2.1.3 Schizophrenia
Schizophrenia
Prevalence and incidence:
Schizophrenia is a severe and chronic mental illness that affects approximately 1% of the global population. The onset of schizophrenia typically occurs in late adolescence or early adulthood, and the condition affects men and women equally.
| Topic | Information |
| Incidence | The global incidence of schizophrenia is similar to diagnostic criteria, with around 15 new cases per 100,000 population in the UK and USA. Males and females are affected equally, but males have an earlier onset (23 vs 26 years) and more severe illness. Incidence may have decreased over time. |
| Prevalence | The lifetime risk of schizophrenia is 15-19 per 1,000 population, and point prevalence is 2-7 per 1,000. Differences between countries are minimized with restrictive definitions based on first-rank symptoms. |
The genetic transmission of schizophrenia is complex and does not conform to straightforward Mendelian inheritance, where traits are passed from parents to offspring through clear-cut dominant or recessive alleles. Two principal theories have been proposed to explain the inheritance pattern of schizophrenia:
- Schizophrenia may arise from the combined influence of multiple gene variations, each contributing a small effect. This suggests that the susceptibility to schizophrenia is not a binary condition but rather exists along a spectrum shared with the general population, implying that everyone has some degree of risk, with those having more of these variations being at higher risk.
- The term “schizophrenia” might encompass a variety of disorders with diverse genetic roots. This view posits that what we refer to as schizophrenia could actually be a collection of different disorders, each with its own unique genetic factors. Some forms of schizophrenia might be primarily caused by genetic factors, while others might result from a combination of genetic predispositions and environmental influences.
Heritability estimates range from 60% to 80%. The risk of developing schizophrenia when one has an affected relative is shown below:
| Family Member(s) Affected | Risk (Approximate) (%) |
| Identical twin | 46 |
| One sibling/fraternal twin | 12-15 |
| Both parents | 40 |
| One parent | 12-15 |
| One grandparent | 6 |
| No relatives affected | 0.5-1 |
Aetiology:
The exact cause of schizophrenia is unknown, but genetic, environmental, social and neurobiological factors are believed to contribute to its development. Genetic studies have identified several genes that are associated with an increased risk of schizophrenia. Environmental factors such as prenatal stress, maternal infection, and substance abuse during adolescence can also increase the risk of developing schizophrenia.
Neurochemical abnormality hypotheses for schizophrenia:
| Hypothesis | Key Points |
| Dopaminergic overactivity | – Antipsychotics as DA antagonists. – Correlation between antipsychotic efficacy and DA receptor antagonism. – Psychotic symptoms induced by dopaminergic agents. – Imaging studies show a predisposition to graphic DA release. – DA metabolite HVA levels correlate with symptom severity and treatment response. |
| Glutaminergic hypoactivity | – NMDA receptor antagonists induce schizophrenia symptoms. – Antipsychotics attenuate ketamine effects. – NMDA receptor function facilitation by glycine and D-cycloserine improves symptoms. |
| Serotonergic (5-HT) overactivity | – LSD induces sensory distortions and hallucinations through partial 5-HT agonism. – Clozapine’s efficacy due to combined dopaminergic and serotonergic antagonism. |
| Alpha-adrenergic overactivity | – Some antipsychotics exhibit adrenergic antagonism. – graphic levels of NA in CSF linked to acute psychotic symptoms. – Antipsychotic treatment affects firing rates in locus coeruleus. |
| Gamma-aminobutyric acid hypoactivity | – Loss of GABA inhibition causes neurotransmitter system overactivity. – Loss of GABAergic neurons in the hippocampus. – BZDs may enhance antipsychotic effects by facilitating GABA. |
Neuropsychological, neuroanatomical, and functional studies (SPECT, PET, fMRI and EEG) have discovered:
- Extensive grey matter reductions in schizophrenia, especially in the temporal lobe.
- Memory and frontal lobe function impairments within the context of broad cognitive abnormalities.
- Diminished correlation between frontal and temporal blood flow during particular cognitive tasks.
- Decreased integrity of white matter connections between the frontal and temporal lobes.
- Increased amounts of theta, fast activity and paroxysmal activity. Decreased synchronisation of electrical activity in the prefrontal cortex, suggestive of ‘noisy’ or inefficient cortical processing in schizophrenia.
These observations have prompted conjecture that frontal-temporal/parietal connectivity might be the ultimate shared pathway for schizophrenia development.
The aetiology of schizophrenia is multifaceted, with significant contributions from social and environmental factors. Research indicates a higher prevalence of schizophrenia among lower social classes, which can be explained by both social causation and the ‘downward drift’ hypothesis, the latter suggesting that individuals descend into lower social classes as a result of the illness. Urban living has also been identified as a risk factor, with a consistent dose-response relationship between the level of urbanicity and schizophrenia incidence, suggesting a causal link that cannot be solely attributed to social drift.
Migration and ethnicity further compound the risk, with migrants and ethnic minorities experiencing higher incidence rates. This is not solely due to social selection; rather, it appears that the social adversity faced by these groups plays a significant role. Moreover, the neighborhood effect suggests that individuals who are more isolated within their community are at increased risk.
Life events and childhood trauma have been linked to the onset of schizophrenia. Studies have shown that adverse childhood experiences can nearly triple the risk of developing psychosis and have a profound influence on cognitive models of psychosis, suggesting that negative early experiences can shape one’s perception of self and others in ways that predispose to paranoid delusions or heightened stress responses.
Obstetric complications, prenatal exposure to influenza, and other prenatal factors, such as respiratory infections and rhesus incompatibility, have been associated with an increased risk of schizophrenia. The overrepresentation of winter-spring births in schizophrenia cases also hints at the role of environmental factors.
Substance misuse, particularly cannabis use, has been demonstrated to have a dose-dependent relationship with the risk of developing schizophrenia. This relationship persists even when controlling for the use of other psychoactive substances and personality traits.
Early developmental indicators, such as delayed motor milestones, speech problems, low educational test scores, and social maladjustment, have been observed in children who later develop schizophrenia. Additionally, a lower IQ and advanced parental age at birth, particularly paternal age, have been associated with an increased risk of schizophrenia, potentially due to an increase in de novo genetic mutations in sperm with advancing paternal age.
Immune System: The stress-diathesis model links early environmental stressors with schizophrenia, focusing on the immune system and brain development. Key aspects:
- Cytokines: Essential in brain development, their imbalance or microglial activation, perhaps due to early maternal infection, can lead to immediate and long-term brain changes.
- Infectious Agents: Agents like influenza and toxoplasma gondii may increase schizophrenia risk by affecting the fetal brain through maternal immune response mechanisms.
- Prenatal Immune Priming: Early inflammatory exposure can prime the immune system for abnormal reactions to future environmental challenges, influencing brain development into adolescence and potentially triggering illness onset.
Presentation:
Schizophrenia is characterised by positive symptoms (hallucinations, delusions, and disorganised thinking), negative symptoms (apathy, social withdrawal, and lack of emotion), and cognitive symptoms (difficulty with attention, memory, and decision-making). The onset of schizophrenia is typically gradual, and individuals may experience a prodromal phase before the onset of full-blown symptoms.
Subtypes of schizophrenia are no longer retained by DSM-5 or by ICD-11.
ICD-11 criteria:
| Criteria | Symptoms |
| At least one of the following: | – Thought echo, insertion, withdrawal, or broadcasting. – Delusions of control, influence, or passivity; clearly referred to body or limb movements or specific thoughts, actions, or sensations; and delusional perception. – Hallucinatory voices giving a running commentary on the patient’s behaviour or discussing him/her between themselves, or other types of hallucinatory voices coming from some part of the body. – Culturally inappropriate or implausible persistent delusions (e.g. religious/political identity, superhuman powers and ability). |
| Or, at least two of the following: | – Persistent hallucinations in any modality, when accompanied by fleeting or half-formed delusions without clear affective content, persistent over-valued ideas, or occurring every day for weeks or months on end. – Breaks of interpolations in the train of thought, resulting in incoherence or irrelevant speech or neologisms. – Catatonic behaviour such as excitement, posturing, or waxy flexibility, negativism, mutism, and stupor. – Negative symptoms such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses. – A significant and consistent change in the overall quality of some aspects of personal behaviour, manifesting as loss of interest, aimlessness, idleness, a self-absorbed attitude, and social withdrawal. |
| Duration | ≥1 month |
DSM-5 criteria:
| Criteria | Description |
| A. Characteristics of symptoms | Two or more of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these must be (1), (2), or (3): 1. Delusions. 2. Hallucinations. 3. Disorganized speech (e.g. frequent derailment or incoherence). 4. Grossly disorganized or catatonic behaviour. 5. Negative symptoms (i.e. diminished emotional expression/avolition). |
| B. Social/occupational dysfunction | For a significant portion of the time since the onset of the disturbance, the level of functioning in one or more major areas, such as work, interpersonal relations, or self-care, is markedly below the level achieved prior to onset (or when the onset is in childhood or adolescence, there is a failure to achieve the expected level of interpersonal, academic, or occupational functioning). |
| C. Duration | Continuous signs of the disturbance persist for at least 6 months, which must include at least 1 month of symptoms meeting criterion A. |
| D-F. Exclusions | – Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out. – Presentation is not attributable to the physiological effects of a substance (e.g. drug of abuse, medication) or other medical condition. – If there is a history of ASD or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are also present for at least 1 month (or less if successfully treated). |
This table categorises the characteristics of schizophrenia into three stages: the Prodrome, the Acute Syndrome, and the Chronic Syndrome. Each stage has distinct symptoms and signs. ​
| The Prodrome | The Acute Syndrome | The Chronic Syndrome |
|---|---|---|
| Difficulty in focusing attention or thinking clearly | Delusions, variable in type and content | Reduced intensity of delusions and hallucinations |
| Minor perceptual disturbances | Passivity phenomena | Underactivity, social withdrawal, lack of drive and volition |
| Anxiety, depression | Hallucinations in any modality, but most commonly auditory – content is very variable | Inappropriate dress |
| Perplexity, suspiciousness | Thought disorder | Neglect of appearance and self-care |
| ‘Negative’ symptoms – reduced drive, amotivation, anergia, social withdrawal, decline in functioning | Affect – delusional mood in the prodrome, euphoria/anxiety/depression, perplexity, incongruity, flattening (blunting) | Deterioration of social behaviour |
| Sleep disturbance | Behaviour change variable – bizarre, withdrawn, suspiciousness, agitation, aggression | Slowness |
| Reduced sense of control | Insight almost always impaired | Thought disorder |
| Delusional mood/atmosphere | Blunted affect | |
| Individual delusions and hallucinations | Cognitive impairment | |
| Movement disorder |
Updating the classification of schizophrenia to align with DSM-5 and ICD-11 involves understanding the key changes and similarities between these two systems:
- First-Rank Symptoms (FRS): DSM-5 does not emphasize Schneider’s First-Rank Symptoms (FRS) as a crucial diagnostic criterion for schizophrenia. In contrast, ICD-11, like its predecessor ICD-10, continues to acknowledge these symptoms but integrates them into a broader symptom framework.
- Duration of Symptoms: DSM-5 requires a minimum of 6 months of symptoms for a schizophrenia diagnosis, which includes at least 1 month of active-phase symptoms (like hallucinations, delusions, or disorganized speech). ICD-11 also requires significant symptom duration but is more flexible, focusing on the overall symptom pattern and impairment.
- Functional Impairment: Both DSM-5 and ICD-11 emphasize functional impairment due to symptoms. This shift marks a move away from a purely symptom-focused approach to considering how symptoms affect a person’s life.
- Schizotypal Disorder: In DSM-5, schizotypal disorder is classified as a personality disorder, whereas in ICD-11, it remains part of the schizophrenia spectrum, similar to ICD-10.
- Subtypes: DSM-5 eliminated the specific subtypes of schizophrenia (like paranoid, disorganized, catatonic), which were present in DSM-IV and ICD-10. ICD-11 also moves away from these subtypes, adopting a more dimensional approach to symptoms and their severity.
- Dimensional Approach: Both DSM-5 and ICD-11 adopt a more dimensional approach to symptoms, acknowledging the spectrum nature of schizophrenia and its symptoms’ variability over time.
In summary, DSM-5 and ICD-11 both reflect an evolving understanding of schizophrenia, with a focus on symptom duration, functional impairment, and a dimensional approach to symptoms. They move away from rigid subtyping towards a more flexible, individualised assessment of symptoms and their impact on functioning.
Treatment:
The treatment of schizophrenia involves a combination of medication and psychotherapy. Antipsychotic medication is the cornerstone of treatment for schizophrenia and can alleviate positive symptoms. Psychotherapy, particularly cognitive-behavioural therapy for psychosis (CBTp), can help individuals manage negative symptoms and improve their quality of life.
The NICE guidelines for schizophrenia recommend a combination of medication and psychological interventions as the primary treatment approach. The specific medications prescribed will depend on the individual’s symptoms and personal preferences, and may be adjusted over time. Some general medication recommendations include:
- For positive symptoms such as hallucinations and delusions:
- An antipsychotic medication such as risperidone, olanzapine, or aripiprazole
- A trial of at least two different antipsychotic medications may be necessary if the first medication is ineffective or poorly tolerated
- For negative symptoms such as social withdrawal and lack of motivation:
- A trial of different antipsychotic medications may be necessary, as some may be more effective for negative symptoms than others
- Psychological interventions such as cognitive remediation and social skills training may also be helpful
- For long-term management and prevention of relapse:
- Continuation of antipsychotic medication at the lowest effective dose
- Psychological interventions such as CBT for psychosis, family therapy, and vocational rehabilitation
It is important to note that medication should always be prescribed and monitored by a qualified healthcare professional. The NICE guidelines stress the importance of regular medication reviews and monitoring for adverse effects, such as weight gain and metabolic problems.
First-generation antipsychotics:
| Category | Subcategory | Drug | Dosage | Other Information |
| First-generation antipsychotics | Phenothiazine derivatives – Group 1: Aliphatic phenothiazines | Chlorpromazine (Largactil®) | 75–300mg daily (max 1g daily) | IM injection (25–50mg every 6–8hrs), 25mg or 100mg suppositories |
| Levomepromazine (Levinan®, Nozinan®) | 100–200mg daily (max 1g daily) | IM or IV injection (25–50mg every 6–8hrs) | ||
| Promazine | 400–800mg daily | Rarely causes haemolytic anaemia; Usually used for agitation and restlessness | ||
| Group 2: Piperidine phenothiazines | Pericyazine | 75–300mg daily | In behavioural management: 15–30mg daily | |
| Group 3: Piperazine phenothiazines | Trifluoperazine (Stelazine®) | 5mg twice daily, increasing based on response | No stated maximum dose | |
| Fluphenazine (Modecate®) | – | Decanoate (long-acting) form available | ||
| Perphenazine | 12–24mg daily | Rarely causes SLE; For behavioural management, usually 4mg three times daily | ||
| Thioxanthines | Flupentixol (Depixol®, Fluanxol®) | 3–9mg twice daily (max 18mg daily) | Depot form available | |
| Zuclopenthixol (Clopixol®, Ciatyl-Z®) | 20–30mg daily (max 150mg daily) | Injectable forms available: acetate (Clopixol acuphase®) and decanoate (Clopixol Conc®) | ||
| Butyrophenones | Haloperidol (Haldol®, Halkid®, Serenace®) | 1.5–5mg twice or three times daily (max 30mg daily) | IM injection (2–10mg every 4–8hrs, max 18mg daily) | |
| Benperidol (Anquil®) | 0.25–1.5mg daily | Used to treat deviant antisocial sexual behaviour | ||
| Diphenybutylpiperidines | Pimozide (Orap®) | 2–20mg daily | Increase slowly by 2–4mg at intervals not less than 1 week; More effective for mono-delusional states | |
| Substituted benzamides | Sulpiride (Dolmatil®) | 200–400mg twice daily | Lower max dose for negative symptoms (800mg daily) than for positive symptoms (2.4g daily) |
Second-generation antipsychotics:
| Drug | Receptor Antagonism | Dosage | Formulations | Side Effects | Additional Info |
| Olanzapine (Zyprexa®, Zalasta®) | 5-HT2A = H1 = M1 > 5-HT2C > D2 > α1 > D1 | 5–20mg daily | Orodispersible tablet, short-acting IM injection, depot | Sedation, weight gain, dizziness, dry mouth, constipation, glucose dysregulation | EPSEs are similar to placebo, with less increase in prolactin |
| Risperidone (Risperdal®) | 5-HT2 > D2 = α1 = α2; little histamine H1 affinity; minimal D1 and 5-HT1 affinity | 4–6mg daily (max 16mg daily) | Orodispersible tablet, depot | Fewer EPSEs at lower doses, dystonias, akathisia, increased prolactin, weight gain | – |
| Paliperidone (Invega®) | As for risperidone | 6mg in the morning, adjusted in increments of 3mg (usual range 3–12mg daily) | Modified-release tablet, depot | Low potential for EPSEs | Reduced drug interactions due to limited hepatic metabolism |
| Quetiapine (Seroquel®, Atrolak®, Biquelle®, Brancico®, Mintreleq®, Sondate®, Zaluron®) | H1 > α1 > 5-HT2 > α2 > D2 | 300–450mg daily (max 750mg daily) | – | Sedation, dizziness, constipation, dry mouth, weight gain, altered triglycerides and cholesterol | EPSEs = placebo, no increase in prolactin |
| Amisulpride (Solian®) | Selective and equipotent antagonism for D2 and D3 | 400–800mg (max 1.2g) daily in two divided doses | – | EPSEs similar to placebo at lower doses, dose-dependent EPSEs and prolactinaemia at higher doses | Less weight gain compared with risperidone or olanzapine |
| Aripiprazole (Abilify®) | D2 receptor partial agonist; partial agonist at 5-HT1A receptors; high-affinity antagonist at 5-HT2A receptors; low-/moderate-affinity antagonist at H1 and α1 receptors; no anticholinergic effect | 10–30mg daily (optimum 10–20mg) | Tablet, orodispersible tablet, oral solution, solution for injection, depot | Low EPSEs similar to placebo, akathisia-like symptoms, insomnia | Does not increase plasma prolactin levels, less likely to cause weight gain |
| Lurasidone (Latuda®) | 5HT2C > D1 > α1 > α2C > 5HT2A > D2 > α2 > 5HT7; partial agonist: 5-HT1A; weak effects: H1 and mACh | Initially 37mg daily, increase if necessary to max 148mg daily | – | Low propensity for QTc interval changes, weight- and lipid-related adverse effects | Absorption increased when taken with food |
Side effects:
The choice of antipsychotic depends substantially on the profile of side effects, what the patient can tolerate and which ones are more important to avoid:
| Medications Suggested due to Side Effects | Recommended | To be Avoided |
|---|---|---|
| Impaired glucose tolerance | Amisulpiride, Aripiprazole, Quetiapine | Clozapine, Olanzapine |
| Acute EPSE | Aripiprazole, Olanzapine, Quetiapine | FGAs |
| Sexual dysfunction | Aripiprazole, Quetiapine | |
| QTc prolongation | Aripiprazole | |
| Sedation | Amisulpiride, Aripiprazole, Haloperidol, Sulpiride, Risperidone | |
| Tardive Dyskinesia | Clozapine | |
| Weight gain | Amisulpiride, Aripiprazole, Haloperidol, Trifluoperazine, Ziprasidone | Olanzapine, Clozapine |
Clozapine:
Clozapine, a second-generation antipsychotic (SGA), belongs to the dibenzodiazepine family. Its clinical use in the mid-1970s was briefly halted due to several cases of fatal agranulocytosis in patients receiving the drug. In the CATIE trial, clozapine demonstrated superior efficacy in treatment response and adherence for patients who did not improve on an SGA and were randomized to receive either another SGA or clozapine. A meta-analysis concluded that clozapine is more effective for treatment-resistant disorders, but if there is no response within six months, alternatives with fewer side effects should be considered.
According to the NICE guideline (2014), clozapine should be offered to individuals with schizophrenia who have not experienced adequate symptom relief despite trying at least two different antipsychotic drugs sequentially (including one non-clozapine SGA).
Treatment initiation and monitoring are ideally conducted in an inpatient setting or a facility with proper monitoring capabilities. All patients must be registered with a monitoring service. A normal white blood cell and neutrophil count must be present before starting treatment. Full blood counts must be performed regularly and sent to the monitoring service.
Dosage begins with 12.5mg once or twice on the first day, then 25-50mg on the second day, gradually increasing over 14-21 days up to 300mg daily in divided doses. The usual dose is 200-450mg daily (maximum 900mg daily). Seizure frequency increases above 600mg/day. Routine blood level monitoring is not advised, but reaching a plasma level of 350mcg/L is sometimes suggested. If side effects occur, the dose should be reduced and increased more slowly afterward.
Lower doses may be necessary for elderly patients, females, non-smokers, or those taking medications that impact clozapine metabolism. If treatment is interrupted for more than 48 hours, it must be restarted with 12.5mg on the first day and gradually increased.
Monitoring results are categorized as green light (normal), amber light (caution), or red light (stop). If the white blood cell or absolute neutrophil count is too low, discontinue clozapine treatment and consult a haematologist.
Common side effects include anticholinergic effects (constipation, dry mouth, blurred vision, urinary difficulties), anti-adrenergic effects (hypotension, sexual dysfunction), and other effects such as sedation, weight gain, nausea, vomiting, ECG changes, headache, fatigue, hypersalivation, tachycardia, hypertension, drowsiness, and dizziness.
Outcome:
The outcome of schizophrenia varies widely, with some individuals achieving symptom remission and others experiencing chronic and severe symptoms. The long-term prognosis is typically better for individuals who receive early and effective treatment.
| Schizophrenia | |
| Prevalence | 1% global population |
| Onset | Late adolescence or early adulthood |
| Gender | Equal prevalence between men and women |
| Aetiology | Genetic, environmental, and neurobiological factors |
| Presentation | Positive symptoms (hallucinations, delusions, and disorganized thinking), negative symptoms (apathy, social withdrawal, and lack of emotion), and cognitive symptoms (difficulty with attention, memory, and decision-making) |
| Treatment | Medication (antipsychotics) and psychotherapy (CBTp) |
| Outcome | Wide variation in outcome, with some achieving symptom remission and others experiencing chronic and severe symptoms |
Schizophrenia presents with a wide array of symptoms and problems, and its course can vary greatly. Recovery from the initial episode is common, but sustained recovery over five years is estimated at only 14%. A seven-year follow-up showed about a quarter of patients achieving symptomatic remission and social/vocational recovery. Over longer periods (15-25 years), global recovery rates are around 50%, but stricter criteria yield lower figures. Most patients experience recurrent episodes, often related to stress, social isolation, and non-adherence to treatment. Longer durations of untreated psychosis are associated with poorer outcomes.
Mortality:
The risk of death from all causes is increased by 1.6 times in people with schizophrenia, with 40% of excess mortality due to unnatural causes, mainly suicide. Cardiovascular and respiratory deaths are also higher, reflecting lifestyle factors and comorbidities like obesity and diabetes.
Suicide Risk:
Suicide risk in schizophrenia is ten times higher, with a 7% lifetime risk. Factors include:
- Early illness stages
- Common demographic risks (e.g., male gender, social isolation, unemployment)
- Depression, hopelessness, and frequent psychosis exacerbations
- Good premorbid functioning
- Hospitalization or post-discharge periods
- Less common in predominantly negative symptoms
- Often in non-psychotic phases in those with prior high achievement
Predictors of Outcome:
The outcome for schizophrenia can be unpredictable; however, some factors are known to influence it:
- Good Prognosis Factors: Sudden onset, presence of precipitants, short episodes, no prior psychiatric history, affective symptoms, family history of affective illness, paranoid type, female gender, younger age of onset, married status, good adjustment, work record, social relationships, treatment compliance, and shorter duration of untreated psychosis.
- Poor Prognosis Factors: Insidious onset, absence of precipitants, long episodes, prior psychiatric history, negative symptoms, hebephrenic type, male gender, enlarged ventricles, cognitive impairment, older age of onset, single or divorced status, poor adjustment, work record, social isolation, poor treatment compliance, and longer duration of untreated psychosis.
Environmental factors can also affect the course of schizophrenia. Understimulation may increase negative symptoms, while overstimulation can worsen positive symptoms. High expressed emotion (EE) environments can lead to higher relapse rates and poor medication response. Life events can trigger relapses.
The AESOP study highlighted disparities in the healthcare experience, showing African-Caribbean and black African patients were more likely to be hospitalized involuntarily during their first episode, even after adjusting for contributing factors such as violence or criminal justice referrals.
References:
- American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596
- Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62(6), 593–602. https://doi.org/10.1001/archpsyc.62.6.593
- Semple, D., Smyth, R., & Burns, J. (Eds.). (2019). Oxford handbook of psychiatry (4th.). Oxford University Press.