Symptom-specific Effects of Omega-3 Across Neurodevelopmental Symptoms

ASD and ADHD are highly diverse neurodevelopmental conditions with significant co-occurrence-some estimates suggest rates as high as 78% (Leitner, 2014). However, research often excludes neurodiverse children with co-occurring conditions or subclinical symptoms, making many study populations unrepresentative of real-world scenarios. Currently, there are no fully safe and effective treatments for ASD or ADHD symptoms (Groom \& Cortese, 2022; Oono et al., 2013; Williams et al., 2010), which leads many parents to explore complementary treatments, such as omega-3 supplements, among the most popular options (Green et al., 2006; Sinha \& Efron, 2005). Omega-3s, essential for brain development and function, are often deficient in UK children, particularly those with behavioral or learning difficulties (Montgomery et al., 2014).

Some clinical trials suggest that omega-3 supplementation, specifically EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), can improve symptoms such as sleep disturbances, hyperactivity-impulsivity, and inattention in children with ADHD and/or ASD-like difficulties (Bent et al., 2014; Richardson \& Montgomery, 2005). However, findings across studies have been inconsistent, with systematic reviews and meta-analyses yielding varied conclusions (Abdullah et al., 2019; Bloch \& Qawasmi, 2011; Gillies et al., 2012). These discrepancies likely arise from variations in study populations, treatments, outcome measures, and trial designs.

A key limitation is the traditional approach of treating ASD and ADHD as distinct diagnostic categories, adhering to the "latent variable" model in psychiatry, which assumes that symptoms reflect an underlying disorder. This approach has two major flaws: (a) it encourages studying groups presumed homogeneous based on diagnosis, ignoring within-group variability and symptom overlap across disorders, and (b) it directs treatment toward presumed underlying diseases rather than focusing on specific symptoms and their interactions. This "one-size-fits-all" model may contribute to the inconsistent findings in omega-3 research for neurodevelopmental conditions.

In contrast, network science offers a more dynamic approach, viewing disorders as networks of interacting symptoms rather than symptoms being caused by a single underlying disorder. This approach enables visualization of symptom networks, including complex connections that explain symptom overlap. For instance, "bridge" symptoms link different disorder domains, while "central" symptoms, which are highly connected, drive other symptoms and may be ideal treatment targets. Monitoring symptom networks during treatment can help identify individuals more likely to benefit based on unique symptom profiles (Bringmann et al., 2022; Bekhuis et al., 2018).

To date, the network approach has not been used to explore how omega-3 supplementation affects ASD and ADHD symptoms. Our study aims to apply this method to: (a) better understand the shared features of ADHD and ASD by identifying "bridge symptoms" and examining whether omega-3 supplementation influences these symptoms; (b) identify phenotypes that cross diagnostic boundaries and might benefit from omega-3 supplementation; and (c) promote a more inclusive approach to treating ADHD/ASD symptoms by focusing on symptom profiles rather than diagnostic labels.

We hypothesize that sleep disturbances and emotional dysregulation will act as "bridge nodes" that connect ADHD and ASD, given their presence across multiple disorders. Based on prior studies (Montgomery et al., 2014; Richardson, 2006; Richardson \& Montgomery, 2005), we also propose that omega-3 supplementation will directly improve a cluster of symptoms related to sleep, emotional regulation, and hyperactivity-impulsivity. Any additional benefits are expected to be indirect, resulting from improvements in these key symptoms.