Psychophysiological Markers of Vulnerability to Psychopathology in Men with an Extra X Chromosome XXYReport as inadecuate

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Studying genetically defined syndromes associated with increased risk for psychopathology may help in understanding neurodevelopmental mechanisms related to risk for psychopathology. Klinefelter syndrome 47,XXY is one of the most common sex chromosomal aneuploidies 1 in 650 male births and associated with increased vulnerability for psychopathology, including psychotic symptoms. Yet, it remains unknown whether this increased risk is associated with underlying psychophysiological mechanisms that are typically deficient in individuals with psychotic disorders. The present study assessed three -classic- psychophysiological markers of psychosis in Klinefelter syndrome KS: smooth pursuit eye movements SPEM, prepulse inhibition PPI and P50 suppression. Fourteen adults with KS and 15 non-clinical adults participated in the study. Data on SPEM reflecting visuo-motor control as well as PPI and P50 suppression reflecting sensory gating were collected. Dysfunctions in SPEM were observed in individuals with KS, with less smooth pursuit as expressed in lower position gain. Also, reduced sensory gating in individuals with KS was suggested by significantly reduced prepulse inhibition of the startle response PPI effect size 1.6. No abnormalities were found in suppression of the P50 effect size 0.6. We speculate that impairments in these psychophysiological mechanisms may reflect core brain dysfunctions that may also mediate the described increased vulnerability for psychotic symptoms in KS. Although speculative, such deficit specific, rather than disorder specific, psychophysiological dysfunctions in KS might convey vulnerability to other types of psychopathology as well. As KS already can be diagnosed prenatally, the predictive value of childhood impairments in prepulse inhibition and smooth pursuit for development of psychopathology later in life could be assessed. In sum, studying individuals with KS may prove to be an avenue of research leading to new hypotheses and insights into -at risk- pathways to psychopathology.

Author: Sophie van Rijn , Hanna Swaab, Maurice Magnée, Herman van Engeland, Chantal Kemner



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