Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits.

OBJECTIVE Patients with schizophrenia spectrum disorders have been shown to have deficits in sensorimotor gating as assessed by prepulse inhibition of the startle response. The authors hypothesized that nonschizophrenic relatives of patients with schizophrenia would also have prepulse inhibition deficits, thereby reflecting a genetically transmitted susceptibility to sensorimotor gating deficits. METHOD Twenty-five comparison subjects, 23 patients with schizophrenia, 34 relatives of the schizophrenic patients, and 11 subjects with schizotypal personality disorder were assessed in an acoustic startle paradigm. The eye-blink component of the startle response was assessed bilaterally by using electromyographic recordings of orbicularis oculi. RESULTS The patients with schizophrenia, their relatives, and subjects with schizotypal personality disorder all had reduced prepulse inhibition relative to comparison subjects, and these deficits were more evident in measures of right eye-blink prepulse inhibition. Comparison subjects demonstrated greater right versus left eye-blink prepulse inhibition, whereas the probands, their relatives, and subjects with schizotypal personality disorder showed less asymmetry of prepulse inhibition. CONCLUSIONS These data suggest a genetically transmitted deficit in prepulse inhibition (sensorimotor gating) in patients with schizophrenia spectrum disorders, including subjects with schizotypal personality disorder and relatives of patients with schizophrenia.

[1]  A. C. Collins,et al.  Inbred mouse strains differ in the regulation of startle and prepulse inhibition of the startle response. , 1997, Behavioral neuroscience.

[2]  D. Braff,et al.  A multimethod approach to assessing perseverations in schizophrenia patients , 1998, Schizophrenia Research.

[3]  J. Crawley,et al.  Inbred strain differences in prepulse inhibition of the mouse startle response , 1997, Psychopharmacology.

[4]  Christian Grillon,et al.  Gating and habituation of the startle reflex in schizophrenic patients. , 1992 .

[5]  Mark Hallett,et al.  Sensorimotor gating in boys with Tourette's syndrome and ADHD: Preliminary results , 1996, Biological Psychiatry.

[6]  L Kruglyak,et al.  Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[7]  G. Martin,et al.  Brainstem projections to the facial nucleus of the opossum. A study using axonal transport techniques , 1983, Brain Research.

[8]  S. Lamberts,et al.  The endocrinology of aging. , 1997, Science.

[9]  Neil E. Grunberg,et al.  Strain and age differences in acoustic startle responses and effects of nicotine in rats , 1995, Pharmacology Biochemistry and Behavior.

[10]  R Freedman,et al.  Schizophrenia, sensory gating, and nicotinic receptors. , 1998, Schizophrenia bulletin.

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

[12]  N. Grunberg,et al.  Prenatal Exposure to Nicotine: Effects on Prepulse Inhibition and Central Nicotinic Receptors , 1997, Pharmacology Biochemistry and Behavior.

[13]  Ronald A. Yeo,et al.  The evolutionary genetic underpinnings of schizophrenia: the developmental instability model , 1999, Schizophrenia Research.

[14]  N. Swerdlow,et al.  Symptom correlates of prepulse inhibition deficits in male schizophrenic patients. , 1999, The American journal of psychiatry.

[15]  M E Shenton,et al.  First-episode schizophrenic psychosis differs from first-episode affective psychosis and controls in P300 amplitude over left temporal lobe. , 1998, Archives of general psychiatry.

[16]  M. Faraday,et al.  Effects of Nicotine and Stress on Startle Amplitude and Sensory Gating Depend on Rat Strain and Sex , 1999, Pharmacology Biochemistry and Behavior.

[17]  G. Holstege,et al.  Mesencephalic projections to the facial nucleus in the cat. An autoradiographical tracing study , 1984, Brain Research.

[18]  M. Annett,et al.  The theory of an agnosic right shift gene in schizophrenia and autism , 1999, Schizophrenia Research.

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

[20]  J. Chapman.  The Early Symptoms of Schizophrenia , 1966, British Journal of Psychiatry.

[21]  D. Braff,et al.  Sensory gating and inhibitory function in late-life schizophrenia. , 1993, Schizophrenia bulletin.

[22]  M. Geyer,et al.  Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder. , 1993, The American journal of psychiatry.

[23]  L. Saugstad.  A lack of cerebral lateralization in schizophrenia is within the normal variation in brain maturation but indicates late, slow maturation , 1999, Schizophrenia Research.

[24]  Jane S. Paulsen,et al.  Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[25]  A. Klar,et al.  Genetic models for handedness, brain lateralization, schizophrenia, and manic-depression , 1999, Schizophrenia Research.

[26]  D L Braff,et al.  Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder. , 2000, The American journal of psychiatry.

[27]  Georg Deutsch,et al.  Left brain, right brain : perspectives from cognitive neuroscience , 1998 .

[28]  I. Weiner,et al.  The effects of smoking on acoustic prepulse inhibition in healthy men and women , 1998, Psychopharmacology.

[29]  A. Raine.  The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. , 1991, Schizophrenia bulletin.

[30]  M. Geyer,et al.  Aging Effects on the Startle Response and Startle Plasticity in Fischer F344 Rats , 1998, Neurobiology of Aging.

[31]  T. J. Harbin,et al.  The effects of age and attention upon reflex inhibition , 1986, Biological Psychology.

[32]  C. Hinrichsen,et al.  Brain stem projections to the facial nucleus of the rat. , 1983, Brain, behavior and evolution.

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

[34]  H. Hoffman,et al.  Reflex modification in the domain of startle: II. The anomalous history of a robust and ubiquitous phenomenon. , 1983, Psychological bulletin.

[35]  R. Oades,et al.  A left temporal lobe impairment of auditory information processing in schizophrenia: an event-related potential study , 1997, Neuroscience Letters.

[36]  K. Nakano,et al.  Mesencephalic and pontine afferent fiber system to the facial nucleus in the cat: A study using the horseradish peroxidase and silver impregnation techniques , 1979, Experimental Neurology.

[37]  R. Gur,et al.  Laterality in functional brain imaging studies of schizophrenia. , 1999, Schizophrenia bulletin.