Schizophrenia Overview^[condition] and NIH Women's Health Research

Schizophrenia is a serious psychiatric disorder. Symptoms can vary between individuals, but they are typically categorized as psychotic (e.g., hallucinations, delusions, disorganized thinking), negative (e.g., loss of motivation or expression), or cognitive (e.g., problems with executive function, memory, or concentration).^{1 , 2} These symptoms can severely impact daily life, making it difficult for people with schizophrenia to form or maintain close relationships or remain employed. Comorbid conditions, including substance use disorder, anxiety, depression, and cardiovascular disease, are also common in affected individuals.^{2 , 3} The lifetime suicide risk among people with schizophrenia is nearly 5%.⁴

Schizophrenia appears to be the result of complex interactions between genetic and environmental factors. While certain genetic variants can greatly increase the risk of developing schizophrenia, this is a polygenic disorder that is caused by contributions from many different genes.² A 2022 genome-wide association study identified single-nucleotide polymorphisms on 120 different genes that are associated with a significant risk for schizophrenia.⁵ These genes were related to the functions of neurons—specifically, synaptic organization, differentiation, and transmission. Environmental factors (e.g., childhood abuse or neglect, exposure to violence, social isolation) can also alter gene expression through epigenetic effects.⁶ Some studies have suggested that similar risk factors for schizophrenia may confer different levels of risk in women and men. For example, physical abuse during childhood appears to be more strongly linked to the risk of developing schizophrenia in women.^{7 , 8}

The incidence of schizophrenia is generally lower among women than among men, and onset occurs several years later in women. The prevalence is different across life stages as well, with schizophrenia being diagnosed more often in women over the age of 40 years; this may be due to the changes in estrogen levels that are associated with menopause.^{2 , 8} When it comes to the presentation of the condition, women are more likely than men to show affective symptoms, such impulsivity and depression.^{8 , 9} In addition, women with schizophrenia are often victims of intimate partner violence; this risk is especially high during pregnancy.⁶

First- and second-generation antipsychotics can alleviate some of the symptoms of schizophrenia. The choice of which medications to use is based on factors such as disease severity, potential adverse effects, and patient preference. The treatment plan may also include psychosocial interventions (e.g., cognitive behavior therapy for psychosis, social skills training, employment services).² When treating women with schizophrenia, clinicians should be aware that life events that significantly alter hormone levels (e.g., pregnancy, lactation, menopause) can affect treatment and psychiatric stability.^{8 , 10}

The available antipsychotics are not equally effective for managing all the symptoms of schizophrenia, so identifying new treatment options and adjunctive therapies is an ongoing area of research.¹¹ Women with schizophrenia spectrum disorders experience more severe positive and negative symptoms and have a higher risk of psychotic relapse during the menopausal transition; these effects have been linked to decreasing estradiol levels. Hormone replacement therapy regimens that include estradiol may be effective treatments for women with schizophrenia before and after this transition.^{9 , 12} Because the long‐term use of estradiol may have adverse effects on breast and endometrial tissue, selective estrogen receptor modulators (e.g., raloxifene) are being evaluated as potential alternatives.^{9 , 11 , 13}

In 2020, the National Institute of Mental Health (NIMH) partnered with the Food and Drug Administration (FDA), the European Medicines Agency, and other organizations to launch the Accelerating Medicines Partnership program for Schizophrenia (AMP SCZ). AMP SCZ is working toward establishing an international research network for studies of people who are at high clinical risk of schizophrenia. Through these studies, AMP SCZ aims to identify biomarkers that can reliably predict an individual’s risk of psychosis and similar health issues, develop more effective treatments for schizophrenia, and improve methods for measuring treatment response.¹⁴ The data collected through this program can be found in the NIMH Data Archive.