Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine. (2016)

Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine.

Recent heuristic models of schizophrenia propose that abnormalities in the gamma frequency cerebral oscillations may be closely tied to the pathophysiology of the disorder, with hypofunction of N-methyl-d-aspartate receptors (NMDAr) implicated as having a crucial role. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating that is disrupted in schizophrenia. We tested the ability for antipsychotic drugs with diverse pharmacological actions to (1) ameliorate NMDAr antagonist-induced disruptions to gamma oscillations and (2) attenuate NMDAr antagonist-induced disruptions to PPI. We hypothesized that antipsychotic-mediated improvement of PPI deficits would be accompanied by a normalization of gamma oscillatory activity. Wistar rats were implanted with extradural electrodes to facilitate recording of electroencephalogram during PPI behavioural testing. In each session, the rats were administered haloperidol (0.25 mg kg(-1)), clozapine (5 mg kg(-1)), olanzapine (5 mg kg(-1)), LY379268 (3 mg kg(-1)), NFPS (sarcosine, 1 mg kg(-1)), d-serine (1800 mg kg(-1)) or vehicle, followed by the NMDAr antagonists MK-801(0.16 mg kg(-1)), ketamine (5 mg kg(-1)) or vehicle. Outcome measures were auditory-evoked, as well as ongoing, gamma oscillations and PPI. Although treatment with all the clinically validated antipsychotic drugs reduced ongoing gamma oscillations, clozapine was the only compound that prevented the sensory-evoked gamma deficit produced by ketamine and MK-801. In addition, clozapine was also the only antipsychotic that attenuated the disruption to PPI produced by the NMDAr antagonists. We conclude that disruptions to evoked, but not ongoing, gamma oscillations caused by NMDAr antagonists are functionally relevant, and suggest that compounds, which restore sensory-evoked gamma oscillations may improve sensory processing in patients with schizophrenia.

That said, I really want to avoid using clozapine again! Would have been interesting to see if other SGAs augmented with NMDAR glycine site agonists etc  performed any better.

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6 thoughts on “Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine. (2016)

  1. This is a long overdue apology but I thought I would still do it. I wasn’t sure how to contact you. I’m sorry for being very odd, around this time last year, I’m sorry for panicking and freaking out. I was in a rough patch. Sorry that this is so out of the blue, I am trying to mend some of my mistakes. I hope it is all going well for you!

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    • Hi – so wonderful to hear from you! Thank you for your very kind apology but it’s not needed – you did nothing wrong. Nothing is odd to me, it’s all interesting and a valid learning experience. Much gratitude for your friendship at the time and for getting back in contact, thank you for supporting me during my rough patch. How are you going at present?

      I’m in a much better place than I was.

      I can be contacted at rohtech@live.com or you’re welcome to add me on facebook: https://www.facebook.com/nick.rohde.7

      Best wishes!

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      • I should also say that a lot has changed for me. My psychiatrist thought it wasn’t schizophrenia, but OCD. It is an odd feeling. That you are classified as one thing and then another. Pushed into different categories, whatever will suit your issues. It has been about five months since then. It has made me feel more at ease. I hope you are doing well, and that everything works out well for you.

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      • I can relate to the limbo of diagnosis… I still live in a grey zone but I’ve realised the lack of solace I personally find in belonging to a ‘diagnosis’ which I feel you can relate to – most of my issues are likely stemming from poor life choices rather than ‘true schizophrenia’ which I’ve started to accept. I’ve recently had comorbid OCD thrown at me and developed tics which is a bit scary personally. My feeling is definitely don’t be defined by diagnosis, whatever it is. Be you! I wish you all the best on your journey. Take care.

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  2. Thanks for your kind words. What are you getting up to these days? I’d really love to connect, don’t hesitate to get in contact if you ever need to talk!

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