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‐ • Mor holo ical chan es –brain as mmetr with decreased cortical/hippocampal size and increased ventricular size • Neurotransmitter changes The theories were largely derived from observations of pharmacological observations, unfortunately not on detail understanding to the neurochemistry of particular neutronasmitter system – Dopamine theory –central and most important one, it will be discussed urther in detail – Glutamate theory –comes from psychotic symptoms induced by administrations o NMDA ‐ antagon sts etamine an p encyc i ine , toget er wit o servations from post ‐ mortem examination • It was proposed that reduced glutamatergic and increased dopaminergic neurotransmissions may impair the gating function of GABA ‐ ergic neurons projecting themselves into the thalamus –which cause deteriorations of the SENSORY „GATE“. – Serotonine theory –schizophrenia ‐ like symptoms induced by LSD , many atypical antipsychotics block also 5 ‐ HT receptors 7 Dopamine theory: dopaminergic systems in CNS • Schema of dopamine pathways in the brain Please se Ran ‐ Dale . 495 Fi . 34.3 8 Dopamine theory of schizophrenia • ymp oms o sc zop ren a ar se rom yperac v y o opam nerg cpa ways n mesolimbic/mesocorticalsystem • It was based on observation that psychotic symptoms and related behavioural – Induced by • Drugs causing dopamine release – e.g., amphetamines • ‐ agon s s e.g., romocryp ne an opam ne precursors e ‐ – Inhibited by • Drugs blocking dopamine storage (e.g., reserpine ) • D ‐ antagonists • Dopamine receptors – D 1 type (D 1 and D 5 ) and D 2 ‐ type (D 2 , D 3 , D 4 ) • D 2 ‐ receptors – Are evidently involved – There is a strong correlation between D 2 ‐ antagonistic effects and antipsychotic action – Clinical response is reached when 80% of D 2 receptors is occupied • Involvement of other D ‐ receptors ??? D 4 –specific antagonists are ineffective • Some theories suggest that the key issue may be the overactivationof D 2 receptors in subsorticalregions (positive symptoms) while activation of D 1 receptors can be deficient (negative symptoms) 9 • Positive symptoms , – Hallucinations (usually hearing of voices, typically spurring) – Incoherent thought: disconnection ‐ loosing of associations, inability of lo ical anal sis of the situation ambivalence –contradictor thou hts Suspiciousness, hostility and potentially agressvity – Disorganised speech – Stereotype/abnormal movements • Negative symptomes – Affective flattening –poor emotional experience n e on a – oss o e capac y o exper ence p easure – Avolition ‐ lack of desire, drive, or motivation to pursue goals – Withdrawal from social contacts • Cognitive symptomes – Impaired attention, working memory and executive function • Clinical picture may vary considerably, especially according to the positive/negative symptoms balance 10 11 • Positive symptoms • Negative symptoms – Hallucinations – Delusions – Social withdrawal – Emotional withdrawal – Disordered thinking – Disorganized speech – Lack of motivation – Poverty of speech – Combativeness – Agitation – Blunted affect – Poor insight – Paranoia – Poor judgement – Poor self ‐ care 12
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