Heritability of overlapping impulsivity and compulsivity dimensional phenotypes

Funder: David Winston Turner Endowment FundAbstract: Impulsivity and compulsivity are traits relevant to a range of mental health problems and have traditionally been conceptualised as distinct constructs. Here, we reconceptualised impulsivity and compulsivity as partially overlapping phenotypes using a bifactor modelling approach and estimated heritability for their shared and unique phenotypic variance within a classical twin design. Adult twin pairs (N = 173) completed self-report questionnaires measuring psychological processes related to impulsivity and compulsivity. We fitted variance components models to three uncorrelated phenotypic dimensions: a general impulsive–compulsive dimension; and two narrower phenotypes related to impulsivity and obsessiveness.There was evidence of moderate heritability for impulsivity (A2 = 0.33), modest additive genetic or common environmental effects for obsessiveness (A2 = 0.25; C2 = 0.23), and moderate effects of common environment (C2 = 0.36) for the general dimension, This general impulsive–compulsive phenotype may reflect a quantitative liability to related mental health disorders that indexes exposure to potentially modifiable environmental risk factors

Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders

The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks

Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits

Individual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains cortical-striatal-thalamic-cortical dysfunction across different disorders remains unclear. Here, we characterized the relationship between cortical-striatal-thalamic-cortical effective connectivity, estimated using dynamic causal modelling of resting-state functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder and gambling disorder. 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 obsessive-compulsive disorder patients, 22 gambling disorder patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Three core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients’ scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and greater bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with lower bottom-up connectivity in the dorsal circuit. In patients, higher clinical severity was also linked to lower bottom-up connectivity in the dorsal circuit, but these findings were independent of phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels and only weak associations were observed for functional connectivity measures. Together, our results demonstrate that cortical-striatal-thalamic-cortical dysfunction across obsessive-compulsive disorder and gambling disorder may be better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes

Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits.

Individual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains cortical-striatal-thalamic-cortical dysfunction across different disorders remains unclear. Here, we characterized the relationship between cortical-striatal-thalamic-cortical effective connectivity, estimated using dynamic causal modelling of resting-state functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder and gambling disorder. 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 obsessive-compulsive disorder patients, 22 gambling disorder patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Three core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients' scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and greater bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with lower bottom-up connectivity in the dorsal circuit. In patients, higher clinical severity was also linked to lower bottom-up connectivity in the dorsal circuit, but these findings were independent of phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels and only weak associations were observed for functional connectivity measures. Together, our results demonstrate that cortical-striatal-thalamic-cortical dysfunction across obsessive-compulsive disorder and gambling disorder may be better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes

Η Διερεύνηση της Παρορμητικότητας σε Ασθενείς με Οριακή Διαταραχή Προσωπικότητας: Το Δίλημμα του Φυλακισμένου ως Κοινωνική Πειραματική Συνθήκη για τη Μελέτη Λήψεως Αποφάσεων

Στην παρούσα διπλωματική εργασία επιχειρείται η έμμεση εξέταση της παρορμητικότητας, ως παράγοντα διερεύνησης εναλλακτικών και διλημματικών επιλογών του ατόμου ανάμεσα σε μια άμεση αλλά μικρή αμοιβή, έναντι μιας μεγάλης αλλά αναβεβλημένης αμοιβής (Delay-Discounting) του ερωτηματολογίου Kirby, η αξιολόγηση μιας σειράς διαστάσεων ψυχοπαθολογίας, παραγόντων προσωπικότητας, καθώς και του δείκτη ηθικής απόκρισης της προσωπικότητας, μεταξύ ασθενών με οριακή διαταραχή προσωπικότητας (ΟΔΠ) και υγιών μαρτύρων, κατά τη συμμετοχή τους στην υπολογιστική εκδοχή του Επαναλαμβανόμενου Παιχνιδιού του Διλήμματος του Φυλακισμένου (IPD), ως κοινωνικής πειραματικής συνθήκης για τη μελέτη λήψεως αποφάσεων. Συμπερασματικά, από τα στοιχεία της έρευνας φαίνεται να προκύπτει ότι οι δύο υπό μελέτη ομάδες οι οποίες υπεβλήθησαν σε αντίστοιχες μετρήσεις ψυχομετρικών δοκιμασιών διαφοροποιούνται συστηματικά ως προς το μεγαλύτερο αριθμό των παραγόντων ψυχοπαθολογίας, των διαστάσεων προσωπικότητας και ηθικής συμπεριφοράς. Σημαντικό εύρημα, ωστόσο, αποτελεί η απουσία διαφοροποίησης τους κατά την έμμεση εξέτασή τους στον ψυχολογικό άξονα της παρορμητικότητας, όπου δεν εντοπίστηκαν ουσιαστικές διαφορές.The present study attempts to examine impulsivity, indirectly, as a factor in exploring the individual&apos;s alternative and dilemmatic choices between an immediate but low reward versus a large but delayed reward (Delay-Discounting) of the Kirby questionnaire, the evaluation of a number of dimensions of psychopathology, personality factors, as well as the index of moral personality response, between patients with borderline personality disorder (BPD) and healthy controls, during their participation in the Repetitive Game of the Prisoner Dilemma - computer version (IPD), as a social treaty for the study of decision-making. In conclusion, the data of the research seem to show that the two study groups that underwent respective measurements of psychometric tests differ systematically in terms of the largest number of psychopathological factors, personality dimensions and moral behavior. An important finding, however, is their lack of differentiation when examined indirectly on the psychological axis of impulsivity, where no significant differences were found

Harnessing brain imaging data to personalise management of fatigue in inflammatory arthritis

Rheumatoid arthritis and psoriatic arthritis are chronic inflammatory conditions in which chronic fatigue persists in the majority of patients despite successful management of disease activity. This multidimensional, disabling fatigue correlates with various brain characteristics. Current treatments inadequately address fatigue, emphasising the importance of exploring its neural underpinnings and what potential imaging the brain has to inform the management of fatigue in these inflammatory arthritis conditions. To do so, I applied brain measures to stratify inflammatory arthritis patients into fatigue-related subgroups with potentially amendable biological differences, identify correlates of different subdimensions of fatigue, and predict fatigue follow-up after fatigue-specific or pharmacological treatments in different inflammatory arthritis cohorts of rheumatoid and psoriatic arthritis. I hypothesised that there are (1) subtypes of fatigue in patients with rheumatoid arthritis, illustrated by distinct subgroups stratified by a relationship between neuroimaging brain characteristics and fatigue; (2) statistically significant correlates of subcomponents of fatigue; (3) statistically significant predictors of fatigue scores after non-pharmacological treatments in rheumatoid arthritis; (4) statistically significant predictors of fatigue scores after pharmacological treatments in rheumatoid and psoriatic arthritis; (5) models that can predict individual fatigue outcomes above chance in a trial of non-pharmacological treatments in rheumatoid arthritis using machine learning to combine multiple neuroimaging and clinical variables. I found a link between neuroimaging brain connectivity and distinct subgroups in rheumatoid arthritis related to fatigue subdimensions, albeit only within a specific cohort. Associations emerged between brain imaging metrics and baseline fatigue subcomponents, showing varied correlations with different metrics. In rheumatoid arthritis patients undergoing exercise or cognitive-behavioural interventions, baseline brain imaging predictors of fatigue centred on structural connectivity from the precuneus to the anterior cingulate cortex. In contrast, I did not find significant neuroimaging predictors of fatigue in rheumatoid arthritis patients who started a new disease-modifying antirheumatic drug. However, I did find such predictors in psoriatic arthritis patients, encompassing cortical thickness of the visual pericalcarine cortex and functional connectivity within the default mode and salience networks, involving the inferior parietal lobule and anterior cingulate cortex. Finally, models using diverse neuroimaging and clinical modalities along with different machine learning algorithms outperformed models using solely the baseline median fatigue. Significantly, these models did not surpass chance level or replicate their utility in usual care patients in an independent rheumatoid arthritis cohort. Overall, despite not finding a model that can predict individual fatigue outcomes, this research advanced our understanding by pinpointing different fatigue-related brain circuits, delineating associations with subcomponents, and identifying group-level predictors of fatigue. If such findings are utilised by future studies using molecular and brain stimulation techniques, neuroimaging can offer innovative solutions to patients to significantly improve their quality of life

The mind’s mirror:A neurocognitive perspective on confidence and metacognition in psychiatry

This thesis investigates the feeling of confidence as a metacognitive construct, exploring its neurobiological foundations, biases, and its relationship with psychiatric symptoms and disorders. Through a series of studies encompassing clinical samples of patients with obsessive-compulsive disorder and/or gambling disorder, healthy controls and general population samples, it investigates the disruptions in metacognitive abilities across different contexts. By employing a range of methodologies such as functional MRI, eye-tracking, cognitive computer tasks, questionnaires and computational modelling, we gain a multifaceted understanding of confidence in psychiatry.This work shows confidence abnormalities across various (sub)clinical psychiatric conditions, with specific directions for different symptom presentations. Moreover, it demonstrates that motivational processes can modulate metacognitive. Confidence is explored across multiple hierarchical levels to look at the interplay between confidence and self-beliefs and their relation to transdiagnostic psychopathology.Additionally, it shows that OCD patients exhibit underconfidence across the confidence hierarchy compared to control subjects, but intact metacognitive sensitivity. In patients with GD our studies indicate overconfidence in gambling-related contexts.This thesis also discusses the generalizability of neurocognitive findings from general population samples to clinical samples. It shows that clinical OCD patients have distinct metacognitive patterns (namely, underconfidence) compared to highly compulsive individuals from the general population (namely, overconfidence).Overall, our findings indicate that disturbances in confidence, and in a broader sense, metacognition, are a central aspect of mental health and thereby a potential therapeutic target