Schizophrenia occurs in fewer than 1% of the population; however, the mental disorder has a huge impact on patients’ lives. Learn more about the prevalence, pathophysiology, diagnosis, and management of schizophrenia here.
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Relationship between negative symptoms, positive symptoms, neurocognitive deficits, and impaired social cognition in schizophrenia and how the symptoms are connected to other comorbid mental health disorders. Adapted with permission from Millan MJ, et al.4
The core symptoms of schizophrenia are categorized into 4 main categories: positive symptoms, negative symptoms, neurocognitive deficits, and impaired social cognition. Positive symptoms are the most familiar symptoms of schizophrenia, but the relationship between all symptoms represent the overall impact that schizophrenia can have on a patient’s life. These symptoms also can be associated with additional comorbid mental health disorders, such as depression and anxiety.4
The positive symptoms of schizophrenia are considered the most characteristic of the disease.5 These include hallucinations, which are most commonly auditory but can occur through any senses; delusions, which are fixed beliefs that cannot be changed in light of conflicting evidence; and a loss of contact with reality.6,32
Negative symptoms of schizophrenia, including reduced emotional expression, motivation, and pleasure,32 can be the most difficult to manage.7 A significantly greater functional impairment has been associated with prominent negative symptoms versus prominent positive symptoms.8
Reduced emotional expression.9 Patients with schizophrenia can experience a decrease in the expression of emotion and reactivity to events, as observed during the spontaneous or elicited expression of emotion (facial and vocal expression and expressive gestures).10 This is also known as a blunted affect.10 Alogia, which is a reduction in quantity of words spoken and in spontaneous elaboration (i.e., amount of information spontaneously given beyond what is needed to answer a question), can also appear.10
Reduced motivation and pleasure. Patients with schizophrenia experiencing reduced motivation and pleasure can exhibit avolition, which is a reduced initiation and persistence of goal-directed activity due to reduced motivation.10 Another common symptom in patients with reduced motivation and pleasure is anhedonia, or reduced experience of pleasure for a variety of activities or events, during the activity or event (consummatory anhedonia) and for future anticipated activities or events (anticipatory anhedonia).10 Finally, asociality is also exhibited by those who have a reduced level of motivation and pleasure. Asociality causes reduced social interactions and initiation due to decreased motivation for, and interest in, forming and maintaining relationships with others.10
Cognitive dysfunction is a cardinal feature of schizophrenia, present in about 70% of patients.11 Symptoms can include lack of attention, lack of declarative memory, impairments in higher-order problem solving, effects on speed of processing, social cognition, and executive function.3 The effects of schizophrenia on memory can be both semantic and explicit and can include changes to working and long-term memory function.5
Impaired social cognition
Functional or social impairment can be a result of cognitive impairment.3 This can manifest as a lack of social behaviors, such as emotional withdrawal and reduction of interpersonal interaction.3
Course of illness
Schizophrenia is divided into phases—prodromal, progressive or active, and recovery or residual—that tend to occur in order and cycle through the course of illness.12
Progression of schizophrenia over time in relation to severity of illness. Adapted with permission from Correll.12
Relapse is common in schizophrenia.13 Approximately 82% of patients with a first episode of schizophrenia experience a relapse within five years when they don’t receive proper medical care.13
What is the burden of schizophrenia?
It is difficult to estimate the precise prevalence of schizophrenia due to the complexity of the schizophrenia diagnosis and its overlap with other disorders.1 In the United States, it is estimated that between 0.25% and 0.64% of the population have diagnoses of schizophrenia and related psychotic disorders.14-16 Onset of schizophrenia typically occurs in adolescence or early adulthood, with an age of onset between 15 and 35 years.17 Schizophrenia may emerge earlier in men (late adolescence to early twenties) than in women (early twenties to early thirties).1 Subtle changes in cognition and social relationships may precede the actual diagnosis of schizophrenia, often by years.1
Schizophrenia is ranked as the 19th leading cause of disability world-wide across all age groups18 and is ranked 5th among young adults (ages 20-24).19 The disability caused by schizophrenia can have a significant impact on employment; the excess rate of unemployment among patients with schizophrenia is 58%.20
An average of 14.5 years of potential life (15.8 years and 13.0 years for men and women, respectively) are lost due to schizophrenia.21 Individuals with schizophrenia have an average life expectancy of 64.7 years.21 The average life expectancy for men with schizophrenia is lower, at about 59.3 years, compared to women at 66.8 years.21
An estimated 4.9% of people with schizophrenia will commit suicide during their lifetime, with the highest risk being in the early stages of illness.22 Patients with schizophrenia are about 13 times more likely to die by suicide than the general population.23
Quality of Life
Reliability of self-reporting in patients with schizophrenia makes it difficult to accurately measure the quality of life burden of the disease.2,3
The following factors may be predictive of whether patients with schizophrenia are more or less likely to experience a worse quality of life when compared to the general population and other physically ill patients:2
|Impaired quality of life more likely:||Impaired quality of life less likely:|
Schizophrenia affects the psychological, emotional, physical, social, and financial life of caregivers as well.3 The majority of caregivers for patients with schizophrenia are parents or stepparents (68%); siblings (12%), spouses or significant others (7%), and children or grandchildern (7%) represent most of the rest of the caregivers.24
For individuals caring for a person with schizophrenia, factors associated with an increased burden of care include:25
- Treatment-resistant schizophrenia
- Longer duration of care
- Increased number of hospital admissions
- Presence of disability
- High expressed emotion and criticism between caregivers and individuals with schizophrenia
- Financial burden
- Challenging symptoms:
In a survey by the National Alliance on Mental Illness (NAMI), caregivers of individuals with schizophrenia were asked to describe the primary challenges they faced.24
2008 survey on challenges reported by caregivers of individuals with schizophrenia. 24
In another study, face-to-face interviews with 12 parents caring for adult children with schizophrenia were conducted to gather their experiences.26 The caregivers identified 4 main areas of burden: psychological and emotional burden, physical burden, social burden, and financial burden.3,26
Factors that can reduce caregiver burden include:25
- Stress management programs improve caregivers’ mental status, coping with stress attitude, and feelings of burden
- Improved access to medication, psychiatric care, and crisis care
- Assertive community treatment, a team-based model for community mental health care delivery
- Peer support groups of caregivers
The etiology of schizophrenia is complex. While the primary causes of schizophrenia are unknown, a variety of factors are thought to be involved.27
Brain Structure and Function
Altered brain structures, including decreased gray matter volume and enlarged ventricles, have been hypothesized as an underlying cause of schizophrenia.27-29 Patients with schizophrenia have been observed to have changes in cortical thickness. Magnetic resonance imaging over a 5-year longitudinal study showed the brains of individuals with schizophrenia had excessive thinning of the cortex over time.30 This thinning occurred across widespread areas of the cortex, starting in the prefrontal and temporal areas where it was most pronounced, and then progressing across other areas over the course of the illness.30
Altered neurotransmitter systems are also thought to be involved in the pathophysiology of schizophrenia.27-29 There are four main neurotransmitter systems implicated (dopamine, glutamine, serotonin, and gamma aminobutyric acid (GABA)), but all are hypothesized to involve increased glutamate transmission in those with schizophrenia.31
Neuronal circuits that may be involved in schizophrenia. Adapted with permission from Freedman R.31 ACH = acetylcholine, DA = dopamine, GABA = g-aminobutyric acid, GLU = glutamate, NE = norepinephrine, 5-HT = serotonin.
During the course of neurodevelopment (both fetal and during childhood), there are multiple factors that have been demonstrated to impact an individual’s chances for developing schizophrenia.27-29 During gestation, maternal infection has been linked to schizophrenia diagnosis.27,29 Research has demonstrated that the risk rate for developing schizophrenia is higher in individuals born following a flu epidemic or exposure to rubella.29 This is called the “season-of-birth” effect, as several studies have demonstrated that more schizophrenic patients are born during the winter. Exposure to viral pathogens is most common in the late fall and early winter, thus exposing mothers during their second trimesters.29
Maternal stress during gestation also can impact the fetus and increase the risk for developing schizophrenia. In mothers who had a spouse die or who experienced military invasion during the pregnancy, children were more likely to develop schizophrenia.29
Obstetric complications have been tied to adverse effects on the development of the fetal brain, which can lead to schizophrenia. Several studies have demonstrated a correlation between schizophrenia diagnosis and a history of obstetric complications including toxemia, preeclampsia, and labor and delivery complications.29 One of the most common labor and delivery complications linked to the development of schizophrenia is hypoxia.29
Schizophrenia has a substantial genetic component, with multiple susceptibility genes identified.27-29 The specific genetics of schizophrenia are not yet fully understood, as susceptibility genes are thought to act in combination with epigenetic and environmental factors.27 Heritability is high in schizophrenia, with genetic factors contributing to about 80% of liability for the illness.28 While two-thirds of schizophrenia diagnoses are sporadic, there is an increased risk if an individual has a family history of schizophrenia, and the level of risk is correlated with the degree of genetic distance to the affected family member.28 One of the more recent genetic discoveries is the association between deletion of the 22q11 gene and development of schizophrenia.29 Approximately 25% of individuals with this deletion meet diagnostic criteria for schizophrenia; however, only 2% of patients with schizophrenia have a 22q11 deletion.29
Environmental factors, particularly sociodemographic, have demonstrated an association with an increased risk of schizophrenia.27 Stressful environmental conditions are a risk factor, with individuals living in poverty and those of lower social class being more likely to develop the disorder.27 Living in an urban setting during childhood also can increase the risk for schizophrenia diagnosis.28 Childhood trauma and abuse, as well as separation from parents or parental death during childhood and the early teen years, are additional risk factors.28 Ultimately, stress exposure within a child’s home environment may trigger underlying genetic predisposition for schizophrenia.27-29
Diagnostic and Screening Tools
While there are no psychometric tools recognized by the DSM-5 for the diagnosis of schizophrenia, there are several scales and instruments that have been developed to aid in research, screening, and monitoring a patient’s illness over time.32,33
The following scales are in-depth, reliable, and validated assessments that are typically used in a research setting. Due to the length of these scales and the associated required training, they might be more difficult to use in a clinical practice.33
Scales of the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms (SANS and SAPS)
These are the original standardized scales for positive and negative symptoms.33 Developed in the 1980s, these assessment tools help providers measure the severity of both positive and negative symptoms.33 The SANS tool is a 25-item, 6-point scale, and the SAPS tool is a 34-item, 6-point scale.33-35
The Positive and Negative Symptom Scale (PANSS)
The PANSS is the gold standard in research and for measuring symptom improvement. It is comprised of 30 items divided into three subscales.33,36 The subscales are independent of one another and focus on positive symptoms, negative symptoms, and general psychopathology.33,36
Negative Symptoms Assessment 16 (NSA-16)
The NSA-16 is an updated scale for monitoring negative symptoms, in particular. The NSA-16 was developed in 1989 and then adapted to the NSA-4 in 1993.33 The NSA-16 analyzes the presence, severity, and range of negative symptoms.33,37 The tool is a 16-item questionnaire that focuses on five factors: (1) communication, (2) emotion/affect, (3) social involvement, (4) motivation, and (5) retardation.33,37
The following scales are shorter and therefore more clinically friendly assessments.
Negative Symptoms Assessment 4 (NSA-4)
The NSA-4 was created by modifying the NSA-16 in 1993.33 This assessment tool only focuses on 4 items from the original NSA-16 and is considered nearly as reliable as the much lengthier NSA-16.33
The Clinical Global Impression-Schizophrenia Scale (CGI-SCH)
The CGI-SCH is a reliable, short assessment tool that is most appropriate for use in observational studies and routine clinical practice, but it is less reliable than other tools for the depression rating.33 The CGI-SCH tool assesses positive, negative, depressive, and cognitive symptoms as well as overall severity of schizophrenia.33,38 This questionnaire has two categories: severity of illness and degree of change.33,38
The Prodromal Questionnaire – Brief Version (PQ-B)
This assessment tool is a self-reported questionnaire used to identify prodromal phase symptoms or patients that are at ultra-high-risk for developing psychosis.39 The PQ-B is adapted from the original Prodromal Questionnaire, which is a 92-item self-report tool.39
The Clinical Assessment Interview for Negative Symptoms and Brief Negative Symptom Scale (CAINS and BNSS)
The CAINS and BNSS were developed by the National Institute of Mental Health in 2005.33 Both tests use 13 items to assess for negative symptoms of schizophrenia.33,40,41
Potential Differential Diagnoses
Schizophrenia has symptoms that overlap with other mental health disorders, and it can also be comorbid with many of these disorders, making it difficult to diagnose.32 For example, patients with delusional disorder experience delusions just like those with schizophrenia.32 However, delusional disorder can be distinguished from schizophrenia through the absence of other symptoms of schizophrenia such as negative symptoms and disorganized speech.32 Due to the overlap in symptoms with multiple other conditions, careful evaluation of the patient and their history is important for proper diagnosis.
Other diagnoses that should be considered prior to making a diagnosis of schizophrenia include the following.32
Major depressive disorder or bipolar disorder with psychotic or catatonic features:
The distinction between these two disorders can be made based on the time between the mood disturbance and psychosis, as well as the severity of the depressive or manic symptoms. If delusions and/or hallucinations occur exclusively during the major depressive or manic episodes, the diagnosis would not be schizophrenia.32
A diagnosis of schizoaffective disorder might be appropriate if a major depressive or manic episode occurs at the same time as active phase symptoms, along with the presence of mood symptoms for most of the active periods.32
Schizophreniform disorder or brief psychotic disorder:
Schizophreniform or brief psychotic disorder do not last the duration required for schizophrenia. Schizophreniform disorder is a disturbance of less than 6 months, and a brief psychotic disorder lasts less than 1 month (but at least 1 day).32
Other than the presence of delusions, delusional disorder does not have any other symptoms that are characteristic of schizophrenia.32
Schizotypal personality disorder:
Schizotypal personality disorder can be differentiated by milder symptoms and associated persistent personality features.32
Obsessive-compulsive disorder and body dysmorphic disorder:
Although individuals with obsessive compulsive disorder and body dysmorphic disorder may present with poor or absent insight, and the preoccupations associated with these disorders may reach the level of delusions, the disorders can be distinguished from schizophrenia by the presence of prominent obsessions, compulsions, preoccupation with appearance or body odor, hoarding, or body-focused repetitive behaviors.32
Posttraumatic stress disorder:
While both disorders may include hallucinations or paranoia, a posttraumatic stress disorder diagnosis requires a traumatic event and symptom features related to reliving or reacting to the traumatic event.32
Autism spectrum disorder or other communication disorders:
Autism spectrum and communication disorders can have symptoms resembling a psychotic episode but are differentiated by social interaction deficits, repetitive and restricted behaviors, and other cognitive and communication deficits.32
Body Weight Gain and Schizophrenia
Accumulation of excess body weight among patients with schizophrenia is multi-factorial and can be caused by a combination of unhealth dietary choices, sedentary lifestyle, a lack of access to appropriate food and physical activity sources, and possible genetic or intrinsic disease-state vulnerability for abdominal adiposity.47
Psychotropic medication, in particular the second-generation antipsychotics, have been associated with weight gain.47 Agents differ in their propensity for weight gain. Switching from one agent to another, when clinically feasible, may help ameliorate weight gain.47
Methodology for Guideline Selection
On April 1, 2021, the following search string was entered into the PubMed database:
(schizophrenia[Title/Abstract]) AND (treatment[Title/Abstract]) AND (guideline[Title] OR guidance[Title] OR recommendations[Title] OR algorithm [Title]). The search was limited to PubMed, the most commonly used medical publications database in the world, to ensure that this list can be consistently maintained and updated.
Results were restricted to those publications from the year 2000 to the date of the search, those published in English, and those indexed as article type, “Practice Guideline.” This search returned 20 results. These results were screened in depth according to the following exclusion criteria: articles that were not guidelines for clinical practice, such as research or study results; guidelines that had a published update (i.e., only the most recent version of a set of guidelines were included); guidelines from any entity other than an established, professional clinical organization or a group of said organizations; guidelines from any non-US organization; guidelines that did not report their process for grading and evaluating recommendations; guidelines written for the use of a specific pharmacological or nutraceutical treatment; guidelines for schizophrenia secondary to another condition; and guidelines for conditions other than schizophrenia.
This list will be updated annually.
Medication Adherence Education
Nearly 75% of patients with schizophrenia discontinue medication treatment within 18 months.54 Preventing discontinuation can allow for continual treatment, which is necessary for treatment success.
As every patient is different, there is no universal intervention that will increase patient adherence.55 However, there are strategies for better supporting patients. These can be divided into 4 main categories: (1) patient-related interventions, (2) psychosocial interventions, (3) physician-related interventions, and (4) pharmacological treatment-related interventions.
- Improving patient understanding of disease state
- Helping to reduce psychotic symptoms
- Addressing the stigma associated with medication
- Helping to improve patient’s cognitive function
- These work best as family interventions, not just for the patient
- Developing community support
- Improving problem solving skills
- Improving physician awareness of adherence issues
- Developing relationship between provider and therapist
- Including the patient in the decision-making process
- Assessing possible risk factors for non-adherence and making attempts to modify them
- Continually re-evaluating where the patient is at in their course of illness
Pharmacological Treatment-Related Interventions55
- Considerations of using ppharmacological monotherapy over polytherapy, because of simplicity, less adverse effects, lower risk of drug interactions and easier response evaluation
- Using treatment schedules as simple as possible, and simplifying instructions on medications as much as possible
- Avoiding unrealistic expectations by explaining to the patient what they can and cannot achieve with the medication
A well-balanced diet can balance health problems associated with schizophrenia.52 Patients who meet nutrition guidelines can have a better perception of body function and are more likely to have a normal weight.56
Disturbed sleep may put patients with schizophrenia at higher risk for developing psychosis.57 A regular sleep schedule can reduce the occurrence of insomnia in patients with schizophrenia.58
Physical activity can create a positive response in the body, which affects both physical and mental health.52 The atypical antipsychotics typically used in treatment of patients with schizophrenia can be associated with increased body weight, BMI, and proportion of weight gained during use.59 Exercise can be helpful to combat weight gain.
Patients incorporate their schizophrenia diagnoses into their lives and identities in different ways. To best prepare a patient for living with a diagnosis of schizophrenia, the APA makes several recommendations.
First, patients should be educated on specific early symptoms of relapse. Proper symptom education allows for early detection prior to or at the beginning of relapse and can help prevent an active episode of psychosis.60 The patient should be educated on the course and outcome of the disease, with particular emphasis placed on the importance of medication adherence to prevent relapse.60
Secondly, not only should the patient receive education, but so too should the patient’s family or support system.60 Of course, this is contingent upon the diagnosis of schizophrenia being shared with the family or loved one. The family should be educated on schizophrenia as a diagnosis to better understand the patient’s symptoms, disease management, and expectations for living with the disease. Additional education surrounding coping mechanism for the patient can help the caregiver aid in prevention of relapses and improving quality of life.60
Both the patient and the family should be made aware of community resources for individuals living with schizophrenia. Setting up services to aid in social function will allow for the patient’s ability to adapt to community life.60
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- Bobes J, et al. Dialogues Clin Neurosci. 2007;9(2):215-226.
- Millier A, et al. J Psych Res. 2014;54:85-93.
- Millan MJ, et al. Eur Neuropsychopharmacol. 2014;24:645-692.
- Simpson EH, et al. Neuron. 2010;65(5):585-596.
- Owen MJ, et al. Lancet. 2016;388(10039):86-97.
- Pompili M, et al. CNS Neurol Disord Drug Targets. 2017;16(8):870-884.
- Rabinowitz J, et al. Schizophr Res. 2013;150:339-342.
- Carbon M and Correll CU, CNS Spectrums. 2014;19:38-53
- Galderisi S, et al. Lancet Psychiatry. 2018;doi.org/10.1016/S2215-0366.
- Allardyce J and van Os J. Psychiatry. 2008;7(10):440-442.
- Correll CU. J Clin Psychiatry. 2013;74(2): e04.
- Robinson D, et al. Arch Gen Psych. 1999;56:241-247.
- Kessler RC, et al. Biol Psychiatry. 2005;58(8):668-76. doi: 10.1016/j.biopsych.2005.04.034
- Wu EQ, et al. Psychol Med. 2006;36(11):1535-40. doi: 10.1017/S0033291706008191
- Desai, PR, et al. J Pharmaceut Health Serv Res. 2013;4(4):187-194. doi/10.1111/jphs.12027/epdf
- Kessler RC, et al. Curr Opin in Psychiatry. 2007;20:359-364.
- James SL, et al. Lancet. 2018;392:1789-1858
- Gore FM, et al. Lancet. 2011;337:2093-2102
- Cloutier M, et al. J Clin Psychiatry. 2016;77(6):764-771.
- Hjorthoj C, et al. Lancet Psychiatry. 2017;4:295-301.
- Palmer BA, et al. Arch Gen Psychiatry. 2005;62:247-253
- Chesney E, et al. World Psychiatry. 2014,13:153-160.
- National Alliance for Mental Illness (NAMI). Jun 2008. https://www.nami.org/About-NAMI/Publications-Reports/Survey-Reports/SchizophreniaSurvey Accessed on Oct 7, 2019.
- Kamil SH and Velligan DI. Curr Opin Psychiatry. 2019;32:157-163.
- Young L, et al. Issues Ment Health Nurs. 2019;40(4):297-303)
- Khan ZU, et al. Curr Pharmaceut Design. 2013;19(36):6451-6461
- Nasrallah H, et al. Epidemiol Psychiatr Sci. 2011;20:317–327.
- Walker E, et al. Annu Rev Psychol. 2004;55:401–430.
- . van Haren NEM, et al. Arch Gen Psychiatry. 2011;68(9):871-880
- Freedman R. N Engl J Med. 2003;349:1783-1749
- American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
- Kumari S, et al. J Addict Res Ther. 2017;8(3):324.
- Andreasen NC: Scale for the Assessment of Negative Symptoms (SANS). Iowa City, University of Iowa, 1984
- Andreasen NC: Scale for the Assessment of Positive Symptoms (SAPS). Iowa City, University of Iowa, 1984
- Positive and negative syndrome scale (PANSS) rating criteria. Accessed February 2, 2021. https://www.psychdb.com/_media/psychosis/panss.pdf
- Rekhi G, et al. European Neuropsychopharmacology. 2019;29:1433-1441.
- Busner J and Targum SD. Psychiatry. 2007;4(7)28-37.
- Loewy RL, et al. Schizophr Res. 2011;129(1):42-46.
- Kring AM, et al. Am Journ Psych. 2013;170(2):165-172
- Kirkpatrick B, et al. Schizophrenia Bulletin. 2011;37(2):300-305.
- Conley RR, et al. Schizophr Res. 2007;90:186-197.
- Swartz MS, et al. J Nerv Ment Dis.2006;194(3):164-172.
- Winterer G. Curr Opin Psychiatry. 2010;23:112-119.
- Hunt GE, et al. Drug Alcohol Depend. 2018;191:234-258.
- Leucht S, et al. Acta Psychiatr Scand. 2007;116:317-333.
- Citrome L and Vreeland L. Mod Trends Pharmacopsychiatry. 2009;26:25-46.
- Kreyenbuhl J, et al. Schiz Bull. 2010;36(1):94-103.
- American Psychiatric Association: Practice Guideline for the Treatment of Patients with Schizophrenia, Third Edition. 2020. doi: 10.1176/appi.books.9780890434841
- Argo TR, et al. Texas Medication Algorithm Project Procedural Manual: Schizophrenia Algorithm. The Texas Department of State Health Services. 2008.
- Pandarakalam JP. BJMP. 2016;9(2):a914
- Ernest D, Vuksic O, Shepard-Smith A, Webb E. Schizophrenia: an information guide. Center for Addiction and Mental Health. 2017. https://www.camh.ca/-/media/files/guides-and-publications/schizophrenia-guide-en.pdf
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- Treating schizophrenia, a quick reference guide. American Psychiatric Association. 2004. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/schizophrenia-guide.pdf