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- Okhuijsen-Pfeifer, C, et al.
(författare)
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Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 145-
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Tidskriftsartikel (refereegranskat)abstract
- Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.
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| 4. |
- Morillo-Mendez, Lucas, 1991-, et al.
(författare)
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Can the robot "see" what I see? Robot gaze drives attention depending on mental state attribution
- 2023
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Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Mentalizing, where humans infer the mental states of others, facilitates understanding and interaction in social situations. Humans also tend to adopt mentalizing strategies when interacting with robotic agents. There is an ongoing debate about how inferred mental states affect gaze following, a key component of joint attention. Although the gaze from a robot induces gaze following, the impact of mental state attribution on robotic gaze following remains unclear. To address this question, we asked forty-nine young adults to perform a gaze cueing task during which mental state attribution was manipulated as follows. Participants sat facing a robot that turned its head to the screen at its left or right. Their task was to respond to targets that appeared either at the screen the robot gazed at or at the other screen. At the baseline, the robot was positioned so that participants would perceive it as being able to see the screens. We expected faster response times to targets at the screen the robot gazed at than targets at the non-gazed screen (i.e., gaze cueing effect). In the experimental condition, the robot's line of sight was occluded by a physical barrier such that participants would perceive it as unable to see the screens. Our results revealed gaze cueing effects in both conditions although the effect was reduced in the occluded condition compared to the baseline. These results add to the expanding fields of social cognition and human-robot interaction by suggesting that mentalizing has an impact on robotic gaze following.
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