Schizophrenia

Overview

Schizophrenia is a complex syndrome often presenting in late teens/early 20s with positive, negative and cognitive symptoms. Positive symptoms include behaviours and thoughts that are not normally present (psychosis). Negative symptoms include social withdrawal and affective flattening. Finally, cognitive symptoms are expressed as a broad set of cognitive dysfunction. The average lifetime prevalence of narrowly defined schizophrenia is just under 1%, but only about half of those affected ever obtain treatment. Schizophrenia on average has a shorter life than the rest of the population. Primary management are 1st and 2nd generation antipsychotics.

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Risk Factors

• Prenatal and perinatal events – complication in fetal life and born in late winter, early spring increases risk
• Paternal age – older fathering increased risk of child
• Urban environment – more common in disadvantaged areas (less support)
• Migration status – increased rates amongst migrants
• Drug abuse – persistant abuse of amphetamine, methamphetamine and cocaine. Cannabis increases rates of psychotic episodes.
• Social adversity – physical abuse, sexual abuse, maltreatment and bullying

Stages of Schizophrenia

Stages of Schizophrenia and its features
Stage	Description	Features
I	Risk (Premorbid)	Genetic and environmental riskAsymptomatic
II	Prodrome	Cognitive and social deficitsHelp seeking
III	Acute psychosis	Relapse and remittingSuicide risk
IV	Chronic psychosis (Residual)	Medical complicationsDisability

Clinical Manifestations

There are two categories of symptoms: positive and negative. The symptoms of schizophrenia usually begin between late adolescence and the mid-30s.

Positive symptoms

• Hallucination
• Delusions
• Disorganised thoughts and speech
• Disorganised behaviour

Negative Symptoms

• Apathy
• Self-neglect
• Blunted mood
• Decreased motivation
• Withdrawal

Cognitive Symptoms

• Attention and processing-speed impairment
• Working memory and learning difficulties
• Executive dysfunction, including impaired planning, problem-solving and judgement

CHARACTERISTICS OF SCHIZOPHRENIA AND MOOD DISORDERS
Diagnosis	Psychotic symptoms	Mood Disorder
Schizophrenia	Present	Brief duration of mood symptoms
Shizoaffective disorder	Present along with and in the absence of mood disorder	Present only with psychotic symptoms
Mood disorder	Present only during mood disorder	Present in the absence of psychotic symptoms

Diagnosis & Investigations

For schizophrenia, diagnosis is clinical—there is no single blood test, scan, or biomarker that confirms it. Investigations are mainly used to exclude medical, neurological, and substance-related causes of psychosis and to establish a baseline before treatment.

Diagnosis

Using DSM-5-TR criteria, schizophrenia requires ≥2 of the following symptoms for a significant portion of at least 1 month, with at least one of the first three present:

• Delusions
• Hallucinations
• Disorganised speech
• Grossly disorganised or catatonic behaviour
• Negative symptoms such as reduced emotional expression, avolition, alogia, anhedonia, or social withdrawal

There must also be:

• Significant decline in work, interpersonal relationships, or self-care
• Continuous disturbance for ≥6 months, including prodromal or residual symptoms
• Symptoms not better explained by schizoaffective disorder, bipolar disorder, major depressive disorder with psychotic features, substances, medications, or another medical condition

Important differentials include substance-induced psychosis, bipolar disorder, severe depression with psychotic features, schizoaffective disorder, delirium, dementia, epilepsy, autoimmune encephalitis, endocrine/metabolic disorders, and medication-related psychosis.

Investigations

Typical first-episode psychosis investigations include:

Investigation	Purpose
FBC	Anaemia, infection, haematological disease
UEC/creatinine	Electrolyte or renal abnormalities
LFTs	Hepatic disease and treatment baseline
Calcium	Hypercalcaemia/hypocalcaemia
Glucose/HbA1c	Metabolic disease and antipsychotic baseline
Lipid profile	Antipsychotic metabolic baseline
TSH	Thyroid dysfunction
B12/folate	Nutritional or neurological causes
Urine drug screen	Substance-induced psychosis
Pregnancy test where relevant	Medication and imaging implications

Depending on the clinical presentation, consider HIV and syphilis serology, inflammatory/autoimmune testing, cortisol or other endocrine investigations.

CT/MRI brain is not routinely diagnostic for schizophrenia but should be considered when there is atypical presentation, focal neurological signs, seizures, cognitive deterioration, head trauma, later-age onset, or concern for an intracranial cause.

EEG may be appropriate if epilepsy or episodic altered awareness is suspected.

Lumbar puncture and autoimmune encephalitis testing, including anti-NMDA receptor antibodies, should be considered when psychosis is accompanied by features such as seizures, abnormal movements, autonomic instability, fluctuating consciousness, catatonia, rapid deterioration, or other neurological abnormalities.

Treatment

Non-pharmacological

• Cognitive behavioral therapy (commence at risk groups)
• Medication review
• Regular review
• Motivational interviewing, social skills training
• Electroconculsive therapy

Pharmacological 

First Generation (typical) antipsychotics

• Haloperidol

Second Generation (atypical) antipsychotics (fewer side effects)

• Risperidone
• Olanzapine (not first-line)
• Closzapine (not first-line)

Serious Side-effects of Anti-psychotics

• Unfortunately, tardive dyskinesia is usually a permanent condition and can be both disfiguring and disabling.
• Neuroleptic malignant syndrome (NMS) is the most severe potential side effect and can occur with any antipsychotic at any time during treatment
• Clozapine is beneficial, especially in treatment-resistant schizophrenia, but has a significant adverse effect in that it can cause agranulocytosis.

Complications & Prognosis

Consequences/Complications

• Psychological – depression (70%), suicide (10%), substance abuse
• Social – isolation, relationship loss, interpersonal issues, poor social function
• Financial – poor academic / work attendance & performance, cost of treatment
• Family – guilt, worry, shame, stigma
• Community – discrimination, social disruption, burden on healthcare system

Prognosis

• 20% -> full recovery
• 30% -> multiple episodes with reasonable inter-morbid function
• 50% -> significant ongoing impairment

Good prognostic factors	Poor prognostic factor
Acute onset	Poor premorbid functioning (most important)
Later age at onset	Early onset
Shorter duration	Negative symptoms
Female gender	Single, divorced, or widowed status
Good cognitive function	Poor support system
Good premorbid function
No family history	Family history of schizophrenia
Presence of affective symptoms
Absence of structural brain abnormalities
Good response
Good support systems

Chronic Schizophrenia

Chronic schizophrenia is an enduring syndrome of delusions, hallucinations, flatness of affect, poverty of speech or incoherence of speech. Other symptoms may occur, including mood symptoms, cognitive problems and movement disorders.

• Symptoms of schizophrenia may be episodic or continuous.
• Up to 90% of people with schizophrenia have a chronic physical illness.
• There is a two-to-three-fold increase in mortality from suicide, accidents and medical disease
• Increase risk of cardiovascular disease

References

1. Holder SD, Wayhs A. Schizophrenia. Am Fam Physician. 2014;90(11):775-82.
2. Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016;388(10039):86-97. doi:10.1016/S0140-6736(15)01121-6.
3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed., text rev. Washington (DC): American Psychiatric Association Publishing; 2022. doi:10.1176/appi.books.9780890425787.
4. Keepers GA, Fochtmann LJ, Anzia JM, Benjamin S, Lyness JM, Mojtabai R, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177(9):868-72. doi:10.1176/appi.ajp.2020.177901.
5. Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N, et al. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019;394(10202):939-51. doi:10.1016/S0140-6736(19)31135-3.
6. Hope J, Keks N. Chronic schizophrenia and the role of the general practitioner. Aust Fam Physician. 2015;44(11):802-8.