What is schizophrenia and how does it manifest?
Schizophrenia is a form of chronic mental illness that plagues around 20 million people worldwide, often intruding on an individual’s ability to function normally in social, educational, and occupational settings. Symptoms of schizophrenia are categorized into two types, positive and negative. Positive symptoms encompass the presence of ideas and perceptions that are not visible to others without the disorder. These symptoms can include hallucinations, delusions, disorganized thought and speech, movement disorders, and attention and memory difficulties. The negative symptoms are the symptoms that result due to an absence of normal cognitive, behavioral, and perceptual functioning. Negative symptoms can include hopelessness, social withdrawal, absence of pleasure or excitement, and a lowered ability to function at a normal standard in various settings within one’s life.
What is the science behind schizophrenia?
As the symptoms of schizophrenia can undoubtedly reduce the quality of an individual’s life, there is a great demand for expanded research and experimentation that explores the etiology, genetic and environmental risk factors, and potential treatments of this mental disorder. In the literature article titled, “An emerging role for Wnt and GSK3 signaling pathways in schizophrenia,” authors Jacques L. Michaud and Olivier Pourquie discuss the role of various pathways in the brain and how disruption of these pathways can lead to the development of schizophrenia. An example of a disrupted pathway is the overactivation of the dopamine pathway and its ability to potentiate the development and effects of schizophrenia. In this context, the neurotransmitter dopamine binds to its inhibitory receptor, called a D2 receptor, in the brain. When dopamine binds to the D2 receptor, the enzyme glycogen synthase kinase 3 (GSK3) is activated and destroys a protein called beta-catenin. This protein is responsible for the initiation of the transcription process of key developmental genes that aid in cognitive and social functioning. However, when excess dopamine binding results in the destruction of this beta-catenin protein and a lack of transcription of important developmental genes, schizophrenia and its associated symptoms can arise. Therefore, the dopamine pathway plays a primary target for antipsychotics and other treatments in the hopes of minimizing the symptoms of schizophrenia.
So, where does estrogen come in?
Through the use of animal studies, it has been shown that the reproductive hormone estrogen plays a role in the regulation of these dopaminergic pathways. The findings of these experiments showed that estrogen reduced both the levels and activity of D2 receptors in the nucleus accumbens and caudate nucleus regions of the brain. Without lowered levels of D2 receptor activation by way of estrogen, GSK3 is active and consequently results in beta-catenin protein degradation. This event leads to the lack of transcription of key developmental genes, resulting in some of the cognitive deficits found in schizophrenia, as mentioned above.
Estrogen levels are low during various biological events, including the menstrual phase of the menstrual cycle, postpartum period, and throughout menopause. During these times, women are therefore more likely to experience more severe psychotic episodes of schizophrenia due to the lack of sufficient estrogen in its action of blocking dopamine receptors. As a result, estrogen therapy is emerging as a promising option for treatment of schizophrenia in both men and women, as it has shown to reduce the severity of symptoms. Supplemental estrogen has also been shown to increase the effectiveness of antipsychotic drugs, as many of these drugs also result in the inhibition of the dopaminergic pathway.
Men and estrogen?
An interesting and potentially controversial finding is that men who have been diagnosed with schizophrenia have lower levels of estrogen than men without the disorder. Estrogen therapy is therefore a legitimate form of treatment for men as well as women. However, it seems unlikely that all men would view estrogen therapy as a treatment option they would consider, as there is a common misconception that this supplemental estrogen would promote the development of female characteristics in men. However, estrogen therapy for schizophrenia is administered at a far lower dose than the estrogen used for the development of secondary female characteristics. Despite scientific evidence that proves that estrogen as a treatment in the context of schizophrenia will not promote “feminisation” of men, it is quite difficult to convince men to utilize this form of treatment due to this unfortunate myth.
Looking ahead
Estrogen therapy in a clinical setting proves itself to be an encouraging option in the future of treatment for schizophrenia. Estrogen supplementation in low doses undermines the intense severity of many of the symptoms of schizophrenia, without causing the potentially damaging side effects that arise with traditional antipsychotic drug use. However, myths and stereotypes regarding the “feminisation” of men continue to serve as an obstacle in the treatment of men using this hormone. Continued research and experimentation will be extremely helpful in both minimizing the prevalence of the myths surrounding estrogen therapy in men and understanding the potential of estrogen to increase the quality of life for those struggling with schizophrenia.
Abstract/Featured Image created by S. Wiger
