Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40.

Stuttering is a common speech disorder that interrupts speech fluency and tends to cluster in families. Typically, stuttering is characterized by speech sounds, words or syllables which may be repeated or prolonged and speech that may be further interrupted by hesitations or 'blocks'. Rare variants in a small number of genes encoding lysosomal pathway proteins have been linked to stuttering. We studied a large four-generation family in which persistent stuttering was inherited in an autosomal dominant manner with disruption of the cortico-basal-ganglia-thalamo-cortical network found on imaging. Exome sequencing of three affected family members revealed the PPID c.808C>T (p.Pro270Ser) variant that segregated with stuttering in the family. We generated a Ppid p.Pro270Ser knock-in mouse model and performed ex vivo imaging to assess for brain changes. Diffusion-weighted MRI in the mouse revealed significant microstructural changes in the left corticospinal tract, as previously implicated in stuttering. Quantitative susceptibility mapping also detected changes in cortico-striatal-thalamo-cortical loop tissue composition, consistent with findings in affected family members. This is the first report to implicate a chaperone protein in the pathogenesis of stuttering. The humanized Ppid murine model recapitulates network findings observed in affected family members.

Effects of an Artificial Intelligence Platform for Behavioral Interventions on Depression and Anxiety Symptoms: Randomized Clinical Trial.

BACKGROUND: The need for scalable delivery of mental health care services that are efficient and effective is now a major public health priority. Artificial intelligence (AI) tools have the potential to improve behavioral health care services by helping clinicians collect objective data on patients' progress, streamline their workflow, and automate administrative tasks. OBJECTIVE: The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of an AI platform for behavioral health in facilitating better clinical outcomes for patients receiving outpatient therapy. METHODS: The study was conducted at a community-based clinic in the United States. Participants were 47 adults referred for outpatient, individual cognitive behavioral therapy for a main diagnosis of a depressive or anxiety disorder. The platform provided by Eleos Health was compared to a treatment-as-usual (TAU) approach during the first 2 months of therapy. This AI platform summarizes and transcribes the therapy session, provides feedback to therapists on the use of evidence-based practices, and integrates these data with routine standardized questionnaires completed by patients. The information is also used to draft the session's progress note. Patients were randomized to receive either therapy provided with the support of an AI platform developed by Eleos Health or TAU at the same clinic. Data analysis was carried out based on an intention-to-treat approach from December 2022 to January 2023. The primary outcomes included the feasibility and acceptability of the AI platform. Secondary outcomes included changes in depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7) scores as well as treatment attendance, satisfaction, and perceived helpfulness. RESULTS: A total of 72 patients were approached, of whom 47 (67%) agreed to participate. Participants were adults (34/47, 72% women and 13/47, 28% men; mean age 30.64, SD 11.02 years), with 23 randomized to the AI platform group, and 24 to TAU. Participants in the AI group attended, on average, 67% (mean 5.24, SD 2.31) more sessions compared to those in TAU (mean 3.14, SD 1.99). Depression and anxiety symptoms were reduced by 34% and 29% in the AI platform group versus 20% and 8% for TAU, respectively, with large effect sizes for the therapy delivered with the support of the AI platform. No group difference was found in 2-month treatment satisfaction and perceived helpfulness. Further, therapists using the AI platform submitted their progress notes, on average, 55 hours earlier than therapists in the TAU group (t=-0.73; P<.001). CONCLUSIONS: In this randomized controlled trial, therapy provided with the support of Eleos Health demonstrated superior depression and anxiety outcomes as well as patient retention, compared with TAU. These findings suggest that complementing the mental health services provided in community-based clinics with an AI platform specializing in behavioral treatment was more effective in reducing key symptoms than standard therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05745103; https://classic.clinicaltrials.gov/ct2/show/NCT05745103.

Self-reported impact of developmental stuttering across the lifespan.

AIM: To examine the phenomenology of stuttering across the lifespan in the largest prospective cohort to date. METHOD: Participants aged 7 years and older with a history of developmental stuttering were recruited. Self-reported phenotypic data were collected online including stuttering symptomatology, co-occurring phenotypes, genetic predisposition, factors associated with stuttering severity, and impact on anxiety, education, and employment. RESULTS: A total of 987 participants (852 adults: 590 males, 262 females, mean age 49 years [SD = 17 years 10 months; range = 18-93 years] and 135 children: 97 males, 38 females, mean age 11 years 4 months [SD = 3 years; range = 7-17 years]) were recruited. Stuttering onset occurred at age 3 to 6 years in 64.0%. Blocking (73.2%) was the most frequent phenotype; 75.9% had sought stuttering therapy and 15.5% identified as having recovered. Half (49.9%) reported a family history. There was a significant negative correlation with age for both stuttering frequency and severity in adults. Most were anxious due to stuttering (90.4%) and perceived stuttering as a barrier to education and employment outcomes (80.7%). INTERPRETATION: The frequent persistence of stuttering and the high proportion with a family history suggest that stuttering is a complex trait that does not often resolve, even with therapy. These data provide new insights into the phenotype and prognosis of stuttering, information that is critically needed to encourage the development of more effective speech therapies. WHAT THIS PAPER ADDS: Half of the study cohort had a family history of stuttering. While 75.9% of participants had sought stuttering therapy, only 15.5% identified as having recovered. There was a significant negative correlation between age and stuttering frequency and severity in adults.

The Validity of the Interpersonal Theory of Suicide in Adolescence: A Review.

Adolescence, when suicidal ideation and behaviors often begin, might offer an important window to understand the causes and prevent the progression of suicide phenomena. The need for frameworks to organize the fragmented field has been noted, but few studies are theoretically driven. An important recent contribution to understanding suicidality is Joiner's (2005) Interpersonal-Psychological Theory of Suicide (IPTS). This article reviews the evidence for the applicability of the IPTS in adolescence. Seventeen studies of adolescents that specifically tested or interpreted findings in the light of Joiner's theory or the IPTS were located. In addition, several recent reviews of the literature on suicidality in adolescence covered information relevant to the IPTS. There is some support for the theory in adolescence, particularly with regard to its most novel component, the association between acquired capability and suicide attempt. In summary, we find this theory to be a promising heuristic to organize the disparate studies in suicide research. Future challenges and directions for researchers seeking to test and elaborate the applicability of the IPTS in adolescence include: adaptations of instruments to the developmental stage, capturing of imminent risk, and consideration of whether the current model is underspecified. Age might moderate adult findings that give impulsivity an indirect role in suicide attempts.

The Association Between Stuttering Burden and Psychosocial Aspects of Life in Adults.

PURPOSE: Stuttering is a speech condition that can have a major impact on a person's quality of life. This descriptive study aimed to identify subgroups of people who stutter (PWS) based on stuttering burden and to investigate differences between these subgroups on psychosocial aspects of life. METHOD: The study included 618 adult participants who stutter. They completed a detailed survey examining stuttering symptomatology, impact of stuttering on anxiety, education and employment, experience of stuttering, and levels of depression, anxiety, and stress. A two-step cluster analytic procedure was performed to identify subgroups of PWS, based on self-report of stuttering frequency, severity, affect, and anxiety, four measures that together inform about stuttering burden. RESULTS: We identified a high- (n = 230) and a low-burden subgroup (n = 372). The high-burden subgroup reported a significantly higher impact of stuttering on education and employment, and higher levels of general depression, anxiety, stress, and overall impact of stuttering. These participants also reported that they trialed more different stuttering therapies than those with lower burden. CONCLUSIONS: Our results emphasize the need to be attentive to the diverse experiences and needs of PWS, rather than treating them as a homogeneous group. Our findings also stress the importance of personalized therapeutic strategies for individuals with stuttering, considering all aspects that could influence their stuttering burden. People with high-burden stuttering might, for example, have a higher need for psychological therapy to reduce stuttering-related anxiety. People with less emotional reactions but severe speech distortions may also have a moderate to high burden, but they may have a higher need for speech techniques to communicate with more ease. Future research should give more insights into the therapeutic needs of people highly burdened by their stuttering. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25582980.

A Theory-Driven Investigation of the Association Between Emotion Dysregulation and Suicide Risk in a Clinical Adolescent Sample.

OBJECTIVE: Emotion dysregulation has been consistently linked to suicide ideation and attempt, but an explanatory model for this relationship has not been adequately investigated in adolescents. This study examined the concurrent relationship among emotion dysregulation, variables from the Interpersonal-Psychological Theory of Suicide (IPTS), and suicide risk (operationalized as a continuous variable that increases in intensity from nonspecific to active suicide ideation to suicide ideation with a plan) in a clinical adolescent sample. METHOD: A total of 151 adolescents (aged 12-17) were recruited from an inpatient psychiatry unit. Cross-sectional analyses were conducted to determine whether the relationship between emotion dysregulation and suicide risk was explained by the variables of perceived burdensomeness (PB), thwarted belongingness, and capability for suicide, as proposed by the IPTS. RESULTS: As hypothesized, the relationship between emotion dysregulation and suicide risk was explained by PB and capability for suicide. Depressive symptoms had an independent relationship with suicide risk after controlling for IPTS variables. CONCLUSIONS: The results from this study suggest that effective treatment strategies that reduce negative cognition tied to PB and depressive symptoms would address the most proximal variables related to suicide risk in adolescents. Enhancing emotion management would serve to maintain low levels of proximal influences on risk.

The Interpersonal-Psychological Theory of Suicide in Adolescents: A Preliminary Report of Changes Following Treatment.

This study investigated change in suicide risk in the framework of the interpersonal theory of suicide. Fifty-four adolescents completed measures of interpersonal needs, acquired capability, depressive symptoms, and suicide risk at entry and exit from treatment. There was a significant drop following treatment in unmet interpersonal needs but not in acquired capability, consistent with the theory. Both change in the interaction between interpersonal needs and in depressive symptoms contributed unique prediction to change in suicide risk. These findings extend the research in understanding changes in suicide risk and inform treatment by suggesting cognitive targets for intervention.

Frequency and Methods of Nonsuicidal Self-Injury in Relation to Acquired Capability for Suicide Among Adolescents.

The objective of this study was to test the Interpersonal Psychological Theory of Suicide (IPTS) proposal that the association of nonsuicidal self-injury (NSSI) with suicide attempt is mediated by acquired capability. Inpatient adolescents (n = 134) reported on suicide ideation and attempts, NSSI frequency and methods, depressive symptoms, and acquired capability for suicide. Consistent with the IPTS, both measures of NSSI were positively associated with acquired capability after accounting for depressive symptoms and past history of attempts. However, both NSSI measures explained independent variance in number of suicide attempts after controlling for suicide ideation and acquired capability. These findings contradict the IPTS and suggest that the role of NSSI in suicide attempt is mediated by variables external to the IPTS.

Frequency of Exposure to and Engagement in Nonsuicidal Self-Injury Among Inpatient Adolescents.

This study examined the relationship between frequency of exposure to non-suicidal self-injury (NSSI) and engagement in NSSI among adolescents. Ninety inpatient adolescents with a history of NSSI, ages 12 to 17, completed a structured interview. The majority of participants had learned about NSSI prior to initiating the behavior themselves. More frequent exposure to specific methods of NSSI was associated with greater frequency of using those same methods. Greater exposure to NSSI in the media and seeking out NSSI content were related to greater frequency of engagement in NSSI. Clinicians may help those who self-injure to become more knowledgeable and educated consumers of media to prevent NSSI behavior and contagion.

Preliminary Examination of the Interpersonal Psychological Theory of Suicide in an Adolescent Clinical Sample.

This study offers a preliminary examination of the Interpersonal-Psychological Theory of Suicide (IPTS; Joiner 2005) in an adolescent clinical sample. The IPTS offers a nuanced framework that has many conceptual and practical merits. Although this theory has a growing base of evidence among adults, it has yet to be tested in adolescents using direct measures of its central constructs. Participants were 147 adolescents (76.2 % girls) on an inpatient psychiatric unit, who completed measures of key IPTS constructs of thwarted belongingness, perceived burdensomeness, acquired capability for suicide, as well as depression severity, hopelessness, and severity of suicidal symptoms. Our findings were largely consistent with hypotheses derived from the IPTS: perceived burdensomeness, and at a marginal level, thwarted belongingness, were independently associated with current suicidal ideation. The thwarted belongingness by perceived burdensomeness interaction marginally distinguished between adolescents with passive and active suicidal ideation. Acquired capability for suicide was associated with recent suicidal intent. Examination of all three IPTS constructs simultaneously revealed main effects of each construct (with a marginal effect of thwarted belongingness), and interaction effects for thwarted belongingness by perceived burdensomeness, and thwarted belongingness by perceived burdensomeness by acquired capability for suicide in association with suicidal symptom severity. Sex, age, depression severity, and hopelessness were controlled in all analyses. This study offers strong, albeit preliminary, support of the IPTS in a clinical adolescent sample. Assessment of IPTS constructs may be useful in determining persistent risk for suicide attempt. Prospective tests of the theory, and extensions to intervention and prevention should be considered in future IPTS research.

Appetite regulatory hormones in women with anorexia nervosa: binge-eating/purging versus restricting type.

OBJECTIVE: Anorexia nervosa is a psychiatric illness characterized by low weight, disordered eating, and hallmark neuroendocrine dysfunction. Behavioral phenotypes are defined by predominant restriction or bingeing/purging; binge-eating/purging type anorexia nervosa is associated with poorer outcome. The pathophysiology underlying anorexia nervosa types is unknown, but altered hormones, known to be involved in eating behaviors, may play a role. METHOD: To examine the role of anorexigenic hormones in anorexia nervosa subtypes, we examined serum levels of peptide YY (PYY; total and active [3-36] forms), brain-derived neurotrophic factor (BDNF), and leptin as primary outcomes in women with DSM-5 restricting type anorexia nervosa (n = 50), binge-eating/purging type anorexia nervosa (n = 25), and healthy controls (n = 22). In addition, women completed validated secondary outcome measures of eating disorder psychopathology (Eating Disorder Examination-Questionnaire) and depression and anxiety symptoms (Hamilton Rating Scales for Depression [HDRS] and Anxiety [HARS]). The study samples were collected from May 22, 2004, to February 7, 2012. RESULTS: Mean PYY 3-36 and leptin levels were lower and BDNF levels higher in binge-eating/purging type anorexia nervosa than in restricting type anorexia nervosa (all P values < .05). After controlling for body mass index, differences in PYY and PYY 3-36 between anorexia nervosa types were significant (P < .05) and differences in BDNF were at the trend level (P < .10). PYY 3-36 was positively (r = 0.27, P = .02) and leptin was negatively (r = -0.51, P < .0001) associated with dietary restraint; BDNF was positively associated with frequency of purging (r = 0.21, P = .04); and leptin was negatively associated with frequency of bingeing (r = -0.29, P = .007) and purging (r = -0.31, P = .004). CONCLUSIONS: Among women with anorexia nervosa, the anorexigenic hormones PYY, BDNF, and leptin are differentially regulated between the restricting and binge/purge types. Whether these hormone pathways play etiologic roles with regard to anorexia nervosa behavioral types or are compensatory merits further study.