This chapter explores the historical evolution of the nomenclature of schizophrenia and the shift towards understanding it as a multi-systemic disease state with significant physical health implications. It highlights the elevated prevalence of cardiometabolic disorders in individuals with schizophrenia, including obesity, diabetes, metabolic syndrome, and liver diseases. These conditions not only contribute to overall illness burden and morbidity but also exacerbate the underlying brain disturbance in schizophrenia. The chapter emphasizes the need for integrated care that prioritizes both mental and physical health to address the disparities in healthcare access and outcomes faced by individuals with schizophrenia. It calls for frameworks of care and prevention, supported by adequate funding and access to high-quality care, to address the treatable and preventable cardiometabolic disorders that significantly impact the quality and duration of life for those living with schizophrenia.

Schizophrenia is known to be a disabling psychiatric condition with wide reaching impact on everyday functioning and outcomes. These functional outcomes include increases in all-cause mortality (especially suicide and injury), cognitive and functional capacity deficits, lower reported levels of quality of life, increased incarceration, higher risk for violence and victimization, and homelessness. Studies have shown that medications and outpatient services can improve each of these functional outcomes in individuals with schizophrenia. However, most studies of pharmacological treatment utilize rating scales which do not reflect the real-world outcomes. This review looks at available studies focused on real-world outcomes and argues for an expansion of this body of research.

This chapter explores the phenomenon of anosognosia—unawareness of illness—in individuals with schizophrenia and related serious mental illnesses (SMI). Drawing on decades of research, Amador argues that anosognosia is not a psychological defense or denial but a neurobiological symptom resulting from brain dysfunction. The chapter critiques the use of the term “insight” and advocates for the more accurate and neutral term “anosognosia.” It reviews the etiology, prevalence, and clinical consequences of this symptom, including treatment nonadherence, increased hospitalization, and criminalization. Amador introduces the Scale to Assess Unawareness of Mental Disorder (SUMD) and other multidimensional tools for assessing anosognosia. The chapter also presents the LEAP (Listen, Empathize, Agree, Partner) communication strategy as an evidence-based, non-confrontational method to build trust and improve treatment adherence in patients with anosognosia. Finally, the chapter discusses the ethical and legal implications of involuntary treatment, emphasizing the need for compassionate, informed approaches that balance civil liberties with the realities of impaired decision-making capacity in SMI.

Anosognosia, defined as a lack of knowledge of the disease, was originally identified in neurological disorders and is common in schizophrenia. These deficits are commonly referred to as “lack of insight” or “unawareness of illness.” They include challenges in accurate judgments of the reality of experience, as well as global and specific personal abilities. Related to inaccuracies in self-assessment are response biases when an incorrect self-assessment is made. We adopted a perspective focused on Introspective Accuracy (IA) and Introspective Bias (IB). IA is the ability to accurately judge several domains of experience and functioning. These include the reality of clinical symptoms, the experience of mood states, momentary competence in the performance of cognitive assessments and everyday functional skills, and the ability to accurately anticipate the success of future performance. IB is the direction of response bias in the context of impairments in IA. Deficits in insight, judgment inaccuracies, and response bias are highly relevant as these difficulties come with downstream impacts including difficulties with treatment adherence, an increase in severity of symptoms, greater everyday disability, reduced response to cognitive training interventions, and a need for increased intensity of interventions to maintain community residence. In this article, we review the research in IA and IB in schizophrenia, including differences in momentary versus global self-assessments, and the clinical correlates and functional impacts of inaccurate self-assessments and response biases in the context of self-assessment errors. We also examine the existing data regarding the neurobiological basis of impairments in IA.

This review article explores the legislative differences across Canadian jurisdictions with respect to involuntary admission and treatment pending appeal. Some jurisdictions restrict involuntary admission for mental illness to when there is a risk for serious bodily harm or physical impairment. However, the majority of jurisdictions recognize non-bodily harms or substantial mental or physical deterioration as grounds for involuntary admission when other criteria are met. Once a person is involuntarily admitted, jurisdictions differ on how treatment is authorized and whether treatment can commence while a person contests a finding of incapacity to treatment to the courts. Some jurisdictions permit treatment pending appeal while others do not. This article compares Canadian jurisdictions’ mental health legislation and addresses discrepancies through the lens of the Canadian Charter of Rights and Freedoms and the Canada Health Act.

The chapter details the journey of Bethany Yeiser, an individual living with schizophrenia, from her promising academic and musical beginnings to her descent into homelessness and psychosis. Despite facing challenges such as delusions, hallucinations, and homelessness, Bethany eventually found help through involuntary hospitalization, leading to her recovery with the use of clozapine. The narrative highlights the lack of education and support for individuals with schizophrenia, emphasizing the importance of effective treatment and advocacy. Bethany’s experiences have inspired her to establish the CURESZ Foundation to provide education, advocacy, and support for those affected by schizophrenia, promoting hope and recovery for those in need.

The origins and treatment-target related mechanisms of schizophrenia remain to be more fully understood. Pharmacological and non-pharmacological treatments require expansion and improvements to meet more peoples’ needs and goals. Nevertheless, antipsychotics are a cornerstone when managing schizophrenia, being essential for reducing symptom severity, preventing relapse, improving long-term functional outcomes and reducing premature mortality risk. This narrative review synthesizes key evidence on the efficacy and risks associated with antipsychotic medications. The concept of effect sizes is introduced allowing to compare antipsychotics across trials with different ratings instruments and across different conditions. The available evidence in schizophrenia and comparison with medications used for medical conditions counters the sometimes voiced criticism that antipsychotics “do not work”. Instead, for a substantial group of people with schizophrenia, positive psychotic symptoms and global psychopathology improve with a medium effect size of about 0.4 vs. placebo. These results are comparable to median effect sizes across commonly used medications for somatic disorders. When patients with initial response are continued on antipsychotics, the effect size increases to 0.9 for relapse prevention, translating into a number-needed-to-treat of about three to prevent on more relapse versus no treatment. This number-needed-to-treat is 10-20 times higher than for the prevention of poor outcomes in some common medical conditions. Nevertheless, further development is needed regarding preventive interventions, the development of medications with mechanisms other than postsynaptic dopamine receptor blockade, with broader efficacy for positive, negative, cognitive, suicidality and/or reward dysregulation symptomatology, and the identification of illness mechanism/biomarker-targeting treatments to enhance treatment personalization.

Schizophrenia is a highly heterogenous disorder with substantial interindividual variationin how the illness is experienced and how it presents clinically. The disorder is composed of primary symptom clusters—positive symptoms, negative symptoms, disorganization, neurocognitive deficits, and social cognitive impairments. These, along with duration, severity, and excluding other possible etiologies, comprise the diagnostic criteria for the disorder outlined in the two commonly used diagnostic classification systems—the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition, Text Revision and the International Classification of Diseases, 11th Revision. These primary symptoms as well as accessory symptoms (mood disturbances, anxiety, violence) and comorbidities (substance use, suicidality) bear upon each other to varying degrees and impact functionaloutcomes. The following review presents two patient cases illustrating the clinical heterogeneity of schizophrenia, the natural history of the illness and diagnosis, followed by the current understanding of the primary symptom clusters, accessory symptoms, and comorbidities. In addition to noting symptom prevalence, onset, and change over time, attention is paid to the impact of symptoms on functional outcome.

Antipsychotics effective for schizophrenia approved prior to 2024 shared the common mechanismof postsynaptic dopamine D2 receptor antagonism or partial agonism. Positive psychosis symptoms correlate with excessive presynaptic dopamine turnover and release, yet this postsynaptic mechanism improved positive symptoms only in some patients, and with concomitant risk for off-target motor and endocrine adverse effects; moreover, these agents showed no benefit for negative symptoms and cognitive dysfunction. The sole exception was data supporting cariprazine’s superiority to risperidone for negative symptoms. The muscarinic M1/M4 agonist xanomeline was approved in September 2024 and represents the first of a new antipsychotic class. This novel mechanism improves positive symptoms by reducing presynaptic dopamine release. Xanomeline also lacks anyD2 receptor affinity and is not associated with motor or endocrine side effects. Of importance, xanomeline treated patients with higher baseline levels of cognitive dysfunction in clinical trials data saw cognitive improvement, a finding likely related to stimulation of muscarinicM1 receptors. Treatment resistance is seen in one-third of schizophrenia patients. These individuals do not have dopamine dysfunction underlying their positive symptoms, and therefore show limited response to antipsychotics that target dopamine neurotransmission. Clozapine remains the only medication with proven efficacy for resistant schizophrenia, and with unique benefits for persistent impulsive aggression and suicidality. New molecules are being studied to address the array of positive, negative and cognitive symptoms of schizophrenia; however, until their approval, clinicians must be familiar with currently available agents and be adept at prescribing clozapine.

Schizophrenia spectrum disorders are brain diseases that are developmental dementias (dementiapraecox). Their pathology begins in utero with psychosis most commonly becoming evident in adolescence and early adulthood. It is estimated they afflict the U.S. population at a prevalence rate of approximately 0.8%. Genetic studies indicate that these brain diseases are about 80% determined by genes and about 20%determined by environmental risk factors. Inheritance is polygenic with some 270 gene loci having been identified as contributing to the risk for schizophrenia. Interestingly, many of the identified gene loci and gene polymorphisms are involved in brain formation and maturation. The identified genetic and epigenetic risks give rise to a brain in which neuroblastsmigrate abnormally, assume abnormal locations and orientations, and are vulnerable to excessive neuronal and synaptic loss, resulting in overt psychotic illness. The illness trajectory of schizophrenia then is one of loss of brain mass related to the number of active psychotic exacerbations and the duration of untreated illness. In this context, molecules such as dopamine, glutamate, and serotonin play critical roles with respect to positive, negative, and cognitive domains of illness. Acutely, antipsychotics ameliorate active psychotic illness, especially positive signs and symptoms. The long-term effects of antipsychotic medications have been debated; however, the bulk of imaging data suggest that antipsychotics slow but do not reverse the illnesstrajectory of schizophrenia. Long-acting injectable antipsychotics (LAI) appear superior in this regard. Clozapine remains the “gold standard” in managing treatment-resistant schizophrenia.

This chapter explores the transformative potential of early intervention in schizophrenia, emphasizing its role in improving clinical, functional, and social outcomes. Through the poignant case of “Roger,” a man whose life was marked by untreated psychosis, homelessness, and missed opportunities for care, the chapter illustrates the consequences of delayed treatment and fragmented systems. It reviews epidemiological data, the importance of reducing the duration of untreated psychosis (DUP), and the neurobiological rationale for early-phase treatment. Models such as Coordinated Specialty Care (CSC), EPPIC, and Assertive Community Treatment (ACT) are discussed as effective frameworks for delivering comprehensive, multidisciplinary care. The chapter also addresses barriers to early intervention—including stigma, misdiagnosis, access limitations, and systemic inequities—and advocates for integrated, culturally responsive, and person-centered approaches. Ultimately, it calls for a shift in healthcare systems to prioritize early identification and treatment as a moral and clinical imperative.

This chapter delves into the ethical dimensions of treating individuals with schizophrenia, emphasizing the need for a new perspective that integrates neuroethics into interventions. The author proposes a bio-systemic model to understand how schizophrenia impacts different levels of consciousness and freedom, highlighting the necessity for tailored interventions that restore autonomy rather than coercive measures. The chapter calls for a shift in policy towards early and assertive treatment, focusing on rebuilding autonomy and dignity for individuals with schizophrenia. Ultimately, the chapter serves as a call to action for a neuroethically informed approach to care that prioritizes the restoration of freedom and dignity for those affected by schizophrenia.

This article provides an overview of individuals with schizophrenia who become unhoused and explores current approaches to managing this severe illness in those who often do not want care or believe they need it. Individuals with schizophrenia and who are unhoused face numerous adverse consequences including premature mortality and increased rates of suicide. There is a dearth of research evidence demonstrating efficacy of the Housing First (HF) model and harm reduction approach in decreasing psychotic symptoms in individuals with schizophrenia. Ensuring medication adherence in individuals with psychosis, both housed and unhoused, is important to prevent delays in untreated psychosis and chronic deterioration.

A description is provided of the current situation in Aotearoa New Zealand with regard to compulsory treatment of people with schizophrenia. This is placed within the context of homelessness in New Zealand and the provision of services to the incarcerated mentally ill. There are high rates of homelessness and incarceration and services are struggling to meet their needs. This is particularly a problem for the indigenous population. The current Mental Health Act allows for compulsory treatment of people who as a result of schizophrenia are seriously impaired in their capacity to care for themselves, and this will include people where there is a nexus between homelessness and their illness. The Mental Health Act is being reformed, with a new act likely to emphasize autonomy and capacity to a greater degree. Finally, the author considers the learnings from 5 years working within the Fixated Threat Assessment Centre, which provides a unique perspective on these issues.

This chapter follows the story of Jordon, a young man with schizophrenia who becomes entangled in the criminal justice system due to his untreated illness. The narrative highlights the challenges faced by individuals with severe mental illness, the failures of the mental health system, and the impact of policy and legal structures on their lives. Through the experiences of healthcare professionals and experts in the field, the chapter explores the need for a paradigm shift in the treatment of psychosis, advocating for humane and effective care for individuals across the spectrum of illness severity. The narrative culminates in a call to action to revolutionize the treatment of psychosis in America, emphasizing the importance of understanding, compassion, and evidence-based interventions for those affected by severe mental illness.

Balancing autonomy and beneficence remains an ongoing challenge in the ethical treatment of patients with schizophrenia and other psychiatric disorders of thought. Psychiatric advance directives (PADs) offer one mechanism through which individuals can guide their own care, but unlike medical advance directives, they are not widely utilized in the United States. They are also highly limited by state law in the scope of their legal authority. This article explores the evidentiary basis for PADs as well as the legal and ethical issues that arise in the use of PADsin individuals with schizophrenia, arguing that providers’ fears of complete opt-out from care by patients are likely unfounded and that PADs offer a powerful tool through which individuals with schizophrenia can ensure meaningful consideration of their own values and goals.

Anosognosia, commonly understood as a lack of insight, renders individuals with schizophreniaand schizoaffective disorder unable to understand that they are living with a disease, often resulting in a refusal to accept treatment. Typically, to impose involuntary commitment in an effort to obtain treatment, an individualmust be a danger to others or themselves. Even if involuntary commitment is imposed, however, an individualmay remain competent to refuse medication—despite symptoms of anosognosia and an inability to understand that they are ill. This article examines the existing legal theories of competency and informed consent and proposes a statutory definition of competency that encompasses the specific needs of people with anosognosia, while considering the significant interests at stake when taking away an individual’s right to choose or refuse treatment.

This chapter provides multiple-choice questions designed to reinforce and expand your knowledge of psychosis and schizophrenia, including symptom presentation and assessment, neurobiology, treatment mechanisms, clinical characteristics of treatments, treatment strategies, and considerations for special populations.