A pszichózisok molekuláris architektúrája, valamint ennek kapcsolata a neurokognitív funkciókkal és a pszichoszociális stresszel = The molecular architecture of psychosis and its relationship with neurocognition and psychosocial stress
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Abstract:
mechanizmusok, a kognitiv funkciok es a pszichoszocialis behatasok kozotti osszefuggeseket vizsgaltuk. Elsősorban a neuregulin 1 (NRG1) es az AKT kaszkad korrelatumaira voltunk kivancsiak. Kimutattuk az NRG1 kockazati genotipusa (pszichozis konverzio magas kockazatu allapotbol) es az intenziv negativ erzelmi kornyezet (expressed emotion) kozotti kapcsolatot. Az NRG1 altal aktivalt AKT foszforilacio osszefuggott a betegseghez tarsulo szenzoros kapuzasi zavarral (P50 habituacio) es a hippocampus szerkezetevel. E mechanizmusok egeszseges szemelyek koreben osszefuggtek a delusiv tendenciakkal es a habituacioval. Az NRG1-gyen felul kimutattuk a ZNF804 kapcsolatat a figyelmi funkciokkal, az FMRP pedig az elemi vizualis jelfeldolgozassal korrelalt (utalas a fragilis X szindroma es a szkizofrenia osszefuggesere). A tarsas műkodesek zavara interperszonalis tranzakciok alatt redukalodott oxytocin felszabadulassal tarsult, amely a negativ tunetek jelentős varianciajat magyarazta, es elettani szinten a habituacioval fuggott ossze. Csokkent habituaciot es abnormalis inger-jutalom kapcsolatokat talaltunk dopamin agonistakat szedő Parkinson-koros betegeknel, amely korrelalt a pszichozis-jellegű szubklinikai tunetekkel. Vegul adatokat nyertunk a pszichologiai trauma es a szkizofrenia kapcsolatarol, kimutatva, hogy ez rosszabb neuropszichologiai teljesitmennyel tarsul, mig a vizualis jelfeldolgozast nem erinti. | We investigated the relationship among the molecular mechanisms of schizophrenia-spectrum disorders, neurocognition, and psychosocial functions. We focused on the correlates of neuregulin 1 (NRG1)-induced AKT phosphorylation. Results indicated that the risk genotype of NRG1 (psychosis conversion from high risk states) influences reaction to harsh interpersonal criticism (expressed emotion). NRG1-induced AKT activation correlated with sensory gating (P50) habituation and structural anomalies of the hippocampus. In non-clinical individuals, these mechanisms were related to delusive tendencies and habituation. Beyond NRG1, we obtained data on the relationship of attentional functions and ZFN804, as well as the relationship between early visual processing and FMRP (a potential link to fragile X syndrome). Impairments in psychosocial functions were associated with decreased oxytocin release during interpersonal interactions, which explained a major portion of variance in negative symptoms, and it was related to habituation. Less habituation/aberrant stimulus-reward associations were present as an effect of dopamine agonists and striatal deficits in Parkinson’s patients, which were related to psychosis-like features. Finally, we studied the role of psychological trauma in schizophrenia and found that it is associated with worse neuropsychological functions but unaltered early visual processing.Keywords:
Neurocognitive
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