ETD

• autism spectrum disorder
• biochemical correlates
• psychotic symptoms

Recent translational and clinical research emphasizes the concept of interacting neurochemical disruptions as a ground for the development of psychosis. At the same time, studies have increasingly documented substantial neurostructural and neurofunctional alterations in autism spectrum disorder (ASD) leading to a growing interest in biochemical markers that may be linked to ASD-related traits. Recent evidences highlighted the presence of shared inflammation, immune pathway alterations in ASD and Schizophrenia hypothesizing potential overlapping biomarkers between the two disorders. However, to the best of our knowledge, data on possible links and causal relations among biological factors and psychotic symptoms in the context of autism spectrum are still scarce. In this perspective, we aimed to investigate possible biochemical correlates of psychotic symptoms in a sample of ASD adults, also considering gender differences. Moreover, we investigated possible positive or negative predictive biological factors of psychotic symptoms in ASD, mainly focusing on inflammatory markers, neuropeptides and growth factors.
For this study, we recruited a total of 22 ASD adult patients assessed through the Structured Clinical Interview for Psychotic Spectrum – Self-Report version (PSY-SR) investigating the psychotic spectrum, ranging from milder manifestations and subclinical conditions to full-blown psychosis.
It is composed of 164 dichotomous (yes/no) items, organized into 5 domains based on clinical and nosographic criteria: Interpersonal sensitivity, investigates an unreasonable and excessive sensitivity to judgment, criticism, and rejection. Moreover, Paranoia domain includes aspects of hypervigilance, suspiciousness, and distrust toward others. Schizoid domain explores the schizotypal area. Finally, Misperceptions domain focuses on illusory or hallucinatory-like perceptual experiences, while Typical symptoms one is related to the classical psychotic presentation. The blood sample was drawn in order to perform biochemical evaluations. For each subject, two aliquots of platelet pellets and approximately 16–18 aliquots of plasma and serum were obtained. All biochemical parameters were detected with ELISA kit.
In particular, the biochemical variables investigated were: homocisteine (HCy), intrapiastrinic and plasmic 5-HT, tryptophan (TRP) and tryptophan pathways such as kynurenin (KYN), kynurenic acid, quinolinic acid, BNDF, IL-1beta, IL-6, IL8, IL10. Results reported female subjects scored significantly higher across several PSY domains and subdomains, including hallucinations, illusions, depersonalization/derealization, schizoid traits, and interpretative thinking, while male patients showed higher micromolar HCy levels.
Spearman correlation analyses revealed significant correlations between PSY total and single domains and biochemical correlates with medium to strong correlations.
Finally, linear regression analyses, performed by using PSY-SR domains, subdomains scores as dependent variables and all biochemical variables as independent ones, revealed interesting results.
In light of these evidences, this worked could help in improving diagnostic procedures, as well as in identifying new targets for therapeutic strategies in ASD and psychoses.
Indeed, monitoring TRP/KYN metabolites, 5-HT, BDNF, and cytokines may aid in predicting psychotic features, informing personalized clinical interventions in ASD populations. Globally, our work highlighted that in ASD adults psychotic symptoms may be associated with specific biochemical alterations, in particular linked to immune/inflammatory system and kynurenine pathway. A further understanding of the biochemical basis of psychotic symptoms in autism may help to reach a better understanding of biochemical underpinnings of ASD and psychosis.