Prepulse inhibition of acoustic startle in subjects with schizophrenia treated with olanzapine or haloperidol

Duncan, Erica; Szilágyi, Sándor; Schwartz, Marion; Kunzova, Alena; Negi, Shobhit; Efferen, Toby R.; Peselow, Eric D.; Chakravorty, Subhajit; Stephanides, Myrsini; Harmon, James W.; Bugarski‐Kirola, Dragana; Gonzenbach, Stephen; Rotrosen, John

doi:10.1016/s0165-1781(03)00161-6

Cited by 46 publications

(29 citation statements)

References 65 publications

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“…The fact that amisulpride did not alleviate our patients' PPI deficits-it even (nonsignificantly) decreased average PPI in all trial types between baseline and 6-week follow-up-indicates that blockade of D2/D3 receptors does not ameliorate sensorimotor gating deficits. This is in agreement with our previous findings showing no effect of risperidone and zuclopenthixol treatment on PPI deficits in a similar cohort of patients (Mackeprang et al, 2002), as well as to an ever-growing body of evidence showing that FGAs in general and haloperidol in specific do not alleviate PPI deficits in patients with schizophrenia (Duncan et al, 2003;Wynn et al, 2007;Oranje et al, 2002;, although in contrast Figure 4 P50 suppression (T/C) for patients and controls showing neither significant group differences nor significant effects of treatment. BL, baseline; FU, follow-up.…”

Section: Discussionsupporting

confidence: 92%

Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive, First-Episode Schizophrenia Patients

Düring

Glenthøj

Andersen

et al. 2014

Neuropsychopharmacol

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It has been suggested that psychophysiological measures of sensory and sensorimotor gating, P50 gating and prepulse inhibition of the startle reflex (PPI), underlie core features of schizophrenia and are linked to dopaminergic pathways in the striatum and prefrontal cortex. In the present study, the effects of a potent D2/D3 receptor antagonist, amisulpride, were investigated on PPI and P50 gating in a large sample of antipsychotic-naive, first-episode patients with schizophrenia. A total of 52 initially antipsychotic-naive, first-episode schizophrenia patients were assessed for their P50 gating, PPI, and habituation/sensitization abilities at baseline and after 2 and 6 weeks of treatment with flexible doses of amisulpride. In addition, 47 matched healthy controls were assessed at baseline and after 6 weeks. At baseline, the patients showed significantly reduced PPI, yet normal levels of P50 gating, habituation, and sensitization. Treatment with amisulpride showed no effects on these measures, either at 2 or 6 weeks of follow-up. This is the first study investigating the effects of monotherapy with a relatively selective dopamine D2/D3 receptor antagonist (amisulpride) on sensory and sensorimotor gating deficits in a longitudinal study of a large group of initially antipsychotic-naive, first-episode patients with schizophrenia. Our finding that amisulpride effectively reduced symptom severity in our patients without reducing their PPI deficits indicates that increased activity of dopamine D2 receptors may be involved in symptomatology of patients with schizophrenia, but not in their sensorimotor gating deficits.

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Section: Discussionsupporting

confidence: 92%

Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive, First-Episode Schizophrenia Patients

Düring

Glenthøj

Andersen

et al. 2014

Neuropsychopharmacol

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“…In patients with schizophrenia, classical antipsychotics working through D2/D3 receptor blockade reduce the psychotic symptoms without affecting PPI deficits. 29,30 The findings for the new generation of antipsychotics with multireceptor profiles are more mixed, 29,31,32 and a cross-sectional study by Kumari and colleagues 33 provided indirect evidence of clozapine being superior to haloperidol for PPI deficits in patients with schizophrenia, which is not reflected by the present data from the Df(h22q11)/+ mice.…”

Section: Discussionmentioning

confidence: 53%

Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome: a study in male mice

Didriksen

Fejgin

Nilsson

et al. 2017

JPN

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IntroductionThe 22q11.2 hemizygous microdeletion confers very high risk for neurodevelopmental disorders, including autism and schizophrenia (22q11.2 deletion syndrome [22q11.2DS]). The estimated prevalence is approximately 1 in 2000.1 The International Consortium on Brain and Behaviour in 22q11.2 has recently reported the cumulated prevalence of schizophrenia to be 24% in adolescence and 41% in adulthood.2 Studies of patients with schizophrenia find that 22q11.2 deletion accounts for approximately 0.3% of the cases. Despite massive efforts there is still no coherent understanding of the etiology of schizophrenia -a highly heritable heterogeneous disorder with strong environmental influence. 4,5 Several neurotransmitters are implicated in the disorder: glutamate, 6 γ-aminobutyric acid (GABA), 7 dopamine (DA) 8 and acetylcholine signalling 9 have all been highlighted in the disease etiology and manifestation. The cognitive impairment and negative symptomatology have been related to dysfunction in regulation of glutamate-GABA transmission leading to excitatory-inhibitory imbalances.7 Like in individuals with schizophrenia, 10,11 cognition 12 and information processing is disrupted in children with 22q11.2 deletion, in whom schizophrenia has not (yet) developed.13,14 Given the highly increased risk for schizophrenia and the phenotypic overlap between schizophrenia and the 22q11.2DS, studying the consequence of the 22q11.2 deletion provides a unique opportunity to add to the understanding of the Background: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neuro developmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. Methods: We present a new mouse model (Df(h22q11)/+) of the deletion syndrome (22q11.2DS) and report on, to our knowledge, the most comprehensive study undertaken to date in 22q11.2DS models. The study was conducted in male mice. Results: We found elevated postpubertal N-methyl-d-aspartate (NMDA) receptor antagonist-induced hyperlocomotion, age-independent prepulse inhibition (PPI) deficits and increased acoustic startle response (ASR). The PPI deficit and increased ASR were resistant to antipsychotic treatment. The PPI deficit was not a consequence of impaired hearing measured by auditory brain stem responses. The Df(h22q11)/+ mice also displayed increased amplitude of loudness-dependent auditory evoked potentials. Prefrontal cortex and dorsal striatal elevations of the dopamine metabolite DOPAC and increased dorsal striatal expression of the AMPA receptor subunit GluR1 was found. The Df(h22q11)/+ mice did not deviate from wild-type mice in a wide range of other behavioural and biochemical assays. Limitations: The 22q11.2 microdeletion has incomplete penetrance in humans, and the severity of disease depends on the complete genetic makeup in concert with environmental factors. In order to obtain more marked phenotypes reflecting the severe conditions related to 22q11.2DS it...

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“…This has been replicated by Oranje et al (2002b); (for a review, see . In contrast to clozapine, Duncan et al (2003a) found that patients treated with olanzapine had levels of PPI comparable to patients treated with haloperidol or patients who are not treated at all, whereas this group as a whole showed significantly less PPI compared with healthy controls. This indicates that not every atypical antipsychotic is capable of normalizing PPI deficits, which also seems to be confirmed by a similar study of this group (Duncan et al, 2003b).…”

Section: Introductionmentioning

confidence: 70%

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

Jensen

Oranje

Wienberg

et al. 2007

Neuropsychopharmacol

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Sensorimotor gating is critical to normal brain functioning, and disruptions are associated with certain mental illnesses, such as schizophrenia. Prepulse inhibition of the acoustic startle reflex (ASR) (PPI) is an operational measure of sensorimotor gating, of which evidence for a serotonergic modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences between the two treatments were observed on PPI, although escitalopram was found to significantly delay habituation of the ASR. In the current study, escitalopram was found to delay habituation, but it did not affect PPI in healthy male volunteers. As escitalopram is a highly specific SSRI, the results suggest that an increased serotonergic activity disrupts habituation, but not PPI in healthy volunteers.

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Prepulse inhibition of acoustic startle in subjects with schizophrenia treated with olanzapine or haloperidol

Cited by 46 publications

References 65 publications

Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive, First-Episode Schizophrenia Patients

Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive, First-Episode Schizophrenia Patients

Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome: a study in male mice

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

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