Braff, DL, Geyer, MA and Swerdlow, NR.
“Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies”.
Psychopharmacology. 2001;156 (2-3):234-258.
RATIONALE: Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI) have increased at an astounding pace as the value of this neurobiologically informative measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30-500 ms before a strong startle-inducing stimulus, and reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different modalities (acoustic, visual, or cutaneous).
OBJECTIVE: This review covers three areas of interest in human PPI studies. First, we review the normal influences on PPI related to the underlying construct of sensori- (prepulse) motor (startle reflex) gating. Second, we review PPI studies in psychopathological disorders that form a family of gating disorders. Third, we review the relatively limited but interesting and rapidly expanding literature on pharmacological influences on PPI in humans.
METHODS: All studies identified by a computerized literature search that addressed the three topics of this review were compiled and evaluated. The principal studies were summarized in appropriate tables.
RESULTS: The major influences on PPI as a measure of sensorimotor gating can be grouped into 11 domains. Most of these domains are similar across species, supporting the value of PPI studies in translational comparisons across species. The most prominent literature describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum patients and their clinically unaffected relatives. These findings support the use of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically disordered patients with neuropathology involving cortico-striato-pallido-pontine circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's syndrome, blepharospasm, temporal lobe epilepsy with psychosis, enuresis, and perhaps posttraumatic stress disorder (PTSD). Several pharmacological manipulations have been examined for their effects on PPI in healthy human subjects. In some cases, the alterations in PPI produced by these drugs in animals correspond to similar effects in humans. Specifically, dopamine agonists disrupt and nicotine increases PPI in at least some human studies. With some other compounds, however, the effects seen in humans appear to differ from those reported in animals. For example, the PPI-increasing effects of the glutamate antagonist ketamine and the serotonin releaser MDMA in humans are opposite to the PPI-disruptive effects of these compounds in rodents.
CONCLUSIONS: Considerable evidence supports a high degree of homology between measures of PPI in rodents and humans, consistent with the use of PPI as a cross-species measure of sensorimotor gating. Multiple investigations of PPI using a variety of methods and parameters confirm that deficits in PPI are evident in schizophrenia-spectrum patients and in certain other disorders in which gating mechanisms are disturbed. In contrast to the extensive literature on clinical populations, much more work is required to clarify the degree of correspondence between pharmacological effects on PPI in healthy humans and those reported in animals.
This paper is a review and exploration of pre-pulse inhibition (PPI) in humans, with comparisons made across species and between human volunteers with and without major mental illnesses. After discussing the parameters of startle response and PPI, the authors address three areas of PPI research; research into PPI in “normal” human volunteers, investigations of PPI in people with various mental illnesses (schizophrenia, OCD and others) and their relatives, and pharmacological challenge studies. Findings in human pharmacological studies were compared with findings in non-human animals (mostly rodents). While some drugs appeared to have similar effects on PPI in human and non-human animals (dopaminergic drugs, nicotine), there were significant cross-species differences in effects on PPI produced by other drugs (MDMA, ketamine and perhaps psilocybin). Specifically, MDMA reduced PPI in rodents, but facilitated PPI in humans, and this effect was attenuated by pre-treatment with the SSRI citalopram.