Schizophrenia

🛑 Schizophrenia :

  • Schizophrenia is a psychosis -> typically presenting in young adults.

🌷Criteria for diagnosis
1- Two (or more) of:
• Delusions
• Hallucinations
• Disorganized speech
• Disorganized behaviors (including catatonia)
• Negative symptoms

2- Impairment (compared to baseline) in one of:
• Self-care
• Work
• Interpersonal relations

3- Duration:
• 6 months with 1 month of active symptoms

🌷epidemiology:

  • life risk =0.8%
  • age = The onset peaks in early adulthood (18 – 25 years)
  • gender = slightly higher in male (Oestrogen’s regulation of dopamine receptor sensitivity may explain these gender differences)
  • Men tend to have a more severe illness and worse prognosis.

🌷Etiology :

1️⃣ Genetic factors

  • positive family history -> so increase the risk

2️⃣Environmental factors

3️⃣ The brain in schizophrenia :

📌Dopamine hypothesis

  • excess of dopamine transmission (‘hyperdopaminergia’) in schizophrenia (whether due to too much dopamine, too many receptors, etc.)
  • evidence of this hypothesis
    1-Antipsychotic drugs are, without exception, dopamine D2 receptor antagonists.
    2-Dopamine agonists (e.g. amphetamines, l-DOPA) can produce a paranoid psychosis.
    3-Some cerebrospinal fluid (CSF) and brain studies of schizophrenia indicate abnormal levels of dopamine, its metabolites, enzymes or receptors.
  • As well as the hyperdopaminergia during acute schizophrenia in the striatum, there is probably insufficient dopaminergic activity in the prefrontal cortex in patients with chronic schizophrenia, which contributes to the cognitive and negative symptoms.
  • dopamine system is unlikely to be the primary abnormality -> downstream of alterations in glutamate transmission.

📌 Functional imaging studies

  • Abnormalities in regional cerebral blood flow and metabolism
  • neuronal circuits are impaired -> especially frontal cortex, hippocampus, thalamus and cerebellum

📌 Structural brain changes

  • enlargement of the lateral ventricles
  • slight decrease in size of the brain
  • preferential involvement of the temporal lobe and a loss of normal cerebral asymmetries.
  • Some of the abnormalities are present in people before they get ill;

4️⃣ Psychological and social theories

5️⃣ neurodevelopmental model

  • most researchers now view schizophrenia as a neurodevelopmental disorder.
  • caused by abnormalities of brain development, largely driven by genetic predisposition and early environmental factors

🌷either acute or chronic schizophrenia

  • acute = episodic , may recurrent
  • chronic = persist for 2 years

🌷Clinical subtypes of schizophrenia:
see the picture below 👇🏻👇🏻

  • paranoid
  • Disorganized
  • Catatonic
  • Undifferentiated

📌Acute schizophrenia

🌱 Clinical features
Usually present with positive symptoms (delusion, hallucination & thought disorder)

— first rank symptoms
1- thought :
*thought insertion
*thought echo
*thought withdrawal
*thought broadcasting
2- passivity of thought, feeling or action
3- third person auditory hallucination (talk about me)
4- running commentary
5- Delusion

— Bizarre delusion
— odd behavior
— Thought disorder (salad of words)
— lake of insight (reality distortion)
— prodromal period of decline in performance & social withdrawal

And these features not secondary to

  • mood disorder
  • organic cause (e.g substance misuse like amphetamines, temporal lobe epilepsy)

📌Chronic schizophrenia. :-

1️⃣ Antipsychotic drugs:

  • use atypical antipsychotic for negative symptoms -> Olanzapine, Risperdone (in negative symptoms the dopamine level is low while serotonin level is high )
  • see the response after 6weeks
  • intervene earlier in schizophrenia – before symptoms become established -> better outcome
  • after single episode of schizophrenia -> continued for 12–24 months -> If the person remains well-> stop medications
  • Patients who have had multiple episodes or persistent symptoms -> remain on medication for many years
  • given in depot form (if there are concerns around poor adherence)
  • Avoid routine co-administration of anticholinergic agents, or of combinations of antipsychotics.

📌 resistance schizophrenia
*definition: it is a failure to respond to two drugs over 6-week treatment trials of antipsychotic medication (at least one of which is an atypical antipsychotic).
*Rx : clozapine

✔️Clozapine

  • has an important role in patients who are :
    *poorly responsive to antipsychotic
    *develop treatment resistant
    *intolerant of other antipsychotics (Change Rx to clozapine when patient develop tradive dyskinesia)
  • It also decreases the risk of suicide and can reduce aggression.

2️⃣ other Treatment

  • Benzodiazepines are useful for short-term sedation.
  • Antidepressants should be used in the normal fashion for depression occurring in schizophrenia.
  • Electroconvulsive therapy (ECT) is not effective, except for catatonic stupor.

3️⃣ Psychological treatments:

A — family approach

  • education about the illness and changing the behaviour of the family
  • high expressed emotion (EE) families could be taught to lower EE
  • decrease relapse rate
  • prevent exacerbates the apathy and withdrawal of chronic schizophrenia.

B — CBT approach

  • treatment of residual symptoms
  • some efficacy against auditory hallucinations and delusions
  • it effects is small, benefit for short term & patient not able or willing to engage in treatment. 4️⃣ Social interventions
  • The nature of chronic schizophrenia means that many patients have problems with daily living.
  • need multidisciplinary team
  • support employment

** Patients with schizophrenia have high risks of type 2 diabetes and cardiovascular disease, contributing to their excess mortality. Some of this is attributable to side effects of antipsychotic medication. The other reasons are unclear, but probably include genetic predisposition, poor diet and lack of exercise.
Regular medical review and investigations (e.g. for diabetes, lipids, blood pressure) should be an integral part of management.

🌱 Clinical features

Acute schizophrenia (positive symptoms) —> Residual schizophrenia (transitional state between acute and chronic schizophrenia. It describes patients with positive symptoms within the past year who have also developed negative symptoms.) —> chronic schizophrenia (negative symptoms) after 2 years

✅ features
📌negative symptoms :

  • flattened or blunted mood
  • apathy and loss of drive (avolition)
    -social isolation
  • poverty of speech
    -poor self care

📌other features

  • positive symptoms may persist or recur at time of stress
  • mild cognitive impairment (common)

✅The positive–acute/negative–chronic distinction is not absolute.
*Positive symptoms regularly persist or re-emerge in chronic cases
*some patients have negative symptoms in their first episode.

✅ deficit syndrome = prominent + persistent of negative symptoms

✅ symptoms of chronic schizophrenia fall more clearly into three clusters

  • distortion (delusions and hallucinations),
  • disorganization (thought disorder)
  • psychomotor poverty (similar to negative symptoms)

🌷Investigations:

  • clinical diagnosis
  • Ix to rule out the organic disorders (se the DDx below)

🌷Treatment
according to the stage of the illness (acute vs chronic)

📌Acute schizophrenia :

  • Admission (for diagnosis, Ix & Rx)
  • family involvement
  • antipsychotic
    *effective for positive symptoms
    *typical -> haloperidol, chlorpromazine, trifluperazine
  • try to intervene earlier in schizophrenia
  • add a benzodiazepine (if behaviour is difficult to manage or the patient is very distressed)
  • may there are comorbid substance misuse -> you must investigate it -> it indicate worsens prognosis and may require intervention
  • Following an acute episode -> postschizophrenic depression (depression psychosis) -> is common, -> treatment with antidepressants.

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