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Selective Estrogen Receptor Modulation Increases Hippocampal Activity during Probabilistic Association Learning in Schizophrenia.

Kindler J, Weickert CS, Skilleter AJ, Catts SV, Lenroot R, Weickert TW - Neuropsychopharmacology (2015)

Bottom Line: A separate region of interest confirmatory analysis in 21 patients vs 36 healthy controls showed a positive association between parahippocampal neural activity and learning in patients, but no such relationship in the parahippocampal gyrus of healthy controls.Thus, selective estrogen receptor modulation by raloxifene concurrently increases activity in the parahippocampal gyrus and improves probabilistic association learning in schizophrenia.These results support a role for estrogen receptor modulation of mesial temporal lobe neural activity in the remediation of learning disabilities in both men and women with schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: 1] School of Psychiatry, University of New South Wales, Randwick, NSW, Australia [2] Neuroscience Research Australia, Randwick, NSW, Australia [3] Department of Psychiatric Neurophysiology, University of Bern, Bern, Switzerland.

ABSTRACT
People with schizophrenia show probabilistic association learning impairment in conjunction with abnormal neural activity. The selective estrogen receptor modulator (SERM) raloxifene preserves neural activity during memory in healthy older men and improves memory in schizophrenia. Here, we tested the extent to which raloxifene modifies neural activity during learning in schizophrenia. Nineteen people with schizophrenia participated in a twelve-week randomized, double-blind, placebo-controlled, cross-over adjunctive treatment trial of the SERM raloxifene administered orally at 120 mg daily to assess brain activity during probabilistic association learning using functional magnetic resonance imaging (fMRI). Raloxifene improved probabilistic association learning and significantly increased fMRI BOLD activity in the hippocampus and parahippocampal gyrus relative to placebo. A separate region of interest confirmatory analysis in 21 patients vs 36 healthy controls showed a positive association between parahippocampal neural activity and learning in patients, but no such relationship in the parahippocampal gyrus of healthy controls. Thus, selective estrogen receptor modulation by raloxifene concurrently increases activity in the parahippocampal gyrus and improves probabilistic association learning in schizophrenia. These results support a role for estrogen receptor modulation of mesial temporal lobe neural activity in the remediation of learning disabilities in both men and women with schizophrenia.

No MeSH data available.


Related in: MedlinePlus

Regions of activation and deactivation during probabilistic association learning in healthy controls and people with schizophrenia. One-sample t-tests, healthy controls (upper row) and people with schizophrenia (lower row), p<0.05, family-wise error rate (FWE) corrected. Activation and deactivation during probabilistic association learning—red-orange: activation; blue: deactivation. Upper row: Healthy controls, T=5.48, n=36, cluster size>20. Lower row: People with schizophrenia, T=5.43, n=21, cluster size>20.
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fig3: Regions of activation and deactivation during probabilistic association learning in healthy controls and people with schizophrenia. One-sample t-tests, healthy controls (upper row) and people with schizophrenia (lower row), p<0.05, family-wise error rate (FWE) corrected. Activation and deactivation during probabilistic association learning—red-orange: activation; blue: deactivation. Upper row: Healthy controls, T=5.48, n=36, cluster size>20. Lower row: People with schizophrenia, T=5.43, n=21, cluster size>20.

Mentions: Results of the one-sample t-tests for healthy controls vs patients are shown in Figure 3 and Supplementary Table S4. During probabilistic association learning healthy controls predominantly activated the dorsolateral prefrontal cortex, the occipital cortex, the parietal cortex, and the basal ganglia (striatum). Deactivations in the healthy control group were detected in the lateral and medial temporal lobe, the hippocampus, and the medial frontal lobe. Patients activated the dorsolateral prefrontal cortex, the occipital cortex, and the parietal cortex to a lesser extent, whereas no significant activations were detected in the basal ganglia/striatum.


Selective Estrogen Receptor Modulation Increases Hippocampal Activity during Probabilistic Association Learning in Schizophrenia.

Kindler J, Weickert CS, Skilleter AJ, Catts SV, Lenroot R, Weickert TW - Neuropsychopharmacology (2015)

Regions of activation and deactivation during probabilistic association learning in healthy controls and people with schizophrenia. One-sample t-tests, healthy controls (upper row) and people with schizophrenia (lower row), p<0.05, family-wise error rate (FWE) corrected. Activation and deactivation during probabilistic association learning—red-orange: activation; blue: deactivation. Upper row: Healthy controls, T=5.48, n=36, cluster size>20. Lower row: People with schizophrenia, T=5.43, n=21, cluster size>20.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4538353&req=5

fig3: Regions of activation and deactivation during probabilistic association learning in healthy controls and people with schizophrenia. One-sample t-tests, healthy controls (upper row) and people with schizophrenia (lower row), p<0.05, family-wise error rate (FWE) corrected. Activation and deactivation during probabilistic association learning—red-orange: activation; blue: deactivation. Upper row: Healthy controls, T=5.48, n=36, cluster size>20. Lower row: People with schizophrenia, T=5.43, n=21, cluster size>20.
Mentions: Results of the one-sample t-tests for healthy controls vs patients are shown in Figure 3 and Supplementary Table S4. During probabilistic association learning healthy controls predominantly activated the dorsolateral prefrontal cortex, the occipital cortex, the parietal cortex, and the basal ganglia (striatum). Deactivations in the healthy control group were detected in the lateral and medial temporal lobe, the hippocampus, and the medial frontal lobe. Patients activated the dorsolateral prefrontal cortex, the occipital cortex, and the parietal cortex to a lesser extent, whereas no significant activations were detected in the basal ganglia/striatum.

Bottom Line: A separate region of interest confirmatory analysis in 21 patients vs 36 healthy controls showed a positive association between parahippocampal neural activity and learning in patients, but no such relationship in the parahippocampal gyrus of healthy controls.Thus, selective estrogen receptor modulation by raloxifene concurrently increases activity in the parahippocampal gyrus and improves probabilistic association learning in schizophrenia.These results support a role for estrogen receptor modulation of mesial temporal lobe neural activity in the remediation of learning disabilities in both men and women with schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: 1] School of Psychiatry, University of New South Wales, Randwick, NSW, Australia [2] Neuroscience Research Australia, Randwick, NSW, Australia [3] Department of Psychiatric Neurophysiology, University of Bern, Bern, Switzerland.

ABSTRACT
People with schizophrenia show probabilistic association learning impairment in conjunction with abnormal neural activity. The selective estrogen receptor modulator (SERM) raloxifene preserves neural activity during memory in healthy older men and improves memory in schizophrenia. Here, we tested the extent to which raloxifene modifies neural activity during learning in schizophrenia. Nineteen people with schizophrenia participated in a twelve-week randomized, double-blind, placebo-controlled, cross-over adjunctive treatment trial of the SERM raloxifene administered orally at 120 mg daily to assess brain activity during probabilistic association learning using functional magnetic resonance imaging (fMRI). Raloxifene improved probabilistic association learning and significantly increased fMRI BOLD activity in the hippocampus and parahippocampal gyrus relative to placebo. A separate region of interest confirmatory analysis in 21 patients vs 36 healthy controls showed a positive association between parahippocampal neural activity and learning in patients, but no such relationship in the parahippocampal gyrus of healthy controls. Thus, selective estrogen receptor modulation by raloxifene concurrently increases activity in the parahippocampal gyrus and improves probabilistic association learning in schizophrenia. These results support a role for estrogen receptor modulation of mesial temporal lobe neural activity in the remediation of learning disabilities in both men and women with schizophrenia.

No MeSH data available.


Related in: MedlinePlus