title: N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth.
abstract: Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones - mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life.
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Psychiatry, Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gonzalez-Heydrich
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Psychiatry, Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA.
authors.forename: Michelle Bosquet
authors.initials: MB
authors.lastname: Enlow
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Psychiatry, Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: D'Angelo
authors.affiliation: Department of Psychiatry, Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA; Department of Psychiatry, Commonwealth Research Center, Beth Israel Deaconess Medical Center, 75 Fenwood Road, Boston, MA 02115, USA; Department of Psychiatry, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gumlak
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: April
authors.initials: A
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA; Department of Psychiatry, Commonwealth Research Center, Beth Israel Deaconess Medical Center, 75 Fenwood Road, Boston, MA 02115, USA.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Woodberry
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Rober
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Sahil
authors.initials: S
authors.lastname: Tembulkar
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: O'Donnell
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Psychiatry, Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA.
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Hamoda
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Kimball
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rotenberg
authors.affiliation: Neuroplasticity and Autism Spectrum Disorder Program and Department of Psychiatry and Human Behavior, E.P. Bradley Hospital and Warren Alpert Medical School, Brown University, 1011 Veterans Memorial Parkway, East Providence, RI 02915, USA.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Oberman
authors.affiliation: Department of Psychiatry, Commonwealth Research Center, Beth Israel Deaconess Medical Center, 75 Fenwood Road, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
authors.affiliation: Department of Psychiatry, Harvard Medical School, 401 Park Drive, Boston, MA 02215, USA; Department of Psychiatry, Commonwealth Research Center, Beth Israel Deaconess Medical Center, 75 Fenwood Road, Boston, MA 02115, USA.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: Frank H
authors.initials: FH
authors.lastname: Duffy
mesh_terms: D000161:Acoustic Stimulation; D000222:Adaptation, Physiological; D000293:Adolescent; D015415:Biomarkers; D002540:Cerebral Cortex / Q000503:physiopathology*; D004569:Electroencephalography; D005071:Evoked Potentials; D005072:Evoked Potentials, Auditory; D005260:Female; D006801:Humans; D008297:Male; D009473:Neuronal Plasticity; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*
chemical_list: D015415:Biomarkers