Development and pilot implementation of guidelines for culturally tailored research recruitment materials for African Americans and Latinos.

BACKGROUND: Previous studies support cultural tailoring of recruitment materials as a strategy to promote the enrollment of minoritized groups in clinical trials. However, there is a lack of guidance for research teams to create culturally tailored materials, potentially contributing to low recruitment rates of minoritized groups. We describe the development and pilot testing of recruitment material guidelines used to culturally tailor clinical trial recruitment materials targeting African Americans and Latinos. METHODS: The guideline development team consisted of investigators, research staff, and community leaders and members experienced in the recruitment and community engagement of minoritized groups. The recruitment material guidelines were developed using the literature, focus groups with African Americans and Latinos, the teams' research experience, and guidance from a community advisory board. To assess the effectiveness of the guidelines, a pilot study was conducted comparing advertisement click-through rates and enrollment outcomes between two institutions differing in use of culturally tailored versus non-tailored Facebook banner ads for the "Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness" (ADAPTABLE) study. RESULTS: Five themes emerged from focus groups: (1) employ diversity and inclusion in recruitment efforts; (2) access multiple recruitment channels to increase reach and possible participation; (3) increase your "footwork"; (4) personalize outreach and recruitment to specific groups' beliefs and values; (5) align recruitment messaging with language preferences and motivations for study participation; and (6) specify incentives for participation. Guidelines were: 1) be inclusive; 2) use all forms of media; 3) take a personalized approach; 4) align recruitment messaging with motivations for study participation; 5) specify incentives; and 6) get out into the community. Additional guidelines were developed addressing specific considerations for images and language when targeting African American and Latino populations. Pilot study results demonstrated that clicks per impression ratio (0.47 clicks per impression vs. 0.03 clicks per impression) and the percentage of African American enrollment were significantly higher when using tailored compared to non-tailored ads (12.8% vs. 8.3%, respectively). CONCLUSION: The recruitment material guidelines offer practical recommendations to reach diverse populations for clinical trial participation more effectively. Our preliminary data supports use of these guidelines as a strategy to enhance recruitment of minoritized groups into clinical research studies.

Design and implementation of a massive open online course on enhancing the recruitment of minorities in clinical trials - Faster Together.

BACKGROUND: Racial and ethnic minorities are often underrepresented in clinical trials, threatening the generalizability of trial results. Several factors may contribute to underrepresentation of minorities in clinical trials, including lack of training for researchers and staff on the importance of diversity in clinical trials and effective strategies for recruiting and retaining minority populations. METHODS: Applying community engaged research principles, we developed a massive open online course (MOOC) to help research team members develop knowledge and skills to enhance the recruitment of minorities in clinical trials. A transdisciplinary working group, consisting of clinical researchers, community engagement specialists, minority clinical trial recruitment and retention educators and specialists, and knowledge management information scientists, was formed to develop an evidence-based curriculum. Feedback from the Recruitment Innovation Center Community Advisory Board was incorporated to help finalize the curriculum. The course was implemented in Coursera, an online learning platform offering MOOCs. A bootstrap paired sample t-test was used to compare pre- and post-assessments of knowledge, attitudes, and intentions as it relates to minority recruitment. RESULTS: The final course, entitled Faster Together, was divided into eight 1-h modules. Each module included video presentations, reading assignments, and quizzes. After 10 months, 382 individuals enrolled in the course, 105 participants completed the pre-test, and 14 participants completed the post-test. Participants' knowledge scores were higher with an increase in the mean number of correct answers from 15.4 (95% CI:12.1-18.7) on the pre-test to 18.7 (95% CI:17.42-20.2) on the post-test. All post-test respondents (n = 14) indicated that the course improved their professional knowledge, and 71.4% of respondents indicated that they were very likely to make changes to their recruitment practices. CONCLUSIONS: Faster Together, a massive open online course, is an acceptable, accessible approach to educating research teams on minority recruitment in clinical trials. Preliminary evidence indicates the course increased knowledge on how to recruit minorities into clinical trials and could promote change in their recruitment practices.

Convergent individual differences in visual cortices, but not the amygdala across standard amygdalar fMRI probe tasks.

The amygdala (AMG) has been repeatedly implicated in the processing of threatening and negatively valenced stimuli and multiple fMRI paradigms have reported personality, genetic, and psychopathological associations with individual differences in AMG activation in these paradigms. Yet the interchangeability of activations in these probes has not been established, thus it remains unclear if we can interpret AMG responses on specific tasks as general markers of its reactivity. In this study we aimed to assess if different tasks that have been widely used within the Affective Neuroscience literature consistently recruit the AMG. METHOD: Thirty-two young healthy subjects completed four fMRI tasks that have all been previously shown to probe the AMG during processing of threatening stimuli: the Threat Face Matching (TFM), the Cued Aversive Picture (CAP), the Aversive and Erotica Pictures (AEP) and the Screaming Lady paradigm (SLp) tasks. Contrasts testing response to aversive stimuli relative to baseline or neutral stimuli were generated and correlations between activations in the AMG were calculated across tasks were performed for ROIs of the AMG. RESULTS: The TFM, CAP and AEP, but not the SLp, successfully recruit the AMG, among other brain regions, especially when contrasts were against baseline or nonsocial stimuli. Conjunction analysis across contrasts showed that visual cortices (VisCtx) were also consistently recruited. Correlation analysis between the extracted data for right and left AMG did not yield significant associations across tasks. By contrast, the extracted signal in VisCtx showed significant associations across tasks (range r=0.511-r=0.630). CONCLUSIONS: Three of the four paradigms revealed significant AMG reactivity, but individual differences in the magnitudes of AMG reactivity were not correlated across paradigms. By contrast, VisCtx activation appears to be a better candidate than the AMG as a measure of individual differences with convergent validity across negative emotion processing paradigms.

Specificity proteins 1 and 4, hippocampal volume and first-episode psychosis.

We assessed specificity protein 1 (SP1) and 4 (SP4) transcription factor levels in peripheral blood mononuclear cells and conducted a voxel-based morphometry analysis on brain structural magnetic resonance images from 11 patients with first-episode psychosis and 14 healthy controls. We found lower SP1 and SP4 levels in patients, which correlated positively with right hippocampal volume. These results extend previous evidence showing that such transcription factors may constitute a molecular pathway to the development of psychosis.

Ensuring Stakeholder Feedback in the Design and Conduct of Clinical Trials for Rare Diseases: ISCTM Position Paper of the Orphan Disease Working Group.

The 1983 Orphan Drug Act in the United States (US) changed the landscape for development of therapeutics for rare or orphan diseases, which collectively affect approximately 300 million people worldwide, half of whom are children. The act has undoubtedly accelerated drug development for orphan diseases, with over 6,400 orphan drug applications submitted to the US Food and Drug Administration (FDA) from 1983 to 2023, including 350 drugs approved for over 420 indications. Drug development in this population is a global and collaborative endeavor. This position paper of the International Society for Central Nervous System Clinical Trials and Methodology (ISCTM) describes some potential best practices for the involvement of key stakeholder feedback in the drug development process. Stakeholders include advocacy groups, patients and caregivers with lived experience, public and private research institutions (including academia and pharmaceutical companies), treating clinicians, and funders (including the government and independent foundations). The authors articulate the challenges of drug development in orphan diseases and propose methods to address them. Challenges range from the poor understanding of disease history to development of endpoints, targets, and clinical trials designs, to finding solutions to competing research priorities by involved parties.

Spanish validation of the Premorbid Adjustment Scale (PAS-S).

BACKGROUND: The Premorbid Adjustment Scale (PAS) has been the most widely used scale to quantify premorbid status in schizophrenia, coming to be regarded as the gold standard of retrospective assessment instruments. AIMS: To examine the psychometric properties of the Spanish version of the PAS (PAS-S). METHOD: Retrospective study of 140 individuals experiencing a first episode of psychosis (n=77) and individuals who have schizophrenia (n=63), both adult and adolescent patients. Data were collected through a socio-demographic questionnaire and a battery of instruments which includes the following scales: PAS-S, PANSS, LSP, GAF and DAS-sv. The Cronbach's alpha was performed to assess the internal consistency of PAS-S. Pearson's correlations were performed to assess the convergent and discriminant validity. RESULTS: The Cronbach's alpha of the PAS-S scale was 0.85. The correlation between social PAS-S and total PAS-S was 0.85 (p<0.001); while for academic PAS-S and total PAS-S it was 0.53 (p<0.001). Significant correlations were observed between all the scores of each age period evaluated across the PAS-S scale, with a significance value less than 0.001. There was a relationship between negative symptoms and social PAS-S (0.20, p<0.05) and total PAS-S (0.22, p<0.05), but not with academic PAS-S. However, there was a correlation between academic PAS-S and general subscale of the PANSS (0.19, p<0.05). Social PAS-S was related to disability measures (DAS-sv); and academic PAS-S showed discriminant validity with most of the variables of social functioning. PAS-S did not show association with the total LSP scale (discriminant validity). CONCLUSION: The Spanish version of the Premorbid Adjustment Scale showed appropriate psychometric properties in patients experiencing a first episode of psychosis and who have a chronic evolution of the illness. Moreover, each domain of the PAS-S (social and academic premorbid functioning) showed a differential relationship to other characteristics such as psychotic symptoms, disability or social functioning after onset of illness.

How do Hispanics/Latinos Perceive and Value the Return of Research Results?

Introduction: Interest in the return of research results has been increasing; however, little is known about how Hispanics/Latinos perceive and value receiving results. This study examined differences among Hispanics/Latinos by education and income in the experience and expectations about the return of research results, perceived value of specific types of information, and the least and most valuable specific information. Method: Retrospective observational design using a cross-sectional national survey sample of Hispanics/Latinos (n = 327). Results: Higher educational attainment was positively associated with the expectation to receive research results, likelihood to participate in research if given study findings, and likelihood to trust researchers if given results. Higher income was positively associated with the perceived value of getting results. Respondents with higher education specifically perceived greater value in information about how lifestyle and genetics affect their risk of disease, how genetics affect how they respond to medications, their ancestry, available clinical trials near them, and how to connect with other study participants. Respondents with higher income perceived greater value in information about how genetics affect their risk of disease and how they respond to medications. Conclusion: The findings offer important insights for planning research initiatives and for developing culturally targeted educational materials for Hispanics/Latinos.

Engaging the community through a longitudinal, interprofessional, interinstitutional experiential learning collaboration.

Background Interprofessional education (IPE) and training in community settings is not commonly described in the literature. Studies primarily focus on clinical education of interprofessional teams in clinical practice and primary care. This is a description of a longitudinal, collaborative interinstitutional IPE project that engages community partners (CP) while delivering core IPE competencies. Interprofessional Education Activity: Twenty-seven students from five universities representing ten healthcare academic programs participated in the project. Participating CP were non-profit agencies developed to meet the needs of specific vulnerable, underserved populations. Students were divided into teams and then paired with CP. This was a six-month project, with students committing to 30 hours over two semesters. At the end of the project, students presented project deliverables to CP, faculty collaborative and other students. Interprofessional education collaborative (IPEC) domains were qualitatively assessed and students completed the Interprofessional Socialization and Valuing Scale (ISVS) at the beginning and conclusion of the project. Students provided written reflections at the conclusion of the project. Faculty completed the Team Observed Structured Clinical Encounter (TOSCE). Discussion" Twenty-seven students (100%) students completed the project and twenty-one students (77.8%) completed the evaluation tools. Students demonstrated a statistically significant difference between pre- and post-project ISVS total scores (5.81 +/- 0.64 vs. 6.51 +/- 0.37). Teamwork, communication skills, and increased comfort with those from other professions were common themes in the student reflections. Implications: Community-based IPE provides a venue for healthcare professionals to engage and partner with community organizations. This project demonstrates an effective inter-institutional, interprofessional method of delivering IPE.

Clinician- and Patient-reported Endpoints in CNS Orphan Drug Clinical Trials: ISCTM Position Paper on Best Practices for Endpoint Selection, Validation, Training, and Standardization.

OBJECTIVE: The International Society of CNS Clinical Trials Methodology (ISCTM) Working Group on Rare Disease/Orphan Drug Development is dedicated to improving and streamlining trials to best develop new treatments for rare diseases. The rarity of these disorders requires a drug development strategy that differs from those of nonrare conditions. Rare disease drug development programs are challenged with small sample sizes, heterogeneous clinical presentations, and few, if any, off-the-shelf endpoints. When disease-specific clinical endpoints exist, they might not be validated and are typically not well known or broadly used in clinical practice. This paper aims to provide an overview of the special issues surrounding endpoints in rare disease drug development, with guidance, practical applications, and discussion. DISCUSSION: The paper covers regulatory considerations in endpoint selection; identification of relevant measurement domains; methods of quantifying clinical meaningfulness; incorporation of patient- and clinician-reported outcomes; considerations for global clinician- and patient-rated clinical assessments; cognition assessment challenges in rare diseases; translation considerations; training, standardization, and calibration of assessors; and endpoint quality assurance. Additionally, it provides guidance and resources for those involved in drug development for rare diseases. CONCLUSION: In keeping with the mission of ISCTM and the rare disease/orphan drug development working group, this article is designed to encourage thoughtful consideration and provide insight and guidance to promote and further efforts in in central nervous system (CNS) rare disease drug development efforts.

Sex differences in associations of socioemotional dispositions measured in childhood and adolescence with brain white matter microstructure 12 years later.

Predictive associations were estimated between socioemotional dispositions measured at 10-17 years using the Child and Adolescent Dispositions Scale (CADS) and future individual differences in white matter microstructure measured at 22-31 years of age. Participants were 410 twins (48.3% monozygotic) selected for later neuroimaging by oversampling on risk for psychopathology from a representative sample of child and adolescent twins. Controlling for demographic covariates and total intracranial volume (TICV), each CADS disposition (negative emotionality, prosociality, and daring) rated by one of the informants (parent or youth) significantly predicted global fractional anisotropy (FA) averaged across the major white matter tracts in brain in adulthood, but did so through significant interactions with sex after false discovery rate (FDR) correction. In females, each 1 SD difference in greater parent-rated prosociality was associated with 0.43 SD greater FA (p < 0.0008). In males, each 1 SD difference in greater parent-rated daring was associated with 0.24 SD lower FA (p < 0.0008), and each 1 SD difference in greater youth-rated negative emotionality was associated with 0.18 SD greater average FA (p < 0.0040). These findings suggest that CADS dispositions are associated with FA, but associations differ by sex. Exploratory analyses suggest that FA may mediate the associations between dispositions and psychopathology in some cases. These associations over 12 years could reflect enduring brain-behavior associations in spite of transactions with the environment, but could equally reflect processes in which dispositional differences in behavior influence the development of white matter. Future longitudinal studies are needed to resolve the causal nature of these sex-moderated associations.

Understanding What Information Is Valued By Research Participants, And Why.

There is growing public demand that research participants receive all of their results, regardless of whether clinical action is indicated. Instead of the standard practice of returning only actionable results, we propose a reconceptualization called "return of value" to encompass the varied ways in which research participants value specific results and more general information they receive beyond actionable results. Our proposal is supported by a national survey of a diverse sample, which found that receiving research results would be valuable to most (78.5 percent) and would make them more likely to trust researchers (70.3 percent). Respondents highly valued results revealing genetic effects on medication response and predicting disease risk, as well as information about nearby clinical trials and updates on how their data were used. The information most valued varied by education, race/ethnicity, and age. Policies are needed to enable return of information in ways that recognize participants' differing informational needs and values.

Racial differences in two measures of trust in biomedical research.

OBJECTIVE: Lack of trust toward medical research is a major barrier to research participation, particularly among some population groups. Valid measures of trust are needed to develop appropriate interventions. The study purpose was to compare two previously validated scales that measure trust in biomedical research - one developed by Hall et al. (H-TBR; 2006) and the other by Mainous et al. (M-TBR; 2006) - in relation to socio-demographic variables and attitudes toward research. Differences between Black and White respondents were explored. METHODS: Two nearly identical surveys - one with H-TBR and the other with M-TBR - were systematically administered to a convenience sample. Internal consistency reliability of each scale was assessed. Associations were computed between scores on each scale with attitudes toward biomedical research and demographic variables (i.e., gender, age, race, and socioeconomic status). The difference between White and Black respondents on each TBR score while controlling for age, education, and race was also investigated. RESULTS: A total of 2020 participants completed the H-TBR survey; 1957 completed the M-TBR survey. Mean item scores for M-TBR were higher (F = 56.05, p < 0.001) among Whites than Blacks. Whites also had higher mean item scores than Blacks on H-TBR (F = 7.09, p < 0.001). Both scales showed a strong association with participants' perceived barriers to research (ps < 0.001) and significant, positive correlations with interest in research participation (ps < 0.001). Age and household income were positive predictors of TBR scores, but the effects of education differed. CONCLUSIONS: Both scales are internally consistent and show associations with attitudes toward research. Whites score higher than Blacks on both TBR scales, even while controlling for age and socioeconomic status.

White matter microstructure correlates of general and specific second-order factors of psychopathology.

Increasing data indicate that prevalent forms of psychopathology can be organized into second-order dimensions based on their correlations, including a general factor of psychopathology that explains the common variance among all disorders and specific second-order externalizing and internalizing factors. Nevertheless, most existing studies on the neural correlates of psychopathology employ case-control designs that treat diagnoses as independent categories, ignoring the highly correlated nature of psychopathology. Thus, for instance, although perturbations in white matter microstructure have been identified across a range of mental disorders, nearly all such studies used case-control designs, leaving it unclear whether observed relations reflect disorder-specific characteristics or transdiagnostic associations. Using a representative sample of 410 young adult twins oversampled for psychopathology risk, we tested the hypothesis that some previously observed relations between white matter microstructure properties in major tracts and specific disorders are related to second-order factors of psychopathology. We examined fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). White matter correlates of all second-order factors were identified after controlling for multiple statistical tests, including the general factor (FA in the body of the corpus callosum), specific internalizing (AD in the fornix), and specific externalizing (AD in the splenium of the corpus callosum, sagittal stratum, anterior corona radiata, and internal capsule). These findings suggest that some features of white matter within specific tracts may be transdiagnostically associated multiple forms of psychopathology through second-order factors of psychopathology rather with than individual mental disorders.

Do needs, symptoms or disability of outpatients with schizophrenia influence family burden?

BACKGROUND: Most needs of outpatients with schizophrenia are met by the family. This could cause high levels of family burden. The objective of this study is to assess the relationship between the patients' needs and other clinical and disability variables and the level of family burden. METHOD: A total sample of 231 randomly selected outpatients with schizophrenia was evaluated with the Camberwell Assessment of Needs, Positive and Negative Syndrome Scale, Global Assessment of Functioning and Disability Assessment Scale. A total of 147 caregivers also answered the objective and subjective family burden questionnaire (ECFOS-II). Correlations between total number of needs and family burden, t tests between presence or absence of need for each domain of family burden and regression models between family burden and needs, symptoms, disability and sociodemographic variables were computed. RESULTS: The number of patients' needs was correlated with higher levels of family burden in daily life activities, disrupted behaviour and impact on caregiver's daily routine. The patients' needs most associated with family burden were daytime activities, drugs, benefits, self-care, alcohol, psychotic symptoms, money and looking after home. In a regression model, a higher number of needs, higher levels of psychopathology and disability, being male and older accounted for higher levels of family burden. CONCLUSION: Patients with schizophrenia with more needs cause greater family burden but not more subjective concerns in family members. The presence of patients' needs (daytime activities, alcohol and drug), severity of psychotic symptoms and disability are related to higher levels of family burden.

Development and validation of the Person-Centeredness of Research Scale.

AIM: Person-centeredness shifts the focus of healthcare and research to the needs and priorities of patients and communities, and may improve health outcomes. There are no instruments available, however, with which we can assess the degree to which research is indeed person-centered. Our aim was to develop and validate a quantitative instrument to rate person-centeredness of research. MATERIALS & METHODS: Scale development and validation entailed a multistep approach that led to the seven-item Person Centeredness of Research Scale (PCoR Scale) that uses a 5-point Likert rating scale. The scale was validated using ratings of the Patient-Centered Outcomes Research Institute-funded research abstracts or abstracts submitted to a translational science meeting. RESULTS: Psychometric properties of the PCoR Scale showed high internal consistency (α = 0.96). All seven items were highly correlated with the total score (rs range from 0.63 to 0.90). An exploratory factor analysis demonstrated that all of the items loaded on a single factor, explaining 80% of the variance. The Patient-Centered Outcomes Research Institute-funded research abstracts had a mean PCoR Scale score of 6.52 (±8.01) that was significantly higher than the abstracts submitted to the translational science meeting (-2.56 (±9.18); t = 8.09; p < 0.0001). Inter-rater reliability in the validation of the revised instrument was high (Intraclass Correlation Coefficient [ICC](group1) = 0.89; ICC(group2) = 0.95). CONCLUSION: This brief, quantitative rating scale is the first to assess the main constructs that describe person-centeredness of research products. The PCoR Scale can be used to assess person-centeredness in research products; for example, by funders evaluating proposals, data networks evaluating data requests or researchers evaluating their research designs.

Right Fronto-Subcortical White Matter Microstructure Predicts Cognitive Control Ability on the Go/No-go Task in a Community Sample.

Go/no-go tasks are widely used to index cognitive control. This construct has been linked to white matter microstructure in a circuit connecting the right inferior frontal gyrus (IFG), subthalamic nucleus (STN), and pre-supplementary motor area. However, the specificity of this association has not been tested. A general factor of white matter has been identified that is related to processing speed. Given the strong processing speed component in successful performance on the go/no-go task, this general factor could contribute to task performance, but the general factor has often not been accounted for in past studies of cognitive control. Further, studies on cognitive control have generally employed small unrepresentative case-control designs. The present study examined the relationship between go/no-go performance and white matter microstructure in a large community sample of 378 subjects that included participants with a range of both clinical and subclinical nonpsychotic psychopathology. We found that white matter microstructure properties in the right IFG-STN tract significantly predicted task performance, and remained significant after controlling for dimensional psychopathology. The general factor of white matter only reached statistical significance when controlling for dimensional psychopathology. Although the IFG-STN and general factor tracts were highly correlated, when both were included in the model, only the IFG-STN remained a significant predictor of performance. Overall, these findings suggest that while a general factor of white matter can be identified in a young community sample, white matter microstructure properties in the right IFG-STN tract show a specific relationship to cognitive control. The findings highlight the importance of examining both specific and general correlates of cognition, especially in tasks with a speeded component.

Measuring the hierarchical general factor model of psychopathology in young adults.

There is evidence that models of psychopathology specifying a general factor and specific second-order factors fit better than competing structural models. Nonetheless, additional tests are needed to examine the generality and boundaries of the general factor model. In a selected second wave of a cohort study, first-order dimensions of psychopathology symptoms in 499 23- to 31-year-old twins were analyzed. Using confirmatory factor analysis, a bifactor model specifying a general factor and specific internalizing and externalizing factors fit better than competing models. Factor loadings in this model were sex invariant despite greater variances in the specific internalizing factor among females and greater variances in the general and specific externalizing factors among males. The bifactor structure was robust to the exclusion of any single first-order dimension of psychopathology. Furthermore, the results were essentially unchanged when all overlapping symptoms that define multiple disorders were excluded from symptom dimensions. Furthermore, the best-fitting bifactor model also emerged in exploratory structural equation modeling with freely estimated cross-loadings. The general factor of psychopathology was robust across variations in measurement and analysis.

Enhancing translational researchers' ability to collaborate with community stakeholders: Lessons from the Community Engagement Studio.

Community engagement is considered essential to effectively translate research into practice and is increasingly recognized as a key to successful clinical trial recruitment. Challenges to engaging community stakeholders in research persist and new methods are needed to facilitate meaningful stakeholder involvement. The Community Engagement Studio (CE Studio), a consultative model, has been used at every stage of the research process. Best practices drawn from the model could inform other methods of engagement. Using a mixed-methods approach that included evaluation surveys, impact surveys and interviews, we assessed the CE Studio program. We analyzed data from 75 CE Studios; 65 researchers and 591 community members completed surveys and 10 researchers completed interviews. Surveys indicate that 100% of researchers would request a CE Studio in the future, and 99.3% of community members would participate in a CE Studio again. We identified 6 practices to enhance community engagement in clinical and translational research: early input, researcher coaching, researcher humility, balancing power, neutral facilitator, and preparation of community stakeholders. These best practices may enhance the quality of existing community engagement approaches and improve the effectiveness of translational researchers' efforts to engage community stakeholders in their work.

Brain alterations in low-frequency fluctuations across multiple bands in obsessive compulsive disorder.

The extent of functional abnormalities in frontal-subcortical circuits in obsessive-compulsive disorder (OCD) is still unclear. Although neuroimaging studies, in general, and resting-state functional Magnetic Resonance Imaging (rs-fMRI), in particular, have provided relevant information regarding such alterations, rs-fMRI studies have been typically limited to the analysis of between-region functional connectivity alterations at low-frequency signal fluctuations (i.e., <0.08 Hz). Conversely, the local attributes of Blood Oxygen Level Dependent (BOLD) signal across different frequency bands have been seldom studied, although they may provide valuable information. Here, we evaluated local alterations in low-frequency fluctuations across different oscillation bands in OCD. Sixty-five OCD patients and 50 healthy controls underwent an rs-fMRI assessment. Alterations in the fractional amplitude of low-frequency fluctuations (fALFF) were evaluated, voxel-wise, across four different bands (from 0.01 Hz to 0.25 Hz). OCD patients showed decreased fALFF values in medial orbitofrontal regions and increased fALFF values in the dorsal-medial prefrontal cortex (DMPFC) at frequency bands <0.08 Hz. This pattern was reversed at higher frequencies, where increased fALFF values also appeared in medial temporal lobe structures and medial thalamus. Clinical variables (i.e., symptom-specific severities) were associated with fALFF values across the different frequency bands. Our findings provide novel evidence about the nature and regional distribution of functional alterations in OCD, which should contribute to refine neurobiological models of the disorder. We suggest that the evaluation of the local attributes of BOLD signal across different frequency bands may be a sensitive approach to further characterize brain functional alterations in psychiatric disorders.

Neurocognitive performance and negative symptoms: are they equal in explaining disability in schizophrenia outpatients?

OBJECTIVE: The aim of this study is to assess if cognitive variables and symptom dimensions can predict disability in a sample of outpatients with schizophrenia. METHOD: A cross-sectional sample of 113 individuals with a diagnosis of schizophrenia (DSM-IV criteria) was selected from a computerized register of five Community Mental Health Centers. Patients were assessed by two trained psychologists, with a neuropsychological battery comprising measures for verbal memory, attention, operative memory and abstraction and flexibility functions. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS); a socio-demographic and clinical questionnaire, comprising the Disability Assessment Scale (DAS), was also completed. Test scores were standardized (t scores) to performance of healthy controls. To assess the relationship between clinical and sociodemographic factors and disability and cognitive functioning Pearson's correlation coefficients were computed. In order to establish the predictive capacity of the cognitive, clinical and symptom variables on disability linear regression models were fitted. RESULTS: Mean age of patients was 41.6 years and 68% were male. Higher ratings in the negative dimension were associated with more cognitive deficits. Association with the positive dimension was present but less strong. All disability areas, except for disability in occupational functioning, were partially explained by the negative dimension. Disability in family functioning was also partially explained by attention and number of admissions since onset. CONCLUSION: Negative symptoms are the major source of disability of our sample and are also associated to cognitive functioning. The present findings suggest that further investigation on the mediators between clinical and social outcomes may help to design specific treatments to reduce disability.