TY - JOUR
T1 - Clozapine Enhances Prepulse Inhibition in Healthy Humans with Low But Not with High Prepulse Inhibition Levels
AU - Vollenweider, Franz X.
AU - Barro, Martine
AU - Csomor, Philipp A.
AU - Feldon, Jorame
N1 - Funding Information:
This investigation was supported by the Heffter Research Center, Zurich, Switzerland, and a grant from the Selo Foundation, Zug, Switzerland (to FXV).
PY - 2006/9/15
Y1 - 2006/9/15
N2 - Background: Atypical antipsychotics have been assessed for normalization effects on deficient sensory gating as indexed by prepulse inhibition (PPI) in schizophrenics with generally positive, although somewhat conflicting, results. Methods: We tested the acute effect of clozapine on startle, PPI, and attention, working memory, and executive functioning in 28 healthy male volunteers with low versus high PPI levels using a placebo-controlled within-subject design. Results: Clozapine significantly increased PPI levels obtained at short lead intervals of 60 and 120 msec in subjects with low PPI performance but showed no effect in subjects with high PPI. Clozapine also caused a mild cognitive impairment on attention and pattern recognition memory tests. No correlations between cognitive measures and PPI performance were found. Moreover, low and high PPI performers were shown to exhibit stable levels of PPI across three separate nondrug testing days. Conclusions: Clozapine increases sensorimotor gating in healthy subjects with low but not high PPI levels in a manner comparable to that seen in clozapine-treated schizophrenia patients. Healthy subjects with low PPI level in combination with genetic studies may provide a translational model to elucidate the neuronal basis of PPI deficits and to test the efficacy of novel antipsychotic medication.
AB - Background: Atypical antipsychotics have been assessed for normalization effects on deficient sensory gating as indexed by prepulse inhibition (PPI) in schizophrenics with generally positive, although somewhat conflicting, results. Methods: We tested the acute effect of clozapine on startle, PPI, and attention, working memory, and executive functioning in 28 healthy male volunteers with low versus high PPI levels using a placebo-controlled within-subject design. Results: Clozapine significantly increased PPI levels obtained at short lead intervals of 60 and 120 msec in subjects with low PPI performance but showed no effect in subjects with high PPI. Clozapine also caused a mild cognitive impairment on attention and pattern recognition memory tests. No correlations between cognitive measures and PPI performance were found. Moreover, low and high PPI performers were shown to exhibit stable levels of PPI across three separate nondrug testing days. Conclusions: Clozapine increases sensorimotor gating in healthy subjects with low but not high PPI levels in a manner comparable to that seen in clozapine-treated schizophrenia patients. Healthy subjects with low PPI level in combination with genetic studies may provide a translational model to elucidate the neuronal basis of PPI deficits and to test the efficacy of novel antipsychotic medication.
KW - Cambridge Neuropsychological Test Automated Battery (CANTAB)
KW - PPI
KW - Prepulse inhibition of acoustic startle
KW - antipsychotic
KW - clozapine
KW - normal volunteers
KW - schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=33748751284&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2006.03.058
DO - 10.1016/j.biopsych.2006.03.058
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AN - SCOPUS:33748751284
SN - 0006-3223
VL - 60
SP - 597
EP - 603
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 6
ER -