Psychiatry SC072: Schizophrenia And Related Psychoses Flashcards
Psychosis vs Psychotic disorder vs Schizophrenia
Psychosis: “Out of reality”
Neurosis: Depression, Anxiety, Insomnia, etc. (Milder)
Psychosis:
- Broad umbrella term
- **Syndrome (a group of symptoms without established cause) characterised by hallmarks of symptoms:
1. **Delusion
2. **Hallucination
3. **Disorganisation (Thinking / Behaviour)
4. ***Lack of insight
Classification of Psychosis:
1. **Organic (identifiable physical conditions leading to psychotic symptoms e.g. drug-induced, dementia, thyroid disease, endocrine disease, brain tumour, epilepsy, encephalitis etc.)
2. **Psychiatric
Psychotic disorder:
- Group of conditions e.g. Schizophrenia, Delusional disorder, Brief psychotic disorder, Mood disorder with psychotic symptoms
- **Affective / **Non-affective
- Non-affective: Schizophrenia, Delusional disorder, Brief psychotic disorder
Schizophrenia:
- 1 type of Psychotic disorder
Chinese term in HK (since 2001): 思覺失調
- 思: Delusion + Disorganisation
- 覺: Hallucination
- 失調: Lost balance
***DSM-5 diagnostic criteria of Schizophrenia
A. **>=2 of the following, each present for a **significant portion of time during a **1-month period (or less if successfully treated). **>=1 of these must be (1), (2), or (3):
1. **Delusions
2. **Hallucinations
3. **Disorganized speech (e.g., frequent derailment or incoherence)
4. **Grossly disorganized / Catatonic behavior
5. ***Negative symptoms (i.e., diminished emotional expression or avolition)
B. For a significant portion of the time since the onset of the disturbance, 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 the onset (or when the onset is in childhood or adolescence, there is failure to achieve expected level of interpersonal, academic, or occupational functioning).
C. Continuous signs of the disturbance persist for **>=6 months. This 6-month period must include **>=1 month of symptoms (or less if successfully treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or by two or more symptoms listed in Criterion A present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences).
D. Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either 1) no major depressive or manic episodes have occurred concurrently with the active-phase symptoms, or 2) if mood episodes have occurred during active-phase symptoms, they have been present for a minority of the total duration of the active and residual periods of the illness.
E. The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition.
F. If there is a history of autism spectrum disorder 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 >=1 month (or less if successfully treated).
***Schizophrenia-spectrum + Other Non-affective psychoses
- Schizophrenia-spectrum
- **Schizophrenia
- **Schizoaffective disorder (concurrent schizophrenic + mood symptoms **equally prominent (fulfilling a major mood episode e.g. manic / depressive episode))
- **Schizotypal personality disorder (no psychotic symptoms, very mild trait, high risk of developing schizophrenia later) - Other Non-affective psychoses
- Brief psychotic disorder / **Acute + Transient psychotic disorders (ATPD)
—> Acute onset + Brief period + Complete remission (1-3 months, depends on criteria) (better prognosis)
—> DSM-5: **>1 day, ***<1 month
—> Polymorphic features (~cycloid psychosis): rapidly changing clinical pictures, prominent fluctuated mood state, perplexity
(- Schizophreniform disorder: **>1, **<6 months of illness)
-
**Delusional disorder
—> **Systematised, likely **single-theme delusion, **non-bizarre in nature (classic definition)
—> ***No / Non-prominent hallucination
—> Minimal negative symptoms, reported of having better functioning
—> Over-represented by women + adult-onset
—> Relatively rare
***Subtypes of Schizophrenia + Historical background
- Unitary psychosis (1861)
- Dementia praecox (1896)
- Schizophrenia (1911)
Kraepelian dichotomy on Psychosis:
- Dementia praecox (now known as Schizophrenia) vs Manic-depressive insanity (i.e. Bipolar disorder)
- Diagnostic classification based mainly on longitudinal outcome
- Dementia praecox: Progressive downhill course (but now recognised that some schizophrenia patients may actually improve)
—> Dementia: **Cognitive decline
—> Praecox: **Precocious
—> Kraepilian: Schizophrenia is NOT just psychotic symptoms but also early decline in cognitive function
Schizophrenia:
- Greek: Splitting of mind / psychic functions
- A group of schizophrenia with fundamental symptoms: Loosening of association, Affect flattening, Autism, Ambivalence
- 4 classic subtypes:
1. **Paranoid schizophrenia
- Prominent **positive symptoms (not just paranoid delusion)
-
**Hebephrenic (Disorganised)
- Younger age of onset
- Prominent **thought disorder / ***incongruous affect
- Poor prognosis - ***Catatonic
- Constellation of specific motor signs (e.g. posturing, waxy flexibility, mutism) -
**Simple
- Lack of positive symptoms (No psychotic symptoms at all)
- **Prominent negative symptoms (Cognitive impairment)
- Gradual functional decline
- Worst prognosis
- Rare now
—> Subtype can change over patient’s disease course
—> Subtype classification NO longer included in DSM-5 (∵ not accurate in predicting prognosis)
—> Catatonia is ***NOT specific to schizophrenia and now a specifier in DSM-5
***Symptomatology of Schizophrenia
Symptom dimensions in Schizophrenia (+ related psychoses):
1. **Positive symptoms
- Delusions
- Hallucinations
2. **Negative symptoms
- Affect flattening
- Alogia
- Anhedonia
- Avolition
- Asociality
3. Disorganisation (Formal thought disorder)
- Direction
- Tempo
- Amount
- Continuity
- Form
- Others
4. **Affective / Mood symptoms (Depression / Mania)
5. **Motor signs (Catatonia)
6. Cognitive impairment
Positive symptoms:
Most common:
- **Delusion of reference
- **Delusion of persecution
- ***Auditory verbal hallucination (AVH)
Positive symptoms
Schneiderian ***First Rank Symptoms (FRS): (i.e. first rank of importance, specific to schizophrenia —> facilitate diagnosis)
- now know that FRS are NOT specific to schizophrenia + minimal prognostic predictive value
- but still widely applied + emphasised in current classifications
Delusion:
1. **Thought alienation (thought insertion, withdrawal, broadcasting)
2. **Delusion of Passivity / Control (i.e. feelings, actions, impulse etc. experienced as made / influenced by external agents)
3. ***Delusional perception (a true perception in which a patient attributes a false meaning)
Hallucination:
4. **3rd person AVH with voices conversing with each other
5. 3rd person AVH in the form of **running commentary (hallucination of voice continuously commenting on one’s actions)
6. ***Thought echo (AVH with voice repeating one’s own thoughts aloud)
7. Somatic hallucination
***Delusion
- **A firmly held belief (unshakeable) on **inadequate ground
- ***Not subject to reason / contradictory evidence
- ***Not explained by a person’s usual cultural and religious background
- Important issue: Collect collateral information from informant for uncertain situation
Possible theme:
1. **Delusion of reference
2. **Delusion of persecution
3. **Grandiose delusion
4. **Delusion of guilt
5. **Delusion of poverty
6. Delusion of infidelity / jealousy
7. Delusion of control / passivity
8. **Erotomania (de Clérambault’s Syndrome)
9. Nihilistic delusion (Cotard’s syndrome, delusional belief of being dead)
10. Religious delusion
11. Somatic delusion (Hypochondriacal)
12. **Misidentification (Capgras syndrome (belief that a close person has been replaced by an identical imposter i.e. faked), **Fregoli syndrome (an unfamiliar person as a familiar person))
13. **Thought alienation
14. **Hypochondriacal delusion
15. Dysmorphophobic delusion
16. Shared delusions (Folie a deux)
Characteristics of delusion:
1. Content?
2. How did the belief form?
3. Can it be explained by the person’s educational / cultural / religious background?
4. **Any other possible alternative explanation? (會唔會巧合呀?)
5. Extent of conviction?
6. **Response to contrary evidence?
7. **Mood-congruent? (Mood disorder with Psychotic symptoms are usually congruent vs Schizoaffective)
8. Bizarre?
9. **Reaction (e.g. Acting out)
10. ***Impact (Physical, Psychological, Social)
(Ryan Ho:
Classification of Delusions:
1. Primary delusions (un-understandable, not occurring with other psychiatric illness)
- Autochthonous delusion (Delusional intuition) (occur out of blue)
- Delusional perception
- Delusional atmosphere (foreboding feeling in which the patient experiences everything around him in a sinister, peculiar way i.e. 不祥的預感)
- Delusional memory (delusional interpretation of normal memory)
- Secondary delusions (delusion arise from other psychiatric illness e.g. schizophrenia)
vs Partial delusions:
- ***Less conviction
vs Overvalued ideas:
- Beliefs ***plausible in nature (i.e. understandable) but Overvalued (i.e. preoccupied to an unreasonable extent)
- in Anorexia nervosa, Hypochondriacal disorder
vs Obsessions:
- ***Egodystonic (i.e. patient does not believe + actively resist the idea but have compulsion)
***Hallucination
- ***Perception without stimulus
- ***Cannot be controlled
- Important issue: Clarify if it’s a perception without stimulus! (Other people cannot hear / feel)
Form:
1. **Auditory (most common)
2. **Visual
3. Gustatory
4. Olfactory
5. ***Tactile / Somatic
Characteristics of Auditory hallucination:
1. External (真係無人?)
2. Elementary (non-verbal, hissing, whistling, an extended tone, tinnitus etc.) / Complex (**verbal, voices, music)
3. **2nd person / 3rd person
4. **Number of voices
5. **Identity (e.g. gender, age, familiarity)
6. **Content (derogatory, command etc.)
7. **Pattern (Frequency, Duration, Intensity, Setting **真係無人?)
8. **Vividness (係咪清楚?)
9. **Uncontrollable
10. **Reaction
11. ***Impact (Physical, Psychological, Social)
Negative symptoms
- Symptoms where there is a **decrease / **loss in a mental ***function compared to normal functioning
- Core feature of schizophrenia
- ***KEY determinant of functional outcome
- Unmet therapeutic need, ***NOT respond to Antipsychotic
- Important issue: Need to rule out ***secondary causes such as antipsychotic side effect and depression
- Multi-dimensional construct comprising 5”A”s
5“A”s:
1. ***Affect flattening
- reduced affect response (facial expression, gesture, spontaneous movement, intonation, eye contact)
- diminished non-verbal emotional expression
- ***Alogia
- poverty of speech
- diminished verbal emotional expression - ***Anhedonia
- reduced capacity to experience pleasure
- similar but not same as Anhedonia in depression - ***Avolition
- reduced motivation with reduced goal-directed behaviour - ***Asociality
- reduced motivation with reduced social drive with social withdrawal
Cognitive impairment
- Core feature of schizophrenia (Dementia praecox)
- ***KEY determinant of functional outcome (some patients may not recover!)
- Unmet therapeutic need, NOT respond to Antipsychotic
***Generalised (NOT Isolated) cognitive impairment encompass multiple cognitive domains:
1. Sustained attention
2. Executive functions (planning, set-shifting, inhibition control)
3. Working memory
4. Verbal + Visual memory
5. Processing speed
- In general, 1-2 SD below normal individuals
- Healthy 1st degree relative also demonstrate deficits (although less severe) in cognition
- Impairment in ***social cognition observed including deficits in ToM (theory of mind: ability to think about mental states, both your own and those of others), emotion recognition etc.
Epidemiology of Schizophrenia + Related psychoses
Epidemiology:
- Prevalence: ~2-3%
- Incidence rates vary widely across regions
- Elevated incidence among:
—> Migrants of ethnic minority (from developing countries to developed countries) (not just 1st generation but also 2nd generation)
—> Urbanicity: Individuals brought up in urban area vs those in rural areas
- One of leading disabilities worldwide
- Direct cost (hospitalisation, medication)
- Indirect cost (loss of productivity, disability allowance)
- Profound disruption in individual’s personality development, social relationship, scholastic, vocational trajectories
- Potentially chronic, remitting-relapse course with significant functional impairment
Schizophrenia:
- **Lifetime risk: ~1%
- Median incidence rate: 15.2 / 100,000 per year
- Onset: Late adolescence + Early adulthood
- **M:F = 1.4:1
- **M: **Earlier age of onset of psychosis
- F: Have **second peak of onset ~40-50 (~age of menopause) (*Estrogen theory: Estrogen block Dopamine receptor —> Protective effect)
Suicide, Mortality in Schizophrenia
**Suicide:
- Single largest cause of premature death in schizophrenia
- **5.6% lifetime risk
- **12x higher than normal population
- Highest risk in **early stage of psychotic disorder
- Rate is highest in first year after FEP
- Depressed mood, one of strongest predictor of suicide, frequently observed in ***early stage of illness
Mortality:
- Excess mortality in schizophrenia patients
- Schizophrenia reduces an affected individual’s lifespan by on average **10-15 years
- Elevated both in **suicide + **natural deaths
- Possible reasons for elevated rate of natural deaths:
1. **Lifestyle (sedentary lifestyle, lack of exercise, poor nutrition)
2. **Cigarette smoking, substance or alcohol abuse
3. **Metabolic syndrome (obesity, DM, hyperlipidaemia etc.)
4. ***2nd generation antipsychotic (contribute to metabolic syndrome)
5. ?Inherent disease process involving accelerated aging and medical morbidity
Development + Course of Schizophrenia
Premorbid phase (Childhood)
—> Prodrome (At risk mental state (ARMS) / **Clinical high-risk (CHR)) (few months-years) (Adolescence / Early adulthood)
—> **First episode of psychosis (FEP) (i.e. onset of psychosis) / No transition to psychosis (Adolescence / Early adulthood)
—> Longitudinal course of illness (very heterogeneous: some can fully recover, some relapse-remit (likely ∵ non-adherence), some resistant to treatment)
—> Residual deficits / Fully recovered
Prodrome:
- Low grade / Attenuated positive symptoms but not above threshold for formal diagnostic category
- e.g. some decline in functioning, poorer social function, mild cognitive impairment
- May not be easily noticed by patient / people around
FEP:
- Good treatment response (>70%)
Causes of Schizophrenia
Gene x Environment interactions
1. Genetic
- **High degree of heritability (estimated as 80% contributed by genetic cause)
—> **First-degree relatives: 10-15%
—> **Monozygotic twin: 50%
- **Polygenic (multiple genes with small effects contributed by each gene)
- Many identified candidate genes are related to dopamine, glutamate, synaptic functions, immune mechanisms
- Rare copy number variants (CNV) with larger effect (e.g. Chromosome 22q11.2 deletion syndrome (DiGeorge Syndrome / Velo-cardio-facial syndrome (VCFS)) (20-30x risk of schizophrenia)
- Environmental
Prenatal + Perinatal risk factors (Distal factors) (Non-specific: also involved in other neurodevelopmental diseases e.g. Autism, Bipolar)
- **Obstetric complications (higher risk of neurodevelopmental diseases)
- **Winter birth, **Maternal infections (e.g. influenza, toxoplasmosis) (trigger immunity —> neuroinflammation in fetus)
- **Advanced paternal age at conception (de novo mutation / epigenetic)
Proximal social risk factors
- **Substance abuse (cannabis, amphetamine, ketamine)
- **Migration (ethnic minority) (social defeat hypothesis / stress dopamine sensitization)
- ***Urbanicity (urban upbringing)
**Neurodevelopmental hypothesis:
- Low IQ / mental retardation associated with higher risk of schizophrenia
- Poor premorbid adjustment
- Motor function deficits occur before onset of illness
- Neurological soft signs
- Cognitive deficits emerge in **prodromal period
***Stress-vulnerability model for psychosis development
- Stress: Social / Environmental factors
- Vulnerability: Genetic
Neurobiological abnormalities in Schizophrenia
- Biochemical
***Dopamine hypothesis:
- ↑ Pre-synaptic dopamine synthesis in Striatum —> Hyperdopaminergic transmission —> Psychosis
Dopamine pathways:
1. Mesolimbic pathway (positive symptoms)
2. Mesocortical pathway (negative + cognitive symptoms)
3. Nigrostriatal pathway (parkinsonism / EPS)
4. Tuberoinfundibular pathway (hyperprolactinaemia)
Other neurotransmitters involved:
- ***Glutamate (NMDA hypofunction) —> Excess glutamate neurotransmission —> Neurotoxicity —> may lead to hyperdopaminergia
- GABA
Neuropathological findings:
- Absence of gliosis + lack of evidence of neuronal loss + reduction in synapse-rich neuropil (—> against neurodegeneration hypothesis)
- Structural / Neuroanatomical abnormalities (by sMRI)
- ↓ Whole brain volume / ***Gray matter (GM) volume (esp. temporal lobe (hippocampus, amygdala, superior temporal gyri (STG)), prefrontal cortex, thalamus, anterior cingulate)
- ↑ Ventricular volume
- ↓ Cortical thickness (cortical thinning)
- ↓ Cortical surface area - Structural + Functional connectivity alterations
- Altered integrity of ***white matter tracts (via DTI)
- Altered resting-state functional connectivity (via fMRI)
- Evidence indicates a ***progressive structural brain changes (volume reduction) across the course of illness, at least in a subgroup of patients
- Alterations in neurophysiological measures + in-vivo brain functions
