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Emily OC Palmer,1 Sheryl Ker,2 Miguel E Rentería,3 Thomas Carmody,4 A John Rush5,6 1Holmusk Europe Ltd, London, UK; 2KKT Technologies, Pte. Ltd, Singapore; 3QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 4Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA; 5Duke University School of Medicine, Duke University School of Medicine, Durham, NC, USA; 6Clinical sciences, Duke-National University of Singapore, SingaporeCorrespondence: Emily OC Palmer, Holmusk Europe Ltd, 414 Linen Hall, 162-168 Regent St, London, W1B 5TE, UK, Email emily.palmer@holmusk.comPurpose: Major depressive disorder (MDD) is a leading cause of disability worldwide. An accurate assessment of depressive symptomology is crucial for clinical management and research. This study assessed the convergent validity, reliability, and total scale score interconversion across the 9-item Patient Health Questionnaire (PHQ-9) self-report, the 16-item Quick Inventory of Depressive Symptomatology-clinician report (QIDS-C) (two widely used clinical ratings) and the 5-item Very Brief Quick Inventory of Depressive Symptoms-clinician report (VQIDS-C), which evaluate the core features of MDD.Patients and Methods: This study leveraged electronic health record (EHR)-derived, de-identified data from the NeuroBlu Database (Version 23R1), a longitudinal behavioural health real-world platform. Classical Test Theory (CTT) and Item Response Theory (IRT) analyses were used to evaluate the reliability, validity of, and conversions between the scales. The Test Information Function (TIF) was calculated for each scale, with greater test information reflecting higher precision and reliability in measuring depressive symptomology. IRT was also used to generate conversion tables so that total scores on each scale could be compared to the other.Results: The study sample (n = 2,156) had an average age of 36.4 years (standard deviation [SD] = 13.0) and 59.7% were female. The mean depression scores for the PHQ-9, QIDS-C, and VQIDS-C were 12.9 (SD = 6.6), 12.0 (SD = 4.9), and 6.18 (SD = 3.2), respectively. The Cronbach’s alpha coefficients for PHQ-9, QIDS-C, and VQIDS-C were 0.9, 0.8, and 0.7, respectively, suggesting acceptable internal consistency. PHQ-9 (TIF = 30.3) demonstrated the best assessment of depressive symptomology, followed by QIDS-C (TIF = 25.8) and VQIDS-C (TIF = 17.7).Conclusion: Overall, PHQ-9, QIDS-C, and VQIDS-C appear to be reliable and convertible measures of MDD symptomology within a US-based adult population in a real-world clinical setting.Keywords: psychometrics, linking, patient health questionnaire, quick inventory of depressive symptoms, depression, real-world data

Charlotte L Haley,1 Betsy D Kennard,1,2 David W Morris,1 Ira H Bernstein,3 Thomas Carmody,4 Graham J Emslie,1,2 Taryn L Mayes,1 A John Rush5– 7 1Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Children’s Health, Children’s Medical Center of Dallas, Dallas, TX, USA; 3Department of Psychology, The University of Texas at Arlington, Arlington, TX, USA; 4Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA; 5Department of Psychiatry and Clinical Sciences, Duke-National University of Singapore, Singapore, Singapore; 6Department of Psychiatry and Behavioral Sciences, Texas Tech University – Health Sciences Center, Permian Basin, TX, USA; 7Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USACorrespondence: Betsy D Kennard, University of Texas Southwestern Medical Center, Child Psychiatry, 5323 Harry Hines Blvd, Dallas, TX, 75390-8589, USA, Tel +1 214.645.8680, Fax +1 214.648.3914, Email beth.kennard@utsouthwestern.eduObjective: The current study aimed to evaluate the psychometric features of the Quick Inventory of Depressive Symptomatology, Adolescent version (QIDS-A17) and the clinician-rated Children’s Depression Rating Scale-Revised (CDRS-R).Methods: Altogether, 103 outpatients (8 to 17 years) completed the self-report QIDS-A17-SR. Clinician interviews of adolescents (QIDS-A17-C (Adolescent)) and of parents (QIDS-A17-C (Parent)) were combined to create the QIDS-A17-C(Composite) and the CDRS-R.Results: All QIDS-A17 measures and the CDRS-R evidenced high total score correlations and internal consistency. Factor analysis found all four measures to be unidimensional. Item Response Theory (IRT) analysis found results that complemented the reliability results found in CTT. All four also demonstrated discriminant diagnostic validity based on logistic regression and ANOVA analyses.Conclusion: The psychometric properties of the self-report and composite versions of the QIDS-A17 suggest acceptability as a measure of depression in adolescents either as a measure of depressive symptoms or severity of illness in adolescents. The self-report version may be a helpful tool in busy clinical practices.Keywords: pediatric depression, rating scale, psychometric properties, self-report measures

Soon Nan Wee,1,* Christian Liman,1,* Heidi C Waters,2 Christy R Houle,3 Miguel Renteria,1 Sankha S Mukherjee,1 Subina Surendran,1 Joshua Marcovici,1 Malaak Brubaker,2 Stine Rasmussen Meehan,4 Anne de Jong-Laird,2 A John Rush,5– 7 Joydeep Sarkar1 1Holmusk Technologies, Inc, New York, NY, USA; 2Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, NJ, USA; 3Lundbeck, Deerfield, IL, USA; 4H. Lundbeck A/S, Valby, Denmark; 5Department of Psychiatry, Duke-National University of Singapore, Singapore, Singapore; 6Department of Psychiatry, Duke University School of Medicine, Durham, NC, USA; 7Health Sciences Center, Texas Tech University, Odessa, TX, USA*These authors contributed equally to this workCorrespondence: Heidi C Waters, Otsuka Pharmaceutical Development & Commercialization, Inc, 508 Carnegie Center Drive, Princeton, NJ, 08540, USA, Tel +1 609 535 9626, Email heidi.waters@otsuka-us.comPurpose: Life engagement encompasses concepts such as life fulfillment, well-being, and participation in meaningful activities, encompassing cognitive, physical, social, and emotional dimensions. Patients with MDD experience impaired functioning across multiple domains of life engagement and have ranked concepts related to life engagement and fulfillment as important predictors of treatment success. Post-hoc analyses of three clinical trials of patients with MDD treated adjunctively with brexpiprazole have reported a significantly greater improvement in life engagement. This study investigated improvements in life engagement among patients with MDD following initiation of brexpiprazole treatment using a real-world dataset.Patients and Methods: Information was extracted from semi-structured clinical notes of the Mental Status Examination (MSE) of patients in a real-world setting to develop an outcome measure for quantifying life engagement of psychiatric patients. Measures of life engagement and its four sub-domains (emotional, physical, social, and cognitive) were calculated at each clinical visit for 624 adult patients with MDD during the 6 months following brexpiprazole initiation. Paired t-tests assessed differences between the index event and time periods within 6 months of the index event. Kaplan–Meier survival analyses were used to quantify the improvement in life engagement scores following brexpiprazole initiation.Results: The study identified 54 clinical features associated with life engagement. Statistically significant improvements were observed from as early as 1 month following brexpiprazole initiation, with 20.6%, 37.9%, and 53.9% of the patients demonstrating improved life engagement scores within 1, 3, and 6 months, respectively. The improvements were particularly apparent for the emotional and social sub-domains.Conclusion: The results of this study provide evidence of improved life engagement following brexpiprazole initiation in a real-world dataset.Keywords: brexpiprazole, major depressive disorder, real-world evidence, mental status examination, life engagement

A John Rush,1– 3 Nancy D Madia,4 Thomas Carmody,5 Madhukar H Trivedi6,7 1Department of Psychiatry, Texas Tech University Health Science Center, Midland, TX, USA; 2Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA; 3Duke-National University of Singapore, Singapore; 4Texas Tech University Health Sciences Center Permian Basin, Odessa, TX, USA; 5Department of Population and Data Science, University of Texas Southwestern Medical Center, Dallas, TX, USA; 6Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA; 7Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USACorrespondence: Madhukar H Trivedi, Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9119, USA, Tel +1 214-648-0188, Fax +1 214-648-0167, Email madhukar.trivedi@utSouthwestern.eduPurpose: Evaluate the psychometric properties of the 5-item Very Quick Inventory of Depressive Symptomatology self-report and clinician-rated versions (VQIDS-SR5/VQIDS-C5), compare their relative performance, create crosswalks between their total scores and other accepted depressive symptom ratings, and define clinically relevant depressive symptom severity thresholds and categorical outcomes for both versions.Patients and Methods: The Sequenced Treatment Alternatives to Relieve Depression trial obtained baseline and exit 17-item Hamilton Rating Scale for Depression (HRSD17) and 30-item Inventory of Depressive Symptomatology – Clinician-rated scores, and baseline and visit-wise QIDS-SR16 and QIDS-C16 ratings from the first treatment step (citalopram). The VQIDS-C5 and the VQIDS-SR5 items (sad mood, self-outlook, involvement, fatigue, psychomotor slowing) (each rated 0– 3), extracted from the corresponding 16-item ratings, were selected to best reflect the 6-item HRSD (HRSD6) (exclusive of anxiety). Classical Test Theory (CTT) and Item-Response Theory (IRT) analyses assessed psychometric features. IRT analyses produced total score crosswalks between the VQIDS5, QIDS-C16, QIDS-SR16 and HRSD6. Clinically relevant VQIDS symptom severity thresholds and treatment outcomes were estimated based on cross-walks from the parent QIDS16 ratings.Results: Both VQIDS versions were unifactorial with acceptable internal consistencies (Cronbach’s alphas > 0.80), item-total correlations (0.57– 0.74) by CCT, and strong IRT item performance. Based on QIDS16 severity thresholds (none 0– 5; mild 6– 10; moderate 11– 15; severe 16– 20; and very severe 21– 27), comparable thresholds were 0– 2; 3– 5; 6– 9; 9– 12; and > 12 for VQIDS-C5, and 0– 2; 2– 5; 6– 8; 9– 12; and > 12 for VQIDS-SR5. Kappa values were acceptable in comparing categories of outcomes (eg, no benefit, remission, etc) based on VQIDS and corresponding QIDS categories.Conclusion: The VQIDS-C5 and VQIDS-SR5 assess selected core depressive symptoms with psychometrically acceptable properties. Theelf-report and clinician-rated versions provide virtually identical information, symptom severity thresholds and symptom change categories. Both are as sensitive to change as the corresponding QIDS16, making them suitable for use in busy practices.Keywords: depression, self-report, psychometrics, rating scales, QIDS, symptoms

Sheryl Ker,1,* Jennifer Hsu,2,* Anisha Balani,1,* Sankha Subhra Mukherjee,1 A John Rush,3– 5 Mehreen Khan,2 Sara Elchehabi,2 Seth Huffhines,2 Dustin DeMoss,2,6 Miguel E Rentería,1 Joydeep Sarkar1 1Holmusk Technologies, Inc., New York, NY, USA; 2John Peter Smith Health Network, Fort Worth, TX, USA; 3Department of Psychiatry, Duke-National University of Singapore (NUS), Singapore; 4Duke University School of Medicine, Durham, NC, USA; 5Texas Tech Health Sciences Center, Odessa, TX, USA; 6University of North Texas Health Science Center/Texas Christian University, Fort Worth, TX, USA*These authors contributed equally to this workCorrespondence: Miguel E Rentería; Joydeep SarkarHolmusk Technologies, Inc., 4th Floor, 54 Thompson St, New York, NY, 10012, USAEmail miguel.renteria@holmusk.com; joydeep.sarkar@holmusk.comPurpose: To describe attrition patterns of opioid use disorder (OUD) patients treated with buprenorphine (BUP) and to assess how clinical, sociodemographic, or BUP medication dosing features are associated with attrition.Patients and Methods: Electronic health records of adults (16+ year-olds) with OUD treated with BUP from 23 different substance use or mental health care programs across 11 US states were examined for one year following BUP initiation in inpatient (IP), intensive outpatient (IOP), or outpatient (OP) settings. Treatment attrition was declared at > 37 days following the last recorded visit. Survival analyses and predictive modelling were used.Results: Retention was consistently 2– 3 times higher following BUP initiation in OP (n = 2409) than in IP/IOP (n = 2749) settings after 2 (50% vs 25%), 6 (27% vs 9%) and 12 months (14% vs 4%). Retention was higher for females, whites (vs blacks), and those with less severe OUD, better global function, or not using non-psychotropic medications. Comorbid substance use, other psychiatric disorders, and the number of psychotropic medications were variously related to retention depending on the setting in which BUP was initiated. Predictive modelling revealed that a higher global assessment of functioning and a smaller OUD severity based on the Clinical Global Impression – Severity led to longer retentions, a higher initial BUP dose led to higher retention in a few cases, an OP setting of BUP initiation led to longer retentions, and a lower total number of psychotropic and non-psychotropic medications led to longer retentions. These were the most important parameters in the model, which identified 75.2% of patients who left BUP treatment within three months post-initiation, with a precision of 90.5%.Conclusion: Of all the OUD patients who began BUP, 50– 75% left treatment within three months, and most could be accurately identified. This could facilitate patient-centered management to better retain OUD patients in BUP treatment.Keywords: opioids, buprenorphine, buprenorphine dosing, treatment engagement, treatment retention, treatment dropout, predictors

Augustus John Rush, 1– 3 Charles South, 4 Shailesh Jain, 1 Raafae Agha, 1 Mingxu Zhang, 1 Shristi Shrestha, 1 Zershana Khan, 1 Mudasar Hassan, 1 Madhukar H Trivedi 5 1Department of Psychiatry, Texas Tech University Health Science Center, Midland, TX, USA; 2Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA; 3Professor Emeritus, Duke-National University of Singapore, Singapore; 4Department of Statistical Science, Southern Methodist University, Dallas, TX, USA; 5Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USACorrespondence: Madhukar H TrivediDepartment of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9119, USATel +1 214-648-0188Fax +1 214-648-0167Email madhukar.trivedi@utsouthwestern.eduObjective: To develop clinically meaningful improvement thresholds in both the 17-item and the 6-item Hamilton Rating Scale for Depression (HRSD) total scores in depressed outpatients.Methods: The post-hoc analysis included all adult outpatients with non-psychotic major depressive disorder in the STAR*D trial who entered and exited the first treatment step (up to 14 weeks of citalopram) with a complete set of study measures at baseline and exit and at least one post-baseline measure. Within-patient change and linear regression anchor-based analyses were conducted to define meaningful and substantial changes in the HRSD 17 and HRSD 6 using three patient-reported outcomes [Work and Social Adjustment Scale (WSAS), Quality of Life Enjoyment and Satisfaction-Short Form (Q-LES-Q-SF); Mini-Q-LES-Q] obtained at baseline and exit from the first treatment step in STAR*D.Results: Linear regression analyses identified a meaningful change threshold for the HRSD 17 as 3.9 [3.7– 4.1] [lower, upper 95% CI] and a substantial change as 7.8 [7.4– 8.3] with the WSAS. Analogous thresholds based on the Q-LES-Q-SF were 5.8 [5.5– 6.1] and 11.6 [11.0– 12.2], respectively, and 4.9 [4.7– 5.2] and 9.9 [9.3– 10.4] for the Mini-QLES-Q, respectively. For the HRSD 6, linear regression analyses with the WSAS identified a meaningful change as 2.2 [2.1– 2.4], while a substantial change was 4.5 [4.2– 4.7]. Analogous figures based on the Q-LES-Q-SF were 3.2 [3.0– 3.4] and 6.4 [6.1– 6.8]. Similarly, based on the Mini-QLESQ, results were 2.8 [2.6– 2.9] and 5.6 [5.3– 5.9]. For both the HRSD 17 and the HRSD 6, within-patient analyses produced less precise estimates of the same change thresholds with substantial overlap between groups. Based on the WSAS, a clinically meaningful change in the HRSD 17 total score was 9.6 (SD = 6.5), while a substantial change was 15.0 (SD = 6.7). Analogous change thresholds based on the Q-LESQ-SF were 12.9 (SD = 6.2) and 16.8 (SD = 6.4), respectively. For the Mini-Q-LES-Q, thresholds were 10.9 (SD = 6.5) and 16.1 (SD = 6.2).Conclusion: A 4– 6 point change in the HRSD 17 is clinically meaningful; a 7– 12 point change is clinically substantial. For the HRSD 6, analogous estimates were 2– 3 and 4– 7 point changes, respectively.Keywords: depression ratings, patient-reported outcomes, meaningful change

Kristin Martin-Cook,1 Lucy Palmer,1 Larry Thornton,1 A John Rush,2 Carol A Tamminga,1 Hicham M Ibrahim1 1Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2National University of Singapore, Singapore; Department of Psychiatry, Duke University School of Medicine, Durham, NC, USA; Department of Psychiatry, Texas Tech Health Sciences Center, Midland, TX, USACorrespondence: Kristin Martin-CookDepartment of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75235, USATel +1-214-648-1983Fax +1-214-648-4947Email Kristin.Martin-Cook@UTSouthwestern.eduAbstract: Measurement-based care (MBC) involves the systematic use of standardized measurements to inform treatment decisions. MBC can enhance clinical decision-making and quality of care by prompting personalized changes in treatment based on measured patient outcomes. MBC can also promote more precise communications between patients and clinicians around individual patient care. While commonly employed in psychiatric clinical research, the use of MBC in everyday practice can be complicated by clinic operations and variability across patients. We implemented MBC in the UT Southwestern Psychiatry Multispecialty Outpatient Clinic during the expansion of our general psychiatry clinic and subspecialty targeted programs. This article describes the top 10 lessons we learned as we confronted practical obstacles around implementing the ideals of MBC into a pre-existing, busy psychiatric clinical practice and how doing so impacts care, provider engagement, patient engagement, and research opportunity.Keywords: measurement-based care, clinic operations, quality improvement, quality care, screening, outpatient

Fang Liu-Walsh,1 Neena K Tierney,1 James Hauschild,2 Allison K Rush,1 John Masucci,3 Gregory C Leo,3 Kimberly A Capone1 1Johnson & Johnson Consumer Inc., Skillman, NJ, USA; 2Johnson & Johnson Microbiological Quality & Sterility Assurance, Johnson & Johnson Inc., Raritan, NJ, USA; 3Janssen R&D Companies of Johnson & Johnson, Springhouse, PA, USACorrespondence: Fang Liu-Walsh; Kimberly A CaponeJohnson & Johnson Consumer Inc., 199 Grandview Road, Skillman, NJ 08558-9418, USAEmail fliuwals@ITS.JNJ.com; KCapone@its.jnj.comBackground: Multiple skin conditions have been associated with alterations in the diversity and composition of the skin microbiome, including dry skin and atopic dermatitis. In these conditions, a number of commensal skin bacteria have been implicated in supporting a healthy skin barrier, including Staphylococcus epidermidis. Recent clinical studies in patients with mild-to-moderate atopic dermatitis and dry/itchy skin have shown significantly improved skin barrier function and microbial diversity upon treatment with moisturizers containing 1% colloidal oat. We hypothesized that direct use of colloidal oat by skin microbes contributes to these therapeutic benefits.Methods: Skin bacterial growth was assessed using the BacT/ALERT system. Staphylococcus aureus and S. epidermidis growth rates and metabolism were compared in an in vitro competition assay. The effect of a 1% colloidal oat–containing moisturizer on lactic acid content of the stratum corneum was clinically assessed in subjects with moderate-to-severe dry skin. S. epidermidis gene expression was evaluated by next-generation mRNA sequencing. Short-chain fatty acids were quantified in bacterial culture supernatants.Results: In vitro, colloidal oat increased the growth rate of S. epidermidis vs S. aureus, as well as the metabolism of S. epidermidis. Colloidal oat also significantly increased lactic acid concentrations in supernatants of both strains and decreased pH, consistent with clinical findings that 6-week use of a 1% colloidal oat–containing lotion significantly increased lactic acid on dry skin. Further analyses suggest that colloidal oat alters the gene expression profile of S. epidermidis.Conclusion: Colloidal oat directly affects the growth, metabolism, lactic acid production, and gene expression of skin commensal bacteria, as shown via in vitro studies. The increased production of lactic acid reflects clinical observations with colloidal oat–containing skin moisturizers. Our findings suggest a new mechanism for colloidal oat as a skin prebiotic, which may contribute to improvements in skin and microbiome diversity in various skin conditions, including dry/itchy skin and atopic dermatitis.Keywords: atopic dermatitis, dry skin, colloidal oat, skin barrier function, skin microbiome, skin moisturizer, S. epidermidis

Harold A Sackeim,1 Maxine Dibué,2,3 Mark T Bunker,4 A John Rush5– 7 1Departments of Psychiatry and Radiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; 2Department of Neurosurgery, Heinrich Heine University, Düsseldorf, Germany; 3Medical Affairs Europe, LivaNova Deutschland GmbH, Munich, Germany; 4LivaNova USA PLC, Houston, TX, USA; 5Duke-NUS Medical School, Singapore; 6Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; 7Department of Psychiatry, Texas Tech University, Permian Basin, TX, USACorrespondence: Harold A SackeimDepartments of Psychiatry and Radiology, Vagelos College of Physicians and Surgeons, Columbia University, 2124 Moselem Springs Road, Fleetwood, PA 10522, USATel +1 917 273-5379Email has1@columbia.eduPurpose: The Vagus Nerve Stimulation (VNS) Therapy System has been studied for more than 20 years in patients with severe, treatment-resistant, chronic mood disorder, i.e., difficult-to-treat depression (DTD). This review distills some of the implications of this research for future therapeutic trials in this population.Methods: A narrative review is provided on VNS in DTD. Protocols for a new, large, sham-controlled trial and a global, longitudinal observational study are described.Results: Following encouraging results in open studies, a randomized, masked, sham-controlled trial of VNS for DTD failed to demonstrate an effect on the primary outcome. The negative results may have been partly due to inadequate treatment duration (10 weeks). In long-term observational studies, adjunctive VNS, combined with treatment-as-usual (VNS+TAU), was administered to more than 1100 DTD patients and compared with TAU alone in more than 400 patients. VNS+TAU had superior antidepressant effects, but maximal symptom reduction was often observed after 12 months or longer of stimulation. VNS+TAU had also marked superiority in durability of benefit. Sustained levels of symptom reduction below the traditional cutoff for response (i.e. < 50%) were associated with improved quality of life.Limitations: Most comparisons of VNS+TAU and TAU were derived from observational, open label studies.Conclusion: The history of VNS in DTD has implications for interventional studies in this population, and perhaps other chronic medical disorders. The slow onset of benefit with VNS necessitates considerably longer controlled observation periods to establish efficacy. Durability of benefit should be routinely incorporated in efficacy assessment. New outcome metrics are needed to both categorically identify clinically meaningful benefit and to integrate information on symptom burden over time.Keywords: vagus nerve stimulation, major depressive episode, difficult-to-treat depression, treatment-resistant depression, antidepressant, efficacy, regulatory process

Youth purpose was investigated using a two-phase embedded design with youth participating in Scouts BSA (N = 3,943), ages 9-20 (M = 14.0, SD = 1.9). Participating Scouts were mostly White (91%) and male (98%). In Phase 1, we conducted a two-step cluster analysis on Scouts' survey responses to three purpose dimensions (personal meaning, goal-directedness, beyond-the-self orientation). Four clusters emerged: "Purposeful", "Explorers", "Dreamers", "Nonpurposeful." In Phase 2, we explored qualities of purpose within each cluster and programmatic features and relationships within the scouting context fostering youth purpose with a Scout subsample (N = 30) who completed semi-structured interviews. Results demonstrated that adults supporting scouting, inspiration from older peers, and opportunities to help others and explore new activities supported youth purpose.

Arun Kumar,1 Mark T Bunker,1 Scott T Aaronson,2 Charles R Conway,3 Anthony J Rothschild,4,5 Giacomo Mordenti,6 Augustus J Rush7,8 1LivaNova USA PLC, Houston, TX, USA; 2Department of Clinical Research, Sheppard Pratt Health System, Baltimore, MD, USA; 3Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, USA; 4Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, USA; 5Department of Psychiatry, UMass Memorial Medical Center, Worcester, MA, USA; 6LivaNova PLC, London, UK; 7Department of Psychiatry and Behavioral Sciences, National University of Singapore, Singapore; 8Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA Objective: To compare the durations of response achieved with adjunctive vagus nerve stimulation (VNS + TAU) vs treatment as usual (TAU) alone in treatment-resistant depression (TRD) over a 5-year period in the TRD registry. Materials and methods: Data from 271 participants on TAU and 328 participants on VNS + TAU were analyzed. Response was defined as ≥50% decrease in baseline Montgomery–Åsberg Depression Rating Scale (MADRS) score at postbaseline visit and was considered retained until the decrease was

Poor parental mental health and stress have been associated with children's mental disorders, including attention-deficit/hyperactivity disorder (ADHD), through social, genetic, and neurobiological pathways. To determine the strength of the associations between parental mental health and child ADHD, we conducted a set of meta-analyses to examine the association of parent mental health indicators (e.g., parental depression, antidepressant usage, antisocial personality disorder, and stress and anxiety) with subsequent ADHD outcomes in children. Eligible ADHD outcomes included diagnosis or symptoms. Fifty-eight articles published from 1980 to 2019 were included. We calculated pooled effect sizes, accounting for each study's conditional variance, separately for test statistics based on ADHD as a dichotomous (e.g., diagnosis or clinical cutoffs) or continuous measurement (e.g., symptoms of ADHD subtypes of inattentiveness and hyperactivity/impulsivity). Parental stress and parental depression were significantly associated with increased risk for ADHD overall and both symptoms and diagnosis. Specifically, maternal stress and anxiety, maternal prenatal stress, maternal depression, maternal post-partum depression, and paternal depression were positively associated with ADHD. In addition, parental depression was associated with symptoms of ADHD inattentive and hyperactive/impulsive subtypes. Parental antisocial personality disorder was also positively associated with ADHD overall and specifically ADHD diagnosis. Prenatal antidepressant usage was associated with ADHD when measured dichotomously only. These findings raise the possibility that prevention strategies promoting parental mental health and addressing parental stress could have the potential for positive long-term impacts on child health, well-being, and behavioral outcomes.

Although neurobiologic and genetic factors figure prominently in the development of attention deficit/hyperactivity disorder (ADHD), adverse physical health experiences and conditions encountered during childhood may also play a role. Poor health is known to impact the developing brain with potential lifelong implications for behavioral issues. In attempt to better understand the relationship between childhood physical health and the onset and presence of ADHD symptoms, we summarized international peer-reviewed articles documenting relationships between a select group of childhood diseases or health events (e.g., illnesses, injuries, syndromes) and subsequent ADHD outcomes among children ages 0-17 years. Drawing on a larger two-phase systematic review, 57 longitudinal or retrospective observational studies (1978-2021) of childhood allergies, asthma, eczema, head injury, infection, or sleep problems and later ADHD diagnosis or symptomatology were identified and subjected to meta-analysis. Significant associations were documented between childhood head injuries, infections, and sleep problems with both dichotomous and continuous measures of ADHD, and between allergies with dichotomous measures of ADHD. We did not observe significant associations between asthma or eczema with ADHD outcomes. Heterogeneity detected for multiple associations, primarily among continuously measured outcomes, underscores the potential value of future subgroup analyses and individual studies. Collectively, these findings shed light on the importance of physical health in understanding childhood ADHD. Possible etiologic links between physical health factors and ADHD are discussed, as are implications for prevention efforts by providers, systems, and communities.

Parenting and family environment have significant impact on child development, including development of executive function, attention, and self-regulation, and may affect the risk of developmental disorders including attention-deficit/hyperactivity disorder (ADHD). This paper examines the relationship of parenting and family environment factors with ADHD. A systematic review of the literature was conducted in 2014 and identified 52 longitudinal studies. A follow-up search in 2021 identified 7 additional articles, for a total of 59 studies that examined the association of parenting factors with ADHD outcomes: ADHD overall (diagnosis or symptoms), ADHD diagnosis specifically, or presence of the specific ADHD symptoms of inattention and hyperactivity/impulsivity. For parenting factors that were present in three or more studies, pooled effect sizes were calculated separately for dichotomous or continuous ADHD outcomes, accounting for each study's conditional variance. Factors with sufficient information for analysis were parenting interaction quality (sensitivity/warmth, intrusiveness/reactivity, and negativity/harsh discipline), maltreatment (general maltreatment and physical abuse), parental relationship status (divorce, single parenting), parental incarceration, and child media exposure. All factors showed a significant direct association with ADHD outcomes, except sensitivity/warmth which had an inverse association. Parenting factors predicted diagnosis and overall symptoms as well as inattentive and hyperactive symptoms when measured, but multiple factors showed significant heterogeneity across studies. These findings support the possibility that parenting and family environment influences ADHD symptoms and may affect a child's likelihood of being diagnosed with ADHD. Prevention strategies that support parents, such as decreasing parenting challenges and increasing access to parent training in behavior management, may improve children's long-term developmental health.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by persistent patterns of inattention, hyperactivity, and impulsiveness. Among US children and adolescents aged 3-17 years, 9.4% have a diagnosis of ADHD. Previous research suggests possible links between parental substance use and ADHD among children. We conducted a systematic review and meta-analysis of 86 longitudinal or retrospective studies of prenatal or postnatal alcohol, tobacco, or other parental substance use and substance use disorders and childhood ADHD and its related behavioral dimensions of inattention and hyperactivity-impulsivity. Meta-analyses were grouped by drug class and pre- and postnatal periods with combined sample sizes ranging from 789 to 135,732. Prenatal exposure to alcohol or tobacco and parent substance use disorders were consistently and significantly associated with ADHD among children. Other parental drug use exposures resulted in inconsistent or non-significant findings. Prevention and treatment of parental substance use may have potential for impacts on childhood ADHD.

Charles South,1–3 A John Rush,4,* Thomas J Carmody,1–3 Manish K Jha,1,2 Madhukar H Trivedi1,2,*1Center for Depression Research and Clinical Care, 2Department of Psychiatry, 3Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Department of Psychiatry and Behavioral Sciences, Duke-National University of Singapore, Singapore; Duke Medical School, Durham, NC, USA*These authors contributed equally to this work Objective: The objective of the study was to determine whether a unique analytic approach – as a proof of concept – could identify individual depressed outpatients (using 30 baseline clinical and demographic variables) who are very likely (75% certain) to not benefit (NB) or to remit (R), accepting that without sufficient certainty, no prediction (NP) would be made.Methods: Patients from the Combining Medications to Enhance Depression Outcomes trial treated with escitalopram (S-CIT) + placebo (n=212) or S-CIT + bupropion-SR (n=206) were analyzed separately to assess replicability. For each treatment, the elastic net was used to identify subsets of predictive baseline measures for R and NB, separately. Two different equations that estimate the likelihood of remission and no benefit were developed for each patient. The ratio of these two numbers characterized likely outcomes for each patient.Results: The two treatment cells had comparable rates of remission (40%) and no benefit (22%). In S-CIT + bupropion-SR, 11 were predicted NB of which 82% were correct; 26 were predicted R – 85% correct (169 had NP). For S-CIT + placebo, 13 were predicted NB – 69% correct; 44 were predicted R – 75% correct (155 were NP). Overall, 94/418 (22%) patients were identified with a meaningful degree of certainty (69%–85% correct). Different variable sets with some overlap were predictive of remission and no benefit within and across treatments, despite comparable outcomes.Conclusion: In two separate analyses with two different treatments, this analytic approach – which is also applicable to pretreatment laboratory tests – identified a meaningful proportion (over 20%) of depressed patients for whom a treatment outcome was predicted with sufficient certainty that the clinician can elect to strongly recommend for or choose to avoid a particular treatment. Different persons seem to be remitting or not benefiting with these two different treatments.Keywords: patient selection, depression, elastic net, analytic approach, treatment response

Manish K Jha,1 Raymond B Teer,2 Abu Minhajuddin,3 Tracy L Greer,1 A John Rush,4 Madhukar H Trivedi1 1Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, Dallas, 2University of Texas, Austin, 3Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Duke-NUS, Singapore, Singapore Background: Major depressive disorder (MDD) significantly impacts performance of both work- and nonwork-related routine daily activities. We have shown that work productivity is significantly impaired in employed MDD patients, but the extent of impairments in nonwork-related routine activities and its association with antidepressant treatment outcomes has not been established. Materials and methods: Activity impairment was measured using the sixth item of Work Productivity and Activity Impairment Scale in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (n=665). Published norms were used to define activity impairment levels. The relationship between activity impairment and baseline sociodemographic and clinical characteristics was evaluated along with changes in activity impairment and its relationship with other clinical outcomes such as symptom severity, function, and side effect burden. Remission status at 3 and 7 months was predicted based on week 6 activity impairment level. Results: Higher psychosocial and cognitive impairments and greater number of comorbid medical conditions were associated with greater activity impairment at baseline. Proportion of participants with severe activity impairment declined from 47.6% at baseline to 18.7% at 3 months, while mean activity impairment decreased from 57.1 at baseline to 32.8 at 3 months. During course of treatment, levels of activity impairment correlated most strongly with psychosocial function among measures of symptom severity, function, quality of life, and side effect burden. No or minimal activity impairment at week 6 was associated with two to three times higher rates of remission at 3 and 7 months as compared to moderate or severe activity impairment levels even after controlling for remission status at week 6 and select baseline variables. Conclusion: Depressed patients have high levels of nonwork-related activity impairment at baseline that improves significantly with treatment and independently predicts long-term clinical outcomes. Brief systematic assessment of activity impairment during the course of antidepressant treatment can help inform clinical decision-making. Keywords: depression, activity impairment, predictors, functional recovery, productivity