Key result
AUT00206 significantly increased reward anticipation-related neural activation in the left associative striatum compared to baseline in male patients with schizophrenia.
Why the study?
Schizophrenia involves abnormal reward processing linked to striatal dysfunction, and targeting Kv3.1/3.2 channels on GABAergic interneurons was hypothesized to augment striatal function during reward processing.
Does AUT00206 improve reward anticipation-related striatal activation in patients with schizophrenia?
RCT (n=24)
Double-blind
2:1 ratio
Yes
Does AUT00206 improve reward anticipation-related striatal activation in patients with schizophrenia?
AUT00206, a Kv3.1/3.2 potassium channel modulator, may improve reward-related striatal abnormalities in patients with schizophrenia.
Answers are grounded in this paper and cite their sources.
May inform GABA-targeted interventions in schizophrenia; leaves open causal role of striatal interneurons in reward deficits.
The pathophysiology of schizophrenia involves abnormal reward processing, thought to be due to disrupted striatal and dopaminergic function. Consistent with this hypothesis, functional magnetic resonance imaging (fMRI) studies using the monetary incentive delay (MID) task report hypoactivation in the striatum during reward anticipation in schizophrenia. Dopamine neuron activity is modulated by striatal GABAergic interneurons. GABAergic interneuron firing rates, in turn, are related to conductances in voltage-gated potassium 3.1 (Kv3.1) and 3.2 (Kv3.2) channels, suggesting that targeting Kv3.1/3.2 could augment striatal function during reward processing. Here, we studied the effect of a novel potassium Kv3.1/3.2 channel modulator, AUT00206, on striatal activation in patients with schizophrenia, using the MID task. Each participant completed the MID during fMRI scanning on two occasions: once at baseline, and again following either 4 weeks of AUT00206 or placebo treatment. We found a significant inverse relationship at baseline between symptom severity and reward anticipation-related neural activation in the right associative striatum ( r = -0.461, p = 0.035). Following treatment with AUT00206, there was a significant increase in reward anticipation-related activation in the left associative striatum (t (13) = 4.23, peak-level p (FWE) < 0.05)), but no significant effect in the ventral striatum. This provides preliminary evidence that the Kv3.1/3.2 potassium channel modulator, AUT00206, may address reward-related striatal abnormalities in schizophrenia.
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Kaar et al. (2022) conducted an RCT in Schizophrenia (n=24). AUT00206 vs. Placebo was evaluated on Change in reward anticipation-related activation in the associative striatum (fMRI BOLD activation) (p=0.04). AUT00206 significantly increased reward anticipation-related neural activation in the left associative striatum compared to baseline in male patients with schizophrenia.
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