ONE-CARBON METABOLISM AND STRESS IN CHILDREN AND ADOLESCENTS WITH PSYCHOSIS RISK SYNDROME: PRELIMINARY DATA

Abstract Background A dysregulation in one-carbon metabolism, involving folate, vitamin B12 and homocysteine (Hcys) could be implicated in the physiopathology of schizophrenia (for a review, Frankenburg, 2007). Higher Hcys levels have been associated with the disease compared to healthy controls in adults as well as in children and adolescents (Levere et al, 2014). Up to our knowledge, there are no studies in children and adolescents at risk for schizophrenia and other psychosis (Psychosis Risk Syndrome, PRS) testing the one-carbon metabolism parameters. Only a few groups have published results focused only in this population (for a review, Tor et al, 2018). This study aims to compare blood parameters associated with one-carbon metabolism, the clinical and demographic characteristics and stressful life events of a sample of children and adolescents with PRS and healthy controls (HC). Methods A prospective longitudinal study in which help-seeking subjects who met PRS criteria were recruited from the Child and Adolescent Psychiatry and Psychology departments of Hospital Clinic and Hospital Sant Joan de Déu (Barcelona, Spain). Inclusion criteria were: 1) Attenuated positive or negative symptoms in the previous 12 months; 2) Brief intermittent psychotic symptoms; 3)First or second degree relative with schizophrenia or schizotypical disorder plus impairment of functioning; age:10–17 years. Exclusion criteria: IQ<70 and a diagnosis of neurodevelopmental disorder. At baseline, the Semistructured Interview for Prodromal Syndromes and Scale of Prodromal Symptoms (SIPS/SOPS) were administered, as well as a clinical scale battery including measures of stress such as the Stressful Live Events Scale. Blood analysis measuring vitamin B12, folic acid and homocysteine were done. Types of treatment, and dosages were also registered. A sample of age and gender matched HCs were also included. Exclusion criteria: 1st or 2nd degree familiar with a psychotic disorder; a diagnosis of neurodevelopmental disorder and IQ<70.The same assessment was performed in the HC sample. Results 60 PRS subjects (14.9±1.8 years, range: 11–17 years; 74.1% females) and 40 HC (15.4±1.5 years, range: 11–17 years; 65% females) were included. In the PRS sample, 59.4% met criterion 1 for inclusion. 59.4% had familiar history of psychotic disorder. All the SOPS, GAF, LSP, Hamilton and Young scores were significantly higher in PRS than in HC. Number of stressful life events and their subjective affectation were also higher in PRS subjects than in HC (t=-4.939, p<<0.001; t=-5.380, p<0.001). There were no differences in Hcys and, folic acid levels between PRS subjects and HC. However, vitamin B12 levels were different between them, with lower levels in PRS vs HC (425.7±185.7 vs.526.4±159.1, t=2.755, p=0.007) without reaching deficit levels (<300 pg/mL). Higher Hcys levels was correlated with higher number of life events (R=0.245, p=0.037). Lower levels of vitamin B12 were correlated with higher number of stressful life events (R=-0.393, p=0.001) and higher subjective affectation (R=-0.381, p=0.001). Discussion In children and adolescents with PRS, lower vitamin B12 levels than HC have been found, which were associated with higher stressful life events and their subjective affectation. Vitamin B12 is key for brain development, and the possible dysregulation of one carbon metabolism and their association with stress in children and adolescents at risk for psychosis should be further explored as well as the diet of these subjects in a bigger sample to draw consistent conclusions.