Network-specific selectivity of functional connections in the neonatal brain.

The adult human brain is organized into functional brain networks, groups of functionally connected segregated brain regions. A key feature of adult functional networks is long-range selectivity, the property that spatially distant regions from the same network have higher functional connectivity than spatially distant regions from different networks. Although it is critical to establish the status of functional networks and long-range selectivity during the neonatal period as a foundation for typical and atypical brain development, prior work in this area has been mixed. Although some studies report distributed adult-like networks, other studies suggest that neonatal networks are immature and consist primarily of spatially isolated regions. Using a large sample of neonates (n = 262), we demonstrate that neonates have long-range selective functional connections for the default mode, fronto-parietal, and dorsal attention networks. An adult-like pattern of functional brain networks is evident in neonates when network-detection algorithms are tuned to these long-range connections, when using surface-based registration (versus volume-based registration), and as per-subject data quantity increases. These results help clarify factors that have led to prior mixed results, establish that key adult-like functional network features are evident in neonates, and provide a foundation for studies of typical and atypical brain development.

Individual-specific functional connectivity of the amygdala: A substrate for precision psychiatry.

The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cingulo-opercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala-cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.

Irritability-related neural responses to frustrative nonreward in adolescents with trauma histories: A preliminary investigation.

Irritability, conceptualized as a lowered frustration response threshold to blocked goal attainment (i.e., frustrative nonreward), is a common, detrimental symptom in adolescence. Yet, neural mechanisms of irritability are not well understood. This preliminary study aims to identify irritability-related neural patterns using a novel frustrative nonreward paradigm. Our study used a diverse sample of N = 31 non-White adolescent participants (mean age 14.53 years, SD = 1.74; 83.87% Hispanic/Latinx) to improve generalizability. During fMRI acquisition, participants performed a child-friendly monetary incentive delay task, modified to provide incorrect, negative feedback on performance. Irritability was associated with alterations in amygdala connectivity with basal ganglia, prefrontal, temporal, and parietal regions, and in activation of prefrontal and posterior cortical structures. Across clusters, youths with greater irritability showed activation/connectivity differences between reward blocked versus received conditions in the opposite direction compared to youths with lowered irritability. Alterations in amygdala-temporoparietal connectivity and lingual gyrus activation demonstrated an altered irritability-related recovery effect from the previous trial. These findings support the central role of frustrative nonreward as a key irritability pathway. Our work is one of the first to document neural correlates of difficult recovery from frustration characteristic of irritability and provides insight into novel treatment targets for irritability in diverse populations.

On the Nature of Monozygotic Twin Concordance and Discordance for Autistic Trait Severity: A Quantitative Analysis.

The characterizing features of autism spectrum disorder (ASD) are continuously distributed in nature; however, prior twin studies have not systematically incorporated this knowledge into estimations of concordance and discordance. We conducted a quantitative analysis of twin-twin similarity for autistic trait severity in three existing data sets involving 366 pairs of uniformly-phenotyped monozygotic (MZ) twins with and without ASD. Probandwise concordance for ASD was 96%; however, MZ trait correlations differed markedly for pairs with ASD trait burden below versus above the threshold for clinical diagnosis, with R2s on the order of 0.6 versus 0.1, respectively. Categorical MZ twin discordance for ASD diagnosis is rare and more appropriately operationalized by standardized quantification of twin-twin differences. Here we provide new evidence that although ASD itself is highly heritable, variation-in-severity of symptomatology above the diagnostic threshold is substantially influenced, in contrast, by non-shared environmental factors which may identify novel targets of early ASD amelioration.

Roads Diverged: Developmental Trajectories of Irritability From Toddlerhood Through Adolescence.

OBJECTIVE: Irritability is a dimensional trait that manifests from early life and is a robust transdiagnostic risk factor for psychopathology and impairment. A large, national dataset was leveraged to identify and broadly characterize trajectories from toddlerhood through adolescence, which is crucial for timely, targeted interventions. METHOD: Data on irritability and a broad array of potential factors affecting irritability development from 4,462 children assessed longitudinally at ages 3, 5, 9, and 15 were included. Latent class growth models identified groups of children based on their nonlinear irritability trajectories from toddlerhood to adolescence. LASSO regression then identified key characteristics differentiating trajectory groups. RESULTS: Five distinct irritability trajectories were identified, two of which were stable, maintaining medium or high irritability from age 3 to 15. Three trajectories showed undulating change over development, with an inflection point at the transition to adolescence (age 9): Most children had consistently low irritability. Two smaller groups started with high irritability at age 3 but diverged, sharply decreasing or increasing until a turning point at age 9. Developmental patterning of harsh/neglectful parenting and child internalizing symptoms most strongly differentiated trajectory groups. Sociodemographic characteristics, attachment style, neighborhood support, cognitive functioning, and genetic variation also differentiated trajectories. CONCLUSION: The results demonstrated the importance of the transition to adolescence as a critical inflection point for youths with fluctuating irritability trajectories. Identifying these patterns and multiple malleable factors associated with stably high or rising trajectories is an important step toward targeted interventions for the most vulnerable subgroups. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.

Toward an optimized assessment of adolescent psychopathology risk: Multilevel environmental profiles and child irritability as predictors.

Background: Adolescence is a developmental period during which youth experience vulnerability to psychopathology. To build the foundation for a parsimonious psychopathology risk calculator while capturing the complexity and dynamic nature of the environment, the current study aimed to identify distinct risk and resilience profiles with a wide range of environmental factors guided by Bronfenbrenner's biopsychosocial ecological system theory. The association between the early-mid childhood risk profiles and psychopathology in adolescence were examined. Moreover, the predictive utility of early childhood irritability was evaluated in addition to the risk profiles. Methods: The data from Future of Families and Child Wellbeing Study a nation-wide longitudinal study, were used in the latent profile analyses to identify the risk profiles with family, school, and neighborhood characteristics from 3 to 9 years old. To capture the socio-environmental and cultural nuances, we extracted three subsamples, including Black/African American (n = 2587), Hispanic/Latinx (n = 1577), and White (n = 776) for separate analyses. Risk profile memberships were used to predict adolescence psychopathology, including depression, anxiety, attention deficits, oppositional defiant disorder, and conduct disorder symptoms. The predictive utility of early childhood irritability above and beyond environmental risk profiles was evaluated using stepwise regression. Results: Three risk profiles were identified in the Hispanic/Latinx and Black/African American subsamples, while four profiles were identified in White subsample. Almost all risk profile membership predicted both internalizing and externalizing psychopathology, while some profiles are predictive of externalizing symptoms only. Higher level of irritability predicted higher symptomatology in all five mental health outcomes above and beyond the environmental profiles. Conclusions: Distinct risk and resilience profiles primarily driven by parent and family characteristics were identified for all three major race/ethnicity groups. Our findings lay the foundation for a more efficient multi-tiered information gathering process in mental health clinical settings to aid the decision making for intervention and prevention.

Advancing earlier transdiagnostic identification of mental health risk: A pragmatic approach at the transition to toddlerhood.

OBJECTIVES: In light of the youth mental health crisis, as 1 in 5 children have a mental disorder diagnosis by age 3, identification of transdiagnostic behavioral vulnerability prior to impairing psychopathology must occur at an earlier phase of the clinical sequence. Here, we lay the groundwork for a pragmatic irritability measure to identify at-risk infant-toddlers. METHODS: Data comprised N = 350 diverse infant-toddlers and their mothers assessed at ∼14 months old for irritability (Multidimensional Assessment Profiles- Temper Loss-Infant/Toddler (MAPS-TL-IT) and impairment (Early Childhood Irritability-Related Impairment Interview, E-CRI; and Family Life Impairment Scale (FLIS). Bimonthly follow-up surveys assessed impairment (FLIS) over the following year. RESULTS: Stepwise logistic regression indicated that 5 MAPS-TL-IT items were most informative for differentiating concurrent impairment on the FLIS: "frustrated about small things"; "hit, bite, or kick during tantrums"; "trouble cheering up when grumpy"; "grumpy during fun activities" and "tantrums in public". With this summed score, Receiver Operating Characteristics analysis differentiating concurrent impairment on the E-CRI indicated good classification accuracy for (Area under the curve = 0.755, p < 0.05), with a cutoff of 5 maximizing sensitivity (71.4%) and specificity (70.6%). Elevated irritability on this MAPS-TL-IT clinically optimized screener increased likelihood of persistently elevated FLIS impairment trajectories over the following year more than fourfold (OR = 4.37; Confidence intervals = 2.40-7.97, p < 0.001). CONCLUSIONS: Our findings represent the first step toward a pragmatic tool for screening for transdiagnostic mental health risk in toddlers, optimized for feasibility in clinical care. This has potential to strengthen resilience pathways via earlier identification of mental health risk and corollary prevention in toddlers.

A Novel Cognitive Training Program Targets Stimulus-Driven Attention to Alter Symptoms, Behavior, and Neural Circuitry in Pediatric Anxiety Disorders: Pilot Clinical Trial.

Objective: Pediatric anxiety disorders are associated with increased stimulus-driven attention (SDA), the involuntary capture of attention by salient stimuli. Increased SDA is linked to increased activity in the right ventrolateral prefrontal cortex (rVLPFC), especially in the portion corresponding to the ventral attention network (VAN). In this study, we present a small clinical trial using a novel attention training program designed to treat pediatric anxiety by decreasing SDA and activity in the rVLPFC. Methods: Children ages 8-12 with anxiety disorders (n = 18) participated in eight sessions of attention training over a 4-week period. At baseline and after completing training, participants completed clinical anxiety measures and a battery of cognitive tasks designed to measure three different aspects of attention: SDA, goal-oriented attention, and threat bias. A subset of participants (n = 12) underwent baseline and post-training neuroimaging while engaged in an SDA task. Brain analyses focused on activity within the rVLPFC. Results: Parent (p < 0.001)-, child (p < 0.002)-, and clinician-rated (p < 0.02) anxiety improved significantly over the course of training. Training significantly altered SDA [F(1,92) = 8.88, corrected p-value (pcor) < 0.012, uncorrected p-value (puncor) < 0.004]. Anxiety improvement correlated with improvements in goal-directed attention [r(10) = 0.60, pcor < 0.12 puncor < 0.04]. Within an area of the rVLPFC corresponding to the cingulo-opercular network (CON), there was a main effect of training [F(1,20) = 6.75, pcor < 0.16, puncor < 0.02], with decreasing signal across training. There was a significant interaction between training and anxiety on this region's activity [F(1,20) = 9.48, pcor < 0.048, puncor < 0.006]. Post hoc testing revealed that post-training activity within this CON area correlated with residual anxiety [r(10) = 0.68, p < 0.02]. Conclusions: SDA and rVLPFC neural activity may be novel therapeutic targets in pediatric anxiety. After undergoing a training paradigm aimed at modifying this aspect of attention and its underlying neural circuitry, patients showed lower anxiety, changes in SDA and goal-oriented attention, and decreased activity in the CON portion of the rVLPFC.

Neural correlates of attachment in adolescents with trauma: a preliminary study on frustrative non-reward.

Despite the proposed early life origins of attachment style and its implications for risk for psychopathology, little is known about its neurodevelopmental course. Adolescence represents a key transition period when neural substrates of emotion regulation and reward undergo dramatic maturational shifts. Thus, maladaptive coping strategies associated with insecure attachment styles may have an exaggerated effect during adolescence. The current study, therefore, examined the neural correlates of insecure attachment in a diverse sample of adolescents using a frustrative non-reward task (i.e. repeatedly being denied an expected reward). Although there were no significant interactions in the whole-brain activation averaged over the course of the task, the use of complementary analytic approaches (connectivity, change in activation over the course of the task) revealed widespread alterations associated with avoidant attachment during the immediate reaction to, and ensuing recovery from, being denied a reward. Most strikingly, increased avoidant attachment, adjusting for anxious attachment, predicted functional connectivity and change in activity over time in amygdala-prefrontal and frontostriatal networks to reward blocked vs received trials. These patterns were in the opposite direction compared to those exhibited by adolescents lower in avoidant attachment. The findings suggest that negative emotional experiences, such as receiving frustrating feedback, may be uniquely aversive internal experiences for avoidantly attached adolescents and provide preliminary evidence that early coping strategies may persist into adolescence in the form of altered emotion- and reward-related neural patterns.

White matter integrity in adolescent irritability: A preliminary study.

Irritability is a prevalent, impairing transdiagnostic symptom, especially during adolescence, yet little is known about irritability's neural mechanisms. A few studies examined the integrity of white matter tracts that facilitate neural communication in irritability, but only with extreme, disorder-related symptom presentations. In this preliminary study, we used a group connectometry approach to identify white matter tracts correlated with transdiagnostic irritability in a community/clinic-based sample of 35 adolescents (mean age = 14 years, SD = 2.0). We found positive and negative associations with irritability in local white matter tract bundles including sections of the longitudinal fasciculus; frontoparietal, parolfactory, and parahippocampal cingulum; corticostriatal and thalamocortical radiations; and vertical occipital fasciculus. Our findings support functional neuroimaging studies that implicate widespread neural pathways, particularly emotion and reward networks, in irritability. Our findings of positive and negative associations reveal a complex picture of what is "good" white matter connectivity. By characterizing irritability's neural underpinnings, targeted interventions may be developed.

Contributions of childhood abuse and neglect to reward neural substrates in adolescence.

BACKGROUND: Childhood adverse experiences may come to bear particularly during adolescence, when neural reward systems are developing rapidly and psychopathology spikes. Despite prior work differentiating threat- (abuse) vs. deprivation- (neglect) related adversity, no research has yet identified their relative nor interactive contributions to reward neural substrates during adolescence. In the present study, we leveraged a diverse sample of adolescents with different childhood adversity profiles to examine neural responses to reward in relation to varying degrees of abuse vs. neglect. METHODS: Adolescents (N = 45; 23 females; mean age = 14.9 years, SD = 1.9) completed a child-friendly monetary incentive delay task during fMRI acquisition. The self-report Childhood Trauma Questionnaire assessed childhood abuse and neglect. Whole brain ANCOVA analyses evaluated reward anticipation (reward vs. no reward expected) and feedback (hitting vs. missing the target with a reward vs. no reward) in relation to abuse and neglect dimensions. RESULTS: Whole-brain analyses revealed that abuse, adjusted for neglect, is associated with greater differences between task conditions (reward vs. no reward, hit vs. miss) in regions associated with threat/emotion regulation (prefrontal and temporal cortices, as well as posterior regions including fusiform and posterior cingulate/precuneus). Additionally, level of neglect modulated neural response associated with abuse in prefrontal and temporoparietal regions, such that youths with high levels of both abuse and neglect showed qualitatively different, more exaggerated neural patterns compared to youths with elevated adversity in only one dimension. CONCLUSIONS: Our findings suggest that early experiences of abuse and neglect have a long developmental reach resulting in reward-related neural alterations in adolescence. Moreover, our results bolster theoretical conceptualizations of adversity along threat and deprivation dimensions and provide evidence that "adding up" adverse life events may not be sufficient to capture the qualitatively different neural profiles produced by differing combinations of types of adversity, which may in turn necessitate different treatment approaches.

Attention Alterations in Pediatric Anxiety: Evidence From Behavior and Neuroimaging.

BACKGROUND: Pediatric anxiety disorders involve greater capture of attention by threatening stimuli. However, it is not known if disturbances extend to nonthreatening stimuli, as part of a pervasive disturbance in attention-related brain systems. We hypothesized that pediatric anxiety involves greater capture of attention by salient, nonemotional stimuli, coupled with greater activity in the portion of the inferior frontal gyrus (IFG) specific to the ventral attention network (VAN). METHODS: A sample of children (n = 129, 75 girls, mean 10.6 years of age), approximately half of whom met criteria for a current anxiety disorder, completed a task measuring involuntary capture of attention by nonemotional (square boxes) and emotional (angry and neutral faces) stimuli. A subset (n = 61) completed a task variant during functional magnetic resonance imaging. A priori analyses examined activity in functional brain areas within the right IFG, supplemented by a whole-brain, exploratory analysis. RESULTS: Higher clinician-rated anxiety was associated with greater capture of attention by nonemotional, salient stimuli (F1,125 = 4.94, p = .028) and greater activity in the portion of the IFG specific to the VAN (F1,57 = 10.311, p = .002). Whole-brain analyses confirmed that the effect of anxiety during capture of attention was most pronounced in the VAN portion of the IFG, along with additional areas of the VAN and the default mode network. CONCLUSIONS: The pathophysiology of pediatric anxiety appears to involve greater capture of attention to salient stimuli, as well as greater activity in attention-related brain networks. These results provide novel behavioral and brain-based targets for treatment of pediatric anxiety disorders.

Whole-Brain Resting-State Functional Connectivity Patterns Associated With Pediatric Anxiety and Involuntary Attention Capture.

BACKGROUND: Pediatric anxiety disorders are linked to dysfunction in multiple functional brain networks, as well as to alterations in the allocation of spatial attention. We used network-level analyses to characterize resting-state functional connectivity (rs-fc) alterations associated with 1) symptoms of anxiety and 2) alterations in stimulus-driven attention associated with pediatric anxiety disorders. We hypothesized that anxiety was related to altered connectivity of the frontoparietal, default mode, cingulo-opercular, and ventral attention networks and that anxiety-related connectivity alterations that include the ventral attention network would simultaneously be related to deviations in stimulus-driven attention. METHODS: A sample of children (n = 61; mean = 10.6 years of age), approximately half of whom met criteria for a current anxiety disorder, completed a clinical assay, an attention task, and rs-fc magnetic resonance imaging scans. Network-level analyses examined whole-brain rs-fc patterns associated with clinician-rated anxiety and with involuntary capture of attention. Post hoc analyses controlled for comorbid symptoms. RESULTS: Elevated clinician-rated anxiety was associated with altered connectivity within the cingulo-opercular network, as well as between the cingulo-opercular network and the ventral attention, default mode, and visual networks. Connectivity between the ventral attention and cingulo-opercular networks was associated with variation in both anxiety and stimulus-driven attention. CONCLUSIONS: Pediatric anxiety is related to aberrant connectivity patterns among several networks, most of which include the cingulo-opercular network. These results help clarify the within- and between-network interactions associated with pediatric anxiety and its association with altered attention, suggesting that specific network connections could be targeted to improve specific altered processes associated with anxiety.

Brain connectivity and socioeconomic status at birth and externalizing symptoms at age 2 years.

Low childhood socioeconomic status (SES) predisposes individuals to altered trajectories of brain development and increased rates of mental illness. Brain connectivity at birth is associated with psychiatric outcomes. We sought to investigate whether SES at birth is associated with neonatal brain connectivity and if these differences account for socioeconomic disparities in infant symptoms at age 2 years that are predictive of psychopathology. Resting state functional MRI was performed on 75 full-term and 37 term-equivalent preterm newborns (n = 112). SES was characterized by insurance type, the Area Deprivation Index, and a composite score. Seed-based voxelwise linear regression related SES to whole-brain functional connectivity of five brain regions representing functional networks implicated in psychiatric illnesses and affected by socioeconomic disadvantage: striatum, medial prefrontal cortex (mPFC), ventrolateral prefrontal cortex (vlPFC), and dorsal anterior cingulate cortex. Lower SES was associated with differences in striatum and vlPFC connectivity. Striatum connectivity with frontopolar and medial PFC mediated the relationship between SES and behavioral inhibition at age 2 measured by the Infant-Toddler Social Emotional Assessment (n = 46). Striatum-frontopolar connectivity mediated the relationship between SES and externalizing symptoms. These results, convergent across three SES metrics, suggest that neurodevelopmental trajectories linking SES and mental illness may begin as early as birth.

Hazardous alcohol use among female heads-of-household in rural Mozambique.

Hazardous drinking places individuals at risk for adverse health events, resulting in a major public health burden globally. Patterns of alcohol consumption among women in Africa remain poorly understood. We aimed to describe alcohol consumption in a representative sample of female heads-of-household in Mozambique. A 2014 population-based cross-sectional study of 3892 heads-of-household was conducted in Zambézia Province. Data on alcohol use were collected using the Alcohol Use Disorders Identification Test (AUDIT). Sociodemographic characteristics were summarized by alcohol use. A multivariable proportional odds model adjusted for age, education, Portuguese fluency, marital status, income, social support, depression, food insecurity, currently pregnant, and child mortality was used for the ordinal AUDIT scale as outcomes with robust covariance to account for clustering of respondents. The overall prevalence of current alcohol consumption among female heads-of-household was 15%. The mean PHQ-8 score was 2.7 (SD 4.7). The prevalence of women considered "hazardous drinkers" (score >4) was 8%. In bivariate analyses, depression, marital status, currently being pregnant, food insecurity, and death of a child were associated with higher risk of hazardous drinking. After adjusting for multiple characteristics, depression (aOR: 2.20 [1.28, 3.76] p = 0.004), death of a child (aOR: 2.44 [1.46, 4.07] p = 0.001), and being currently pregnant (aOR: 1.83 [0.99, 3.39] p = 0.002) were associated with hazardous drinking behavior. Being single (aOR: 0.48 [0.29, 0.80], p = 0.017) and food insecure (aOR: 0.96 [0.92, 1.00], p = 0.050) showed a protective effect on hazardous drinking behavior. The percentage of female heads-of-household in north-central Mozambique that regularly drink alcohol was lower than expected. This may be due to the unique characteristics of female heads-of-household and the extreme poverty pervasive in Zambézia.

Depression among female heads-of-household in rural Mozambique: A cross-sectional population-based survey.

BACKGROUND: An estimated 350 million people live with depression worldwide. In Mozambique, there are no national data quantifying the burden of mental illnesses. With the sixth highest suicide rate in the world, there is strong evidence of an unmet mental health need. We conducted a survey to measure the prevalence of depression among female heads of household and assess individual, social, and cultural risk factors associated with a positive depression screening. METHODS: This survey was conducted across 14 rural districts in central Mozambique in 2014. We gathered information from 3543 female heads of household (100% response rate) on > 500 variables, including a depression screening tool (PHQ-8). Weighted percentages of survey responses are reported. RESULTS: Among female heads of household, 14% screened positive for depression (PHQ-8 score ≥ 10). Our adjusted models show increased odds of depression per additional year of age (aOR: 1.02 [1.01, 1.04]; p = 0.002), additional year of education (aOR: 1.06 [1.02, 1.11]; p = 0.006), and additional kilometer from the nearest clinic (aOR: 1.05 [1.02, 1.07]; p = < 0.001). Experiencing food insecurity (aOR: 1.05 [1.02, 1.08]; p = 0.003) was associated with increased odds of depression. Being single (aOR: 0.42 [0.29, 0.60]) or divorced/widowed/separated (aOR: 0.57 [0.34, 0.98]; p < 0.001) vs. married was protective against depression, as was a perceived "sufficient" household income (aOR: 0.37 [0.19, 0.69]; p = 0.008). LIMITATIONS: Social desirability bias may have led women to underreport feelings of depression. CONCLUSIONS: The association of more education and marriage with increased odds of depression may reflect a frustration with limited opportunity for success experienced by some women in rural Mozambique.