schizophrenia

1 – 4 % • Earlier first episode in men; men have higher and longer hospitalisation and worse prognosis than women • Higher rate among the urban poor • In part a genetic disorder

• extensive hallucinations • systemised delusions • intense or formal presentation

• hallucinations/delusions • disorganised and body centric • internal focus – external neglect • voluble/ incoherent presentation • marked lack of hygiene

• hallucinations/ delusions - excessively excited/agitated or frozen motor activity

• isolation/withdrawal • flat/inappropriate emotive expression • bizzare/incomprehensible thought • apathy/loss of motivation

• sudden onset • hallucination/delusion, thought disorder • positive symptoms • excess dopamine activity -> neuroleptics

• flat effect • motivation/volition loss • impaired speech • negative symptoms • structural changes in the brain - smaller frontal lobes - enlarged ventricles - neuronal degeneration

rapid, sudden onset precipitating incident/experince

• Evidence of neural connectivity impairment, particularly involving hippocampus and frontal lobe areas • Less task-related frontal lobe activation

• Positive symptoms of schizophrenia could be due to excess dopamine activity • Some recent studies show larger number of dopamine receptors (type D2) in patients’ brains • Dopamine agonists (amphetamine, L-Dopa, etc.) can generate psychosis • Typical antipsychotics: Chlorpromazine and haloperidol block D2 type dopamine receptors Reduce positive symptoms, but not effective against negative symptoms

• depression, disturbed bowel movements, weight deregulation, drowsiness, menstrual problems

• Extrapyramidal effects (Parkinson-like tremor and rigidity) • Tardive dyskinesia (smacking lips, sucking and sudden movements

• Clozapine and Risperidone • block fewer D2 dopamine receptors but also block some types of serotonin receptors • more effective on positive and negative symptoms and much better with respect to major side effects • However, clozapine can produce agranulocytosis, a white blood cell disorder

• 14% first time sufferers and 25% of repeat sufferers do not respond adequately to antipsychotics • 25% to 50% of patients who benefit from drugs continue to have positive symptoms years after their first episode • Some of this failure could be due non-compliance with drug schedule • Drugs help moderate symptoms, even reduce relapse risk, but fall far short of ‘curing’ psychotic conditions

Fornito et al (2011) recently used this AX-continuous performance task to isolate differences in functional connectivity between schizophrenia sufferers and matched healthy controls. Each trial in the task involves a CUE letter and a PROBE letter. Only when the CUE is the letter A and the probe is the letter X, the response should be a button-press with the right index finger. In all other cases, the response should be a button-press with the right middle-finger. Notice that the AX pairing is most frequent, setting up a tendency towards the index finger response when the probe is X. When the combination seen is BX, however, cognitive load is high, because inhibitory mechanisms need to kick in (along with working memory, which holds the response rule and the identity of the cue letter) to suppress the index finger response and initiate the middle finger response.