Sleep Apnea-Specific Hypoxic Burden, Symptom Subtypes, and Risk of Cardiovascular Events and All-Cause Mortality.

Rationale: Data from population-based cohorts suggest that symptom subtypes and obstructive sleep apnea (OSA)-specific hypoxic burden (HB) could help to better identify patients with OSA at high cardiovascular (CV) risk. Objectives: We aimed to evaluate whether those new markers are associated with the risk of major adverse CV events (MACE) in clinical setting. Methods: Data from the Pays de la Loire cohort were linked to health administrative data to identify the occurrence of MACE (a composite outcome including all-cause mortality, acute myocardial infarction, stroke, and unplanned coronary revascularization) in patients with newly diagnosed OSA and no overt CV disease. Latent class analysis was used to identify subtypes based on eight clinically relevant variables. HB was defined as the total area under the respiratory event-related desaturation curve. Cox proportional hazards models were used to evaluate the association of symptom subtypes and HB with MACE. Measurements and Main Results: Four symptom subtypes were identified (minimally symptomatic [22.0%], disturbed sleep [17.5%], excessively sleepy [49.8%], and moderately sleepy [10.6%]). After a median follow-up of 78 months (interquartile range, 52-109), 592 (11.05%) of 5,358 patients experienced MACE. In a fully adjusted model, HB and overall nocturnal hypoxemia assessed by sleep time with oxygen saturation <90% were the only predictors of MACE (hazard ratio, 1.21; 95% confidence interval, 1.07-1.38; and hazard ratio, 1.34; 95% confidence interval, 1.16-1.55, respectively). The association appeared stronger toward younger patients and women. Conclusion: In clinical setting, patients with OSA who demonstrate elevated OSA-specific HB are at higher risk of a CV event and all-cause mortality. Symptom subtypes were not associated with MACE after adjustment for confounders.

Symptom Subtypes of Obstructive Sleep Apnea Predict Incidence of Cardiovascular Outcomes.

Rationale: Symptom subtypes have been described in clinical and population samples of patients with obstructive sleep apnea (OSA). It is unclear whether these subtypes have different cardiovascular consequences.Objectives: To characterize OSA symptom subtypes and assess their association with prevalent and incident cardiovascular disease in the Sleep Heart Health Study.Methods: Data from 1,207 patients with OSA (apnea-hypopnea index ≥ 15 events/h) were used to evaluate the existence of symptom subtypes using latent class analysis. Associations between subtypes and prevalence of overall cardiovascular disease and its components (coronary heart disease, heart failure, and stroke) were assessed using logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether subtypes were associated with incident events, including cardiovascular mortality.Measurements and Main Results: Four symptom subtypes were identified (disturbed sleep [12.2%], minimally symptomatic [32.6%], excessively sleepy [16.7%], and moderately sleepy [38.5%]), similar to prior studies. In adjusted models, although no significant associations with prevalent cardiovascular disease were found, the excessively sleepy subtype was associated with more than threefold increased risk of prevalent heart failure compared with each of the other subtypes. Symptom subtype was also associated with incident cardiovascular disease (P < 0.001), coronary heart disease (P = 0.015), and heart failure (P = 0.018), with the excessively sleepy again demonstrating increased risk (hazard ratios, 1.7-2.4) compared with other subtypes. When compared with individuals without OSA (apnea-hypopnea index < 5), significantly increased risk for prevalent and incident cardiovascular events was observed mostly for patients in the excessively sleepy subtype.Conclusions: OSA symptom subtypes are reproducible and associated with cardiovascular risk, providing important evidence of their clinical relevance.

Propensity to Sexual Response among Adults with Obsessive-Compulsive Disorder.

BACKGROUND: Propensity to sexual excitation and inhibition is one of the key dimensions of sexuality. Clinicians working with Obsessive-Compulsive Disorder (OCD) patients rarely assess this and other aspects of sexuality, since treatment targets generally symptom reduction. Literature on sexual functioning in OCD patients is scarce and no study has focused on symptom subtypes, nor investigated the psychological processes related to sexual response. OBJECTIVE: In the present short report, we describe an exploratory study investigating the association between symptom subtypes and propensity towards sexual excitation/inhibition in OCD patients, controlling for gender, age and antidepressant treatment. METHODS: Seventy-two OCD patients (mean age = 34.50 years, 37.50% women) completed the Obsessive-Compulsive Inventory-Revised and the Sexual Inhibition/Sexual Excitation Scales. RESULTS: Patients with more severe compulsive washing habit had a lower propensity towards excitation and a higher one towards inhibition due to threat of performance consequences (i.e., contamination with sexually transmitted diseases/having an unwanted pregnancy). Patients with more severe symptoms of checking showed a higher propensity towards inhibition due to the threat of performance consequences. Gender, age and antidepressant treatment were not related to sexual functioning. CONCLUSION: Specific OCD symptom subtypes may be associated with some psychological processes involved in sexual response. Sexual well-being should be carefully evaluated by practitioners and should be regarded as a treatment target. Future studies should investigate more comprehensively the processes involved in sexuality.

Loop Gain as a Predictor of Blood Pressure Response in Patients Treated for Obstructive Sleep Apnea: Secondary Analysis of a Clinical Trial.

Rationale: Randomized trials have shown inconsistent cardiovascular benefits from obstructive sleep apnea (OSA) therapy. Intermittent hypoxemia can increase both sympathetic nerve activity and loop gain ("ventilatory instability"), which may thus herald cardiovascular treatment benefit. Objectives: To test the hypothesis that loop gain predicts changes in 24-hour mean blood pressure (MBP) in response to OSA therapy and compare its predictive value against that of other novel biomarkers. Methods: The HeartBEAT (Heart Biomarker Evaluation in Apnea Treatment) trial assessed the effect of 12 weeks of continuous positive airway pressure (CPAP) versus oxygen versus control on 24-hour MBP. We measured loop gain and hypoxic burden from sleep tests and identified subjects with a sleepy phenotype using cluster analysis. Associations between biomarkers and 24-h MBP were assessed in the CPAP/oxygen arms using linear regression models adjusting for various covariates. Secondary outcomes and predictors were analyzed similarly. Results: We included 93 and 94 participants in the CPAP and oxygen arms, respectively. Overall, changes in 24-hour MBP were small, but interindividual variability was substantial (mean [standard deviation], -2 [8] and 1 [8] mm Hg in the CPAP and oxygen arms, respectively). Higher loop gain was significantly associated with greater reductions in 24-hour MBP independent of covariates in the CPAP arm (-1.5 to -1.9 mm Hg per 1-standard-deviation increase in loop gain; P ⩽ 0.03) but not in the oxygen arm. Other biomarkers were not associated with improved cardiovascular outcomes. Conclusions: To our knowledge, this is the first study suggesting that loop gain predicts blood pressure response to CPAP therapy. Eventually, loop gain estimates may facilitate patient selection for research and clinical practice. Clinical trial registered with www.clinicaltrials.gov (NCT01086800).

Transdiagnostic Symptom Subtypes to Predict Response to Therapeutic Transcranial Magnetic Stimulation in Major Depressive Disorder and Posttraumatic Stress Disorder.

The diagnostic categories in psychiatry often encompass heterogeneous symptom profiles associated with differences in the underlying etiology, pathogenesis and prognosis. Prior work demonstrated that some of this heterogeneity can be quantified though dimensional analysis of the Depression Anxiety Stress Scale (DASS), yielding unique transdiagnostic symptom subtypes. This study investigated whether classifying patients according to these symptom profiles would have prognostic value for the treatment response to therapeutic transcranial magnetic stimulation (TMS) in comorbid major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). A linear discriminant model was constructed using a simulation dataset to classify 35 participants into one of the following six pre-defined symptom profiles: Normative Mood, Tension, Anxious Arousal, Generalized Anxiety, Anhedonia and Melancholia. Clinical outcomes with TMS across MDD and PTSD were assessed. All six symptom profiles were present. After TMS, participants with anxious arousal were less likely to achieve MDD remission compared to other subtypes (FET, odds ratio 0.16, p = 0.034), exhibited poorer PTSD symptom reduction (21% vs. 46%; t (33) = 2.025, p = 0.051) and were less likely to complete TMS (FET, odds ratio 0.066, p = 0.011). These results offer preliminary evidence that classifying individuals according to these transdiagnostic symptom profiles may offer a simple method to inform TMS treatment decisions.

Functional Connectivity within the Frontal-Striatal Network Differentiates Checkers from Washers of Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with high clinical heterogeneity manifested by the presence of obsessions and/or compulsions. The classification of the symptom dimensional subtypes is helpful for further exploration of the pathophysiological mechanisms underlying the clinical heterogeneity of OCD. Washing and checking symptoms are the two major symptom subtypes in OCD, but the neural mechanisms of the different types of symptoms are not yet clearly understood. The purpose of this study was to compare regional and network functional alterations between washing and checking OCD based on resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: In total, 90 subjects were included, including 15 patients in the washing group, 30 patients in the checking group, and 45 healthy controls (HCs). Regional homogeneity (ReHo) was used to compare the differences in regional spontaneous neural activity among the three groups, and local indicators were analyzed by receiver operating characteristic (ROC) curves as imaging markers for the prediction of the clinical subtypes of OCD. Furthermore, differently activated local brain areas, as regions of interest (ROIs), were used to explore differences in altered brain functioning between washing and checking OCD symptoms based on a functional connectivity (FC) analysis. RESULTS: Extensive abnormalities in spontaneous brain activity involving frontal, temporal, and occipital regions were observed in the patients compared to the HCs. The differences in local brain functioning between checking and washing OCD were mainly concentrated in the bilateral middle frontal gyrus, right supramarginal gyrus, right angular gyrus, and right inferior occipital gyrus. The ROC curve analysis revealed that the hyperactivation right middle frontal gyrus had a better discriminatory value for checking and washing OCD. Furthermore, the seed-based FC analysis revealed higher FC between the left medial superior frontal gyrus and right caudate nucleus compared to that in the healthy controls. CONCLUSIONS: These findings suggest that extensive local differences exist in intrinsic spontaneous activity among the checking group, washing group, and HCs. The neural basis of checking OCD may be related to dysfunction in the frontal-striatal network, which distinguishes OCD from washing OCD.

Sex differences within symptom subtypes of mild obstructive sleep apnea.

OBJECTIVES: Prior studies have identified symptom subtypes of moderate to severe (AHI >15) obstructive sleep apnea (OSA). They have not yet been consistently examined in those with mild OSA (AHI 5-15 events/hour). This is important as women are more likely than men to present with mild OSA and may present with different OSA symptoms. The objectives of this study were to determine 1) symptom subtypes in mild OSA and 2) if there are sex differences in the distribution of subtypes. METHODS: The sample included men (n = 921) and women (n = 797) with mild OSA, aged 39-90 years, evaluated with a single night of in-home polysomnography as part of the Sleep Heart Health Study. Latent class analysis determined symptom subtypes. Testing for sex differences relative to OSA severity and symptom subtype used chi-squared test for independence. Bonferroni corrected z-tests compared column proportions. RESULTS: Symptom subtypes of mild OSA were not significantly different than those identified in prior studies of moderate-severe OSA (p > 0.05): minimally symptomatic (36.4%), disturbed sleep (11.6%), moderately sleepy (37%), and excessively sleepy (15%), p > 0.05. Sex differences within the symptom subtypes were significant [χ2(df = 3) = 30.04, p < 0.001, Cramer's V = 0.132]. Relative to men, women were more likely to be in the disturbed sleep subtype (p < 0.05), and the excessively sleepy subtype (p < 0.05) while less likely to be in the moderately sleep (<0.05) subtype. Women and men were equally represented in the minimal symptoms subtype (p > 0.05). CONCLUSIONS: Results suggest symptom reporting among individuals with mild OSA differs as a function of sex. These data have important clinical implications for screening men and women for OSA.

Symptom subtypes and cognitive function in a clinic-based OSA cohort: a multi-centre Canadian study.

BACKGROUND: Distinct symptom subtypes are found in patients with OSA. The association between these subtypes and neurocognitive function is unclear. OBJECTIVE: The purposes of this study were to assess whether OSA symptom subtypes are present in a cohort of Canadian patients with suspected OSA and evaluate the relationship between subtypes and neurocognitive function. METHODS: Patients with suspected OSA who completed a symptom questionnaire and underwent testing for OSA were included. Symptom subtypes were identified using latent class analysis. Associations between subtypes and neurocognitive outcomes (Montreal Cognitive Assessment [MoCA], Rey Auditory Verbal Learning Test [RAVLT], Wechsler Adult Intelligence Scale [WAIS-IV], Digit-Symbol Coding subtest [DSC]) were assessed using analysis of covariance (ANCOVA), controlling for relevant covariates. RESULTS: Four symptom subtypes were identified in patients with OSA (oxygen desaturation index ≥5 events/hour). Three were similar to prior studies, including the Excessively Sleepy (N=405), Disturbed Sleep (N=382) and Minimally Symptomatic (N=280), and one was a novel subtype in our sample defined as Excessively Sleepy with Disturbed Sleep (N=247). After covariate adjustment, statistically significant differences among subtypes (p=0.037) and among subtypes and patients without OSA (p=0.044) were observed in DSC scores; the Minimally Symptomatic subtype had evidence of higher DSC scores than all other groups, including non-OSA patients. No differences were seen in MoCA or RAVLT. CONCLUSIONS: Results support the existence of previously identified OSA symptom subtypes of excessively sleepy, disturbed sleep and minimally symptomatic in a clinical sample from Canada. Subtypes were not consistently associated with neurocognitive function across multiple instruments.

Non-melancholic depressive symptoms increase risk for incident cardiovascular disease: A prospective study in a primary care population at risk for cardiovascular disease and type 2 diabetes.

OBJECTIVE: To assess subtypes of depressive symptoms and their relationship with cardiovascular disease (CVD) morbidity among CVD risk persons. METHODS: A prospective study of 2522 CVD risk persons was conducted. Non-melancholic and melancholic depressive symptoms were assessed by Beck's Depression Inventory. Data on incident CVD was gathered from a national register, after 8 years of follow-up. RESULTS: At baseline, the prevalence of non-melancholic and melancholic depressive symptoms was 14.9% and 5.2%, respectively. A total of 18,413 person-years was followed up, and the incidence of CVD was 9.6% in non-depressive, 14.1% in non-melancholically depressive, and 13.0% in melancholically depressive subjects. When adjusted for age, gender, education, smoking, alcohol use, leisure-time physical activity, hypertension, and dyslipidemia, the incidence rate ratios (IRR) for CVD in subjects with non-melancholic and melancholic depressive symptoms compared to non-depressiveness were IRR 1.69 (95% CI: 1.23-2.31) and IRR 1.31 (95% CI: 0.75-2.26). CONCLUSION: Non-melancholic depressive symptoms seem to increase risk for incident CVD among CVD risk subjects. Considering non-melancholic depressive symptoms might be useful when treating subjects with other CVD risk factors.

Public stigma of obsessive compulsive disorder and schizophrenic disorder: Is there really any difference?

A substantial delay for help-seeking is a serious problem for people with obsessive-compulsive disorder (OCD), a heterogeneous and debilitating mental health condition. Stigma is a major barrier to treatment seeking and further cause social and occupational impairment. Lack of comprehensive research led us to examine the public's stigmatizing attitudes towards checking, contamination, sexuality, aggression, and religion-related OCD symptoms, compared to schizophrenia. After reading one of six random case vignettes, 621 adults completed social distance scale. Analysis of Covariance or ANCOVA indicated that social distance towards violence and sexuality-related OCD symptoms and schizophrenia did not differ; but social distance for those was higher than religion, contamination, and checking subtypes. Although the contamination vignette did not differ from religion and checking vignettes, the theme of religion had a higher social distance than checking symptoms. Consequently, the current findings imply that there is a difference in public stigma among various symptoms of OCD and symptoms related to sexuality and violence, as well as schizophrenia, are associated with more social rejection. Thus, the general public needs access to educational methods of intervention and contact to eliminate stigma and improve the quality of life for people with mental health disorders.

Metacognitive Beliefs and Their Relation with Symptoms in Obsessive-Compulsive Disorder.

INTRODUCTION: Metacognitive constructs have shown promise in explaining the symptoms of Obsessive-Compulsive Disorder (OCD). Few studies have examined the role of metacognitions in symptom dimensions of OCD, despite mounting clinical, neuropsychological and imaging evidence for the distinctiveness of these dimensions. METHODS: Metacognitions were assessed using the Metacognitions Questionnaire (MCQ-30) in 51 participants with DSM IV OCD and 46 healthy controls. The Maudsley Obsessional Compulsive Inventory (MOCI) was used to quantify symptom dimensions, along with the Hamilton Anxiety Rating Scale (HAM-A) for anxiety, and Hamilton Depression Rating Scale (HAM-D) for depression. RESULTS: Individuals with OCD differed from healthy controls on beliefs of uncontrollability and danger when depression and anxiety were controlled for. Correlations between metacognitive beliefs and obsessive-compulsive symptom dimensions were largely similar across the OCD and healthy control groups. Hierarchical regression showed that need to control thoughts contributed to checking, cleaning and rumination symptoms; cognitive self-consciousness to symptoms of slowness; uncontrollability and danger to doubt symptoms; positive beliefs to checking symptoms. CONCLUSIONS: Specific associations between metacognitive variables and the different symptom dimensions of OCD are evident, however, severity of anxiety and depression also contribute to these associations.

The Body Dysmorphic Disorder Symptom Scale: Development and preliminary validation of a self-report scale of symptom specific dysfunction.

The Body Dysmorphic Disorder Symptom Scale (BDD-SS) is a new self-report measure used to examine the severity of a wide variety of symptoms associated with body dysmorphic disorder (BDD). The BDD-SS was designed to differentiate, for each group of symptoms, the number of symptoms endorsed and their severity. This report evaluates and compares the psychometric characteristics of the BDD-SS in relation to other measures of BDD, body image, and depression in 99 adult participants diagnosed with BDD. Total scores of the BDD-SS showed good reliability and convergent validity and moderate discriminant validity. Analyses of the individual BDD-SS symptom groups confirmed the reliability of the checking, grooming, weight/shape, and cognition groups. The current findings indicate that the BDD-SS can be quickly administered and used to examine the severity of heterogeneous BDD symptoms for research and clinical purposes.