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.

This study explores the effectiveness of antipsychotic medications in restoring competency to stand trial in individuals with severe mental illness, particularly psychotic disorders. While antipsychotic medications are known for reducing symptoms of psychosis, this research focuses on their ability to improve functional outcomes necessary for competency to stand trial (CST). Among over 3,000 patients in California’s forensic state hospital system, 86.5% were successfully restored to competency, with 98.8% discharged on antipsychotic medications. Patients on antipsychotic monotherapy demonstrated higher restoration rates compared to those requiring additional mood stabilizers, suggesting that more complex cases demand more intensive treatment. Delusional disorder, traditionally seen as more resistant to treatment, showed a high restoration rate of 93.8% with antipsychotic use.Our findings emphasize the pivotal role of antipsychotics in not only reducing symptoms but also in restoring critical functional abilities for participation in legal proceedings. The functional improvements they enable extend beyond the courtroom. Incorporation of antipsychotic medication as an integral evidence-based mechanism in facilitating community reintegration for individuals with severe mental illness supports the broader goal of transitioning individuals from the legal system back into society, consistent with the ultimate promise of deinstitutionalization.

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 history of Italian general psychiatry and forensic psychiatry over the last 50 years has been unique in the European and Western healthcare landscape. Western politicians often visit Italy to observe the successful community-based systems that have developed in that country. This article represents a first step toward a necessary attempt, to explore how specific political decisions, such as the Italian one, have produced positive outcomes for patients with psychotic disorders, outcomes not observed in many Western countries, which are instead grappling with negative outcomes such as the complicated management of homelessness and the incarceration of people who would instead require psychiatric care. In its historical context, the 1978 decision to abandon the asylum tradition in favor of socialization for patients living with severe mental disorders represented a difficult choice. This choice led to inevitable critical issues, which today are still not completely dormant. This choice has also, undoubtedly, restored dignity to people living with serious mental illness, even when that person commits a crime. To understand these changes, it is appropriate to mention the regulations that finally led to Lawnumber 180 of 1978, which decreed the closure of psychiatric hospitals (Ospedale Psichiatrico) throughout Italy and continued after 2015 with the closure of high-security psychiatric hospitals (Ospedale Psichiatrico Giudiziario) as well. Culturally, much has changed throughout this time in assistance to the mentally ill in Europe.

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.

Treatment of patients suffering from schizophrenia in Austria: Treatment of patients with schizophrenia in the healthcare system is generally voluntary. This applies both to outpatient care provided by specialists in private practice, hospital outpatient clinics, or social psychiatric outpatient clinics and to inpatient care in hospitals. However, there is an exceptional situation in which the patient’s freedomofwill is restricted by law. This is the case when acute danger to self or others caused by the disorder is present. With the involvement of the district court, the patientadvocate, a possible adult representative, and an external expert, the patient’s freedom of movement can be restricted for a certain period of time to enable treatment. The acceptance of psychopharmacological therapy remains the patient’s decision in this situation,with the exception of explicit authorization by the court. Treatment under the consideration of proportionality, meaning that coercion is only applied in the case of an acute risk of severe bodily harm, is therefore possible for themajority of patients with schizophrenia. However, this does notmean that patients are able to connect to the care network in all cases. Some patients fail because the contact threshold is still too high. In order to reduce this, outreach care has been integrated into the existing services in many cases. Thesemulti-professional teams oftenmanage to establish contact with the patients and thus create a willingness to undergo treatment in order to counteract the long-term consequences, including complete social isolation and disintegration.

People with serious mental illness (SMI) are over-represented throughout the US criminaljustice system. To address this issue, forensic assertive community treatment has recently emerged as a best-practice intervention. Also known as forensic ACT, ForACT, or most commonly as “FACT,” forensic assertive community treatment is an adaptation of the assertive community treatment (ACT) model. Unlike ACT, however, FACT is purposefully designed to prevent arrest and incarceration among people with SMI who have histories of involvement with the criminal justice system (i.e., “justice-involved” individuals). Although FACT was recognized as a best practice by the Substance Abuse and Mental Health Services Administration (SAMHSA) in 2019, FACT teams vary widely in their structure and daily operations. This lack of a standard FACT model continues to impede FACT program implementation and outcomes research. This article begins with a review of FACT origins, followed by a discussion of what we know (and do not know) about FACT operation and effectiveness. Based on the authors’ experience, the article then discusses key components of FACT and concludes with a discussion of current challenges and research recommendations for FACT model development.

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.

Schizophrenia is a severe and disabling psychiatric illness that profoundly affects a person’s ability to think clearly, perceive reality, manage emotions, and engage in daily activities. While antipsychotic medications have long been the cornerstone of treatment, debates persist around their long-term use and potential impact on brain structure and function. In our review, we examine whether antipsychotic medications improve or worsen long-term outcomes in schizophrenia, particularly when treatment is refused or discontinued. Drawing from randomized controlled trials, large-scale observational studies, forensic outcome data, international guidelines, and neuroimaging research, the findings demonstrate that sustained antipsychotic treatment significantly reduces relapse, improves functional outcomes, and may protect against neurobiological deterioration. In contrast, untreated or inconsistently treated psychosis is associated with higher relapse rates, treatment resistance, cognitive decline, and progressive brain changes. While treatment must be personalized and compassionate, the cumulative evidence supports the critical role of early and continuous antipsychotic use in preserving health, autonomy, and long-term recovery for individuals living with schizophrenia

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.