Diminished social motivation in early psychosis is associated with polygenic liability for low vitamin D

Alex Hatzimanolis*, Sarah Tosato, Mirella Ruggeri, Doriana Cristofalo, Leonidas Mantonakis, Lida Alkisti Xenaki, Stefanos Dimitrakopoulos, Mirjana Selakovic, Stefania Foteli, Ioannis Kosteletos, Ilias Vlachos, Rigas Filippos Soldatos, Nikos Nianiakas, Irene Ralli, Konstantinos Kollias, Angeliki Aikaterini Ntigrintaki, Pentagiotissa Stefanatou, Robin M. Murray, Evangelos Vassos, Nikos C. Stefanis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Insufficiency of vitamin D levels often occur in individuals with schizophrenia and first-episode psychosis (FEP). However, it is unknown whether this represents a biological predisposition, or it is essentially driven by illness-related alterations in lifestyle habits. Lower vitamin D has also been associated with adverse neurodevelopmental outcomes and predominant negative psychotic symptoms. This study aimed to investigate the contribution of polygenic risk score for circulating 25-hydroxyvitamin D concentration (PRS-vitD) to symptom presentation among individuals with FEP enrolled in the Athens First-Episode Psychosis Research Study (AthensFEP n = 205) and the Psychosis Incident Cohort Outcome Study (PICOS n = 123). The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale at baseline and follow-up assessments (AthensFEP: 4-weeks follow-up, PICOS: 1-year follow-up). Premorbid intelligence and adjustment domains were also examined as proxy measures of neurodevelopmental deviations. An inverse association between PRS-vitD and severity of negative symptoms, in particular lack of social motivation, was detected in the AthensFEP at baseline (adjusted R 2 = 0.04, p < 0.001) and follow-up (adjusted R 2 = 0.03, p < 0.01). The above observation was independently validated in PICOS at follow-up (adjusted R 2 = 0.06, p < 0.01). No evidence emerged for a relationship between PRS-vitD and premorbid measures of intelligence and adjustment, likely not supporting an impact of lower PRS-vitD on developmental trajectories related to psychotic illness. These findings suggest that polygenic vulnerability to reduced vitamin D impairs motivation and social interaction in individuals with FEP, thereby interventions that encourage outdoor activities and social engagement in this patient group might attenuate enduring negative symptoms.

Original languageEnglish
Article number36
JournalTranslational psychiatry
Issue number1
Early online date18 Jan 2024
Publication statusE-pub ahead of print - 18 Jan 2024


Dive into the research topics of 'Diminished social motivation in early psychosis is associated with polygenic liability for low vitamin D'. Together they form a unique fingerprint.

Cite this