The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?
Prepulse Inhibition (PPI) of startle is an operational measure of the pre-attentive filtering process known as sensorimotor gating. Originally identified in patients with schizophrenia, PPI deficits have been observed in multiple but not all psychiatric disorders. Thus, as with most signs and symptoms of psychiatric disorders, deficits in PPI cut across diagnostic categories. It remains unclear whether the diversity of disorders exhibiting deficient PPI bespeaks diagnostic overlaps or comorbidities. Given the recent focus on treatments for cognitive deficits of schizophrenia independently of treating psychosis, the relationship of PPI deficits to cognitive deficits becomes of interest. Although PPI cannot be considered to be a cognitive process per se, abnormalities in pre-attentive information processing may be predictive of or lead to complex cognitive deficits. Animal models of PPI deficits produced by dopamine agonists reliably predict existing antipsychotics. Nevertheless, since neither PPI nor cognitive deficits in schizophrenia are ameliorated by standard antipsy-chotics, current research is exploring the predictive value of non-dopaminergic PPI models in identifying treatments for gating disturbances independently of their relevance to specific disorders. Both PPI and cognitive deficits in schizophrenia patients are not reversed by first generation antipsychotics but may be attenuated by clozapine. Similarly, effects of glutamate antagonists on symptoms in patients and PPI in animals appear to be reduced by clozapine. Hence, treatment-induced reversals of deficits in PPI produced by glutamate antagonists may provide animal, and human, models to aid in the discovery of treatments of cognitive deficits in patients already treated with existing antipsychotics.
KeywordsPrepulse inhibition Schizophrenia NMDA Antipsychotics MATRICS
- Geyer MA and A Markou (2002) The role of preclinical models in the development of psychotropic drugs, In:Neuropsychopharm-acology: The Fifth Generation of Progress (Davis KL, D Charney, J.T. Coyle and C Nemeroff, Eds.) (Lippincott Williams and Wilkins:Philadelphia, PA), pp 445–455.Google Scholar
- Geyer MA and B Moghaddam (2002) Animal models relevant to schizophrenia disorders, In:Neuropsychopharmacology: The Fifth Generation of Progress (Davis KL, D Charney, J.T. Coyle and C Nemeroff, Eds.) (Lippincott Williams and Wilkins:Philadelphia, PA), pp 689–701.Google Scholar
- Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia?Am. J. Psych. 153, 321–330.Google Scholar
- Green MF, SR Kerns and RK Heaton (2004a) Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS.Schizophr. Res. 72, 45–51.Google Scholar
- LudewigS, MA Geyer, M Ramseier, FX Vollenweider, E Rechsteiner and K Ludewig (2005) Information processing deficits and cognitive dysfunctions in panic disorder.J. Psychiatr. Neurosci. 30, 37–43.Google Scholar
- Perriol M-P, K Dujardin, P Derambure, A Marcq, J-L Bourriez, E Laureau, F Pasquier, L Defebvre and A Deste’e (2005) Disturbance of sensory filtering in dementia with Lewy bodies comparison with Parkinson’s disease dementia and Alzheimer’s disease.J. Neurol. Neurosurg. Psychiatry 76, 106–108.PubMedCrossRefGoogle Scholar
- Swerdlow NR, ZA Martinez, F Hanlon, A Platten, M Farid, P Auerbach, DL Braff and MA Geyer (2000) Towards understanding the biology of a complex phenotype: rat strain and substrain differences in the sensorimotor gating-disruptive effects of dopamine agonists.J. Neurosci. 20, 4325–4336.PubMedGoogle Scholar
- Swerdlow NR, AS Krupin, MJ Bongiovanni, JM Shoemaker, JC Goins and RP Hammer (2006) Heritable differences in the dopaminergic regulation of behavior in rats: relationship to D2-like receptor G-protein function.Neuropsychopharmacology doi: 10.1038/sj.npp. 1300877Google Scholar