A clinical trial of adjunctive oestrogen treatment in women with schizophrenia

Kulkarni, J; Riedel, Axel; Castella, Anthony R. de; Fitzgerald, Paul B.; Rolfe, T.; Taffe, John Raymond; Burger, Henry G.

doi:10.1007/s00737-002-0001-5

Cited by 58 publications

(36 citation statements)

References 14 publications

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“…A few studies have suggested a relationship between estrogen and negative symptoms in schizophrenia. Kulkarni et al [19,31] showed that estradiol adjuvant treatment with antipsychotics has a beneficial effect on positive symptoms, and partially on negative symptoms in women with the acute phase of schizophrenia. Interestingly, in a study on postmenopausal schizophrenia, Lindamer et al [18] showed that HRT users received lower average daily doses of antipsychotic medication, and that they had less severe negative symptoms compared with women who did not use HRT.…”

Section: Discussionmentioning

confidence: 99%

Estrogen, Cognitive Function and Negative Symptoms in Female Schizophrenia

Joe

Cho

et al. 2006

Neuropsychobiology

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The aim of this study was to evaluate the relationship of serum reproductive hormone levels with cognitive function and negative symptoms in schizophrenic women during the follicular phase of the menstrual cycle. Thirty-five women with chronic schizophrenia who had minimal positive symptoms participated in this study. We evaluated the correlation of serum reproductive hormone levels with the Scale for the Assessment of Negative Symptoms (SANS) and cognitive function tests such as the Immediate Visual Recognition Scale, Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Tests A and B, and Digit Symbol Test. The patients were divided into two subgroups (low estradiol group and normal estradiol group) using the normal serum reference range for estradiol. Significant correlation between SANS subcategories, such as Alogia and Attention Impairment, and estradiol were found. Moreover, significant relationships between the estradiol level and the Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Test B and Digit Symbol Test were observed. In the low estradiol group, the SANS scores, except for Anhedonia-Asociality and Avolition-Apathy, were significantly higher than those in the normal estradiol group. Patients in the low estradiol group had a significantly lower performance in the cognitive function tests, except Visual Recognition Scale, when compared to patients in the normal estradiol group. These results suggest that for schizophrenic women of reproductive age, lower levels of estrogen are associated with more severe negative symptomatology as well as reduced performance in cognitive function, especially verbal performance and executive functioning.

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Section: Discussionmentioning

confidence: 99%

Estrogen, Cognitive Function and Negative Symptoms in Female Schizophrenia

Joe

Cho

et al. 2006

Neuropsychobiology

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“…Males typically have an earlier age of onset and more severe symptoms and tend to be less treatment responsive than females with schizophrenia (3). However, women with schizophrenia can have symptom exacerbation at times of low estrogen: during post-partum and menopause (4 -6), and schizophrenic symptoms can be ameliorated with estrogen treatment (7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Transcriptional Interaction of an Estrogen Receptor Splice Variant and ErbB4 Suggests Convergence in Gene Susceptibility Pathways in Schizophrenia

Wong

Weickert

2009

Journal of Biological Chemistry

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Mounting evidence from clinical and basic research suggests that estrogen signaling may be altered in the brains of people with schizophrenia. Previously, we found that DNA sequence variation in the estrogen receptor (ER) ␣ gene, lower ER␣ mRNA levels, and/or blunted ER␣ signaling is associated with schizophrenia. In this study, we asked whether the naturally occurring truncated ER␣ isoform, ⌬7, which acts as a dominant negative, can attenuate gene expression induced by the wildtype (WT) receptor in an estrogen-dependent manner in neuronal (SHSY5Y) and non-neuronal (CHOK1 and HeLa) cells. In addition, we determined the extent to which ER␣ interacts with NRG1-ErbB4, a leading schizophrenia susceptibility pathway. Reductions in the transcriptionally active form of ErbB4 comprising the intracytoplasmic domain (ErbB4-ICD) have been found in schizophrenia, and we hypothesized that ER␣ and ErbB4 may converge to control gene expression. In the present study, we show that truncated ⌬7-ER␣ attenuates WT-ER␣-driven gene expression across a wide range of estrogen concentrations in cells that express functional ER␣ at base line or upon co-transfection of full-length ER␣. Furthermore, we find that ErbB4-ICD can potentiate the transcriptional activity of WT-ER␣ at EREs in two cell lines and that this potentiation effect is abolished by the presence of ⌬7-ER␣. Immunofluorescence microscopy revealed nuclear co-localization of WT-ER␣, ⌬7-ER␣, and ErbB4-ICD, whereas immunoprecipitation assays showed direct interaction. Our findings demonstrate convergence between ER␣ and ErbB4-ICD in the transcriptional control of ER␣-target gene expression and suggest that this may represent a convergent pathway that may be disrupted in schizophrenia.Schizophrenia is a devastating mental illness of unknown cause, afflicting 1% of the population worldwide. At present, the molecular processes underlying the development and progression of schizophrenia have not been clearly identified; however, we have recently found evidence to support the hypothesis that schizophrenia arises from a derailment of normal brain maturation during adolescence where the brain fails to respond to the developmental increase in sex steroids (testosterone and estrogen) (1). Testosterone is commonly converted into estrogen by the action of the enzyme aromatase whereby the converted hormone serves as a ligand for estrogen receptors. Schizophrenia affects both men and women occurring at a ratio of ϳ3:2, respectively (2). Males typically have an earlier age of onset and more severe symptoms and tend to be less treatment responsive than females with schizophrenia (3). However, women with schizophrenia can have symptom exacerbation at times of low estrogen: during post-partum and menopause (4 -6), and schizophrenic symptoms can be ameliorated with estrogen treatment (7-11).Estrogen affects the developing brain by influencing the genesis, development, migration, plasticity, and survival of neurons (12-16). Estrogen has also been shown to act as a trophic factor promoting the grow...

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“…The authors recommended future trials as their n of 214 was too small for clinical application. The majority of the studies were done by Kulkari, in 2001 [21], 2002 [22] and 2008 [23]. These were all done using unopposed estrogen as an adjunct to neuroleptics over a 28 day period to treat acute psychosis in women with an average age of 32-34(much younger than our cases).…”

Section: Etiology Of Schizophrenia Presenting During Menopausal Transmentioning

confidence: 97%

“…Usual treatments are oral estradiol 1 mg daily or equine estrogen 0.625 mg daily or weekly patch with estradiol 0.05 mg/daily. Additionally, these formulations of estrogen were found to be effective in the studies of women with schizophrenia [21][22][23].…”

Section: Ert: Women Without a Uterusmentioning

confidence: 99%

Schizophrenia during Menopausal Transition

Crow¹,

Jasberg²

2016

Ment Health Fam Med

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Case 3Patient 3 is a 58 y/o woman with 2 months of delusional thinking. According to her family, she was disorganized and unsafe in the home. She called police due to paranoid delusions and requested admission for her safety. She declined medication. She felt that her family was plotting against her and that people were watching her through hospital windows. Her husband reported that when she was entering menopause, she had a very similar episode where she became delusional and paranoid, and acted on delusional content. She was treated at an outside hospital for depression at that time, and stabilized on citalopram. She then was stable without medication for 5 years, until two months prior to this presentation. The result of her hospitalization was civil commitment for psychiatric treatment and olanzapine therapy, which was effective. She declined a first episode workup, and did not offer a reproductive history. The patient was not pregnant nor on hormone replacement therapy.

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A clinical trial of adjunctive oestrogen treatment in women with schizophrenia

Cited by 58 publications

References 14 publications

Estrogen, Cognitive Function and Negative Symptoms in Female Schizophrenia

Estrogen, Cognitive Function and Negative Symptoms in Female Schizophrenia

Transcriptional Interaction of an Estrogen Receptor Splice Variant and ErbB4 Suggests Convergence in Gene Susceptibility Pathways in Schizophrenia

Schizophrenia during Menopausal Transition

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