The Relationship of Rumination, Worry and OCD Symptoms During Technology Supported Mindfulness Therapy for OCD.

BACKGROUND: In this study, we re-examined data from a previous randomized controlled trial investigating 'technology supported mindfulness' (TSM)-an 8-week treatment intervention for individuals experiencing OCD. The current analysis involves an examination of the longitudinal relationships between rumination, worry and OCD symptom changes during mindfulness treatment, in comparison to a waitlist control. METHODS: Participants experiencing OCD (n = 71) were randomly assigned to 8 weeks of (1) TSM or (2) waitlist control. We tested the extent to which rumination (using the Ruminative Response Scale) and worry (using the Penn State Worry Questionnaire) are associated with OCD symptom changes during the acute phase of treatment, concurrently (i.e., within the same longitudinal model). RESULTS: Generalized linear model (GLM) results indicated a significant time (week 1 vs. week 8) by condition interaction involving decreased rumination in the TSM condition: F(1, 61) = 13.37, p = 0.001, partial η2 = 0.18 and observed power = 0.94. A second GLM demonstrated decreased worry in the TSM condition: F(1, 69) = 37.34, p = 0.001, partial η2 = 0.35 and observed power = 0.83. Longitudinal 'latent difference' structural equation analyses demonstrated a cross-lagged association between worry (but not rumination) and OCD symptom changes. CONCLUSIONS: Individuals in the TSM condition experienced greater reductions in rumination and worry during 8 weeks of TSM treatment compared to the waitlist control, and reduced worry predicted subsequent OCD symptom reduction.

Investigating the association of anxiety disorders with heart rate variability measured using a wearable device.

BACKGROUND: Reduced vagally-mediated heart rate variability (HRV) has been associated with anxiety disorders (AD). The aim of this study was to use a wearable device and remote study design to re-evaluate the association of HRV with ADs, anxiety-related traits, and confounders. METHODS: 240 individuals (AD = 120, healthy controls = 120) completed an at-home assessment of their short-term resting vagally-mediated HRV using a wristband, monitored over videoconference. Following quality control, analyses were performed investigating differences in HRV between individuals with AD (n = 119) and healthy controls (n = 116), associations of HRV with anxiety-related traits and confounders, and antidepressants effects on HRV in patients, including analyses stratified by ancestry (i.e., European, East Asian, African). RESULTS: Among the confounders investigated, only age had a significant association with HRV. Patients with an AD had significantly lower vagally-mediated HRV than healthy controls in the European subsample, with a trend of significance in the whole sample. HRV was significantly associated with the Hamilton Anxiety Rating Scale (HAM-A) but not with antidepressant use in the European subsample. LIMITATIONS: The study measures occurred in a non-standardized at-home setting, and the three ancestry group sample sizes were unequal. CONCLUSIONS: This study demonstrates reduced vagally-mediated HRV among patients with ADs compared to healthy controls. Results also point to low HRV being related to more physical anxiety symptoms (measured via HAM-A), suggesting a possible anxiety subtype. Overall, this study highlights the feasibility of using wearables for patients and encourages exploration of the biological and clinical utility of HRV as a risk factor for ADs.

Genetic and polygenic investigation of heart rate variability to identify biomarkers associated with Anxiety disorders.

Given that anxiety disorders (AD) are associated with reduced vagally-mediated heart rate variability (HRV), genetic variants related to HRV may provide insight into anxiety etiology. This study used polygenic risk scores (PRS) to explore the genetic overlap between AD and HRV, and investigated whether HRV-related polymorphisms influence anxiety risk. Resting vagally-mediated HRV was measured using a wearable device in 188 European individuals (AD=101, healthy controls=87). AD PRS was tested for association with resting HRV, and HRV PRS for association with AD. We also investigated 15 significant hits from an HRV genome-wide association study (GWAS) for association with resting HRV and AD and if this association is mediated through resting HRV. The AD PRS and HRV PRS showed nominally significant associations with resting HRV and anxiety disorders, respectively. HRV GWAS variants associated with resting HRV were rs12980262 (NDUFA11), rs2680344 (HCN4), rs4262 and rs180238 (GNG11), and rs10842383 (LINC00477). Mediation analyses revealed that NDUFA11 rs12980262 A-carriers and GNG11 rs180238 and rs4262 C-carriers had higher anxiety risk through lower HRV. This study supports an anxiety-HRV genetic relationship, with HRV-related genetic variants translating to AD. This study encourages exploration of HRV genetics to understand mechanisms and identify novel treatment targets for anxiety.

Neurocognitive performance in the context of acute symptom reduction in OCD: Treatment effects and the impact of BDNF.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with neurocognitive impairments. The present study examined the effect of treatment on neurocognitive performance in OCD and the relationship between neurocognitive change and symptom change. The present study also examined polymorphisms influencing brain derived neurotrophic factor (BDNF) as predictors of neurocognitive change. METHOD: Treatment-seeking participants with OCD (N = 125) were assigned to cognitive behavioural therapy (CBT) alone, CBT combined with regular physical exercise, exercise alone, or a waitlist control group. Measures of OCD symptom severity and a neuropsychological battery were completed pre- and post-treatment. Blood or saliva samples were used to genotype the BDNF Val66Met polymorphism. RESULTS: OCD symptom severity was not cross-sectionally associated with neurocognitive performance. Several neurocognitive measures improved over treatment. The BDNF Val66Met polymorphism was significantly associated with worse performance on the Stroop test but did not significantly predict change in neurocognitive performance over time. LIMITATIONS: Limitations include lack of a healthy control group. CONCLUSION: Improvement in neurocognitive performance corresponded to symptomatic improvement and was independent of the BDNF Val66Met genotype.

The GABA A-Receptor 2 (GABRG2) Gene in obsessive-compulsive disorder / O gene do receptor GABA A-2 (GABRG2) no transtorno obsessivo-compulsivo

OBJECTIVE: The γ-aminobutyric acid type A (GABA A) system may be implicated in obsessive-compulsive disorder, based on its major role in modulation of anxiety and its function as the principal inhibitory neurotransmitter system in the cortex. In addition, glutamatergic/GABAergic mechanisms appear to play a role in the pathophysiology of obsessive-compulsive disorder, making the GABA A receptor-γ2 (GABργ2) gene a good candidate for susceptibility in this disorder. METHOD: 118 probands meeting DSM-IV criteria for primary obsessive-compulsive disorder and their available parents were recruited for participation in this study and informed consent was obtained. An NciI restriction site polymorphism in the second intron was genotyped and data was analyzed using the Transmission Disequilibrium Test. RESULTS: In total, 61 of the participating families were informative (i.e., with at least one heterozygous parent). No biases were observed in the transmission of either of the two alleles (χ2 = 0.016, 1 d.f., p = 0.898) to the affected probands in the total sample. CONCLUSION/DISCUSSION: While these results do not provide support for a major role for the GABA A receptor-γ2 in obsessive-compulsive disorder, further investigations of this gene in larger samples are warranted.

OBJETIVO: O sistema gabaérgico tipo A (GABA A) pode estar implicado no transtorno obsessivo-compulsivo devido ao seu grande papel na modulação da ansiedade e da sua função como o principal neurotransmissor inibidor no córtex. Além disso, mecanismos glutamatérgicos/gabaérgicos parecem desempenhar um papel na fisiopatologia do transtorno obsessivo-compulsivo, tornando o gene do receptor GABA A-γ2 (GABRG2) um bom gene candidato para a suscetibilidade genética a este transtorno. MÉTODO: 118 probandos que preencheram os critérios do DSM-IV para transtorno obsessivo-compulsivo primário e seus pais (quando disponíveis) foram recrutados para a participação neste estudo; consentimento informado foi obtido. Um polimorfismo no sítio de restrição da enzima NciI, localizado no íntron 2, foi genotipado e os dados foram analisados utilizando-se o Teste de Desequilíbrio de Transmissão. RESULTADOS: No total, 61 das famílias participantes foram informativas (ou seja, com pelo menos um progenitor heterozigoto). Não foi observado desequilíbrio de transmissão de qualquer um dos dois alelos (χ2 = 0,016, 1 g.l., p = 0,898) aos probandos afetados. CONCLUSÃO/DISCUSSÃO: Apesar de estes resultados não fornecerem suporte para um papel importante para o gene GABA A-γ2 no transtorno obsessivo-compulsivo, novas investigações desse gene em amostras maiores são justificadas.