Neurobiological Studies of Sensory Gating in Schizophrenia

Abstract

The sensory disturbance in schizophrenia is often described as an inability to filter out extraneous noise from meaningful sensory inputs. The neurobiological basis of this inability to filter has been examined using auditory evoked potentials, which are computerized averages of the brain's electrical response to sound. The sounds are presented in pairs to test the ability of the brain to inhibit, or gate, its response to a repeated stimulus. Schizophrenic patients lack the ability to gate the neuronal response shown by a particular wave, the P50 wave. The measurement of this deficit in human subjects and the exploration of its neurobiology in animals has produced evidence about several issues in the pathophysiology of schizophrenia: (1) the role of dopamine in improvement of sensory function in schizophrenic patients treated with neuroleptic drugs, (2) the interaction between familial or genetic deficits in sensory functioning in schizophrenic patients and possible abnormalities in dopamine metabolism, and (3) a mechanism by which noradrenergic hyperactivity in mania and other psychiatric illnesses might mimic some pathophysiological deficits in schizophrenia.

Advances in endophenotyping schizophrenia

“…Studies initiated by Freedman and colleagues, and replicated by others, have identified P50 suppression as an important endophenotype of schizophrenia (3,(20)(21)(22)(23)(24)(25). In response to the presentation of paired auditory "clicks", there is normally an 80% diminution of the second P50 wave relative to the first, and this is attributed to the activation of inhibitory neural circuitry by the first auditory stimulus.…”

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

“…1,[33][34][35] Compared with controls, patients with schizophrenia and psychotic bipolar disorder have a relatively larger P50 response to the second stimulus, from only 20-50% suppression. 31,[36][37][38][39][40][41][42][43][44][45][46][47] Clinically unaffected first-degree relatives of patients with schizophrenia and psychotic bipolar disorder also have poor P50 suppression, suggesting that this might act as a marker of genetic risk for these disorders, [46][47][48][49][50][51][52][53] as it is heritable. [54][55][56][57] We have examined the effects of CHRFAM7A CNV/2 bp deletion variants on the major psychoses and the P50 sensory gating deficit.…”

Nitric Oxide Signaling in the Medial Prefrontal Cortex is Involved in the Biochemical and Behavioral Effects of Phencyclidine

“…This has led to the hypothesis that these patients are afflicted by impairment in information processing mechanisms resulting in sensory flooding followed by a cognitive fragmentation (McGhie and Chapman, 1961;Braff et al, 1978;Freedman et al, 1987;Braff, 1993). Sensorimotor gating deficits, as measured by prepulse inhibition (PPI), and dysfunctions in cognitive domains such as social cognition and reasoning appear to be closely related in some, but not all, clinical studies of schizophrenia (Perry et al, 1999;Wynn et al, 2005).…”