Castro-Fornieles J, Janssen J, Moreno D, Baeza I, Bargallo N, Gonzalez-Pinto A, Graell M, Ortuno F, Otero S, Arango C, Desco M. Multicenter study of brain volume abnormalities in children and adolescent-onset psychosis  Schizophr Bull. 2011;37(6):1270-1280Google ScholarCrossref
27.
Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data.  J Am Acad Child Adolesc Psychiatry. 1997;36(7):980-9889204677PubMedGoogle ScholarCrossref
28.
Soutullo C. Traducción al Español de la Entrevista Diagnóstica: Kiddie-Schedule for Affective Disorders& Schizophrenia, Present& Lifetime Version (K-SADS-PL, 1996). http://www.cun.es/la-clinica/departamentos-yservicios-medicos/psiquiatria-y-psicologia-medica/mas-sobreel-departamento/unidades/psiquiatria-infantil-y-adolescente;1999. Accessed May 2003
29.
Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia.  Schizophr Bull. 1987;13(2):261-2763616518PubMedGoogle Scholar
30.
Peralta Martín V, Cuesta Zorita MJ. Validation of positive and negative symptom scale (PANSS) in a sample of Spanish schizophrenic patients  Actas Luso Esp Neurol Psiquiatr Cienc Afines. 1994;22(4):171-1777810373PubMedGoogle Scholar
31.
Shaffer D, Gould MS, Brasic J, Ambrosini P, Fisher P, Bird H, Aluwahlia S. A children's global assessment scale (CGAS).  Arch Gen Psychiatry. 1983;40(11):1228-12316639293PubMedGoogle ScholarCrossref
32.
Cannon-Spoor HE, Potkin SG, Wyatt RJ. Measurement of premorbid adjustment in chronic schizophrenia.  Schizophr Bull. 1982;8(3):470-4847134891PubMedGoogle Scholar
33.
Satler J. Assessment of Children Cognitive Applications. 4th ed. San Diego, CA: San Diego State University Publisher Inc; 2001
34.
Rey MJ, Schulz P, Costa C, Dick P, Tissot R. Guidelines for the dosage of neuroleptics, I: chlorpromazine equivalents of orally administered neuroleptics.  Int Clin Psychopharmacol. 1989;4(2):95-1042568378PubMedGoogle ScholarCrossref
35.
Woods SW. Chlorpromazine equivalent doses for the newer atypical antipsychotics.  J Clin Psychiatry. 2003;64(6):663-66712823080PubMedGoogle ScholarCrossref
36.
Reig S, Sánchez-González J, Arango C, Castro J, González-Pinto A, Ortuño F, Crespo-Facorro B, Bargalló N, Desco M. Assessment of the increase in variability when combining volumetric data from different scanners.  Hum Brain Mapp. 2009;30(2):355-36818064586PubMedGoogle ScholarCrossref
37.
Desco M, Pascau J, Reig S, Gispert JD, Santos A, Benito C, Molina V, Garcia-Barreno P. Multimodality image quantification using Talairach grid. In: Sonka M, Hanson KM, eds. Proceedings from the International Society for Optical Engineering; February 18-22, 2001; San Diego, CA
38.
Andreasen NC, Rajarethinam R, Cizadlo T, Arndt S, Swayze VW II, Flashman LA, O’Leary DS, Ehrhardt JC, Yuh WTC. Automatic atlas-based volume estimation of human brain regions from MR images.  J Comput Assist Tomogr. 1996;20(1):98-1068576490PubMedGoogle ScholarCrossref
39.
Kates WR, Warsofsky IS, Patwardhan A, Abrams MT, Liu AMC, Naidu S, Kaufmann WE, Reiss AL. Automated Talairach atlas-based parcellation and measurement of cerebral lobes in children.  Psychiatry Res. 1999;91(1):11-3010496689PubMedGoogle ScholarCrossref
40.
Ashburner J, Friston K. Multimodal image coregistration and partitioning: a unified framework.  Neuroimage. 1997;6(3):209-2179344825PubMedGoogle ScholarCrossref
41.
Talairach J, Tournoux P. Co-planar Stereotaxic Atlas of the Human Brain New York, NY: Thieme; 1988
42.
Hollingshead AB, Redlich FC. Schizophrenia and social structure.  Am J Psychiatry. 1954;110(9):695-70113124560PubMedGoogle Scholar
43.
Jernigan TL, Trauner DA, Hesselink JR, Tallal PA. Maturation of human cerebrum observed in vivo during adolescence.  Brain. 1991;114(pt 5):2037-20491933232PubMedGoogle ScholarCrossref
44.
Lenroot RK, Gogtay N, Greenstein DK, Wells EM, Wallace GL, Clasen LS, Blumenthal JD, Lerch J, Zijdenbos AP, Evans AC, Thompson PM, Giedd JN. Sexual dimorphism of brain developmental trajectories during childhood and adolescence.  Neuroimage. 2007;36(4):1065-107317513132PubMedGoogle ScholarCrossref
45.
Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW. Mapping cortical change across the human life span.  Nat Neurosci. 2003;6(3):309-31512548289PubMedGoogle ScholarCrossref
46.
Molina V, Galindo G, Cortes B, de Herrera AG, Ledo A, Sanz J, Montes C, Hernandez-Tamames JA. Different gray matter patterns in chronic schizophrenia and chronic bipolar disorder patients identified using voxel-based morphometry.  Eur Arch Psychiatry Clin Neurosci. 2010;261(5):313-32221188405PubMedGoogle ScholarCrossref
47.
Rimol LM, Hartberg CB, Nesvåg R, Fennema-Notestine C, Hagler DJ Jr, Pung CJ, Jennings RG, Haukvik UK, Lange E, Nakstad PH, Melle I, Andreassen OA, Dale AM, Agartz I. Cortical thickness and subcortical volumes in schizophrenia and bipolar disorder.  Biol Psychiatry. 2010;68(1):41-5020609836PubMedGoogle ScholarCrossref
48.
Janssen J, Reig S, Parellada M, Moreno D, Graell M, Fraguas D, Zabala A, Garcia Vazquez V, Desco M, Arango C. Regional gray matter volume deficits in adolescents with first-episode psychosis.  J Am Acad Child Adolesc Psychiatry. 2008;47(11):1311-132018827723PubMedGoogle ScholarCrossref
49.
Ellison-Wright I, Bullmore E. Anatomy of bipolar disorder and schizophrenia: a meta-analysis.  Schizophr Res. 2010;117(1):1-1220071149PubMedGoogle ScholarCrossref
50.
Gur RE, Cowell P, Turetsky BI, Gallacher F, Cannon T, Bilker W, Gur RC. A follow-up magnetic resonance imaging study of schizophrenia: relationship of neuroanatomical changes to clinical and neurobehavioral measures.  Arch Gen Psychiatry. 1998;55(2):145-1529477928PubMedGoogle ScholarCrossref
51.
Mathalon DH, Sullivan EV, Lim KO, Pfefferbaum A. Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study.  Arch Gen Psychiatry. 2001;58(2):148-15711177116PubMedGoogle ScholarCrossref
52.
Gogtay N, Lu A, Leow AD, Klunder AD, Lee AD, Chavez A, Greenstein D, Giedd JN, Toga AW, Rapoport JL, Thompson PM. Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry.  Proc Natl Acad Sci U S A. 2008;105(41):15979-1598418852461PubMedGoogle ScholarCrossref
53.
Jacobsen LK, Rapoport JL. Research update: childhood-onset schizophrenia: implications of clinical and neurobiological research.  J Child Psychol Psychiatry. 1998;39(1):101-1139534088PubMedGoogle ScholarCrossref
54.
Cannon TD, Mednick SA, Parnas J. Genetic and perinatal determinants of structural brain deficits in schizophrenia.  Arch Gen Psychiatry. 1989;46(10):883-8892802928PubMedGoogle ScholarCrossref
55.
Huttenlocher PR, Dabholkar AS. Regional differences in synaptogenesis in human cerebral cortex.  J Comp Neurol. 1997;387(2):167-1789336221PubMedGoogle ScholarCrossref
56.
Keshavan MS, Anderson S, Pettegrew JW. Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? the Feinberg hypothesis revisited.  J Psychiatr Res. 1994;28(3):239-2657932285PubMedGoogle ScholarCrossref
57.
Arango C, Kirkpatrick B, Koenig J. At issue: stress, hippocampal neuronal turnover, and neuropsychiatric disorders.  Schizophr Bull. 2001;27(3):477-48011596848PubMedGoogle ScholarCrossref
58.
McGlashan TH. Is active psychosis neurotoxic?  Schizophr Bull. 2006;32(4):609-61316914639PubMedGoogle ScholarCrossref
59.
Weinberger DR, McClure RK. Neurotoxicity, neuroplasticity, and magnetic resonance imaging morphometry: what is happening in the schizophrenic brain?  Arch Gen Psychiatry. 2002;59(6):553-55812044198PubMedGoogle ScholarCrossref
60.
Kalmar JH, Wang F, Spencer L, Edmiston E, Lacadie CM, Martin A, Constable RT, Duncan JS, Staib LH, Papademetris X, Blumberg HP. Preliminary evidence for progressive prefrontal abnormalities in adolescents and young adults with bipolar disorder.  J Int Neuropsychol Soc. 2009;15(3):476-48119402934PubMedGoogle ScholarCrossref
61.
Dorph-Petersen KA, Pierri JN, Perel JM, Sun Z, Sampson AR, Lewis DA. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation.  Neuropsychopharmacology. 2005;30(9):1649-166115756305PubMedGoogle ScholarCrossref
62.
Ho BC, Andreasen NC, Ziebell S, Pierson R, Magnotta V. Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia.  Arch Gen Psychiatry. 2011;68(2):128-13721300943PubMedGoogle ScholarCrossref
63.
Lieberman J, Chakos M, Wu HW, Alvir J, Hoffman E, Robinson D, Bilder R. Longitudinal study of brain morphology in first episode schizophrenia.  Biol Psychiatry. 2001;49(6):487-49911257234PubMedGoogle ScholarCrossref
64.
Cahn W, Rais M, Stigter FP, van Haren NE, Caspers E, Hulshoff Pol HE, Xu Z, Schnack HG, Kahn RS. Psychosis and brain volume changes during the first five years of schizophrenia.  Eur Neuropsychopharmacol. 2009;19(2):147-15119056248PubMedGoogle ScholarCrossref
65.
DeLisi LE, Hoff AL. Failure to find progressive temporal lobe volume decreases 10 years subsequent to a first episode of schizophrenia.  Psychiatry Res. 2005;138(3):265-26815854794PubMedGoogle ScholarCrossref
66.
Antonova E, Sharma T, Morris R, Kumari V. The relationship between brain structure and neurocognition in schizophrenia: a selective review.  Schizophr Res. 2004;70(2-3):117-14515329292PubMedGoogle ScholarCrossref
67.
Rüsch N, Spoletini I, Wilke M, Bria P, Di Paola M, Di Iulio F, Martinotti G, Caltagirone C, Spalletta G. Prefrontal-thalamic-cerebellar gray matter networks and executive functioning in schizophrenia.  Schizophr Res. 2007;93(1-3):79-8917383859PubMedGoogle ScholarCrossref
68.
Sanfilipo M, Lafargue T, Rusinek H, Arena L, Loneragan C, Lautin A, Rotrosen J, Wolkin A. Cognitive performance in schizophrenia: relationship to regional brain volumes and psychiatric symptoms.  Psychiatry Res. 2002;116(1-2):1-2312426030PubMedGoogle ScholarCrossref
69.
Arango C, Moreno C, Martínez S, Parellada M, Desco M, Moreno D, Fraguas D, Gogtay N, James A, Rapoport J. Longitudinal brain changes in early-onset psychosis.  Schizophr Bull. 2008;34(2):341-35318234701PubMedGoogle ScholarCrossref
Original Article
Jan 2012

Progressive Brain Changes in Children and Adolescents With First-Episode Psychosis

Author Affiliations

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 d’Investigacions 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).

Arch Gen Psychiatry. 2012;69(1):16-26. doi:10.1001/archgenpsychiatry.2011.150
Abstract

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.

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