Central neurodegeneration in Kennedy's disease accompanies peripheral motor dysfunction.

Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease (KD), is a rare hereditary neuromuscular disorder demonstrating commonalities with amyotrophic lateral sclerosis (ALS). The current study aimed to define functional and central nervous system abnormalities associated with SBMA pathology, their interaction, and to identify novel clinical markers for quantifying disease activity. 27 study participants (12 SBMA; 8 ALS; 7 Control) were recruited. SBMA patients underwent comprehensive motor and sensory functional assessments, and neurophysiological testing. All participants underwent whole-brain structural and diffusion MRI. SBMA patients demonstrated marked peripheral motor and sensory abnormalities across clinical assessments. Increased abnormalities on neurological examination were significantly associated with increased disease duration in SBMA patients (R2 = 0.85, p < 0.01). Widespread juxtacortical axonal degeneration of corticospinal white matter tracts were detected in SBMA patients (premotor; motor; somatosensory; p < 0.05), relative to controls. Increased axial diffusivity was significantly correlated with total neuropathy score in SBMA patients across left premotor (R2 = 0.59, p < 0.01), motor (R2 = 0.63, p < 0.01), and somatosensory (R2 = 0.61, p < 0.01) tracts. The present series has identified involvement of motor and sensory brain regions in SBMA, associated with disease duration and increasing severity of peripheral neuropathy. Quantification of annualized brain MRI together with Total Neuropathy Score may represent a novel approach for clinical monitoring.

Conceptualizing impulsivity as a construct in relation to posttraumatic stress disorder symptom severity among women.

Despite the established association between posttraumatic stress disorder (PTSD) and impulsivity, the literature is limited regarding impulsivity as a multifaceted construct. That is, the field's understanding of how PTSD symptoms may increase particular impulsive tendencies and behaviors is constrained by examining impulsivity solely as an umbrella term. The aim of the present study was to determine if there are differential associations between PTSD symptom severity and various components of impulsivity across multiple self-report measures. A sample of 215 undergraduate women (M age = 19.77 years, SD = 1.91, Range: 18-39 years) completed the PTSD Checklist for DSM-5 (PCL-5), Barratt Impulsiveness Scale (BIS-11), short version of the UPPS-P Impulsive Behavior Scale (SUPPS-P), and Delaying Gratification Inventory (DGI). Structural equation modeling was used to examine associations between PTSD symptoms and each measure's subscales. The findings included significant predictions from PTSD symptoms to the BIS-11 Attentional Impulsiveness subscale, ß = .23, SE = .07, 95% CI [.09, .37]; DGI Physical Pleasures, ß = -.24, SE = .07, 95% CI [-.38, -.11], and Achievement subscales, ß = -.19, SE = .08, 95% CI [-.34, -.04]; and the SUPPS-P Positive Urgency, ß = .22, SE = .08, 95% CI [.07, .37], and Negative Urgency subscales, ß = .32, SE = .07, 95% CI [.19, .46]. These results have implications for precision medicine approaches that emphasize targeting these specific facets of impulsivity, with likely downstream effects on health risk behaviors for emerging adult women.

Differential Indirect Effects of Military Sexual Trauma on Posttraumatic Stress Disorder Symptom Clusters via Past-Year Intimate Partner Violence Experiences.

Women who serve in the military are at high risk for experiencing military sexual trauma (MST) and intimate partner violence (IPV), both of which are associated with symptoms of posttraumatic stress disorder (PTSD). To improve understanding of the psychological effects of experiencing multiple forms of interpersonal violence, it is important to identify the ways in which recent IPV experiences differentially increase the risk of specific PTSD symptom clusters for women with a history of MST. We aimed to identify if past-year IPV experiences mediate the relation between MST experiences and PTSD symptom clusters (i.e., intrusions, avoidance, negative alterations in cognitions/mood, hyperarousal) using structural equation modeling. A mail survey was administered to a sample of US female veterans at two time points 12 months apart. Among 198 participants, 108 women (54.5%) reported MST at Time 1, and 73 women (36.9%) reported IPV experiences in the past year at Time 2. PTSD symptom severity ranged from asymptomatic to beyond the diagnostic cutoff for a probable PTSD diagnosis. Past-year IPV experiences significantly mediated the association between MST history and PTSD avoidance symptoms, and MST history and PTSD negative alterations in cognitive/mood symptoms. No significant mediating effect was found for intrusion symptoms or hyperarousal symptoms. These findings can inform evidence-based practices for appropriate screening, assessment, detection, and intervention, including primary and secondary prevention efforts to instrumentally reduce future experiences of violence for female survivors of interpersonal violence.

Novel approaches to assessing upper motor neuron dysfunction in motor neuron disease/amyotrophic lateral sclerosis: IFCN handbook chapter.

Identifying upper motor neuron (UMN) dysfunction is fundamental to the diagnosis and understanding of disease pathogenesis in motor neuron disease (MND). The clinical assessment of UMN dysfunction may be difficult, particularly in the setting of severe muscle weakness. From a physiological perspective, transcranial magnetic stimulation (TMS) techniques provide objective biomarkers of UMN dysfunction in MND and may also be useful to interrogate cortical and network function. Single, paired- and triple pulse TMS techniques have yielded novel diagnostic and prognostic biomarkers in MND, and have provided important pathogenic insights, particularly pertaining to site of disease onset. Cortical hyperexcitability, as heralded by reduced short interval intracortical inhibition (SICI) and increased short interval intracortical facilitation, has been associated with the onset of lower motor neuron degeneration, along with patterns of disease spread, development of specific clinical features such as the split hand phenomenon, and may provide an indication about the rate of disease progression. Additionally, reduction of SICI has emerged as a potential diagnostic aid in MND. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction in MND. Separately, sophisticated brain imaging techniques have uncovered novel biomarkers of neurodegeneration that have bene associated with progression. The present review will discuss the utility of TMS and brain neuroimaging derived biomarkers of UMN dysfunction in MND, focusing on recently developed TMS techniques and advanced neuroimaging modalities that interrogate structural and functional integrity of the corticomotoneuronal system, with an emphasis on pathogenic, diagnostic, and prognostic utility.

Session-level effects of cognitive processing therapy and prolonged exposure on individual symptoms of posttraumatic stress disorder among U.S. veterans.

OBJECTIVE: To compare the course of change in individual posttraumatic stress disorder (PTSD) symptoms during prolonged exposure therapy (PE) and cognitive processing therapy (CPT). METHOD: We analyzed data from a previously published randomized clinical trial comparing PE and CPT among male and female U.S. military veterans with PTSD (Schnurr et al., 2022). Using data from a self-rated PTSD symptom measure administered before each therapy session, we evaluated individual symptom change from pretreatment to final therapy session (N = 802). Then, using network intervention analysis, we modeled session-by-session PTSD symptom networks that included treatment allocation (CPT vs. PE) as a node in the networks, allowing us to compare individual symptom change following each session in each treatment. RESULTS: Relative to CPT, PE was associated with greater reduction in 10 PTSD symptoms from first to final session of therapy. Numerous treatment-specific effects on individual symptoms emerged during the treatment period; these session-level effects occurred only in symptoms relatively specific to the diagnosis of PTSD (e.g., avoidance, hypervigilance). PE was associated with greater reduction in avoidance following the introduction and early weeks of imaginal exposure. The treatments yielded comparable effects on trauma-related blame and negative beliefs from pretreatment to final therapy session. However, there were differences in session-level change in these symptoms that may reflect differential timing of interventions that reduce distorted cognitions within each treatment. CONCLUSIONS: Findings may facilitate the shared decision-making process for patients choosing between CPT and PE. Session-level results provide direction for future research on the specific intervention components of CPT and PE. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Efficacy and safety of CNM-Au8 in amyotrophic lateral sclerosis (RESCUE-ALS study): a phase 2, randomised, double-blind, placebo-controlled trial and open label extension.

Background: CNM-Au8® is a catalytically-active gold nanocrystal neuroprotective agent that enhances intracellular energy metabolism and reduces oxidative stress. The phase 2, randomised, double-blind, placebo-controlled trial and open label extension RESCUE-ALS trial evaluated the efficacy and safety of CNM-Au8 for treatment of amyotrophic lateral sclerosis (ALS). Methods: RESCUE-ALS and its long-term open label extension (OLE) were conducted at two multidisciplinary ALS clinics located in Sydney, Australia: (i) the Brain and Mind Centre and (ii) Westmead Hospital. The double-blind portion of RESCUE-ALS was conducted from January 16, 2020 (baseline visit, first-patient first-visit (FPFV)) through July 13, 2021 (double-blind period, last-patient last-visit (LPLV)). Participants (N = 45) were randomised 1:1 to receive 30 mg of CNM-Au8 or matching placebo daily over 36 weeks in addition to background standard of care, riluzole. The primary outcome was mean percent change in summed motor unit number index (MUNIX), a sensitive neurophysiological biomarker of lower motor neuron function. Change in total (or summated) MUNIX score and change in forced vital capacity (FVC) were secondary outcome measures. ALS disease progression events, ALS Functional Rating Scale (ALSFRS-R) change, change in quality of life (ALSSQOL-SF) were assessed as exploratory outcome measures. Long-term survival evaluated vital status of original active versus placebo randomisation for all participants through at least 12 months following last-patient last-visit (LPLV) of the double-blind period. RESCUE-ALS and the open label study are registered in clinicaltrials.gov with registration numbers NCT04098406 and NCT05299658, respectively. Findings: In the intention-to-treat (ITT) population, there was no significant difference in the summated MUNIX score percent change (LS mean difference: 7.7%, 95% CI: -11.9 to 27.3%, p = 0.43), total MUNIX score change (18.8, 95% CI: -56.4 to 94.0), or FVC change (LS mean difference: 3.6, 95% CI: -12.4 to 19.7) between the active and placebo treated groups at week 36. In contrast, survival analyses through 12-month LPLV demonstrated a 60% reduction in all-cause mortality with CNM-Au8 treatment [hazard ratio = 0.408 (95% Wald CI: 0.166 to 1.001, log-rank p = 0.0429). 36 participants entered the open label extension (OLE), and those initially randomised to CNM-Au8 exhibited a slower rate of disease progression, as measured by time to the occurrence of death, tracheostomy, initiation of non-invasive ventilatory support, or gastrostomy tube placement. CNM-Au8 was well-tolerated, and no safety signals were observed. Interpretation: CNM-Au8, in combination with riluzole, was well-tolerated in ALS with no identified safety signals. While the primary and secondary outcomes of this trial were not significant, the clinically meaningful exploratory results support further investigation of CNM-Au8 in ALS. Funding: The RESCUE-ALS was substantially funded by a grant from FightMND. Additional funding was provided by Clene Australia Pty Ltd.

Comparing the Prevalence of Probable DSM-IV and DSM-5 Posttraumatic Stress Disorder in a Sample of U.S. Military Veterans Using the PTSD Checklist.

Posttraumatic stress disorder (PTSD) changed substantially when Diagnostic and Statistical Manual of Mental Disorders transitioned from fourth (DSM-IV) to fifth (DSM-5) edition. Hoge et al. found that although diagnostic prevalence remained consistent across nomenclatures, diagnostic concordance was low (55%). Study goals were to examine both the generalizability of these findings and whether either diagnosis systematically excluded patients. U.S. veterans (N = 1,171) who completed the PTSD Checklist for DSM-IV (PCL-S) and DSM-5 (PCL-5) were classified as: probable PTSD on both measures; probable PTSD on PCL-S only; probable PTSD on PCL-5 only; or no PTSD on either measure. Diagnostic prevalence was equivalent. Unlike Hoge et al.'s findings, diagnostic concordance was high (91.3%). Furthermore, observed demographic and severity differences were driven by disparities between veterans in the no PTSD versus the probable PTSD groups, not diagnostic changes. Findings suggest translatability across measures and that diagnostic changes do not systematically exclude patients.

The moderating roles of emotion regulation and coping self-efficacy on the association between PTSD symptom severity and drug use among female sexual assault survivors.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and substance use disorders are a significant comorbid concern among sexual assault survivors. Thus, underlying risk and protective factors are critical to investigate in understanding how to prevent this comorbidity. METHOD: The current study assessed potential moderating effects of coping self-efficacy (CSE) and emotion dysregulation on the association between sexual assault-related PTSD symptom severity and drug use severity in a sample of college women. In this study, 518 female undergraduate students completed self-report measures of nonconsensual sexual experiences, PTSD symptoms, CSE, emotion dysregulation, and drug use severity. RESULTS: Of these participants, 287 women reported at least 1 incident of attempted or completed rape. We found evidence of a significant moderation effect, suggesting that high levels of CSE and low levels of emotion dysregulation reduce the likelihood of drug use issues for female sexual assault survivors. CONCLUSIONS: These findings suggest that assessment tools, interventions, and trauma-related policies should target CSE and emotion dysregulation in attenuating the risk of drug use for women with assault-related PTSD symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Ongoing traumatic stress during a global pandemic.

OBJECTIVE: The COVID-19 pandemic has been conceptualized as a potentially traumatic event, although heterogeneity in experience (e.g., isolation) and in type and severity of traumatic stress response (e.g., hygiene hypervigilance) query the applicability of the posttraumatic stress disorder (PTSD) diagnostic construct. Parallels may be drawn to chronic illness and continuous traumatic situations (CTS) literature, which suggests unique symptom presentations that may occur during cumulative, ongoing traumas. METHOD: Eighty-four adults completed the PTSD Checklist with appended questions evaluating pandemic index events, temporality of intrusive symptoms, self-appraised abnormality, and context dependence of symptoms. Using exploratory latent profile analysis, we modeled the latent structure of traumatic stress response to COVID-19 in order to evaluate possible nuanced patterns of symptoms differentiating PTSD from a transient ongoing trauma response. RESULTS: Two profiles broadly delineated by severity across all variables emerged, suggesting the framework of PTSD is apt when applied to COVID-19. However, secondary analyses revealed subtle signals supporting chronic illness and CTS frameworks. Specifically, some participants who met criteria for PTSD did not endorse index events meeting Criterion A, most endorsed intrusive symptoms related to a present or future threat (versus a past trauma), and 30% reported their symptoms to be context dependent. CONCLUSION: Results highlight a need for improved assessment and opportunities for treatment modification. (PsycInfo Database Record (c) 2023 APA, all rights reserved).