Blood-brain Barrier and Neurovascular Unit Dysfunction in Parkinson's Disease: From Clinical Insights to Pathogenic Mechanisms and Novel Therapeutic Approaches.

The blood-brain barrier (BBB) plays a crucial role in the central nervous system by tightly regulating the influx and efflux of biological substances between the brain parenchyma and peripheral circulation. Its restrictive nature acts as an obstacle to protect the brain from potentially noxious substances such as blood-borne toxins, immune cells, and pathogens. Thus, the maintenance of its structural and functional integrity is vital in the preservation of neuronal function and cellular homeostasis in the brain microenvironment. However, the barrier's foundation can become compromised during neurological or pathological conditions, which can result in dysregulated ionic homeostasis, impaired transport of nutrients, and accumulation of neurotoxins that eventually lead to irreversible neuronal loss. Initially, the BBB is thought to remain intact during neurodegenerative diseases, but accumulating evidence as of late has suggested the possible association of BBB dysfunction with Parkinson's disease (PD) pathology. The neurodegeneration occurring in PD is believed to stem from a myriad of pathogenic mechanisms, including tight junction alterations, abnormal angiogenesis, and dysfunctional BBB transporter mechanism, which ultimately causes altered BBB permeability. In this review, the major elements of the neurovascular unit (NVU) comprising the BBB are discussed, along with their role in the maintenance of barrier integrity and PD pathogenesis. We also elaborated on how the neuroendocrine system can influence the regulation of BBB function and PD pathogenesis. Several novel therapeutic approaches targeting the NVU components are explored to provide a fresh outlook on treatment options for PD.

The Role of Antenatal and Postnatal Maternal Bonding in Infant Development.

OBJECTIVE: The affectional bond experienced by a mother toward her developing fetus/infant has been theorized to be a critical factor in determining infant developmental outcomes; yet there remains a paucity of research in this area, and a lack of high-quality longitudinal studies. This study aimed to examine the extent to which mother-to-infant bonding predicted infant development in a multi-wave longitudinal pregnancy cohort study (N = 1,347). METHOD: Self-reported bonding was assessed using the Maternal Antenatal Attachment Scale at each trimester, and the Maternal Postnatal Attachment Scale at 8 weeks and 12 months postpartum. Infant development was assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 12 months. RESULTS: Bonding predicted indicators of infant social-affective development, including social-emotional, behavioral, and temperamental outcomes. Effect sizes ranged from small to moderate, increasing over the perinatal period (ß = 0.11-0.27). Very small effects were also identified in the relationship between bonding and cognitive, language, and motor development (ß = 0.06-0.08). CONCLUSION: Findings suggest that a mother's perceived emotional connection with her child plays a role in predicting social-affective outcomes; prediction may not extend to other domains of infant development. Maternal bonding may therefore be a potentially modifiable predictor of infant social-affective outcomes, offering important considerations for preventive intervention.

Short-term outcomes of the Therapist-assisted Online Parenting Strategies intervention for parents of adolescents treated for anxiety and/or depression: A single-arm double-baseline trial.

OBJECTIVE: This study aimed to evaluate whether the Therapist-assisted Online Parenting Strategies programme increased parenting behaviours known to be supportive of adolescents experiencing anxiety and/or depression. Secondary parenting outcomes of parental self-efficacy, parental accommodation, carer burden, parent-adolescent attachment, family functioning and parent distress were also examined, along with adolescent outcomes of anxiety and depression symptoms, suicidal ideation and sleep. METHOD: Seventy-one parents (94.4% females) and their adolescents (73.2% females) aged 12-18 years (Mean = 15.02, SD = 1.56) being treated for depression and/or anxiety in Australia were recruited into a single-arm double-baseline open-label trial. Parents received Therapist-assisted Online Parenting Strategies, which comprised up to nine web-based modules each supplemented with coaching sessions via videoconferencing. Outcomes were analysed using latent growth curve modelling to determine if changes to outcomes at post-intervention (4 month post-second baseline) exceeded changes between two baselines measured 1 month apart. RESULTS: Sixty-five parents (91.6%) completed at least one module of the online parenting intervention and on average received nine coaching sessions (SD = 2). Parenting behaviours targeted by Therapist-assisted Online Parenting Strategies improved at post-intervention (Cohen's d = 1.16, 95% confidence interval [0.78, 1.51]). Parent-reported parental self-efficacy and parent-adolescent attachment increased (Cohen's d = 1.44 [1.05, 1.82] and 0.39 [0.05, 0.74], respectively), while impairments to family functioning and parent distress decreased (Cohen's d = -0.51 [-0.86, -0.16] and -0.84 [-1.23, -0.44], respectively). Changes to adolescent anxiety, depression and sleep were not significant. CONCLUSION: The Therapist-assisted Online Parenting Strategies intervention improved self-reported parenting behaviours, parental self-efficacy, parent levels of distress, parent-adolescent attachment, and family functioning in parents with adolescents being treated for anxiety and/or depression. However, significant changes in adolescent mental health and sleep outcomes at post-intervention were not observed. The usefulness of a therapist-supported online parenting programme in addressing a service gap for parents seeking professional help is indicated. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ACTRN) 12618000290291, prospectively registered on 26 February 2018; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368031.

Subjective wellbeing in parents during the COVID-19 pandemic in Australia.

OBJECTIVES: To examine (1) the subjective wellbeing of Australian parents raising children and adolescents (0-18 years) during April 2020 'stage three' COVID-19 restrictions, in comparison with parents assessed over 18-years prior to the pandemic; and (2) socio-demographic and COVID-19 predictors of subjective wellbeing during the pandemic. METHODS: Cross-sectional data were from the COVID-19 Pandemic Adjustment Survey (CPAS, N = 2365 parents of a child 0-18 years, 8-28th April 2020); and a pre-pandemic national database containing 18 years of annual surveys collected in 2002-2019 (N = 17,529 parents). RESULTS: Levels of subjective wellbeing during the pandemic were considerably lower than ratings prior to the pandemic (Personal Wellbeing Index, mean[SD] = 65.3 [17.0]; compared to [SD] = 75.8 [11.9], p < 0.001). During the pandemic, lower subjective wellbeing was associated with low education (adjusted regression coefficient, 95% confidence interval [95% CI] = -5.19, -0.93), language other-than-English (95% CI = -7.22, -1.30), government benefit (95% CI = -6.99, -0.96), single parents (95% CI = -8.84, -4.59), child neurodevelopmental condition (95% CI = -3.44, -0.76), parent physical/mental health problems (95% CI = -3.23, -0.67), COVID-environmental stressors (95% CI = -3.48, -2.44), and fear/worry about COVID-19 (95% CI = -8.13, -5.96). Unexpectedly, parent engagement with news media about the pandemic was associated with higher subjective wellbeing (95% CI = 0.35, 1.61). CONCLUSION: Subjective wellbeing in parents raising children aged 0-18 years appears to be disproportionately impacted by the COVID-19 pandemic and restrictions in Australia. Specific at-risk groups, for which government intervention may be warranted, include parents in socially disadvantaged contexts, parents with pre-existing mental health difficulties, and parents facing significant COVID-19-related work changes.

Modifiable parental factors in adolescent sleep: A systematic review and meta-analysis.

Sleep problems are prevalent during adolescence, but parents may be able to support adolescents to sleep better. A systematic search of records from six databases from inception up to November 2019, identified 103 peer-reviewed publications that examined behaviourally and cognitively modifiable parental factors associated with sleep in adolescents aged 12-18 years. Although included studies were largely cross-sectional and heterogeneous, with heavy reliance on self-reported measures, associations with sound, convergent levels of evidence were found for: 1) parental rule-setting for bedtimes and parent sleep behaviours with longer sleep duration in adolescents; 2) healthy parent sleep and family functioning with better adolescent sleep quality; and 3) parental warmth with better adolescent daytime functioning. Effect sizes were in the small to moderate range. The identified parental factors are recommended targets for inclusion in parenting programs to support adolescent sleep, however, would require validation in intervention studies. Opportunities for research are outlined for the identified parental factors, sleep domains with limited evidence, and better understanding the mechanisms or possible moderators in the associations between parental factors and sleep outcomes.

Maternal bonding, negative affect, and infant social-emotional development: A prospective cohort study.

BACKGROUND: Theoretical perspectives and empirical evidence suggest that maternal bonding and negative affect play a role in supporting infant social-emotional development (Branjerdporn et al., 2017; Kingston et al., 2012; O'Donnell et al., 2014; Van den Bergh et al., 2017). However, the complex pathways likely to exist between these constructs remain unclear, with limited research examining the temporal and potentially bi-directional associations between maternal bonding and negative affect across pregnancy and infancy. METHODS: The interrelationships between maternal bonding, negative affect, and infant social-emotional development were examined using multi-wave perinatal data from an Australian cohort study (N = 1,579). Self-reported bonding and negative affect were assessed at each trimester, and 8 weeks and 12 months postpartum. The Bayley-III social-emotional scale was administered at age 12 months. RESULTS: Results revealed strong continuities in bonding and negative affect across pregnancy and postpartum. Small associations (ß = -.10 to -.20) existed between maternal negative affect during pregnancy and poor early bonding. Higher postnatal maternal bonding predicted infant social-emotional development (ß = .17). LIMITATIONS: Limitations include a somewhat advantaged and predominantly Anglo-Saxon sample of families, and the use of self-report measures (though with strong psychometric properties). These limitations should be considered when interpreting the study findings. CONCLUSIONS: Maternal bonding and negative affect are interrelated yet unique constructs, with suggested developmental interplay between mother-to-infant bonding and infant social-affective development.

Efficacy of a Smartphone App Intervention for Reducing Caregiver Stress: Randomized Controlled Trial.

BACKGROUND: Caregivers play a pivotal role in maintaining an economically viable health care system, yet they are characterized by low levels of psychological well-being and consistently report unmet needs for psychological support. Mobile app-based (mobile health [mHealth]) interventions present a novel approach to both reducing stress and improving well-being. OBJECTIVE: This study aims to evaluate the effectiveness of a self-guided mobile app-based psychological intervention for people providing care to family or friends with a physical or mental disability. METHODS: In a randomized, single-blind, controlled trial, 183 caregivers recruited through the web were randomly allocated to either an intervention (n=73) or active control (n=110) condition. The intervention app contained treatment modules combining daily self-monitoring with third-wave (mindfulness-based) cognitive-behavioral therapies, whereas the active control app contained only self-monitoring features. Both programs were completed over a 5-week period. It was hypothesized that intervention app exposure would be associated with decreases in depression, anxiety, and stress, and increases in well-being, self-esteem, optimism, primary and secondary control, and social support. Outcomes were assessed at baseline, postintervention, and 3-4 months postintervention. App quality was also assessed. RESULTS: In total, 25% (18/73) of the intervention participants were lost to follow-up at 3 months, and 30.9% (34/110) of the participants from the wait-list control group dropped out before the postintervention survey. The intervention group experienced reductions in stress (b=-2.07; P=.04) and depressive symptoms (b=-1.36; P=.05) from baseline to postintervention. These changes were further enhanced from postintervention to follow-up, with the intervention group continuing to report lower levels of depression (b=-1.82; P=.03) and higher levels of emotional well-being (b=6.13; P<.001), optimism (b=0.78; P=.007), self-esteem (b=-0.84; P=.005), support from family (b=2.15; P=.001), support from significant others (b=2.66; P<.001), and subjective well-being (b=4.82; P<.001). On average, participants completed 2.5 (SD 1.05) out of 5 treatment modules. The overall quality of the app was also rated highly, with a mean score of 3.94 out of a maximum score of 5 (SD 0.58). CONCLUSIONS: This study demonstrates that mHealth psychological interventions are an effective treatment option for caregivers experiencing high levels of stress. Recommendations for improving mHealth interventions for caregivers include offering flexibility and customization in the treatment design. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12616000996460; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371170.