Schizophrenia Flashcards
What is involved in schizophrenia?
Breakdown in the relation between:
Thought, emotion and behaviour
Leading to:
Faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation
How is schizophrenia characterised?
Divorcement from reality in the mind (psychosis)
What is the pathogensis?
Unknown
Onset of schizophrenia
Late teens/ early 20s
What percentage of people are effected?
1%
What are the positive symptoms?
Hallucinations, delusions, paranoia, ideas of reference
What are the negative symptoms?
Apathy, social withdrawal, anhedonia, emotional blunting, cognitive deficits, extreme inattentiveness or lack of motivation to interact with the environment
Cognitive symptoms
Poor ‘executive functioning’ (understanding information and making decisions)
Difficulty in focussing & paying attention
Problems with ‘working memory’ (using information immediately and learning it)
Features of schizophrenia
Positive Negative Cognitive Disorganisation Mood symptoms
Cause/Affect Functional Impairments Work Interpersonal relationships Self-care
How is schizophrenia diagnosed?
DSM - American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders
Dependant on presence and duration of signs and symptoms (6 months) with one month of active symptoms
Such as significantly impaired by symptoms, difficulty working or with social relationships, compared to before
Also it can’t be explained by another diagnosis such as dug use or other mental illness
No blood test or biomarker
What criteria must be met to diagnose?
At least 2 of:
- Delusions
- Hallucinations
- Disorganised speech
- Disorganised or catatoinic behaviour
- Negative symptoms
Chance of complete recovery?
5-10%
Patients’ suicide rate?
4.9% - 50 times higher than general population
Factors affecting prognosis
- Age of onset (women 26-32 and men 20-28)
- Sex (1.4 x more frequently in males)
- Premorbid function
- Abrupt versus insidious onset
- Family history
- Duration of untreated illness
- Substance abuse
Two classifications of antipsychotic drugs
Typical and atypical
Typical antipsychotic drugs
- Phenothiazines (Chlorpromazine, Perphenazine, Fluphenazine, Thioridazine)
- Thioxanthenes (Flupenthixol, Clopenthixol)
- Butyrophenones (Haloperidol, Droperidol)
Atypical antipsychotics
Clozapine Risperidone Sulpiride Olanzapine Aripiprazole
Distinction between ‘typical’ and ‘atypical’
- Incidence of extrapyramidal side-effects (less in ‘atypical’ group)
- Efficacy in treatment-resistant group of patients
- Efficacy against negative symptoms.
Typical Antipsychotics D receptor preference?
Blockade of D2 receptors specifically in the mesolimbic dopamine pathway
phenothiazines, thioxanthines and butyrophenones, show preference for D2 over D1 receptors
Atypical Antipsychotics D receptor preference?
clozapine is relatively non-selective between D1 and D2, but has high affinity for D4
Adverse Effects
Extrapyramidal motor disturbances:
- Parkinson-like symptoms
- Neuroleptic Malignant Syndrome
- Tardive dyskinesia (involuntary movements of face, tongue and limbs, appearing after months or years of antipsychotic treatment). (longterm blockade of nigrostriatal Dopamine pathway)
- Acute dystonias
- D2 receptors in mesolimbic system = reward system D2 blockade = ↓reward mechanism
- Seizures
- Cardiac toxicity Produce hypotension (primarily postural) by α-adrenergic blocked.
What are the 4 dopaminergic pathways and their relevance antipsycohotic effects?
– The mesolimbic pathway (positive symptoms)
– The mesocortical pathway (negative symptoms)
– The nigrostriatal pathway (extrapyramidal symptoms and tardive dyskinesia)
– The tuberoinfundibular pathway (hyperprolactinemia)
Where does the mesolimbic pathway start and end?
Ventral tegmental area(VTA) to the nucleus accumbens
Where does the mesocortical pathway start and end?
Ventral tegmental area(VTA) to the prefrontal cortex
Where does the nigrostriatal pathway start and end?
Substantia nigra to the striatum
Where does the tuberohypophyseal pathway start and end?
Within the hypothalamus - tuberal region to the median eminence
Mesolimbic pathway’s role
Key reward circuit, Detects rewarding stimuli. Activation tells individual to repeat the action. (motivation , positive reinforcement)
SCZ ↑ Dopamine = Positive symptoms
D2 antagonists reduce positive symptoms
Mesocortical pathway’s role
important in motivation, emotion and executive functions .
SCZ ↓ Dopamine = Negative symptoms
Treatments aim to increase dopamine in this pathway
Nigrostriatal dopamine pathway’s role
Related to neurological effects caused by D2 antagonists.
- contains about 80% of the brain’s dopamine.
- This pathway is involved in motor planning, dopaminergic neurons stimulate purposeful movement.
- D2 antagonism induces extrapyramidal symptoms
Tuberohypophyseal pathway’s role?
D2 antagonism block dopamine in the tuberoinfundibular pathway, which can cause an increase in bloodprolactinlevels (hyperprolactinemia)
Limitations of typical antipsychotics
- Approximately one-third of patients with schizophrenia fail to respond
- Limited efficacy against negative symptoms
- High proportion of patients relapse
- Side effects and compliance issues
- Atypical/New generation Antipsychotics are preferred for the treatment of various psychotic disorders.
