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Both childhood adversity (CA) and first-episode psychosis (FEP) have been linked to alterations in cortical thickness (CT). The interactive effects between different types of CAs and FEP on CT remain understudied.
Methods
One-hundred sixteen individuals with FEP (mean age = 23.8 ± 6.9 years, 34% females, 80.2% non-affective FEP) and 98 healthy controls (HCs) (mean age = 24.4 ± 6.2 years, 43% females) reported the presence/absence of CA <17 years using an adapted version of the Childhood Experience of Care and Abuse (CECA.Q) and the Retrospective Bullying Questionnaire (RBQ) and underwent magnetic resonance imaging (MRI) scans. Correlation analyses were used to assess associations between brain maps of CA and FEP effects. General linear models (GLMs) were performed to assess the interaction effects of CA and FEP on CT.
Results
Eighty-three individuals with FEP and 83 HCs reported exposure to at least one CA. CT alterations in FEP were similar to those found in participants exposed to separation from parents, bullying, parental discord, household poverty, and sexual abuse (r = 0.50 to 0.25). Exposure to neglect (β = −0.24, 95% CI [−0.37 to −0.12], p = 0.016) and overall maltreatment (β = −0.13, 95% CI [−0.20 to −0.06], p = 0.043) were associated with cortical thinning in the right medial orbitofrontal region.
Conclusions
Cortical alterations in individuals with FEP are similar to those observed in the context of socio-environmental adversity. Neglect and maltreatment may contribute to CT reductions in FEP. Our findings provide new insights into the specific neurobiological effects of CA in early psychosis.
Higher white matter hyperintensity (WMH) volume is a marker of cardiovascular disease (CVD) risk. CVD risk factors increase risk for Alzheimer’s disease and related dementias (ADRD). Mexican Americans (MA) and individuals of other Hispanic/Latino heritages have higher risk for CVD and ADRD. However, knowledge of associations between WMH volume and cognition in these groups remains limited.
Method:
We conducted a cross-sectional study of associations between WMH volume and neuropsychological performance (attention/executive functioning, memory) in MA (n = 851) and non-Hispanic White (NHW; n = 747) adults in the Health and Aging Brain Study: Health Disparities.
Results:
The MA group (mean age = 63.72 ± 7.90 years; 66.3% female) had higher rates of consensus diagnoses of hypertension and diabetes, whereas the NHW group (mean age = 69.18 ± 8.65 years; 55.2% female) had higher rates of diagnosed CVD (ps < .01). WMH volumes were higher among individuals with CVD risk factors/conditions (ps < .01). There were differential associations between WMH and neuropsychological performance across ethnoracial groups (ps < .001), wherein associations were steeper in the NHW group than in the MA group. Lower educational level was associated with higher WMH volume in the NHW group (p < .001), but no association was seen in the MA group (p > .05).
Conclusions:
Negative effects of pathological changes in the form of WMH on cognition may be less robust or consistent for MA adults than NHW adults. Furthermore, the impact of WMH on cognition in NHW adults may be mitigated by cognitive reserve related to educational attainment.
Migrants and refugees face elevated risks for mental health problems but have limited access to services. This study compared two strategies for training and supervising nonspecialists to deliver a scalable psychological intervention, Group Problem Management Plus (gPM+), in northern Colombia. Adult women who reported elevated psychological distress and functional impairment were randomized to receive gPM+ delivered by nonspecialists who received training and supervision by: 1) a psychologist (specialized technical support); or 2) a nonspecialist who had been trained as a trainer/supervisor (nonspecialized technical support). We examined effectiveness and implementation outcomes using a mixed-methods approach. Thirteen nonspecialists were trained as gPM+ facilitators and three were trained-as-trainers. We enrolled 128 women to participate in gPM+ across the two conditions. Intervention attendance was higher in the specialized technical support condition. The nonspecialized technical support condition demonstrated higher fidelity to gPM+ and lower cost of implementation. Other indicators of effectiveness, adoption and implementation were comparable between the two implementation strategies. These results suggest it is feasible to implement mental health interventions, like gPM+, using lower-resource, community-embedded task sharing models, while maintaining safety and fidelity. Further evidence from fully powered trials is needed to make definitive conclusions about the relative cost of these implementation strategies.
The developmental origins of health and disease hypothesis have highlighted the link between early life environment and long-term health outcomes in offspring. For example, maternal protein restriction during pregnancy and lactation can result in adverse metabolic and cognitive outcomes in offspring postnatal. Hence, in the present study, we assess whether an isocaloric low-protein diet (ILPD) affects the fatty acid profile in breast milk, the hippocampal synaptophysin (Syn) ratio, and the oxidative stress markers in the neonatal stage of male and female offspring. The aim of this work was to assess the effect of an ILPD on the fatty acid profile in breast milk, quantified the hippocampal synaptophysin (Syn) ratio and oxidative stress markers in neonatal stage of male and female offspring. Female Wistar rats were fed with either a control diet or an ILPD during gestation to day 10 of lactation. Oxidative stress markers were assessed in serum and liver. All quantifications were done at postnatal day 10. The results showed: ILPD led to decreases of 38.5% and 17.4% in breast milk volume and polyunsaturated fatty acids content. Significant decreases of hippocampal Syn ratio in male offspring (decreases of 98% in hippocampal CA1 pyramidal and CA1 oriens, 83%, stratum pyramidal in CA3, 80%, stratum lucidum in CA3, and 81% stratum oriens in CA3). Male offspring showed an increase in pro-oxidant status in serum and liver. Thus, the data suggest that male offspring are more vulnerable than females to an ILPD during gestation and lactation.
The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties.
Method:
MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart.
Results:
All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability.
Conclusions:
Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.
The presence of the Catholic Church and the imposition of religious beliefs and practices onto the newly found inhabitants of the Americas was perhaps one of the biggest catalysts of transition during the early modern period. This chapter focuses on the literature that was produced for, and by indigenous peoples within the religious realm. It considers different discursive genres that are emblematic of the transitions that natives experienced when they were into close and sustained contact with religious institutions, such as plays for conversion and evangelization, sermons, catechisms, spiritual biographies, and other prescriptive literature.
We investigated the impact of culturally relevant social, educational, and language factors on cognitive test performance among Spanish speakers living near the US–Mexico border.
Methods:
Participants included 254 healthy native Spanish speakers from the Neuropsychological Norms for the US–Mexico Border Region in Spanish (NP-NUMBRS) project (Age: M = 37.3, SD = 10.4; Education: M = 10.7, SD = 4.3; 59% Female). A comprehensive neuropsychological battery was administered in Spanish. Individual test scaled scores and T-scores (based on region-specific norms adjusted for age, education, and sex) were averaged to create Global Mean Scaled and T-scores. Measures of culturally relevant factors included a self-reported indicator of educational quality/access (proportion of education in Spanish-speaking country, quality of school/classroom setting, stopped attending school to work), childhood socioeconomic environment (parental education, proportion of time living in Spanish-speaking country, childhood socioeconomic and health status, access to basic resources, work as a child), and Spanish/English language use and fluency.
Results:
Several culturally relevant variables were significantly associated with unadjusted Global Scaled Scores in univariable analyses. When using demographically adjusted T-scores, fewer culturally relevant characteristics were significant. In multivariable analyses, being bilingual (p = .04) and working as a child for one’s own benefit compared to not working as a child (p = .006) were significantly associated with higher Global Mean T-score, accounting for 9% of variance.
Conclusions:
Demographically adjusted normative data provide a useful tool for the identification of brain dysfunction, as these account for much of the variance of sociocultural factors on cognitive test performance. Yet, certain culturally relevant variables still contributed to cognitive test performance above and beyond basic demographics, warranting further investigation.
Attention allows us to select relevant information from the background. Although several studies have described that cannabis use induces deleterious effects on attention, it remains unclear if cannabis dependence affects the attention network systems differently.
Objectives:
To evaluate whether customary consumption of cannabis or cannabis dependence impacts the alerting, orienting, and executive control systems in young adults; to find out whether it is related to tobacco or alcohol dependence and if cannabis use characteristics are associated with the attention network systems.
Method:
One-hundred and fifty-four healthy adults and 102 cannabis users performed the Attention Network Test (ANT) to evaluate the alerting, orienting, and executive control systems.
Results:
Cannabis use enhanced the alerting system but decreased the orienting system. Moreover, those effects seem to be associated with cannabis dependence. Out of all the cannabis-using variables, only the age of onset of cannabis use significantly predicted the efficiency of the orienting and executive control systems.
Conclusion:
Cannabis dependence favors tonic alertness but reduces selective attention ability; earlier use of cannabis worsens the efficiency of selective attention and resolution of conflicts.
OBJECTIVES/GOALS: The history of immune suppression, especially CD4 nadir, has been shown to be a strong predictor of HIV-associated neurocognitive disorders (HAND). However, the potential mechanism of this association is not well understood. This study examined the relationship between CD4 nadir and brain atrophy. METHODS/STUDY POPULATION: Fifty-nine people with HIV participated in the cross-sectional study (mean age, 56.5 ± 5.8; age range, 41-69; 15 females; 46 African-Americans). High resolution structural MRI images were obtained using a 3T Siemens scanner. From a comprehensive 7-domain neuropsychological test battery, a global deficit score (GDS) and HAND diagnoses were determined for each participant. The correlation between CD4 nadir (the lowest ever lymphocyte CD4 count) and cortical thickness was investigated using a vertex-wise non-parametric approach with a conservative statistical threshold of p < 0.05 (FWE-corrected). RESULTS/ANTICIPATED RESULTS: Out of the 59 participants, 12 met standard Frascati criteria for asymptomatic neurocognitive impairment (ANI) and two met the criteria for mild neurocognitive disorder (MND). Across all participants, low CD4 nadir was associated with widespread cortical thinning, especially in the frontal and temporal regions. Higher GDS (indicating worse global neurocognitive function) was associated with bilateral frontal cortical thinning, and the association largely persisted in the subset of participants who did not meet HAND criteria. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that the low CD4 nadir may be associated with widespread neural injury in the brain, especially in the frontal and temporal regions. This spatial profile might contribute to the prevalence/phenotypes of HAND in the cART era, such as the frequently observed deficits in the executive domain.
Non-suicidal self-injury (NSSI) behaviors are self-injurious behaviors inflicted without intending death. Literature has shown the relationship between stressful life events (SLE) and NSSI behaviors. The Strengths and Difficulties Questionnaire-Dysregulation Profile (SDQ-DP) is defined as an index of self-regulatory problems, related to higher risk for suicidal ideation and attempts in adolescents. In this study the relationship between SDQ-DP and NSSI behaviors, mediated by SLE in a clinical sample of children and adolescents is analyzed. A cross-sectional study was conducted on 239 subjects (aged from 11 to 17) to test the mediation model. SDQ-DP significantly correlates with NSSI behaviors (Wald = 6.5477, p = .0105); SDQ-DP significantly correlates with SLE (T = 5.7229, p < .001); SLE significantly correlates NSSI behaviors, and the relation remains significant whilst controlling for SDQ-DP (Wald = 4.1715, p = .041); the relation between SDQ-DP and NSSI behaviors stops being significant whilst controlling for the potential mediator (SLE) (Wald = 2.9951, p = .0835). Study of indirect effect supports the mediation model (.0585 CI [.0016, .1266]). Findings are compatible with the complete mediation scenario. These results point out the importance of self-regulatory problems in coping strategies with regards to SLE and the development of NSSI behaviors.
To determine the prevalence of and modifiable factors associated with prediabetes in the Comcáac Indians.
Design
Cross-sectional study where prediabetes was defined using fasting plasma glucose, 2 h plasma glucose and glycated Hb (HbA1c). Physical, anthropometric and biochemical measurements, medical record, socio-economic, dietary and physical activity information were collected. The modifiable factors associated with prediabetes were assessed using multiple logistic regression.
Settings
Comcáac Indian communities of Punta Chueca and El Desemboque, Sonora, Mexico.
Subjects
Adults (n 227) aged 20 years or older.
Results
The sex- and age-adjusted prevalence (95 % CI) of prediabetes was 47·1 (40·8, 53·5) % in the overall population; age-adjusted prevalence was 47·3 (35·6, 59·0) % in men and 46·7 (39·1, 54·3) % in women. The modifiable factors associated with a risk of prediabetes (OR; 95 % CI) were light-intensity physical activity (per 1 h/week increase: 1·04; 1·01, 1·07) and insulin resistance (homeostasis model assessment of insulin resistance score >6·1 v. <4·1: 4·62; 1·37, 15·51). Increased consumption of a traditional dietary pattern based on fish and seafood, low-fat cereals, fruits and vegetables was a protective factor (0·49; 0·31, 0·79). All variables were modelled together and adjusted for age and sex.
Conclusions
The high prediabetes prevalence found in the Comcáac community is alarming because it represents a large number of people who are at risk for type 2 diabetes. The identification of modifiable factors associated with prediabetes that are specific to this population may be useful for designing effective strategies to prevent prediabetes.
There is a need for clinical tools to identify cultural issues in diagnostic assessment.
Aims
To assess the feasibility, acceptability and clinical utility of the DSM-5 Cultural Formulation Interview (CFI) in routine clinical practice.
Method
Mixed-methods evaluation of field trial data from six countries. The CFI was administered to diagnostically diverse psychiatric out-patients during a diagnostic interview. In post-evaluation sessions, patients and clinicians completed debriefing qualitative interviews and Likert-scale questionnaires. The duration of CFI administration and the full diagnostic session were monitored.
Results
Mixed-methods data from 318 patients and 75 clinicians found the CFI feasible, acceptable and useful. Clinician feasibility ratings were significantly lower than patient ratings and other clinician-assessed outcomes. After administering one CFI, however, clinician feasibility ratings improved significantly and subsequent interviews required less time.
Conclusions
The CFI was included in DSM-5 as a feasible, acceptable and useful cultural assessment tool.
The written traces and cultural legacy left by colonial Spanish American women, especially interpreters, translators, nuns, and other religious women, provided the foundation for modern women's creations. Women played important roles in the production of culture during the early modern period throughout the Atlantic world and participated actively in the settlement of colonial societies. The most well-known woman from early modern period is Malinche, as she is known today, though she was called Marina by the Spaniards and Malintzin by the natives. A young native woman given to Hernan Cortes, leader of the Spanish expedition that conquered Mexico-Tenochtitlan, along with nineteen other women when he arrived with his entourage on the coast of Tabasco in 1519. Malinche became a feminine paradigm that survived throughout the colonial period, was revived in the nineteenth century as a literary character, became a scapegoat in the construction of the patria. She was then promoted as the epitome of Mexican consciousness in the twentieth century.
Chemical genetics describes the use of molecules as “chemical probes” to investigate biological systems [1–3]. In contrast with traditional genetics, in which gene knockouts on the level of the DNA are used, chemical genetics uses biologically active small molecules to directly attenuate the corresponding biological macromolecular (usually protein) product. Thus, the ready availability of bioactive small molecules is of crucial importance in chemical genetics studies. Such small molecules can be identified by screening compound collections (libraries) in suitably designed assays. This chapter describes the use of diversity-oriented synthesis (DOS) to prepare structurally diverse small molecule libraries. Structurally diverse libraries show a greater variety in not only their physiochemical properties but also, and of most relevance here, in their biological activities. Herein we describe some of the most effective strategies that have been used in DOS library design and preparation.
Small molecules, chemical genetics, and chemical genomics
Chemical genetics experiments can be performed in either a forward or a reverse sense (Figure 4.1). The first step of both approaches requires the identification of a small molecule that either induces a desired phenotype (forward chemical genetics) or modulates the function of a specific protein of interest (reverse chemical genetics). Thus, in the former case, investigations proceed from phenotype to protein, whereas in the latter case, investigations progress from protein to phenotype.
Sleep is a process occurring in all living animals. Although it is still controversial whether insects and other animals sleep alike; there is no doubt that they rest, as many studies in Drosophila melanogaster have shown. In this context, several seminal studies have documented species-dependent variations in sleep patterns. These findings along with obvious non-learned characteristics of sleep in general, such as the total time of sleep, the alternating NREM–REM sleep pattern, among many others, suggest strong regulation by genes. Clearly, the way genes may influence sleep physiology is via proteins. Hence, the importance of proteins in the regulation of sleep is observed in every minute event occurring to trigger or to maintain sleep. In this chapter we discuss families of proteins that are grouped by their effect on food ingestion, immunological response, trophic activity, and intracellular signaling, all of them affecting the sleep–waking cycle. Although we do not fully discuss the mechanisms of action, we put our effort in highlighting their effects on sleep. Along with the proteins and their effects we have listed those genes encoding them. We also show examples of proteins and the way they affect sleep. Hence, we hope that the overall message that readers will gather from this chapter is the importance of several proteins in the regulation of sleep. Also, by observing the effects of each family of proteins we can infer at least some functions of sleep and, finally, that sleep is a multigenic trait.