The goddess who spins the thread of life: Klotho, psychiatric stress, and accelerated aging.

BACKGROUND: Longevity gene klotho (KL) is associated with age-related phenotypes but has not been evaluated against a direct human biomarker of cellular aging. We examined KL and psychiatric stress, including posttraumatic stress disorder (PTSD), which is thought to potentiate accelerated aging, in association with biomarkers of cellular aging. METHODS: The sample comprised 309 white, non-Hispanic genotyped veterans with measures of epigenetic age (DNA methylation age), telomere length (n = 252), inflammation (C-reactive protein), psychiatric symptoms, metabolic function, and white matter neural integrity (diffusion tensor imaging; n = 185). Genotyping and DNA methylation were obtained on epi/genome-wide beadchips. RESULTS: In gene by environment analyses, two KL variants (rs9315202 and rs9563121) interacted with PTSD severity (peak corrected p = 0.044) and sleep disturbance (peak corrected p = 0.034) to predict advanced epigenetic age. KL variant, rs398655, interacted with self-reported pain in association with slowed epigenetic age (corrected p = 0.048). A well-studied protective variant, rs9527025, was associated with slowed epigenetic age (p = 0.046). The peak PTSD interaction term (with rs9315202) also predicted C-reactive protein (p = 0.049), and white matter microstructural integrity in two tracts (corrected ps = 0.005 - 0.035). This SNP evidenced a main effect with an index of metabolic syndrome severity (p = 0.015). Effects were generally accentuated in older subjects. CONCLUSIONS: Rs9315202 predicted multiple biomarkers of cellular aging such that psychiatric stress was more strongly associated with cellular aging in those with the minor allele. KL genotype may contribute to a synchronized pathological aging response to stress and could be a therapeutic target to alter the pace of cellular aging.

Misophonia is related to stress but not directly with traumatic stress.

The relationship between misophonia, stress, and traumatic stress has not been well characterized scientifically. This study aimed to explore the relationships among misophonia, stress, lifetime traumatic events, and traumatic stress. A community sample of adults with self-reported misophonia (N = 143) completed structured diagnostic interviews and psychometrically validated self-report measures. Significant positive correlations were observed among perceived stress, traumatic stress, and misophonia severity. However, multivariate analyses revealed that perceived stress significantly predicted misophonia severity, over and above traumatic stress symptoms. The number of adverse life events was not associated with misophonia severity. Among symptom clusters of post-traumatic stress disorder, only hyperarousal was associated with misophonia severity. These findings suggest that transdiagnostic processes related to stress, such as perceived stress and hyperarousal, may be important phenotypic features and possible treatment targets for adults with misophonia.

Examining emotional functioning in misophonia: The role of affective instability and difficulties with emotion regulation.

Misophonia is a newly described condition characterized by sensory and emotional reactivity (e.g., anxiety, anger, disgust) to repetitive, pattern-based sounds (e.g., throat clearing, chewing, slurping). Individuals with misophonia report significant functional impairment and interpersonal distress. Growing research indicates ineffective coping and emotional functioning broadly (e.g., affective lability, difficulties with emotion regulation) are central to the clinical presentation and severity of misophonia. Preliminary evidence suggests an association between negative emotionality and deficits in emotion regulation in misophonia. Still, little is known about (a) the relationships among specific components of emotional functioning (e.g., emotion regulation, affective lability) with misophonia, and (b) which component(s) of misophonia (e.g., noise frequency, emotional and behavioral responses, impairment) are associated with emotional functioning. Further, despite evidence that mood and anxiety disorders co-occur with misophonia, investigation thus far has not controlled for depression and anxiety symptoms. Examination of these relationships will help inform treatment development for misophonia. The present study begins to disambiguate the relationships among affective lability, difficulties with emotion regulation, and components of misophonia. A sample of 297 participants completed questionnaires assessing misophonia, emotional functioning, depression, anxiety, and COVID-19 impact. Findings indicated that misophonia severity was positively associated with each of these constructs with small to medium effect sizes. When controlling for depression, anxiety, and COVID-19 impact, results from this preliminary study suggest that (a) difficulties with emotion regulation may be correlated with misophonia severity, and (b) misophonic responses, not number of triggers or perceived severity, are associated with difficulties with emotion regulation. Overall, these findings begin to suggest that emotion regulation is important to our understanding the risk factors and treatment targets for misophonia.

Development and Initial Validation of the Duke Misophonia Questionnaire.

Misophonia is characterized by decreased tolerance and accompanying defensive motivational system responding to certain aversive sounds and contextual cues associated with such stimuli, typically repetitive oral (e. g., eating sounds) or nasal (e.g., breathing sounds) stimuli. Responses elicit significant psychological distress and impairment in functioning, and include acute increases in (a) negative affect (e.g., anger, anxiety, and disgust), (b) physiological arousal (e.g., sympathetic nervous system activation), and (c) overt behavior (e.g., escape behavior and verbal aggression toward individuals generating triggers). A major barrier to research and treatment of misophonia is the lack of rigorously validated assessment measures. As such, the primary purpose of this study was to develop and psychometrically validate a self-report measure of misophonia, the Duke Misophonia Questionnaire (DMQ). There were two phases of measure development. In Phase 1, items were generated and iteratively refined from a combination of the scientific literature and qualitative feedback from misophonia sufferers, their family members, and professional experts. In Phase 2, a large community sample of adults (n = 424) completed DMQ candidate items and other measures needed for psychometric analyses. A series of iterative analytic procedures (e.g., factor analyses and IRT) were used to derive final DMQ items and scales. The final DMQ has 86 items and includes subscales: (1) Trigger frequency (16 items), (2) Affective Responses (5 items), (3) Physiological Responses (8 items), (4) Cognitive Responses (10 items), (5) Coping Before (6 items), (6) Coping During (10 items), (7) Coping After (5 items), (8) Impairment (12 items), and Beliefs (14 items). Composite scales were derived for overall Symptom Severity (combined Affective, Physiological, and Cognitive subscales) and Coping (combined the three Coping subscales). Depending on the needs of researchers or clinicians, the DMQ may be use in full form, individual subscales, or with the derived composite scales.

Psychometric Performance of the Miller Forensic Assessment of Symptoms Test (M-FAST) in Veteran PTSD Assessment.

This study examined the psychometric properties of a widely used measure of symptom exaggeration, the Miller Forensic Assessment of Symptoms Test (M-FAST, Miller, 2001), in a sample of 209 (83.7% male) trauma-exposed veterans (57.9% probable current posttraumatic stress disorder; PTSD). M-FAST total scores evidenced acceptable internal consistency, but several subscales showed poor internal consistency. Factor analytic and item-response theory analyses identified seven poorly performing items. Comparisons with other measures of psychopathology and response validity (including subscales from the Minnesota Multiphasic Personality Inventory-2 Restructured Form) revealed that M-FAST scores were highly correlated with indices of psychopathology while less strongly associated with measures of symptom over-reporting. Empirically and clinically-derived (using a follow-up testing-the-limits procedure) revised M-FAST scores failed to improve the measure's psychometric performance. Results raise concerns about the validity of the M-FAST for identifying malingering in veterans with PTSD and carry implications for access to care and forensic evaluations in this population.

Psychometric Properties of the Dissociative Subtype of PTSD Scale: Replication and Extension in a Clinical Sample of Trauma-Exposed Veterans.

The addition of the dissociative subtype of posttraumatic stress disorder (PTSD) to the DSM-5 has spurred investigation of its genetic, neurobiological, and treatment response correlates. In order to reliably assess the subtype, we developed the Dissociative Subtype of PTSD Scale (DSPS; Wolf et al., 2017), a 15-item index of dissociative features. Our initial investigation of the dichotomous DSPS lifetime items in a veteran epidemiological sample demonstrated its ability to identify the subtype, supported a three-factor measurement structure, distinguished the three subscales from the normal-range trait of absorption, and demonstrated the greater contribution of derealization and depersonalization symptoms relative to other dissociative symptomatology. In this study, we replicated and extended these findings by administering self-report and interview versions of the DSPS, and assessing personality and PTSD in a sample of 209 trauma-exposed veterans (83.73% male, 57.9% with probable current PTSD). Results replicated the three-factor structure using confirmatory factor analysis of current symptom severity interview items, and the identification of the dissociative subtype (via latent profile analysis). Associations with personality supported the discriminant validity of the DSPS and suggested the subtype was marked by tendencies towards odd and unusual cognitive experiences and low positive affect. Receiver operating characteristic curves identified diagnostic cut-points on the DSPS to inform subtype classification, which differed across the interview and self-report versions. Overall, the DSPS performed well in psychometric analyses, and results support the utility of the measure in identifying this important component of posttraumatic psychopathology.