Page 125 - Read Online

Page 111 De Francesco et al. J Transl Genet Genom 2024;8:102-18 https://dx.doi.org/10.20517/jtgg.2023.51

childhood, where the family environment predominates, shared experiences are expected to have a greater
influence on behavior compared to adolescence or adulthood, where shared family experiences give their
[45]
way to more individual ones . An emblematic study that clearly exemplifies the mechanism just described
is the one conducted by Gjone and Stevenson in 1997, one of the first twin studies investigating the nature
of comorbidity between INT-EXT symptoms in childhood and adolescence. The analysis of the authors
emphasized a strong contribution of the shared environment as the primary factor determining covariation
among transdiagnostic factors, but also a consistent genetic influence that was more pronounced in the
[45]
adolescent age group . Despite the variability, one clear trend in subsequent twin studies examining this
comorbidity pattern is the fundamental role played by genetics in its occurrence. For instance, a study by
Cosgrove et al. on a twin sample aged 12 to 18 found a high correlation coefficient between the two macro-
categories of symptoms (r = 0.72), which was due mostly to genetic and partially to unique environmental
factors, explaining 62% and 38% of the shared variance, respectively . As time passed and studies
[43]
continued, twin research provided us with one of the most significant insights regarding the structure of
latent variables underlying the frequent simultaneous occurrence of behavioral and emotional symptoms,
indicating the presence of a unique genetic factor at the basis of this phenomenon [46,47] . These results are
important as they substantially support the hypothesis of the existence of a single latent factor (the “p”
factor) responsible for the latent susceptibility to INT-EXT symptoms. One particularly notable study in this
regard was conducted by Allegrini’s research group . For the first time, they used twin analysis to
[48]
determine the genetic architecture of the “p” factor itself, assessing also its stability across different
childhood and adolescence age groups. The authors found that the model that best fitted their data was a
Common Pathway Model, in which the heritability of the common latent variable was 50%-60%. This
finding, despite the significant influence of specific genetic and environmental factors on each phenotype,
was fundamental to further confirm the presence of a unique latent susceptibility factor, mainly genetic in
nature, responsible for nearly all the symptomatic manifestations .
[48]
Cognitive Disengagement Syndrome (CDS) CDS: A subtype of ADHD or a distinct disorder?
Although initially emerging from studies assessing the dimensionality of ADHD, it is now evident that CDS
symptoms are distinct, though closely associated, with the inattentive symptoms of ADHD [49,50] . The latest
research tends towards the attribution of these symptoms to a specific diagnostic category with peculiarities
that differ from ADHD. Firstly, the inattention typical of CDS would appear to have different characteristics
from that of ADHD. In the first case, the inability to maintain attentive focus would be elicited by internal
stimuli, more similar to rumination observed in Internalizing disorders, which would lead the individual to
engage more frequently in "daydreaming" compared to the general population. Vice versa, the inattention
typical of ADHD appears to be more strongly elicited by external stimuli originating from the
environment [51,52] . Secondly, regarding potential pharmacotherapeutic intervention, it has been highlighted
that the presence of CDS as the main subtype of ADHD appears to predict low adherence and limited
effectiveness to methylphenidate treatment. This outcome would support the hypothesis that a distinction
[53]
can be made between the CDS dimension and ADHD . Finally, CDS and ADHD also exhibit different
[54]
longitudinal stability. Vu et al. , through an assessment of CDS and ADHD symptomatology in a sample
of subjects aged 6 to 12 years followed over a period of 7 years, highlighted how hyperactivity/impulsivity
and inattention symptoms of ADHD tended to remain stable over time. In contrast, CDS symptomatology
showed a declining trend with development, ultimately resulting in its absence in the final measurement,
indicating lower longitudinal stability compared to the ADHD control group. According to the authors, this
result suggests the actual existence of specific symptomatology associated with CDS, with which ADHD is
[54]
often comorbid .