Pervasively thinner neocortex as a transdiagnostic feature of general psychopathology

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Neuroimaging research has revealed that structural brain alterations are common across broad diagnostic families of disorders rather than specific to a single psychiatric disorder. Such overlap in the structural brain correlates of mental disorders mirrors already well-documented phenotypic comorbidity of psychiatric symptoms and diagnoses, which can be indexed by a general psychopathology or <jats:italic>p</jats:italic> factor. We hypothesized that if general psychopathology drives the convergence of structural alterations common across disorders then 1) there should be few associations unique to any one diagnostic family of disorders, and 2) associations with the <jats:italic>p</jats:italic> factor should overlap with those for the broader diagnostic families.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Analyses were conducted on structural MRI and psychopathology data collected from 861 members of the population representative Dunedin Study at age 45.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Study members with high scores across three broad diagnostic families of disorders (Externalizing, Internalizing, Thought Disorder) exhibited highly overlapping patterns of reduced global and widely distributed parcel-wise neocortical thickness. Study members with high <jats:italic>p</jats:italic> factor scores exhibited patterns of reduced global and parcel-wise neocortical thickness nearly identical to those associated with the three broad diagnostic families.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>A pattern of pervasively reduced neocortical thickness appears common across all forms of mental disorders and may represent a transdiagnostic feature of general psychopathology. As has been documented with regard to symptoms and diagnoses, the underlying brain structural correlates of mental disorders may not exhibit specificity, the continued pursuit of which may limit progress toward more effective strategies for etiological understanding, prevention, and intervention.</jats:p></jats:sec>

Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure

“…This dimensional scoring can be accomplished with a bifactor model 20 , which yields specific factors (e.g., externalizing, psychosis) that are orthogonal to the general factor and to each other. Previous research has revealed that such psychopathology dimensions relate to differences in brain structure 19 , 21 – 24 . However, it remains unclear whether these psychopathology dimensions help to elucidate abnormal neurodevelopment; furthermore, it remains unknown to what extent they can help to dissociate disorder-general from disorder-specific abnormalities.…”

Building Theories on Top of, and Not Independent of, Statistical Models: The Case of the p-factor

“…Reasonablyestablished correlates of the p-factor include lower levels of intelligence and executive functioning, income, conscientiousness, and agreeableness, as well as higher levels of family history of psychopathology, impairment, childhood maltreatment, harsh parenting, peer delinquency, self-harm, neuroticism, impulsivity, sensation seeking, aggression, and hopelessness (e.g., Albott et al, 2018;Caspi et al, 2014;Harden et al, 2020;Lahey et al, 2012;Tackett et al, 2013;Watts et al, 2019). Other work has shown that a general factor of psychopathology is moderately heritable (Tackett et al, 2013;Waldman et al, 2016), with a smattering of neurobiological substrates (e.g., altered connectivity in the anterior cingulate cortex and cerebellum, reduced grey matter volume; Kaczkurkin et al, 2018;Romer, Elliott, et al, 2019;Romer, Knodt, et al, 2019).…”

Building theories on top of, and not independent of, statistical models: The case of the p-factor

“…Reasonablyestablished correlates of the p-factor include lower levels of intelligence and executive functioning, income, conscientiousness, and agreeableness, as well as higher levels of family history of psychopathology, impairment, childhood maltreatment, harsh parenting, peer delinquency, self-harm, neuroticism, impulsivity, sensation seeking, aggression, and hopelessness (e.g., Albott et al, 2018;Caspi et al, 2014;Harden et al, 2020;Lahey et al, 2012;Tackett et al, 2013;Watts et al, 2019). Other work has shown that a general factor of psychopathology is moderately heritable (Tackett et al, 2013;Waldman et al, 2016), with a smattering of neurobiological substrates (e.g., altered connectivity in the anterior cingulate cortex and cerebellum, reduced grey matter volume; Kaczkurkin et al, 2018;Romer, Elliott, et al, 2019;Romer, Knodt, et al, 2019).…”