Reduced prepulse inhibition in adolescents at risk for psychosis: a 2-year follow-up study.

BACKGROUND Reduced prepulse inhibition (PPI) of the auditory startle reflex is a hallmark feature of attention-processing deficits in patients with schizophrenia and other psychotic disorders. Recent evidence suggests that these deficits may also be present before the onset of psychosis in individuals at ultra-high risk (UHR) and become progressively worse as psychosis develops. We conducted a longitudinal follow-up study to observe the development of PPI over time in UHR adolescents and healthy controls. METHODS Two-year follow-up data of PPI measures were compared between UHR adolescents and a matched control group of typically developing individuals. RESULTS We included 42 UHR adolescents and 32 matched controls in our study. Compared with controls, UHR individuals showed reduced PPI at both assessments. Clinical improvement in UHR individuals was associated with an increase in PPI parameters. LIMITATIONS A developmental increase in startle magnitude partially confined the interpretation of the association between clinical status and PPI. Furthermore, post hoc analyses for UHR individuals who became psychotic between assessments had limited power owing to a low transition rate (14%). CONCLUSION Deficits in PPI are present before the onset of psychosis and represent a stable vulnerability marker over time in UHR individuals. The magnitude of this marker may partially depend on the severity of clinical symptoms.

[1]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[2]  J. Leza,et al.  The relationship between prepulse inhibition and general psychopathology in patients with schizophrenia treated with long-acting risperidone , 2009, Schizophrenia Research.

[3]  H. Engeland,et al.  No evidence for structural brain changes in young adolescents at ultra high risk for psychosis , 2009, Schizophrenia Research.

[4]  L. Bour,et al.  Quantification of the auditory startle reflex in children , 2009, Clinical Neurophysiology.

[5]  Stephen D. Benning,et al.  The onset of puberty: Effects on the psychophysiology of defensive and appetitive motivation , 2009, Development and Psychopathology.

[6]  A. Bechdolf,et al.  Validation of “prodromal” criteria to detect individuals at ultra high risk of psychosis: 2 year follow-up , 2008, Schizophrenia Research.

[7]  N. Swerdlow,et al.  Realistic expectations of prepulse inhibition in translational models for schizophrenia research , 2008, Psychopharmacology.

[8]  W. Maier,et al.  Impaired Sensorimotor Gating of the Acoustic Startle Response in the Prodrome of Schizophrenia , 2008, Biological Psychiatry.

[9]  H. Engeland,et al.  Pathways to psychosis: A comparison of the pervasive developmental disorder subtype Multiple Complex Developmental Disorder and the “At Risk Mental State” , 2008, Schizophrenia Research.

[10]  G. Thaker,et al.  Neurophysiological endophenotypes across bipolar and schizophrenia psychosis. , 2007, Schizophrenia bulletin.

[11]  Joyce Sprock,et al.  Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function. , 2006, Archives of general psychiatry.

[12]  B. Turetsky,et al.  Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures. , 2006, Schizophrenia bulletin.

[13]  K. A. Olsen,et al.  Prospective investigations of the prodromal state of schizophrenia: review of studies , 2006, Acta psychiatrica Scandinavica.

[14]  W. Maier,et al.  Sensorimotor Gating and Habituation of the Startle Response in Schizophrenic Patients Randomly Treated With Amisulpride or Olanzapine , 2006, Biological Psychiatry.

[15]  Elizabeth Zachariah,et al.  A behavioural and functional neuroimaging investigation into the effects of nicotine on sensorimotor gating in healthy subjects and persons with schizophrenia , 2006, Psychopharmacology.

[16]  S. E. Woods,et al.  Lies, damned lies and statistics? Reliability and personal accounts of smoking among young people. , 2006, Social science & medicine.

[17]  R. Snowden,et al.  Prepulse inhibition of startle and its moderation by schizotypy and smoking. , 2005, Psychophysiology.

[18]  T. Sharma,et al.  Sex differences in prepulse inhibition deficits in chronic schizophrenia , 2004, Schizophrenia Research.

[19]  M. Geyer,et al.  The acoustic startle reflex and its modulation: effects of age and gender in humans , 2003, Biological Psychology.

[20]  M. Geyer,et al.  The relationship of age to prepulse inhibition and habituation of the acoustic startle response , 2003, Biological Psychology.

[21]  Franz X. Vollenweider,et al.  Stability of the acoustic startle reflex, prepulse inhibition, and habituation in schizophrenia , 2002, Schizophrenia Research.

[22]  J. Klosterkötter,et al.  Diagnosing schizophrenia in the initial prodromal phase , 2000, Schizophrenia Research.

[23]  N. Swerdlow,et al.  Changes in sensorimotor inhibition across the menstrual cycle: Implications for neuropsychiatric disorders , 1997, Biological Psychiatry.

[24]  N. Swerdlow,et al.  Men are more inhibited than women by weak prepulses , 1993, Biological Psychiatry.

[25]  M. Geyer,et al.  Prestimulus effects on human startle reflex in normals and schizophrenics. , 1978, Psychophysiology.

[26]  F. Graham,et al.  Presidential Address, 1974. The more or less startling effects of weak prestimulation. , 1975, Psychophysiology.

[27]  J. B. Gillespie.  Presidential Address—1974 , 1974, Pediatrics.

[28]  Tyrone D. Cannon,et al.  Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. , 2008, Archives of general psychiatry.

[29]  A. Yung,et al.  The "close-in" or ultra high-risk model: a safe and effective strategy for research and clinical intervention in prepsychotic mental disorder. , 2003, Schizophrenia bulletin.

[30]  T. McGlashan,et al.  Pre-onset detection and intervention research in schizophrenia psychoses: current estimates of benefit and risk. , 2001, Schizophrenia bulletin.

[31]  J. Gray,et al.  Smoking withdrawal, nicotine dependence and prepulse inhibition of the acoustic startle reflex , 1999, Psychopharmacology.

[32]  E. Ornitz,et al.  Maturation of prestimulation-induced startle modulation in girls. , 1991, Psychophysiology.

[33]  D. Saccuzzo,et al.  Information-processing abnormalities: trait- and state-dependent components. , 1986, Schizophrenia bulletin.