Multisite Collaborative Study Research Articles

Transmit Radiant Individuality to Offspring (TRIO) study: investigating intergenerational transmission effects on brain development.

Intergenerational transmission is a crucial aspect of human development. Although prior studies have demonstrated the continuity of psychopathology and maladaptive upbringing environments between parents and offspring, the underlying neurobiological mechanisms remain unclear. We have begun a novel neuroimaging research project, the Transmit Radiant Individuality to Offspring (TRIO) study, which focuses on biological parent-offspring trios. The participants of the TRIO study were Japanese parent-offspring trios consisting of offspring aged 10-40 and their biological mother and father. Structural and functional brain images of all participants were acquired using magnetic resonance imaging (MRI). Saliva samples were collected for DNA analysis. We obtained psychosocial information, such as intelligence, mental health problems, personality traits, and experiences during the developmental period from each parent and offspring in the same manner as much as possible. By April 2023, we completed data acquisition from 174 trios consisting of fathers, mothers, and offspring. The target sample size was 310 trios. However, we plan to conduct genetic and epigenetic analyses, and the sample size is expected to be expanded further while developing this project into a multi-site collaborative study in the future. The TRIO study can challenge the elucidation of the mechanism of intergenerational transmission effects on human development by collecting diverse information from parents and offspring at the molecular, neural, and behavioral levels. Our study provides interdisciplinary insights into how individuals' lives are involved in the construction of the lives of their descendants in the subsequent generation.

A Multi-Site Collaborative Study of the Hostile Priming Effect

In a now-classic study by Srull and Wyer (1979), people who were exposed to phrases with hostile content subsequently judged a man as being more hostile. And this “hostile priming effect” has had a significant influence on the field of social cognition over the subsequent decades. However, a recent multi-lab collaborative study (McCarthy et al., 2018) that closely followed the methods described by Srull and Wyer (1979) found a hostile priming effect that was nearly zero, which casts doubt on whether these methods reliably produce an effect. To address some limitations with McCarthy et al. (2018), the current multi-site collaborative study included data collected from 29 labs. Each lab conducted a close replication (total N = 2,123) and a conceptual replication (total N = 2,579) of Srull and Wyer’s methods. The hostile priming effect for both the close replication (d = 0.09, 95% CI [-0.04, 0.22], z = 1.34, p = .16) and the conceptual replication (d = 0.05, 95% CI [-0.04, 0.15], z = 1.15, p = .58) were not significantly different from zero and, if the true effects are non-zero, were smaller than what most labs could feasibly and routinely detect. Despite our best efforts to produce favorable conditions for the effect to emerge, we did not detect a hostile priming effect. We suggest that researchers should not invest more resources into trying to detect a hostile priming effect using methods like those described in Srull and Wyer (1979).

Reproducibility in the absence of selective reporting: Anillustration from large-scale brain asymmetry research.

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used sample sizes.

An overview of the Italian contribution to the international multisite SPRISTAD study on psychotherapy training.

The Interest Section on Therapist Training and Development of the Society for Psychotherapy Research (SPRISTAD) has launched a multisite collaborative longitudinal study of psychotherapy trainees’ development, a large-scale study involving a number of countries all over the world. In the present article, we present an overview of the early Italian contribution to the SPRISTAD study, based on preliminary paper-and-pencil data collection. Our preliminary findings showed cross-sectional differences at different years of training and two-years longitudinal changes in trainees’ perceived development. Moreover, trainees’ characteristics such as their motivation, relational manner, current life, and personal background have shown to deserve attention in research on trainees’ development. These findings encourage the continuation of the SPRISTAD online data collection.

Same Content, Different Methods: Comparing Lecture, Engaged Classroom, and Simulation.

There is a push to use classroom technology and active teaching methods to replace didactic lectures as the most prevalent format for resident education. This multisite collaborative cohort study involving nine residency programs across the United States compared a standard slide-based didactic lecture, a facilitated group discussion via an engaged classroom, and a high-fidelity, hands-on simulation scenario for teaching the topic of acute dyspnea. The primary outcome was knowledge retention at 2 to 4 weeks. Each teaching method was assigned to three different residency programs in the collaborative according to local resources. Learning objectives were determined by faculty. Pre- and posttest questions were validated and utilized as a measurement of knowledge retention. Each site administered the pretest, taught the topic of acute dyspnea utilizing their assigned method, and administered a posttest 2 to 4 weeks later. Differences between the groups were compared using paired t-tests. A total of 146 residents completed the posttest, and scores increased from baseline across all groups. The average score increased 6% in the standard lecture group (n=47), 11% in the engaged classroom (n=53), and 9% in the simulation group (n=56). The differences in improvement between engaged classroom and simulation were not statistically significant. Compared to standard lecture, both engaged classroom and high-fidelity simulation were associated with a statistically significant improvement in knowledge retention. Knowledge retention after engaged classroom and high-fidelity simulation did not significantly differ. More research is necessary to determine if different teaching methods result in different levels of comfort and skill with actual patient care.

Impact of intraventricular hemorrhage on cognitive and behavioral outcomes at 18 years of age in low birth weight preterm infants.

Although high-grade intraventricular hemorrhage (IVH; grades III-IV) in preterm and low birth weight infants are clearly associated with increased risk of long-term adverse neurodevelopmental sequelae, the impact of low-grade IVH (grades I-II) has been less clear. Some studies have followed these infants through early school age and have shown some conflicting results regarding cognitive outcome. Such studies that assess children at younger ages may not accurately predict outcomes in later childhood, as it is known that fluid and crystallized intelligence peak at age 26 years. There is paucity of data in current medical literature, which correlates low-grade IVH with outcomes in early adulthood. To determine the link between the occurrence of low-grade IVH in low birth weight (birth weight ⩽2500 g) infants born prematurely (gestational age <37 weeks) and intellectual function, academic achievement, and behavioral problems to the age of 18 years. This study is an analysis of data derived from the Infant Health and Development Program (IHDP), a multisite national collaborative study and a randomized controlled trial of education intervention for low birth weight infants from birth until 3 years of age with follow-up through 18 years of age. A total of 985 infants were enrolled in the IHDP. Of the 462 infants tested for IVH, 99 demonstrated sonographic evidence of low-grade IVH, whereas 291 showed no sonographic evidence of IVH. Several outcomes were compared between these two groups. Intelligence was assessed using Stanford-Binet Intelligence scales at age 3 years, Wechsler Intelligence Scale for Children (WISC-III) at age 8 years, Wechsler Abbreviated Scale of Intelligence (WASI) at age 18 years and Woodcock Johnson Tests of Achievement at age 8 and 18 years. Behavior was measured using the Achenbach Behavior Checklist at age 3 years and Child Behavior Checklist (CBCL) at age 8 and 18 years. Outcomes were compared between the IVH-positive and IVH-negative groups using analysis of covariance after adjusting for the presence or absence of intervention, birth weight, gestational age, gender, severity of neonatal course, race and maternal education. No statistically significant difference in intelligence as measured by Stanford-Binet Intelligence scales, WISC-III, WASI and Woodcock-Johnson Tests of Achievement could be appreciated between IVH-positive patients and controls at any age group (36 months, 8 years and 18 years of age). In addition, there was no significant difference in problem behavior as assessed by the Achenbach Behavior Checklist and Child Behavior Checklist (CBCL) comparing IVH patients with controls. Low-grade IVH was not demonstrated in our study to be an independent risk factor associated with lower outcomes in intelligence, academic achievement or problem behavior at age 3, 8 and 18 years.

Practical Tips for Managing a Multi-Site Collaborative Study

Practical Tips for Managing a Multi-Site Collaborative Study

Morris B. Parloff (1918–2011).

Morris B. Parloff was considered an elder statesman in the field of psychotherapy research, and his wisdom and stewardship were of enormous benefit to several generations of psychotherapy researchers. Parloff received his bachelor's degree from Western Reserve University (1940), a degree in psychiatric social work from the University of Chicago (1942), and a doctorate in psychology from Western Reserve University (1953). Parloff spent most of his career (from 1953 until his retirement in 1983) as a researcher and administrator at the National Institute of Mental Health (NIMH). He was also on the senior faculty of the Washington School of Psychiatry, taught or consulted at a number of universities, and maintained a private practice of psychotherapy. In the NIMH intramural program, Parloff was chief of the Section on Personality in the Laboratory of Psychology. There he conducted a major longitudinal study on the personality characteristics of adolescent and adult scientists. In the NIMH extramural program, he served as chief of the Psychotherapy and Behavioral Intervention Section in the Clinical Research Branch (1972-1980), after which he became chief of the new Psychosocial Treatments Research Branch. Throughout his career, from his pioneering teaching and research on group psychotherapy through his 30 years at NIMH, Parloff provided researchers and practitioners with a broad understanding of the field of psychotherapy research, the complexity of its subject matter, and its relationship to the "real world." Often ahead of others in the field, Parloff dealt with many topics that retain their importance today, including the need to carefully define criteria for improvement in psychotherapy, the transmission of values in psychotherapy, the concepts of the placebo and of common factors in psychotherapy research, and the role of the patient-therapist relationship (in both individual and group therapy) and its impact on the outcome of therapy. Starting with a 1979 article in the American Psychologist ("Can Psychotherapy Research Guide the Policymaker? Vol. 34, pp. 296-306), Parloff wrote extensively about the relationship among practitioners, psychotherapy researchers, and policymakers. To promote the systematic use of clinical trials and address methodological issues in the field, Parloff obtained support to fund the first NIMH multisite collaborative outcome study in the field of psychotherapy. He and the first author (I. E.) then designed and launched the NIMH Treatment of Depression Collaborative Research Program. This study would serve as a model for future collaborative research by independent investigators. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Genetic association of complement receptor 1 polymorphism rs3818361 in Alzheimer's disease

Complement receptor 1 gene polymorphism rs3818361 was recently shown to increase the risk of Alzheimer's disease (AD). We performed an independent replication study of this genetic variant in 2,470 individuals from Spain. By applying an allelic model, we observed a trend toward an association between this marker and late-onset AD susceptibility in our case-control study (odds ratio = 1.114, 95% confidence interval: 0.958-1.296, P = .16). Meta-analysis of available studies (n = 31,771 individuals), including previous studies and public genome-wide association study resources (Alzheimer's Disease Neuroimaging Initiative, Translational Genomics Research Institute, and Multi-site Collaborative Study for Genotype-Phenotype Associations in Alzheimer's Disease), strongly supports the effect of rs3818361 (odds ratio = 1.180, 95% confidence interval: 1.113-1.252, P < 2.99E-8) and suggests the existence of between-study heterogeneity (P < .05). We concluded that the complement receptor 1 gene may contribute to AD risk, although its effect size could be smaller than previously estimated.

Social Class and Work Functioning in Treatment for Depression

Social Class and Work Functioning in Treatment for Depression

State Effects of Major Depression on the Assessment of Personality and Personality Disorder

The authors sought to determine whether personality disorders diagnosed during a depressive episode have long-term outcomes more typical of those of other patients with personality disorders or those of patients with noncomorbid major depression. The authors used 6-year outcome data collected from the multisite Collaborative Longitudinal Personality Disorders Study (CLPS). Diagnoses and personality measures gathered from the study cohort at the index assessment using interview and self-report methods were associated with symptomatic, functional, and personality measures at 6-year follow-up. Of 668 patients initially recruited to the CLPS, 522 were followed for 6 years. All participants had either a DSM-IV diagnosis of one of four personality disorders (borderline, schizotypal, obsessive-compulsive, or avoidant) or a DSM-IV diagnosis of major depressive disorder with no accompanying personality disorder. Six-year outcomes for patients with comorbid personality disorder and major depressive disorder at the index evaluation were similar to those of patients with pure personality disorder and significantly worse than those of patients with pure major depressive disorder. Stability estimates of personality traits were similar for personality disorder patients with and without major depressive disorder at the index evaluation. These results suggest that personality disorder diagnoses established during depressive episodes are a valid reflection of personality pathology rather than an artifact of depressive mood.

Identification of novel candidate loci for anorexia nervosa at 1q41 and 11q22 in Japanese by a genome-wide association analysis with microsatellite markers

The Japanese Genetic Research Group for Eating Disorders (JGRED) is a multisite collaborative study group that was organized for the systematic recruitment of patients with an eating disorder for the purpose of genetic study in Japan. We conducted a genome-wide case-control association study using 23 465 highly polymorphic microsatellite (MS) markers to identify genomic loci related to anorexia nervosa (AN). Pooled DNA typing in two screening stages, followed by individual typing of 320 AN cases and 341 controls, allowed us to identify 10 MS markers to be associated with AN. To narrow down genomic regions responsible for the association of these MS markers, we further conducted a single-nucleotide polymorphism (SNP) association analysis for 7 of the 10 loci in 331 AN cases and 872 controls, which include the 320 AN cases and the 341 controls genotyped in the MS screening, respectively. Two loci, namely 1q41 and 11q22, remained significantly associated with AN in the SNP-based fine mapping, indicating the success in narrowing down susceptibility regions for AN. Neither of these loci showed a positive evidence of association with bulimia nervosa. The most significant association was observed at SNP rs2048332 (allelic P-value=0.00023) located at 3'-downstream of the SPATA17 gene on the 1q41 locus. The association analysis for MS-SNP haplotypes detected a statistically significant association (permutation P-value=0.00003) of the A-4-G-T haplotype that comprised four SNP/MS markers (rs6590474-D11S0268i-rs737582-rs7947224) on the 11q22 locus with AN. This linkage disequilibrium block spanning a 20.2-kb interval contains exon 9 of the CNTN5 gene encoding contactin 5.

Computerized ambulatory monitoring in psychiatry: a multi‐site collaborative study of acceptability, compliance, and reactivity

Computerized ambulatory monitoring overcomes a number of methodological and conceptual challenges to studying mental disorders, however concerns persist regarding the feasibility of this approach with severe psychiatric samples and the potential of intensive monitoring to influence data quality. This multi-site investigation evaluates these issues in four independent samples. Patients with schizophrenia (n = 56), substance dependence (n = 85), anxiety disorders (n = 45), and a non-clinical sample (n = 280) were contacted to participate in investigations using computerized ambulatory monitoring. Micro-computers were used to administer electronic interviews several times per day for a one-week period. Ninety-five percent of contacted individuals agreed to participate in the study, and minimum compliance was achieved by 96% of these participants. Seventy-eight percent of all programmed assessments were completed overall, and only 1% of micro-computers were not returned to investigators. There was no evidence that missing data or response time increased over the duration of the study, suggesting that fatigue effects were negligible. The majority of variables investigated did not change in frequency as a function of study duration, however some evidence was found that socially sensitive behaviors changed in a manner consistent with reactivity.

Socioeconomic status in the treatment of depression.

This study examined outcomes and attrition across three treatments for depression in relation to socioeconomic status (SES). The study was based on data available from the Treatment of Depression Collaborative Research Program (TDCRP) of the National Institute of Mental Health (NIMH; Elkin, 1994), a multisite collaborative study that examined the effectiveness of two forms of psychotherapy, cognitive behavior therapy and interpersonal psychotherapy, and pharmacotherapy. Results indicated that lower SES, measured by the Hollingshead Index of Social Position, was associated with less improvement across all three treatments for depression. The effect of SES on outcome did not differ by treatment modality. Contrary to expectations, SES was not associated with attrition. These findings suggest that there may be limitations in the use of these empirically validated treatments with lower SES depressed patients, as their improvement rates may be less than those of middle SES depressed patients treated by the same modalities. The results of this study also suggest that a standardized measure of SES may be more sensitive to SES differences in outcome than the more easily obtained measures of education or income. Suggestions are provided for additional research in this area to address the potential mediators and moderators of the association between SES and outcome.

Voxel-based Morphometric Multisite Collaborative Study on Schizophrenia

Regional gray matter (GM) abnormalities are well known to exist in patients with chronic schizophrenia. Voxel-based morphometry (VBM) has been previously used on structural magnetic resonance images (MRI) data to characterize these abnormalities. Two multisite schizophrenia studies, the Functional Biomedical Informatics Research Network and the Mind Clinical Imaging Consortium, which include 9 data collection sites, are evaluating the efficacy of pooling structural imaging data across imaging centers. Such a pooling of data could yield the increased statistical power needed to elucidate effects that may not be seen with smaller samples. VBM analyses were performed to evaluate the consistency of patient versus control gray matter concentration (GMC) differences across the study sites, as well as the effects of combining multisite data. Integration of data from both studies yielded a large sample of 503 subjects, including 266 controls and 237 patients diagnosed with schizophrenia, schizoaffective or schizophreniform disorder. The data were analyzed using the combined sample, as well as analyzing each of the 2 multisite studies separately. A consistent pattern of reduced relative GMC in schizophrenia patients compared with controls was found across all study sites. Imaging center-specific effects were evaluated using a region of interest analysis. Overall, the findings support the use of VBM in combined multisite studies. This analysis of schizophrenics and controls from around the United States provides continued supporting evidence for GM deficits in the temporal lobes, anterior cingulate, and frontal regions in patients with schizophrenia spectrum disorders.

The “Environment” for Autism Research: Signs of Improvement?

Once thought to be rare, autism spectrum disorders (ASD) have gained increasing public attention as prevalence studies have revealed sharp increases over the past two decades. ASD now represents the second most common category of neurodevelopmental disorders. The prevalence data have been instrumental in mobilizing parents to act on behalf of their affected family members for better services and treatments and for greater research investments aimed at understanding what causes these disorders and how they can be prevented.

Using National Health Policies to Improve Access to Palliative Care Medications in the Community

Access to affordable priority palliative care medicines needs to be informed by good clinical data from well-conducted clinical trials designed to address efficacy, cost-effectiveness, and safety. Availability of priority palliative care symptom control medicines improves the provision of palliation in the place of patient's choice including the community. Within Australia, a National Medicines Policy and a Palliative Care Strategy endorsed by Federal and State and Territory health ministers have facilitated a process to improve the evidence for palliative clinical practice and, through this, improve community availability of key medications for people at the end of life. The initiative, coordinated by a working party under government auspices, has brought together medicine regulators, the pharmaceutical industry, government, policy makers, and clinicians. The brief was to improve availability of key palliative care medications within the current national drug regulatory and funding frameworks. The results to date include: a palliative care section within the Pharmaceutical Benefits Scheme generating the first ever patient-defined section; medicines not previously listed now available; commitment of AU$9.46 M for a national multisite collaborative clinical study network to improve the evidence for clinical interventions in the palliative care setting through systematic investigation with rigorous Phase III and IV studies to inform registration and subsidy applications; and establishing a national Communication Network of the Palliative Care Medications Working Group for the health workforce and community to improve the quality use where improved access has been achieved.

Multisite comparison of wheelchair propulsion kinetics in persons with paraplegia

A multisite collaborative study is being conducted on the association between propulsion biomechanics and upper-limb injuries. This substudy compared subject characteristics and pushrim kinetics across three sites and identified early on in the main study any differences that could affect interpretation of the findings or data pooling. A total of 42 manual wheelchair users with paraplegia (14 from each site) performed 0.9 m/s and 1.8 m/s steady state propulsion trials and an acceleration-brake-coastdown trial on a wheelchair dynamometer while propulsion forces and moment about the hub were measured with a SmartWheel. Significant differences between two sites were found in peak and average resultant force (p < 0.05), peak and average moment at the slower steady state speed (p < 0.005), and peak and average torque at the faster steady state speed (p = 0.06). Subjects at the site with significantly lower forces and torques had a slower deceleration rate during coastdown compared with the subjects at the other two sites (p < 0.001). These results imply that rolling resistance is lower at one of the sites and likely due to differences in dynamometer properties. A mechanical method was used to site-normalize the data and enable data pooling for future analyses.

Correlates of Type 2 diabetes mellitus in children, adolescents and young adults in north India: a multisite collaborative case‐control study

In this study we describe the clinical, anthropometric and biochemical characteristics of patients with early onset Type 2 diabetes mellitus (T2DM) (< 30 years of age) and compare them with healthy, non-diabetic individuals. In this multisite collaborative study, 51 patients with T2DM (40 male, 11 female) and 69 non-diabetic individuals of similar age and gender distribution (controls) as the cases (46 male and 23 female) were investigated. The following parameters were measured; anthropometry [body mass index (BMI), waist circumference, waist-hip ratio (WHR) and skin-fold thickness at four sites], percentage body fat (%BF) and lipid profile. The mean (SD) age of diagnosis of T2DM was 21.4 (6.1) years. A significantly higher number of cases had a history of T2DM in first-degree relatives as compared with controls (82.3 vs. 23.2%, P < 0.001). The mean values and the prevalence of abnormal values of measures of generalized obesity (BMI and %BF) and abdominal obesity (waist circumference and WHR) were significantly higher in cases as compared with controls. Hypertriglyceridaemia [OR (95% CI): 4.6 (1.1-20.0)], high WHR [7.9 (2.5-24.4)] and family history of T2DM [7.3 (2.3-23.0)] were independently associated with T2DM. Age and gender adjusted odds ratios of T2DM were 23.3 (5.2-103.6), 37.7 (9.0-158.5) and 86.4 (17.0-438.5), respectively, with the following set of risk factors; hypertriglyceridaemia and high WHR, hypertriglyceridaemia and family history of T2DM, and high WHR and family history of T2DM. Finally, the presence of all three risk factors increased the odds of T2DM to 112.1 (10.8-1164.7). Early identification of the simple clinical, anthropometric and biochemical parameters which are strongly associated with early onset T2DM in young Asian Indians may be useful for primary prevention.

Complex clinical picture of mania: links among mixity, anxiety and instable temperament

"EPIMAN-II Thousand" is a national multi-site collaborative study dedicated to replicate and complete the previous EPIMAN study (Hantouche et al., 2003). It involved training 317 French psychiatrists working in different sites representative of all France. The study actually succeeded in recruiting 1090 cases admitted for acute mania (DSMIV criteria). The MRS was used to assess the intensity of mania and MADRS + CLDS (checklist of depressive symptoms, 10 items) for co-existing depression. Lifetime comorbid anxiety disorders were assessed by using the DSM-IV criteria, and the AMDP Anxiety Scale of Bobon. The full TEPMS-A French version (84 items, Hantouche et al., 2001) was used to assess the Affective Temperaments.