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not associated with EXT behaviors when controlling for ADHD-Inattention [9,64-68] . Specifically, a recent
[69]
report conducted by Becker et al. highlighted that existing studies investigating the relationship between
CDS and Externalizing disorders demonstrate the existence of significant, albeit small, associations between
CDS and a range of EXT behaviors such as ADHD (across its three presentations ), oppositional defiant
disorder, and conduct disorder. However, the majority of these associations become non-significant or even
[49]
negative when co-varying ADHD symptoms . Furthermore, two large nationally representative surveys [4,70]
have shown that the most common (and extensively studied) EXT disorder that tends to co-occur with CDS
is ADHD. Epidemiological studies seem to demonstrate that in 25-40% of youths with ADHD [4,70,71] and in
46% of adults with ADHD , elevated symptoms of CDS coexist. More specifically, in the study conducted
[4]
[4]
by Barkley et al. , more than half of the participants (59%) exhibited comorbidity patterns between CDS
and ADHD, primarily with presentations of ADHD characterized by significant features of inattention,
rather than the hyperactive-impulsive type. This aligns with previous studies that have explored this overlap
[4]
in children [61,64,70] and adults . These findings suggest that the relationship between CDS and ADHD
represents a comorbidity between two distinct yet related disorders, rather than a categorization within a
single common disorder [69,71] .

Furthermore, this comorbidity appears to be associated with increased risks, characterized by the presence
of more pronounced symptoms of both disorders compared to what is observable for each specific disorder
alone, especially when compared to individuals with CDS only [69,71] . Moreover, examining the existing
relationship between CDS and various psychopathological symptoms, some studies have demonstrated that
CDS symptoms are strongly associated with Inattention and INT behaviors of ADHD compared to
hyperactivity-impulsivity and EXT behaviors of ADHD . While the association between CDS and
[49]
internalization is robust and generally tends to persist even when controlling for ADHD symptoms, the
association between CDS and impulsivity-hyperactivity or externalization often turns out to be non-
significant or negative when controlling for ADHD inattention. Despite these findings, the etiology of each
of these associations with CDS remains largely unknown and represents an important area for future
[49]
research on the subject .

THE USE OF TWIN STUDY DESIGN TO ANALYZE THE ETIOLOGY OF THE COMORBIDITY
BETWEEN CDS AND INTERNALIZING/EXTERNALIZING SYMPTOMS
Twin studies on CDS and Internalizing symptoms
As highlighted in the previous paragraphs, there is a large body of twin literature that has focused on
analyzing the underlying causes of the covariance between symptoms belonging to the categories of INT-
EXT disorders, which emphasizes the crucial role of genetics in the occurrence of this pattern [43,48,72] .
Nevertheless, at present, there are very few twin studies that have been concerned with analyzing this
pattern by including CDS within the research design. Regarding the co-occurrence of CDS with
internalizing disorders, the only twin study that has been carried out so far is the one conducted by Scaini et
[73]
al. in 2023 . More specifically, this work focused on the analysis of the underlying causes of comorbidity
between CDS and various anxiety-related phenotypes in a sample of 400 pairs of Italian twins aged 8 to 18
years. From a preliminary analysis, the authors found a significant association between CDS and only two
types of anxiety, namely somatic and generalized anxiety.

Therefore, they tested the goodness of fit to the data of the different multivariate models specific to the twin
methodology, finding that the one with the best fit was a Common pathway model . This model indicated
[73]
that the associations between CDS and the two anxiety phenotypes were influenced by a unique latent
susceptibility factor whose variance was, in turn, significantly determined by both genetic and
environmental common factors.