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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

Flow diagram of raloxifene treatment trial and confirmatory analysis.
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fig1: Flow diagram of raloxifene treatment trial and confirmatory analysis.

Mentions: In a 13-week, randomized, placebo-controlled, double-blind, cross-over trial, with a 1-week ‘wash-out' period, patients received 120 mg encapsulated raloxifene (2 × 60 mg, oral administration) daily in the active condition and oral administration of two placebo (lactose) capsules daily in the placebo condition as an adjunctive treatment to their current antipsychotic medication. Following treatment in the first 6-week phase, patients entered a 1-week wash-out followed by the second 6-week phase consisting of the alternate treatment (raloxifene or placebo). See Figure 1 for the study flow diagram. This study assessed a subset of patients who received the fMRI scan from the larger clinical trial of raloxifene (Weickert et al, 2015).


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)

Flow diagram of raloxifene treatment trial and confirmatory analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Flow diagram of raloxifene treatment trial and confirmatory analysis.
Mentions: In a 13-week, randomized, placebo-controlled, double-blind, cross-over trial, with a 1-week ‘wash-out' period, patients received 120 mg encapsulated raloxifene (2 × 60 mg, oral administration) daily in the active condition and oral administration of two placebo (lactose) capsules daily in the placebo condition as an adjunctive treatment to their current antipsychotic medication. Following treatment in the first 6-week phase, patients entered a 1-week wash-out followed by the second 6-week phase consisting of the alternate treatment (raloxifene or placebo). See Figure 1 for the study flow diagram. This study assessed a subset of patients who received the fMRI scan from the larger clinical trial of raloxifene (Weickert et al, 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