P50 Suppression and Its Neural Generators in Antipsychotic-Naïve First-Episode Schizophrenia Before and After 6 Months of Quetiapine Treatment

Oranje, Bob; Aggernæs, Bodil; Rasmussen, Henrik; Ebdrup, Bjørn H; Glenthøj, Birte

doi:10.1093/schbul/sbr183

Cited by 46 publications

(39 citation statements)

References 38 publications

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“…Similarities such as increased baseline gamma power, decreased evoked gamma power, decreased P1 suppression and decreased PPI (Braff et al, 1992; Freedman et al, 1996, 1983; Hanlon et al, 2005; Kwon et al, 1999; Spencer et al, 2003), as well as decreased MMN amplitude in both disorders (Atkinson et al, 2012; Baldeweg et al, 2002) have been reported in both ASD and schizophrenia. However, other studies indicate that there might be marked differences, such as that some studies found normal levels of both PPI and P1 suppression in children with autism (Kemner et al, 2002; Kemner et al, 1995; Kohl et al, 2014; Madsen et al, 2015; Oranje et al, 2013b; Ornitz et al, 1993), while deficient levels are robustly found in schizophrenia (Aggernaes et al, 2010; Braff et al, 2001; Oranje et al, 2013a; Thibaut et al, 2015). There seems to be at least some overlap between schizophrenia and autism symptoms: in two Danish register based studies it was shown that, dependent on the specific form of autism, up to 30% of individuals with a childhood diagnose of autism develop a schizophrenia spectrum disorder later in life (Mouridsen et al, 2008a,b), while parental reports suggest that up to 60% of patients with schizophrenia have had a history with autistic symptoms (Unenge Hallerback et al, 2012).…”

Section: Overlapping Sensory Processing Deficits In Asd and Schizomentioning

confidence: 99%

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

Sinclair

Oranje

Razak

et al. 2017

Neuroscience & Biobehavioral Reviews

158

148

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Brains are constantly flooded with sensory information that needs to be filtered at the pre-attentional level and integrated into endogenous activity in order to allow for detection of salient information and an appropriate behavioral response. People with Autism Spectrum Disorder (ASD) or Fragile X Syndrome (FXS) are often over- or under-reactive to stimulation, leading to a wide range of behavioral symptoms. This altered sensitivity may be caused by disrupted sensory processing, signal integration and/or gating, and is often being neglected. Here, we review translational experimental approaches that are used to investigate sensory processing in humans with ASD and FXS, and in relevant rodent models. This includes electroencephalographic measurement of event related potentials, neural oscillations and mismatch negativity, as well as habituation and pre-pulse inhibition of startle. We outline robust evidence of disrupted sensory processing in individuals with ASD and FXS, and in respective animal models, focusing on the auditory sensory domain. Animal models provide an excellent opportunity to examine common mechanisms of sensory pathophysiology in order to develop therapeutics.

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Section: Overlapping Sensory Processing Deficits In Asd and Schizomentioning

confidence: 99%

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

Sinclair

Oranje

Razak

et al. 2017

Neuroscience & Biobehavioral Reviews

158

148

View full text Add to dashboard Cite

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“…Effects of haloperidol and reboxetine on sensory gating L Witten et al antipsychotic naive, first-episode patients with schizophrenia (eg, Oranje et al, 2013), our current data raise the possibility that D2 antagonism may contribute to the P50 suppression deficits reported from studies on medicated patients with schizophrenia. Similar to our human P50 gating data, haloperidol disrupted gating (N1) in the hippocampus of rats.…”

Section: Discussionmentioning

confidence: 55%

“…For instance, it has been shown that haloperidol significantly reduces baseline levels of NE in rats (Amato et al, 2011). A growing body of evidence has indicated that an optimal functional PFC is essential for normal levels of gating (Bak et al, 2011;Oranje et al, 2006Oranje et al, , 2013Weisser et al, 2001). Interestingly, there is no dopamine transporter in the rat PFC, nor in humans as a matter of fact: dopamine in the PFC is removed by NET (Carboni et al, 1990;Pozzi et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…The human gating paradigm as well as its processing and assessment have been previously described (Oranje et al, 2013;Oranje and Glenthoj, 2013a). Similarly, the rat gating paradigm as well as its assessment and processing have been described before (Broberg et al, 2010;Witten et al, 2014) with the exception that the coordinates for electrode placement in the current rat study were: frontal cortex (+3.0 mm anterior, − 0.5 mm lateral), ground (−4.5 mm posterior, +4.0 lateral) and a depth electrode in CA-3 region of the hippocampus (−5.2 mm posterior to bregma, − 5.0 mm lateral, − 4.8 mm ventral to dura).…”

Section: Human and Rat Gating Paradigms And Data Processingmentioning

confidence: 99%

“…Extensive research has shown disrupted P50 gating in patients with schizophrenia compared with healthy controls, whether patients were medicated (Adler et al, 1982;Bramon et al, 2004;Nagamoto et al, 1989) or antipsychotic naive, first episode patients (Brockhaus-Dumke et al, 2008;Oranje et al, 2013). Similarly, deficits in N1 gating have been reported in schizophrenic patients compared with healthy controls (Boutros et al, 1999;Brockhaus-Dumke et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Comparing Pharmacological Modulation of Sensory Gating in Healthy Humans and Rats: The Effects of Reboxetine and Haloperidol

Witten

Bastlund

Glenthøj

et al. 2015

Neuropsychopharmacol

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Sensory gating is the brain's ability to filter out irrelevant information before it reaches high levels of conscious processing. In the current study we aimed to investigate the involvement of the noradrenergic and dopaminergic neurotransmitter systems in sensory gating. Furthermore, we investigated cross-species reliability by comparing effects in both healthy humans and rats, while keeping all experimental conditions as similar as possible between the species. The design of the human experiment (n = 21) was a double-blind, placebocontrolled, cross-over study where sensory gating was assessed following a dose of either reboxetine (8 mg), haloperidol (2 mg), their combination or placebo at four separate visits. Similarly in the animal experiment sensory gating was assessed in rats, (n = 22) following a dose of reboxetine (2 mg/kg), haloperidol (0.08 mg/kg), their combination or placebo. The sensory gating paradigms in both experiments were identical. In humans, we found significantly reduced P50 suppression following separate administration of reboxetine or haloperidol, while their combined administration did not reach statistical significance compared with placebo. In the rats, we found a similar significant reduction of sensory gating (N40) following treatment with haloperidol and the combination of haloperidol and reboxetine, but not with separate reboxetine treatment, compared with placebo. Our study indicates that even when experimental conditions are kept as similar as possible, direct human to rat cross-species translation of pharmacological effects on sensory gating is challenging, which calls for more focussed research in this important translational area.

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Normal P50 Gating in Children with Autism, Yet Attenuated P50 Amplitude in the Asperger Subcategory

et al. 2015

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Autism spectrum disorders (ASD) and schizophrenia are separate disorders, but there is evidence of conversion or comorbid overlap. The objective of this paper was to explore whether deficits in sensory gating, as seen in some schizophrenia patients, can also be found in a group of ASD children compared to neurotypically developed children. An additional aim was to investigate the possibility of subdividing our ASD sample based on these gating deficits. In a case-control design, we assessed gating of the P50 and N100 amplitude in 31 ASD children and 39 healthy matched controls (8-12 years) and screened for differences between groups and within the ASD group. We did not find disturbances in auditory P50 and N100 filtering in the group of ASD children as a whole, nor did we find abnormal P50 and N100 amplitudes. However, the P50 amplitude to the conditioning stimulus was significantly reduced in the Asperger subgroup compared to healthy controls. In contrast to what is usually reported for patients with schizophrenia, we found no evidence for sensory gating deficits in our group of ASD children taken as a whole. However, reduced P50 amplitude to conditioning stimuli was found in the Asperger group, which is similar to what has been described in some studies in schizophrenia patients. There was a positive correlation between the P50 amplitude of the conditioning stimuli and anxiety score in the pervasive developmental disorder not otherwise specified group, which indicates a relation between anxiety and sensory registration in this group.

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P50 Suppression and Its Neural Generators in Antipsychotic-Naïve First-Episode Schizophrenia Before and After 6 Months of Quetiapine Treatment

Cited by 46 publications

References 38 publications

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

Comparing Pharmacological Modulation of Sensory Gating in Healthy Humans and Rats: The Effects of Reboxetine and Haloperidol

Normal P50 Gating in Children with Autism, Yet Attenuated P50 Amplitude in the Asperger Subcategory

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