Evidence for Dissociable Linkage of Dimensions of Psychopathology to Brain Structure in Youths

Kaczkurkin, Antonia N.; Park, Sophia Seonyeong; Sotiras, Aristeidis; Moore, Tyler M.; Calkins, Monica E.; Cieslak, Matthew; Rosen, Adon F.G.; Ćirić, Rastko; Xia, Cedric Huchuan; Cui, Zaixu; Sharma, Anup; Wolf, Daniel H.; Ruparel, Kosha; Pine, Daniel S.; Shinohara, Russell T.; Roalf, David R.; Gur, Ruben C.; Davatzikos, Christos; Gur, Raquel E.; Satterthwaite, Theodore D.

doi:10.1176/appi.ajp.2019.18070835

Cited by 90 publications

(96 citation statements)

References 39 publications

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“…Consistent with our hypotheses that general psychopathology (p) drives the convergence of structural alterations common across disorders, we found 1) very few associations unique to the Internalizing, Externalizing, or Thought Disorder diagnostic families and 2) that associations with the p factor highly overlapped with those for the three diagnostic families. The pervasive and transdiagnostic nature of these associations is consistent with studies revealing that most structural brain differences are not unique to categorical mental disorders but rather shared across disorders (3,4,11).…”

Section: Discussionsupporting

confidence: 83%

“…The cohort is primarily white (93%), matching South Island demographics (12). Assessments were carried out at birth and ages 3,5,7,9,11,13,15,18,21,26,32,38, and most recently (completed April 2019) 45 years. The relevant ethics committees approved each phase of the Study and informed consent was obtained from all participants.…”

Section: Study Design and Populationmentioning

confidence: 99%

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Pervasively thinner neocortex as a transdiagnostic feature of general psychopathology

Romer

Elliott

Knodt

et al. 2019

Preprint

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AbstractObjectiveNeuroimaging 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 p 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 p factor should overlap with those for the broader diagnostic families.MethodsAnalyses were conducted on structural MRI and psychopathology data collected from 861 members of the population representative Dunedin Study at age 45.ResultsStudy 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 p factor scores exhibited patterns of reduced global and parcel-wise neocortical thickness nearly identical to those associated with the three broad diagnostic families.ConclusionsA 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.

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Section: Discussionsupporting

confidence: 83%

Section: Study Design and Populationmentioning

confidence: 99%

Pervasively thinner neocortex as a transdiagnostic feature of general psychopathology

Romer

Elliott

Knodt

et al. 2019

Preprint

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“…Brain structural covariance networks reflect intra-individual (Yun et al, 2016;Seidlitz et al, 2018a) or inter-individual (Alexander-Bloch et al, 2013;Kaczkurkin et al, 2019;Wannan et al, 2019) covariation in morphology of different brain areas, which may in turn point to common trajectories in brain development and maturation (Yun et al, 2015(Yun et al, , 2016Hunt et al, 2016). Such networks may focus on a range of morphological features including regional brain volume (Spreng et al, 2019), cortical thickness (Solé-Casals et al, 2019), cortical surface area (Sharda et al, 2017), and cortical white-grey contrast (Makowski et al, 2019), as well as the paired or conjoint patterns between different brain regions (Seidlitz et al, 2018b;Hoagey et al, 2019) Brain structural covariance has been estimated using Pearson's correlation coefficient (Seidlitz et al, 2018a;Solé-Casals et al, 2019;Wannan et al, 2019), partial least squares (Hoagey et al, 2019;Spreng et al, 2019), non-negative matrix factorization (Kaczkurkin et al, 2019), and inverse exponential of the difference between z-score transformed brain morphological values (Wee et al, 2013;Yun et al, 2015Yun et al, , 2016, among others. Structural covariance networks are more similar to patterns of functional connectivity than the architecture of white matter connections, suggesting that areas that co-vary in morphological characteristics also belong to the same functional network (Zielinski et al, 2010;Soriano-Mas et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

OUP accepted manuscript

Yun¹,

Boedhoe²,

Vriend³

et al. 2020

Brain

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Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T 1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach.

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“…However, these studies focused on clinical symptoms or cognitive function. The broader set of behavioral phenotypes in the present study allowed us to explore other dimensions of psychopathology, not constrained within the limits of clinical symptoms commonly investigated in many transdiagnostic studies (15,16,28,30,(46)(47)(48). Prior cerebellar structure studies using factor analyses suggested the presence of latent dimensions of psychopathology such as internalizing symptoms, externalizing symptoms, and psychosis symptoms (49), as well as a general psychopathology (or p) factor (50).…”

Section: Discussionmentioning

confidence: 92%

Linking Cerebellar Functional Gradients to Transdiagnostic Behavioral Dimensions of Psychopathology

Dong

Guell

Genon

et al. 2020

Preprint

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Objective: There is ample evidence for high co-morbidity and substantial overlap across psychiatric disorders, encouraging a transition in psychiatry research from categorical to dimensional approaches that integrate neuroscience and psychopathology. Converging evidence suggests that the cerebellum is involved in a wide range of cognitive functions and mental disorders. The authors examined the extent to which cerebellar function can be linked to transdiagnostic dimensions of psychopathology. Methods: The authors used a multivariate data-driven statistical technique (partial least squares) to identify latent dimensions linking human cerebellar connectome as assessed by functional MRI to a large set of clinical, cognitive, and trait measures in a sample of 198 participants, including healthy controls (n=92) as well as patients diagnosed with attention-deficit/hyperactivity disorder (n=35), bipolar disorder (n=36), and schizophrenia (n=35). Macroscale spatial gradients of connectivity at voxel level were used to characterize cerebellar connectome properties, which provide a low-dimensional representation of cerebellar connectivity, i.e., a sensorimotor-supramodal hierarchical organization. Results: This multivariate analysis revealed significant correlated patterns of cerebellar connectivity gradients and behavioral measures that could be represented into four latent dimensions. Each dimension was associated with a unique spatial pattern of cerebellar connectivity gradients across all participants, and linked to different clusters of behavioral measures including clinical, cognitive, and personality scores. Multiple control analyses and 10-fold cross-validation confirmed the robustness and generalizability of the yielded four 4 dimensions. Conclusions: The robust associations between cerebellar functional gradients and multiple transdiagnostic behavioral dimensions of psychopathology highlight the importance of cerebellar function in transdiagnostic behavioral dimensions of psychopathology. 3 1 scores and the corresponding cerebellar gradient composite scores (FDR correction, q<0.05). (D)Group differences in cerebellar connectivity gradient and behavioral composite scores. Significant differences are indicated by asterisks (FDR correction, q < 0.05).

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Evidence for Dissociable Linkage of Dimensions of Psychopathology to Brain Structure in Youths

Cited by 90 publications

References 39 publications

Pervasively thinner neocortex as a transdiagnostic feature of general psychopathology

Pervasively thinner neocortex as a transdiagnostic feature of general psychopathology

OUP accepted manuscript

Linking Cerebellar Functional Gradients to Transdiagnostic Behavioral Dimensions of Psychopathology

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