Schizophrenia and Related Psychoses

  

Schizophrenia:

Introduction:

Of all the psychiatric syndrome, schizophrenia is the most difficult to define and describe. Over the last 100 years widely divergent concepts have been held in different countries and by different psychiatrists.

Basic concepts are (over simplified)

Acute schizophrenia (Type 1):

Predominated by positive symptoms such as delusions, hallucinations and interference with thinking. Good prognosis

Chronic schizophrenia (Type II):

Negative symptoms: apathy, lack of drive (diminished volition), slowness and social withdrawal. Poor prognosis.

Recent studies proposed more complex delineations correlating to cerebral and psychological symptoms

1. Reality disturbance: delusions and hallucinations, left medial temporal lobe and cingulated cortex. Disorder of self monitoring.

1. Disorganization: Formal thought disorder, inappropriate affect, bizarre behaviour, anterior cingulated, right ventral frontal cortex, bilateral parietal regions. Disorder of selective attention (suppression).

1. Psychomotor poverty: Flat affect, poverty of speech, decreased spontaneous movement, under activity of pre-frontal cortex. Disorder of word generation and planning (initiation)

Other aspect of the clinical syndrome:

•  Depressive symptoms: may be part of the syndrome, post psychotic phase or side-effect of the antipsychotic.

• Cognitive features: impairment in learning, memory and attention.

• Neurological signs: so cold soft signs. Abnormality in sensory integration, coordination, and catatonic features.

• Olfactory dysfunction: affecting the identification, sensitivity and memory for odours usually worse in the left nostril. Clinically may contribute to lack of social drive.

• Water intoxication: in few chronic patient water intoxication characterized by polyuria and hyponatraemia. May indicate hypothalamic regulation abnormality esp. related to antidiuretic hormone.

Diagnosis:

ICD-10:

At least one clear symptom (similar to Schneider's first rank symptoms i.e. break down of self boundary)

a. Thought echo, insertion, withdrawal, broadcast

b. Delusions of control (passivity), delusional perception

c. Voices discussing in the third person, running commentary, voices from some part of the body.

d. Other persistent delusions that are completely impossible

Or at lease 2 symptoms:

a. Persistent hallucinations ± delusions (e.g. persecutory, reference, religious etc).

b. Formal thought disorders (flight of ideas, perseveration, loosening of association, widening of concept)

c. Catatonic behaviour e.g. posturing, stupor

d. Negative symptoms

e. Change in overall quality of personal behaviour

Illness for 1 month (DSM-IV 6 months).

Sub types:

• Paranoid: stable delusions and usually hallucinations
• Hebephrenic: formal thought disorder, inappropriate affect, bizarre behaviour, fleeting delusions and hallucinations, severe illness.
• Catatonic: motor symptoms predominate
• Undifferentiated
• Residual: chronic stage, predominantly negative symptoms
• Simple: only negative symptoms
• Post-schizophrenic depression
• Other schizophrenia
• Unspecified schizophrenia

 (In DSM-IV: Paranoid, Disorganised, Catatonic, Undifferentiated, Residual)

Differences between the ICD-10 and DSM-IV):

• ICD-10 places greater weight on first rank symptoms
• ICD 10 requires 1 month vs. 6 month in DSM-IV
• ICD 10 has more additional sub-types
• Disorganised in DSM-IV is called Hebephrenic in ICD-10.

Duration in DSM-IV:

1 day to 1 monthà Brief Psychotic Disorder

1 month to 6 monthsà Schizophreniform Disorder

More than 6 month à Schizophrenia

Differential Diagnoses

• Organic syndromes "Organic Psychosis" ( as opposed to so called Functional psychosis such as schizophrenia)

e.g. TLE, carcinomas, CVA, AIDS, CJD, CO Poisoning, Fahr's disease, Huntington's, Syphilis, Wilson's and many others.

(ALWAYS EXCLUDE ORGANICITY/MEDICAL CAUSES!!)

• Drug induced psychosis
• Mood disorders with Psychotic Features
• Delusional Disorders
• Personality Disorders

Epidemiology of Schizophrenia

Lifetime risk 1%

Incidence: 0.5 per 1000

Prevalence: 3 per 1000

Median age of onset: M=28 yr, Females 32 yr (but anywhere between 15 to 55)

Gender M=F (early is more common in males, late (Paraphrenia) is more common in Females)

Higher rate in urban than rural areas

Higher rate in immigrant

Aetiology

Very complex, controversial, however the whole range of  biological, psychological and social factors are important.

• Genes: e.g. Neuregulin, Dysbindin
• Environmental: Obstetric complications, maternal influenza, winter birth, early cannabis use, paternal age.
• Social: Migration, urban birth and upbringing, recent life events
• Structural :smaller brain size, reduced synaptic markers
• Functional imaging: Hypofrontality
• Neurophysiological: Abnormal eye tracking, Abnormal esenory evoked potential
• Neurochemical: Dopamine, Glutamate
• Psychological: cognitive impairment, personality factors, psychodynamic theories, family dynamic and communications

Main hypothesis are the Neurodevelopmental (The pathological changes are laid down early in life, presumably through genetic influences and then modified by maturational and environmental factors), aberrant connectivity, Stress-vulnerability.

Key aspect of the present consensus regarding the aetiology are summarised as follows:

The most important influence is genetic, with about 80% of the risk being hereditary. The mode of inheritance is complex and the genes, some of which have been recently identified, act as a risk factor, not determinant of illness. A number of environmental factors contribute too, many of which appear to act prenatally, and which interact with the genetic predisposition. Together these and subsequent risk factors lead to neurodevelopmental disturbance which either causes, or renders the individual vulnerable to,, the later emergence of symptoms, and which manifests itself premorbidly in a range of behavioural, intellectual and neuroanatomical features. In schizophrenia, the brain is slightly smaller than normal, and there are localized differences in its structure and function, leading to the view that the syndrome is a disorder of connectivity within and between brain regions. Acute psychosis is associated with excess dopamine, whereas the persistent cognitive impairment may result from deficient dopamine function in the prefrontal cortex, both maybe secondary to abnormality to the glutamate system.

Course and prognosis

Generally agreed that the outcome of schizophrenia is worse than that of most psychiatric disorders, however, prognosis may not be as bad as previously thought!

 After 13 years follow up:

• 15-20% of first episodes will not recur
• 50% are without psychotic symptoms
• 50% are without negative symptoms
• 55% show good social function.

Mortality and morbidity is much higher than normal population and suicide up to 10%.

Good prognostic Factors:

• Sudden onset
• Short episode
• No previous psychiatric history
• Prominent affective symptoms
• Paranoid type
• Older age of onset
• Married
• Good psychosexual adjustment
• Good premorbid personality
• Good work record
• Good social relationships
• Good compliance.
• Normal brain morphology (e.g. normal ventricles)

 Factors' acting after the illness has been established

• Cultural background: incidence is similar in different countries but the course and outcome is different, studies suggest that patient in developing countries have favourable course compared to developed ones (after emission).
• Life events (stress)
• Social stimulation: under stimulation associated with worsening of the negative symptoms and over stimulation with worsening of the positive symptoms.
• Social background and belief
• Expressed Emotion (hostility, criticism, emotional over involvement) extremely important cause for relapse. Patient living in families with high level of E.E have 2 to 3 times increased risk of relapse.

Management and treatment:

History

MSE

Physical Examination

Investigation (physical and psychological)

Treatment:

• v Pharmacological

Antipsychotic Medications:

1. Conventional antipsychotics:

Chlorpromazine, Thioridazine, Haloperidol (all act to reduce dopamine levels)

Side effects:

•   EPSE (extrapyramidal side effects)

-Acute Dystonia: contraction of muscles to maximal limit, typically sternocleidomastoid and tongue, although can be widespread (e.g. opisthoclonus); eye muscles involvement (oculogyric crises) may occur. Very distressing. Treatment with procyclidine i.v

-Parkinsonism: tremor, rigidity and bradykinesia occurring >1 week after admission. Consider dose reduction or procyclidine oral.

-Akathisia: restlessness, usually of lower limbs, and drive to move. Occurs usually > 1 month after treatment. BDZ and propranolol used for treatment. Often goes undiagnosed. Associated with risk of violence and suicide.

-Tardive dyskinesia: continuous slow writhing movements and sudden involuntary movements, typically of the oral region. Symptoms tend to be irreversible (the older the patient the more likely). Treatment is difficult, procyclidine worsen the condition or reduction of the antipsychotic can make it worse. Vit E may prevent deterioration.

• Anticholinergic side-effects: Dry mouth, blurred vision, difficulty passing urine, urinary retention, constipation, glaucoma, confusion, cognitive impairment.
• Antiadrenergic side-effect: Postural hypotension, tachycardia, sexual dysfunction.
• Antihistaminic side-effect: Sedation, weight gain
• Hyperprolactinemia.
• Cardiovascular risk: prolongation of QTc interval, sudden death (Pimozide)
•  Idiosyncratic: Cholestatic jaundice, altered glucose tolerance, hypersensitivity reaction, skin photosensitivity, yellow pigmentation of the skin, Neuroleptic Malignant Syndrome (rigidity, fluctuating consciousness, and pyrexia. May be fatal , requires ICU admission).

 2.Newer antipsychotic (so called atypical):

 e.g. Olanzapine, Quetiapine, Resperidone, Ziprasidone and many others.

 Safer than the ‘older generation'. Very expensive. Not devoted of serious side effect, depends on the agent. Recently linked to causing DM and hypercholesterolemia. In high doses (and some times within normal dose, could have similar side effect as typical antipsychotic). Other side effect depends on the drug e.g. Olanzapineà weight gain.

All antipsychotics (typical or atypical) have similar clinical effect. None is superior clinically. The exception is Clozapine (only agent licensed for resistant schizophrenia).

Need continuous blood monitoring, weekly for 18 w and then regularly (depends on which guidelines). Risk of agranulocytosis and neutropenia. 

•  Psychosocial approach:

Effective psychosocial interventions include:

• Family Therapy
• Cognitive behavioural therapy
• Social skills training
• Social support
• Illness management skills
• Assertive community treatment.

Delusional Disorder:

The patient present with circumscribed symptoms of non-bizarre delusions, but with absence of prominent hallucinations and no thought disorder or mood disorder. Symptoms should have been present for at least 1 month in The DSM-IV and 3 months in The ICD-10.

Relatively uncommon (0.03% ), but account for up to 2% of hospital admission

Sub-types:

Erotomania (Delusion of Love/ de Clérambault Syndrome)

Patient present with the belief that some important person is secretly in love with them. Clinical samples are often females and forensic samples often males. Patient may make efforts to contact the person, and some cases are associated with dangerous or assaultive behaviour. Stalking.

Grandiose

Patient believes they fill some special role, have some special relationship, or possess some special ability. They may be involved with social or religious organisations.

Jealous (morbid jealousy/ Othello syndrome)

Patient possesses the fixed belief that their spouse or partner has been unfaithful. Often patient try to collect evidence or attempt to restrict their partner's activities. This type of delusional disorder has been associated with forensic cases involving murder.

Persecutory

This is the most common type. Patient are convinced that others are attempting to do them harm. Often they obtain legal recourse, and they sometimes may resort to violence.

Somatic

Varying presentation, from those who have repeat contact with physicians requesting various forms of medical or surgical treatment to patients who are concerned with bodily infestation, or deformity (dysmorphophobia), or odour

Induced or shared delusional disorders (Folie a deux/ Communicated insanity)

A paranoid delusional system which appears to have developed in a person as a result of a close relationship with another person who already has an established delusions. Could be more than one person (e.g. a family, ‘cult'). 90% of cases are members of same family, dominant partner and isolated. F>M. usually separation improve the recipient but not the inducer. Subtypes:

• Folie imposée: primary psychotic illness in one adopted by another
• Folie simultanée: primary psychotic illness in both with identical delusions
• Folie communiqué: primary psychotic illness in both at different times with delusions shared or passed on.
• Folie induite: pre-existing primary psychosis in one patient, adopts fellow patient's delusions.

Delusional misidentifications syndromes:

?Capgras delusions:

The patient believes others have been replaced by identical or near identical impostors. Can apply to animals and other objects, and often associated with aggressive behaviour

?Fregoli delusions:

Patient identifies a familiar person (usually his persecutor) in various other people he encounters (psychologically only).

?Intermetamorphosis syndrome:

The patient believes they can see others change into someone else (both external and internal appearance). Physically and psychologically  

?Subjective doubles delusions (Doppelganger):

The patient believes there is a double who exist and functions independently  

?Reversed subjective double syndrome:

The patient believes that they are an impostor in the process of being physically and psychologically replaced.

Autoscopic syndrome:

The patient sees a double of themselves projected onto other people or objects nearby

  

  

References:

1. Stevens L, Rodin I, Psychiatry: An illustrated colour text, Churchill Livingstone 2001

2. Steple D. Oxford Handbook of Psychiatry, Oxford University Press, 2006

3. World Health Organisation (WHO): ICD10 Classification of Mental and Behavioural Disorders (1992)

4. American Psychiatric Association. The Diagnostic and statistical Manual of Mental Disorders (DSM-IV).1994