Expert Q&A

Challenges, Controversies in the Diagnosis of Schizophrenia

Treatment options for patients with schizophrenia focus on the management of symptoms, improving daily functionality, and achieving educational, career, and relationship goals. Antipsychotic medications, psychosocial treatments, care partner education and support, coordinated specialty care, assertive community treatment, and treatment for drug and alcohol misuse can help a patient manage the symptoms of schizophrenia and find solutions to everyday challenges.1

W. Clay Jackson, MD, DipTh, discusses some of the controversies surrounding the diagnosis of schizophrenia and strategies for the best practices in the management of schizophrenia. Dr Jackson is an assistant professor of clinical psychiatry and family medicine at the University of Tennessee College of Medicine in Memphis, Tennessee.

Consultant360: What are the positive symptoms of schizophrenia? 

W. Clay Jackson, MD: The positive symptoms of schizophrenia are noticeable disruptions in thought, speech, and behavior, expressed as delusions and/or hallucinations, incoherence, and gross disorganization.

C360: What are the negative symptoms of schizophrenia?

Dr Jackson: The negative symptoms of schizophrenia center around diminished expression and motivation. Patients will typically exhibit poverty of speech, affective flattening, apathy, asociality, and/or hedonic deficits. Whereas the positive symptoms usually are more striking, the negative symptoms can be equally troublesome, and historically have been more difficult to manage.

C360: There are therapeutic challenges in patients with schizophrenia. What are they?

Dr Jackson: Recent research into the natural history of schizophrenia has shown that developmental abnormalities often predate the presenting episode of psychosis that typically results in diagnosis. There is hope that an earlier diagnosis might result in more timely treatment, which could prevent or reduce the severity of alterations in brain structure and function that accompany the advanced disease. Once diagnosed, pharmacologic treatment is much more effective for positive symptoms than for negative symptoms, but negative symptoms cause a great deal of distress and disability for patients. Traditional antipsychotic medications are often associated with significant adverse events, including movement disorders and metabolic changes. In addition to the diagnostic and pharmacotherapeutic challenges to treatment, persons with schizophrenia often require a complex system of interdisciplinary support to maximize their potential, and our current health care system is not well-designed to deliver such interdisciplinary care and community support.

C360: Is exercise beneficial in the prevention and treatment of schizophrenia disorders? If so, what is the benefit?

Dr Jackson: Persons with schizophrenia have an increased risk of cardiovascular disease, metabolic syndrome, obesity, hypertension, and hyperlipidemia compared with the general population. Therefore, aerobic exercise should improve overall health, and multiple studies have shown these effects. In addition, studies have shown a benefit for psychiatric symptoms (both positive and negative), and for patients' perception of their own wellness. In terms of prevention, there are intriguing signals from preclinical research that low-intensity exercise training may prevent the incidence of some types of schizophrenia behaviors; the implications for the natural history of schizophrenia in humans is not completely understood.

C360: Is schizophrenia more common among men or women? Can you provide some context?

Dr Jackson: Multiple studies have indicated about a 40% greater risk of developing schizophrenia for men vs women. Researchers have attempted to explain this epidemiological finding by several hypotheses, noting genetic differences in dopamine and GABA processing, hormonal differences, and changes in the rates of early life adversity and subsequent responses.

 C360: Please discuss the controversies in the diagnosis and management of patients with schizophrenia. For example, the controversies in cannabis use, childhood adversity as a causative factor, and progressive brain change in the onset of schizophrenia.

Dr Jackson: With respect to controversies in diagnosis, the gender disparity in prevalence has been challenged. More recent research has demonstrated that, unlike men, who show a single peak of incidence and more severe disease, women have a bimodal distribution of incidence, with milder severity and more predominance of depressive symptoms. This pattern of onset, quality of symptom severity, and distribution may have led historically to under- and misdiagnosis of schizophrenia in women.

For a time, many experts minimized the importance of environmental factors in the development of schizophrenia, in favor of a genetic hypothesis. However, subsequent research has demonstrated a strong correlation between childhood traumatic experiences and the development of multiple psychiatric conditions, including schizophrenia, in a dose-response relationship. The recent increase in the understanding of epigenetic effects (eg, DNA methylation of brain-derived neurotrophic factor) has led to the development of a more complete hypothesis, which accounts for both genetic and environmental factors.

Among vulnerable persons, heavy cannabis use has been associated with nearly a 4-fold risk of the development of schizophrenia. Correlation is, of course, not causality, and causal links have been difficult to establish. However, given the dose-response relationship, harm reduction efforts are warranted.

The emerging understanding of the neurodevelopmental changes associated with schizophrenia has undermined a simplistic model of schizophrenia as a neurodegenerative disorder in the classical sense. Although imaging abnormalities are demonstrable after diagnosis, it is unknown which of these findings reflect contributory or compensatory mechanisms, and the observed phenomena await a unifying model of pathophysiology.

C360: According to the World Health Organization, more than 2 out of 3 people with psychosis in the world do not receive specialist mental health care.2 What are the barriers?

Dr Jackson: Historically, the stigma of mental illness has limited access to care; however, this barrier has been reduced in many cultures globally. But even when diagnosis and treatment are desired, patients with mental health challenges are not evenly distributed around major medical centers in metropolitan areas, which is where the lion's share of psychiatrists are located. Recent advances in telehealth applications may help to mitigate geographic and logistical barriers. 

C360: Is there anything else you’d like to add?

Dr Jackson: We often focus on the unmet challenges in the diagnosis and treatment of patients with schizophrenia, as well we should. However, I think it is important to place these failures in the context of the tremendous advances that have been made in the lives of persons with schizophrenia compared with previous generations, when institutionalization, incarceration, and dehumanizing treatments (eg, lobotomy) were the foundation of societal response to severe mental illness. We have far to go in maximizing the human potential of those who suffer from this devastating disease, but we have come far, as well.


1. Schizophrenia. National Institution of Mental Health. Updated April 2022. Accessed July 26, 2022.

2. Schizophrenia. World Health Organization. January 10, 2022. Accessed July 26, 2022.