Medical comorbidities in bipolar disorder (BIPCOM): clinical validation of risk factors and biomarkers to improve prevention and treatment. Study protocol.

BACKGROUND: BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities. METHODS: The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology. DISCUSSION: BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases. TRIAL REGISTRATION: ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602 . Registration date: 18/04/2023.

Mindfulness-based cognitive therapy neurobiology in treatment-resistant obsessive-compulsive disorder: A domain-related resting-state networks approach.

Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes -the precuneus and the frontopolar cortex- were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.

Trait anxiety is associated with attentional brain networks.

Trait anxiety is a well-established risk factor for anxiety and depressive disorders, yet its neural correlates are not clearly understood. In this study, we investigated the neural correlates of trait anxiety in a large sample (n = 179) of individuals who completed the trait and state versions of the State-Trait Anxiety Inventory and underwent resting-state functional magnetic resonance imaging. We used independent component analysis to characterize individual resting-state networks (RSNs), and multiple regression analyses to assess the relationship between trait anxiety and intrinsic connectivity. Trait anxiety was significantly associated with intrinsic connectivity in different regions of three RSNs (dorsal attention network, default mode network, and auditory network) when controlling for state anxiety. These RSNs primarily support attentional processes. Notably, when state anxiety was not controlled for, a different pattern of results emerged, highlighting the importance of considering this factor in assessing the neural correlates of trait anxiety. Our findings suggest that trait anxiety is uniquely associated with resting-state brain connectivity in networks mainly supporting attentional processes. Moreover, controlling for state anxiety is crucial when assessing the neural correlates of trait anxiety. These insights may help refine current neurobiological models of anxiety and identify potential targets for neurobiologically-based interventions.

Development and Validation of a Smartphone-Based App for the Longitudinal Assessment of Anxiety in Daily Life.

Current methods to assess human anxiety often ignore that anxiety is a dynamic process and have limitations such as high recall bias and low generalizability to real life. Smartphone apps using ecological momentary assessment (EMA) may overcome such limitations. We developed a smartphone app for the longitudinal evaluation of anxiety symptoms using EMA. We assessed the feasibility (retention and compliance) and psychometric properties (reliability and validity) of the app over 6 months in a sample of 99 participants with different levels of anxiety. The EMA-based smartphone app was highly feasible. It showed excellent within-person and between-person reliability, high convergent and moderate discriminant validity, and significant incremental validity. Assessing anxiety longitudinally using a smartphone and following EMA principles is feasible and can be reliable and valid. Studies combining EMA-based anxiety longitudinal assessments with other assessment methods deserve further research and may offer novel insights into human anxiety.

A functional magnetic resonance imaging study of frontal networks in obsessive-compulsive disorder during cognitive reappraisal.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) present difficulties in the cognitive regulation of emotions, possibly because of inefficient recruitment of distributed patterns of frontal cortex regions. The aim of the present study is to characterize the brain networks, and their dysfunctions, related to emotion regulation alterations observed during cognitive reappraisal in OCD. METHODS: Adult patients with OCD (n = 31) and healthy controls (HC; n = 30) were compared during performance of a functional magnetic resonance imaging cognitive reappraisal protocol. We used a free independent component analysis approach to analyze network-level alterations during emotional experience and regulation. Correlations with behavioral scores were also explored. RESULTS: Analyses were focused on six networks encompassing the frontal cortex. OCD patients showed decreased activation of the frontotemporal network in comparison with HC (F(1,58) = 7.81, p = 0.007) during cognitive reappraisal. A similar trend was observed in the left frontoparietal network. CONCLUSIONS: The present study demonstrates that patients with OCD show decreased activation of specific networks implicating the frontal cortex during cognitive reappraisal. These outcomes should help to better characterize the psychological processes modulating fear, anxiety, and other core symptoms of patients with OCD, as well as the associated neurobiological alterations, from a system-level perspective.

An fMRI study of cognitive regulation of reward processing in generalized anxiety disorder (GAD).

BACKGROUND: Cognitive regulation can affect the process of decision making. Generalized anxiety disorder (GAD) patients seem to have an impairment in cognitive regulation of reward processing concerning food stimuli. This study aims to explore the impact of GAD in cognitive regulation of food-related rewards. METHODS: GAD patients (n=11) and healthy controls (n=15) performed a cognitive regulation craving task with food images while undergoing a functional magnetic resonance imaging (fMRI) acquisition. Between-group differences in functional connectivity were measured using dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) seeds during cognitive regulation. RESULTS: During cognitive regulation, there was a significant interaction for functional connectivity between the right dlPFC and bilateral vmPFC with the thalamus. GAD patients had lower functional connectivity for cognitive regulation conditions (distance and indulge) than for the non-regulated condition in these clusters, while control participants presented the opposite pattern. GAD group presented fixed food valuation scores after cognitive regulation. CONCLUSIONS: GAD participants showed inflexibility while valuating food images, that could be produced by cognitive regulation deficits underpinned by functional connectivity alterations between prefrontal regions and the thalamus. These results show cognitive inflexibility and difficulty in the modulation of cognitive responses during decision making in GAD patients.

An fMRI study of cognitive reappraisal in major depressive disorder and borderline personality disorder.

BACKGROUND: One common denominator to the clinical phenotypes of borderline personality disorder (BPD) and major depressive disorder (MDD) is emotion regulation impairment. Although these two conditions have been extensively studied separately, it remains unclear whether their emotion regulation impairments are underpinned by shared or distinct neurobiological alterations. METHODS: We contrasted the neural correlates of negative emotion regulation across an adult sample of BPD patients (n = 19), MDD patients (n = 20), and healthy controls (HCs; n = 19). Emotion regulation was assessed using an established functional magnetic resonance imaging cognitive reappraisal paradigm. We assessed both task-related activations and modulations of interregional connectivity. RESULTS: When compared to HCs, patients with BPD and MDD displayed homologous decreased activation in the right ventrolateral prefrontal cortex (vlPFC) during cognitive reappraisal. In addition, the MDD group presented decreased activations in other prefrontal areas (i.e., left dorsolateral and bilateral orbitofrontal cortices), while the BPD group was characterized by a more extended pattern of alteration in the connectivity between the vlPFC and cortices of the visual ventral stream during reappraisal. CONCLUSIONS: This study identified, for the first time, a shared neurobiological contributor to emotion regulation deficits in MDD and BPD characterized by decreased vlPFC activity, although we also observed disorder-specific alterations. In MDD, results suggest a primary deficit in the strength of prefrontal activations, while BPD is better defined by connectivity disruptions between the vlPFC and temporal emotion processing regions. These findings substantiate, in neurobiological terms, the different profiles of emotion regulation alterations observed in these disorders.

The Relationship Between Childhood Physical and Sexual Abuse and Adolescent Cannabis Use: A Systematic Review.

Background: Among adolescents, cannabis use is a health concern due to associations with drug addiction and mental health disorders across the life course. It has been shown that childhood maltreatment is associated with drug addiction in adulthood. However, a better understanding of the relationship between maltreatment and drug use may improve targeted prevention and interventions. The aim of this systematic review is to describe the association between exposure to childhood maltreatment, specifically physical and sexual abuse, with adolescent cannabis use. Methods: A systematic search strategy was applied to Embase, PsycINFO, and Ovid MEDLINE(R) databases. Methods followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Abstract and title screening was performed to identify papers which reported an estimate of the association between childhood physical or sexual abuse and adolescent cannabis use. Full text screening of each paper was performed, and data were extracted and study quality assessed. Weighted means meta-analysis was performed on studies reporting odds ratios as effect estimates. Results: Of 8,780 screened articles, 13 were identified for inclusion. Eight papers received a quality rating score indicating lower risk of bias. Eleven papers reported the relationship between childhood sexual abuse and adolescent cannabis use; effect estimates ranged from AOR 0.53-AOR 2.18 (weighted mean OR 1.29, 95% CI 1.08-1.49). The relationship between childhood physical abuse and adolescent cannabis use was reported in 7 papers; effect estimates ranged from AOR 1.25-AOR 1.87 (weighted mean OR 1.39, 95% CI 1.12-1.66). Differences in the strength of the evidence were observed by the method of exposure ascertainment, and there was some evidence of differences in association by gender, age of cannabis initiation, and the severity of the abuse. Conclusions: This systematic review indicates childhood physical or sexual abuse may increase risk of adolescent-onset cannabis use. Few studies considered variation in timing of onset, or by gender. Adolescent cannabis use precedes is strongly associated with increased risk of negative mental health outcomes; further exploration of adolescent cannabis use's place on the causal pathway between childhood abuse and adult mental health problems is warranted to improve intervention.