creation date: 2026-03-05 16:27
tags: Pathologies
Schizophrenia
Background
Definitions
Schizophrenia is a psychiatric disorder involving chronic or recurrent psychosis. It is associated with social and occupational impairment and globally contributes significantly to burden of disease.
Pathogenesis
The pathogenesis of schizophrenia involves interaction between genes and environment. Some hypotheses suggest schizophrenia is a syndrome of multiple diseases with similar signs and symptoms, explaining its heterogeneity.
Genetics
Twin studies have demonstrated strong genetic component suggesting genetic predisposition.
External factors
Several epidemiologic studies have found association of development of schizophrenia with:
- Obstetrics complications such as hemorrhage, preterm labour, blood-group incompatibilities, fetal hypoxia, and maternal infection
- Autoimmune conditions such as acquired hemolytic anemia, bullous pemphigoid, celiac disease, interstitial cystitis, and thyrotoxicosis
- Cannabis use (cannabidiol has been shown to attenuate psychotic symptoms)
- Cigarette smoking has dose dependent response relationship
- Immigration which may be associated with stress or genetics
Neurodevelopment and pathology
Schizophrenia is a disorder that starts with pathologic changes in utero. This is apparent in a reduction of grey matter volumes in multiple brain regions including the prefrontal, and superior and medial temporal lobes.
Schizophrenic patients are also vulnerable to insults that accelerates loss of grey matter and aberrant connectivity.
Some theories suggest decreased glucose metabolism in the frontal cortex may also contribute to the pathophysiology.
Neurotransmitters
Dopamine in excess at the mesolimbic tract is thought to be associated with positive psychotic symptoms.
Other neurotransmitters include serotonin, glutamate, GABA, and acetylcholine, which have been shown to be dysfunctional in schizophrenia.
Clinical Presentation
Signs & Symptoms
Schizophrenia is a syndrome with several symptom domains.
Positive symptoms
Hallucinations (perception of sensory in absence of external source)
- Auditory: most common; often voices but can be in form of other sounds such as music
- Visual: often unformed such as glowing orbs but can be fully formed human figures, faces, or body parts
- Somatic: feelings of being touched, of sexual intercourse, of pain
- Olfactory and gustatory: strange smell or taste
Delusions (fixed, false belief)
- Bizarre delusions: clearly implausible with confusing content; concepts may be unusual (eg. experience of time, space, self, causality)
- Nonbizarre delusions: can be possible and understandable but is not true
- Ideas/delusions of reference: belief that random or neutral events are not random or neutral but includes the individual in some way
- Grandiose delusions: belief that the person has some specific significance or power
- Paranoid delusions: paranoia that someone/something is out to get them
- Nihilistic delusions: belief that a major catastrophe will occur or belief that person is already dead/nonexistent
- Erotomanic delusions: erroneous belief that they have special relationship with someone
Disorganization (disjointed, disconnected speech, and disrupted thought)
- Tangential speech: increasingly further off topic without appropriately answering question
- Circumstantial speech: question is eventually answered but in a markedly roundabout way
- Derailment: person changes topic without any logic or segue
- Neologisms: creation of new, idiosyncratic words
- Word salad: words thrown together without any sensible meaning
Negative symptoms
Negative symptoms can be primary (independent of other symptoms) or secondary (due to another manifestation or treatment).
- Affective flattening (unchanging facial expression, little spontaneous movement or expressive gestures, poor eye contact, lack of vocal inflections, non-reactivity)
- Alogia (poverty of speech, thought blocking, increased latency of response)
- Apathy (poor grooming and hygiene, failure of role responsibility, anergy)
- Asociality/anhedonia (failure to engage with peers socially, no interest in stimulating activities or sex, little or no intimacy with others)
Cognitive impairment
Cognition is often impaired which includes:
- Processing speed
- Attention
- Working memory
- Verbal learning and memory
- Visual learning and memory
- Reasoning/executive functioning
- Verbal comprehension
- Social cognition
Mood and anxiety symptoms
Co-occurring mood and anxiety disorders may be present.
Physical manifestations
Several physical manifestations are associated with schizophrenia.
Neurologic disturbances
- Right-left confusion
- Agraphesthesia (unable to identify letters or numbers traced on skin alone)
- Astereognosia (unable to identify objects by touch alone)
Catatonia
- Extreme negativism (motiveless motor resistance or mutism)
- Catatonic excitement (excessive, purposeless motor activity)
Sleep disturbances
- Disrupted circadian rhythm/sleep architecture
- Obstructive sleep apnea
Metabolic disturbances
- Diabetes
- Hyperlipidemia
- Hypertension
History & Physical Exam
It is common for people with schizophrenia to lack insight. This can make history and treatment difficult.
A thorough psychiatric interview and mental status exam should be performed as well as screening for depression and anxiety disorders.
Risk Factors
Age of onset is typically during adolescence.
Risk factors include:
- Living in urban area
- Immigration
- Obstetrical complications
- Late winter-early spring birth (possible influenza virus exposure during neural development)
- Advanced paternal age at conception
- Cannabis use and cigarette smoking
- Childhood adversity
Schizophrenia is associated with other psychiatric conditions including:
- Depressive disorders
- Anxiety and related disorders
- Alcohol and substance use disorders
Diagnosis
Criteria
Diagnosis of schizophrenia is made using the DSM-5 criteria:
- Two or more of the following for a significant portion of time during a one-month period:
- Delusions
- Hallucinations
- Disorganized speech
- Grossly disorganized or catatonic behaviour
- Negative symptoms
- For a significant portion of time since onset, one or more areas of functioning are markedly below the level prior to onset; or if onset is in childhood/adolescence, failure to achieve expected level of function/achievement
- Continuous signs of disturbance persist for ≥6 months in which at least one month meets criteria 1
- Schizoaffective disorder and mood disorder with psychotic features have been ruled out
- The disturbance is not due to the direct physiologic effect of a substance or general medical condition
- If the patient has a history of autism or another pervasive developmental disorder, prominent delusions or hallucinations must be present for at least a month
Specifiers are used in the DSM-5 for further classification.
Work-up
Initial testing
- CBC
- Electrolytes and creatinine
- Lipid panel
- Urine pregnancy test
- ECG (for QTc elongation or arrythmia)
Additional test
Further testing can be done if an underlying medical condition is suspected:
- Liver function panel
- TSH
- Syphilis screen
- Vitamin B12
- ESR and ANA
- Urinalysis
- Urine drug screen
- HIV test
- Electrolytes (extended, to include for hypercalcemia)
Differential
The differential consist of other psychiatric disorders with similar manifestations.
- Schizophreniform disorder (criteria met but total duration ≤6 months)
- Schizoaffective disorder, bipolar disorder, and major depression with psychotic features (prominent mood component, differences depend on when psychotic symptoms are present relative to mood episodes)
- Substance-induced psychotic disorders (manifestation of intoxication or withdrawal)
- Delusional disorder (delusion but schizophrenia criteria unmet)
- Schizotypal personality disorder (beliefs/disturbances but not at level of delusion/hallucination)
- Schizoid personality disorder (negative symptoms but no psychosis)
- Pervasive developmental disorder (requires criteria 6 to diagnose schizophrenia)
Additionally, psychosis as a result of a general medical condition should be ruled out.
- Cerebrovascular accident or traumatic brain injury
- Major neurocognitive disorder
- Psychosis due to metabolic errors or infection
- Psychosis due to genetic disorder
Management
Acute Treatment of Psychosis
The mainstay of symptomatic treatment is antipsychotics. Second generation antipsychotics are preferred due to their milder side effects (fewer extrapyramidal symptoms).
- Aripiprazole 5-10 mg daily, titrated up to max dose of 30 mg/day
- Olanzapine
- Risperidone
Dosing may be lower if it is the patient’s first episode or is older.
First generation antipsychotic, haloperidol, may be appropriate if the patient had prior treatment with the medication or severe agitation.
Patients should be monitored for resolution of psychotic symptoms (typically several day to 4-6 weeks). Follow-up should occur weekly for the first 3 months of treatment.
Additionally, presence of extrapyramidal symptoms can be managed by adjusting antipsychotic, reducing dose, or adding anticholinergics (eg. benztropine).
Maintenance Therapy
If a patient responds to acute treatment well, that antipsychotic is continued at the lowest effective dose.
In patients with partial response or recurrence, assess adherence, increase dose to therapeutic range, or consider trying another antipsychotic.
In addition to pharmacotherapy, comprehensive psychosocial treatment should be used as an adjunct. These include:
- Cognitive remediation and social skills training
- CBT
- Family-based interventions