Sex Differences in Mood and Psychotic Disorders
By Brooklyn A. Bradley, BS; Medically edited by Dr. Deena E. Kuruvilla, MD
Mood is a conscious state of mind that we experience internally, and it affects how we behave externally in our environment. Mood disorders, also known as affective disorders, are characterized by a disruption in emotions. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classifies mood disorders further into two categories: bipolar disorders and depressive disorders (1). There are many different factors that influence how the brain portrays our feelings and emotions, encompassing biological, genetic, hormonal, psychosocial, and neuroimmunological areas of study (1). These same factors also play a role in the characteristic features of schizophrenia, which is a psychotic disorder involving disturbances in thought, perception, and behavioral tendencies (2). Today’s article will focus on the sex differences in the presentation of mood and psychotic disorders. It is essential to study the way in which males and females differ in their presentation of mood disorders. Once physicians establish the differences, and similarities, they can develop better screening procedures and treatments that are tailored to each gender – supporting the emergence of an era of personalized medicine (3).
Depression is a complex disorder that is characterized by sad mood, feelings of guilt, suicidal ideations, and damage to cognitive processes. The depressive disorder category of mood disorders includes recurrent depression and bipolar disorder, or manic-depressive disorder. Recurrent depression consists of major depression and dysthymia. The lifetime prevalence of major depression is approximately 5% to 17%. It has been discovered that women have almost twice the prevalence rate as men (1). This suggests that there may be biological factors in major depressive disorder, more specifically, a difference in the expression of mood-related genes between the sexes (4). The symptoms of major depressive episodes include change in weight, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness or excessive guilt, diminished ability to concentrate, and recurrent thoughts of death. Studies have shown that women have a higher incidence of depression with symptoms that cause distress, and have more anxious occurrences than men do (3).
It is important to differentiate schizophrenia and other psychotic disorders from bipolar disorder and severe depression (2). Delusions and hallucinations in psychotic disorders are the two main criteria that distinguish schizophrenia from mood disorders (2). Schizophrenia is a chronic and severe mental disorder affecting 20 million people worldwide, and it is one of the most intricate and least comprehended psychiatric disorders. Schizophrenia is characterized by alterations in thinking, perceptions, language, sense of self and behavior. The symptoms of schizophrenia can be further divided into two categories: positive symptoms and negative symptoms. Positive symptoms of this mental disorder indicate the presence of symptoms that add to the psyche or normal behavior, and these include hallucinations, delusions, confused thoughts, disorganized speech, trouble concentrating, and movement disorders. Negative symptoms indicate the absence of a normal behavior; these symptoms may manifest as lack of pleasure, trouble with speech, withdrawal, and struggles with the basics of daily life. It is essential to recognize the sex differences present in this disease, as several studies propose that the incidence of schizophrenia is higher in men, but women have more affective or mood-related symptoms. Age of schizophrenia onset is 3-5 years earlier for men than women (5). While men have earlier age at onset, women experience more affective symptoms and a late onset of the disease (5). Estrogen plays a major role in this process, and we can evaluate this relationship more clearly by studying the fluctuating levels of hormones during the menstrual and menopausal phases. In female schizophrenia patients, symptoms are severe in the low estrogen phase of the menstrual cycle, and there is reduced estrogen after menopause. On a more neuronal basis, male patients with schizophrenia have greater cortical variability in the frontal cortex of the brain (5).
It is crucial to investigate sex differences in the setting of disorders and diseases because they can reveal vital information about the susceptibility to and progression of diseases. Once sex-specific factors are identified, it may be able to protect one sex from a particular disease. This can therefore direct therapies and treatments to either protect both sexes from the disease or mitigate symptom expression (3). The way in which sex chromosome genes (X and Y genes) act in non-gonadal (not related to reproductive organs) tissues can provide information on a patient’s traits and likelihood of developing a disease. By studying the sex differences in mood disorders and addictive disorders, it opens the door to the realm of sex hormones and how therapies need to be targeted toward hormone-driven molecular pathways. The field of sex hormones and neurobiology warrants future research in order to support a model of personalized medicine, where each sex specific therapies that will target their unique symptom expression and hormone level secretion (3).
References:
- Sekhon S, Gupta V (2021) Mood Disorder. In: StatPearls. StatPearls Publishing, Treasure Island (FL)
- Hany M, Rehman B, Azhar Y, Chapman J (2021) Schizophrenia. In: StatPearls. StatPearls Publishing, Treasure Island (FL)
- Rainville JR, Hodes GE (2019) Inflaming sex differences in mood disorders. Neuropsychopharmacol 44:184–199. https://doi.org/10.1038/s41386-018-0124-7
- Seney ML, Sibille E (2014) Sex differences in mood disorders: perspectives from humans and rodent models. Biol Sex Differ 5:17. https://doi.org/10.1186/s13293-014-0017-3
- Li R, Ma X, Wang G, et al (2016) Why sex differences in schizophrenia? J Transl Neurosci (Beijing) 1:37–42