ALS Identified: two-year findings from a sponsored ALS genetic testing program.

OBJECTIVE: To report initial results from the Amyotrophic Lateral Sclerosis (ALS) Identified genetic testing (GT) program on characteristics of individuals tested and frequency of reported disease-causing variants. METHODS: ALS Identified used the Invitae Amyotrophic Lateral Sclerosis panel (Invitae, San Francisco, CA, USA) to assay 22 ALS-associated genes. Sponsored by Biogen (Cambridge, MA, USA), the program was launched in June 2021 and was available at no charge to individuals ≥18 years in the United States and Puerto Rico with an ALS diagnosis or a known family history of ALS. Deidentified data were available to Biogen. RESULTS: As of 26 October 2023, 998 healthcare professionals ordered the panel at 681 unique care sites. Of 8054 individuals examined, 7483 (92.9%) were reported to have a clinical diagnosis of ALS, while 571 (7.1%) were asymptomatic relatives. Of the individuals with a clinical ALS diagnosis, 57.7% were male (n = 4319) and 42.3% female (n = 3164). Mean (SD) age at diagnosis is 62 (13) years. Out of the 7483 clinically diagnosed individuals, 1810 (24.2%) showed genetic variations in ALS-associated genes. Among these, 865 individuals (47.8%) carried pathogenic variants, and 44 (2.4%) had likely pathogenic variants, totaling 12.1% of the clinically diagnosed population. INTERPRETATION: Since 2021 there has been robust uptake and sustained use of the ALS Identified program, one of the largest samples of people with ALS to date across the United States, demonstrating the interest and need for genetic ALS testing.

Paternal history of mental illness associated with posttraumatic stress disorder among veterans.

This study examined the association between parent and family reported history of non-PTSD mental illness (MI), PTSD specifically, and substance use problems, and participant clinical diagnosis of PTSD. Participants were drawn from the US Department of Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center (MIRECC) Post-Deployment Mental Health (PDMH) study (n = 3191), an ongoing multi-site cohort study of US Afghanistan and Iraq conflict era veterans. Participants who recalled a father history of PTSD had a 26-percentage point higher likelihood of meeting criteria for PTSD; while participants reporting any family history of PTSD had a 15-percentage point higher probability of endorsing symptoms consistent with PTSD. Mother history of substance use problems was associated with Veteran current PTSD, but results were sensitive to model specification. Current PTSD was not associated with family/parent history of non-PTSD mental illness, mother history of PTSD, or family/father history of substance use problems. Family history of PTSD may increase PTSD risk among veterans exposed to trauma, particularly when a father history is reported. Knowledge of family history could improve clinical decision-making for trauma-exposed individuals and allow for more effective targeting of programs and clinical services.

Self-Reported Pain in Male and Female Iraq/Afghanistan-Era Veterans: Associations with Psychiatric Symptoms and Functioning.

OBJECTIVE: To examine pain symptoms and co-occurring psychiatric and functional indices in male and female Iraq/Afghanistan-era veterans. DESIGN: Self-reported data collection and interviews of Iraq/Afghanistan-era veterans who participated in a multisite study of postdeployment mental health. SETTING: Veterans were enrolled at one of four participating VA sites. SUBJECTS: Two thousand five hundred eighty-seven male and 662 female Iraq/Afghanistan-era veterans. METHODS: Nonparametric Wilcoxon rank tests examined differences in pain scores between male and female veterans. Chi-square tests assessed differences between male and female veterans in the proportion of respondents endorsing moderate to high levels of pain vs no pain. Multilevel regression analyses evaluated the effect of pain on a variety of psychiatric and functional measures. RESULTS: Compared with males, female veterans reported significantly higher mean levels of headache ( P < 0.0001), muscle soreness ( P < 0.008), and total pain ( P < 0.0001), and were more likely to report the highest levels of headache ( P < 0.0001) and muscle soreness ( P < 0.0039). The presence of pain symptoms in Iraq/Afghanistan-era veterans was positively associated with psychiatric comorbidity and negatively associated with psychosocial functioning. There were no observed gender differences in psychiatric and functional indices when levels of pain were equated. CONCLUSIONS: Although female Iraq/Afghanistan-era veterans reported higher levels of pain than male veterans overall, male and female veterans experienced similar levels of psychiatric and functional problems at equivalent levels of reported pain. These findings suggest that pain-associated psychological and functional impacts are comparable and consequential for both male and female veterans.