A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings

Gogos, Andrea; Sbisa, Alyssa; Sun, Jeehae; Gibbons, Andrew S.; Udawela, Madhara; Dean, Brian

doi:10.1155/2015/615356

Cited by 177 publications

(142 citation statements)

References 218 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…Nearly 50% of women with SZ have irregular menses that are frequently associated with low levels of estradiol, although this is not associated with neuropsychological status [Gleeson et al, 2016]. There is ample evidence of the protective effect of estradiol against SZ as it interacts with neurotransmitters, enhances cognition and memory, and reverses the symptoms [Gogos et al, 2015]. Male patients have, indeed, lower levels of testosterone than healthy controls, with an inverse correlation between serum testosterone and negative symptoms [Ramsey et al, 2013;Sisek-Šprem et al, 2015].…”

Section: Other Featuresmentioning

confidence: 99%

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

et al. 2017

View full text Add to dashboard Cite

Schizophrenia (SZ) is a pervasive neurodevelopmental disorder that entails social and cognitive deficits, including marked language problems. Its complex multifactorial etiopathogenesis, including genetic and environmental factors, is still widely uncertain. SZ incidence has always been high and quite stable in human populations, across time and regardless of cultural implications, for unclear reasons. It has been hypothesized that SZ pathophysiology may involve the biological components that changed during the recent human evolutionary history, and led to our distinctive mode of cognition, which includes language skills. In this paper we explore this hypothesis, focusing on the self-domestication of the human species. This has been claimed to account for many human-specific distinctive traits, including aspects of our behavior and cognition, and to favor the emergence of complex languages through cultural evolution. The “domestication syndrome” in mammals comprises the constellation of traits exhibited by domesticated strains, seemingly resulting from the hypofunction of the neural crest. It is our intention to show that people with SZ exhibit more marked domesticated traits at the morphological, physiological, and behavioral levels. We also show that genes involved in domestication and neural crest development and function comprise nearly 20% of SZ candidates, most of which exhibit altered expression profiles in the brain of SZ patients, specifically in areas involved in language processing. Based on these observations, we conclude that SZ may represent an abnormal ontogenetic itinerary for the human faculty of language, resulting, at least in part, from changes in genes important for the domestication syndrome and primarily involving the neural crest.

show abstract

Section: Other Featuresmentioning

confidence: 99%

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Recent clinical studies have demonstrated that adjunct treatment with 17βestradiol and estrogen-based compounds ameliorate positive, negative and cognitive symptoms experienced by patients diagnosed with schizophrenia or depression [29][30][31][32][33][34] .…”

Section: Discussionmentioning

confidence: 99%

“…Despite these lines of evidence, the exact molecular and cellular mechanisms by which estrogens exert these beneficial effects are not well understood. The beneficial effects of 17β-estradiol in disorders such as SCZ and MDD have been proposed to occur through the modulation of monoamine transmitter systems such as dopamine and 5-HT, or via an anti-inflammatory mechanism 30,33,36,53 . However, increasing evidence suggests that the beneficial effects of 17β-estradiol may also be in part conferred through the modulation of glutamatergic signaling 27,35,36 .…”

Section: Discussionmentioning

confidence: 99%

“…The effect of 17β-estradiol, the principal biologically active estrogen, on cognition is thought to be driven, in part, by activation of specific signaling pathways resulting in alternations in dendritic spine number and the trafficking of key synaptic proteins (reviewed in 13). Recently, clinical studies have shown that treatment with 17β-estradiol has beneficial effects for patients diagnosed with SCZ or MDD, when given as an adjunct treatment to ongoing antipsychotic or antidepressant therapies [29][30][31][32][33][34] . However, the molecular and cellular mechanisms by which 17β-estradiol exert these beneficial effects are currently unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders

Erli

Palmos

Raval

et al. 2018

Preprint

View full text Add to dashboard Cite

Loss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic and cellular studies of SCZ and MDD using in vivo and in vitro systems have supported a key role for dysfunction of excitatory synapses in the pathophysiology of these disorders. Recent clinical studies have demonstrated that the estrogen, 17β-estradiol can ameliorate many of the symptoms experienced by patients. Yet, to date, our understanding of how 17β-estradiol exerted these beneficial effects is limited. In this study, we have tested the hypothesis that 17βestradiol can restore dendritic spine number in a cellular model that recapitulates the loss of synapses associated with SCZ and MDD. Ectopic expression of wildtype, mutant or shRNA-mediated knockdown of Disrupted in Schizophrenia (DISC1) reduced dendritic spine density in primary cortical neurons. Acute or chronic treatment with 17β-estradiol increased spine density to control levels in neurons with altered DISC1 levels. In addition, 17β-estradiol reduced the extent to which ectopic wildtype and mutant DISC1 aggregated. Furthermore, 17β-estradiol also caused the enrichment of synaptic proteins at synapses and increased the number of dendritic spines containing PSD-95 or that overlapped with the pre-synaptic marker bassoon.Taken together, our data indicates that estrogens can restore lost excitatory synapses caused by altered DISC1 expression, potentially through the trafficking of DISC1 and its interacting partners. These data highlight the possibility that estrogens exert their beneficial effects in SCZ and MDD in part by modulating dendritic spine number. S. performed all experiments and subsequent analysis. J.M., S.J.M. and P.P. produced or oversaw production of reagents; J.M., N.J.B., P.P. and D.P.S. wrote the manuscript.

show abstract

“…127 Evidence comes from its interaction with the major neurotransmitter systems implicated in schizophrenia, animal research suggesting it may enhance cognition and reverse deficits reflective of the symptom and cognitive deficits of schizophrenia, and from clinical trials demonstrating additive effects when combined with antipsychotics. Its potential in PR samples is unknown.…”

Section: Characteristics and Correlates Of Psychosis Riskmentioning

confidence: 99%

Progress and Future Directions in Research on the Psychosis Prodrome

Woodberry¹,

Shapiro²,

Bryant³

et al. 2016

Harvard Review of Psychiatry

View full text Add to dashboard Cite

The psychosis prodrome, or period of clinical and functional decline leading up to acute psychosis, offers a unique opportunity for identifying mechanisms of psychosis onset and testing early intervention strategies. We summarize major findings and emerging directions in prodromal research and provide recommendations for clinicians working with individuals suspected to be at high risk for psychosis. The past two decades of research have led to three major advances. First, tools and criteria have been developed that can reliably identify imminent risk for a psychotic disorder. Second, longitudinal clinical and psychobiological data from large multisite studies are strengthening individual risk assessment and offering insights into potential mechanisms of illness onset. Third, psychosocial and pharmacological interventions are demonstrating promise for delaying or preventing the onset of psychosis in help-seeking, high-risk individuals. The dynamic psychobiological processes implicated in both risk and onset of psychosis, including altered gene expression, cognitive dysfunction, inflammation, gray and white matter brain changes, and vulnerability-stress interactions suggest a wide range of potential treatment targets and strategies. The expansion of resources devoted to early intervention and prodromal research worldwide raises hope for investigating them. Future directions include identifying psychosis-specific risk and resilience factors in children, adolescents, and non-help-seeking community samples, improving study designs to test hypothesized mechanisms of change, and intervening with strategies that better engage youth, their environmental contexts, and neurodevelopmental targets to improve functional outcomes. Prospective research on putatively prodromal samples has the potential to substantially reshape our understanding of mental illness and our efforts to combat it.

show abstract

A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings

Cited by 177 publications

References 218 publications

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders

Progress and Future Directions in Research on the Psychosis Prodrome

Contact Info

Product

Resources

About