Significant age by childhood trauma interactions on grey matter volumes: A whole brain VBM analysis.

BACKGROUND: Childhood trauma is deleterious to long term brain development. The changes are variable, and depend on gender, age and the nature of the trauma. In this exploratory analysis, we investigated the effects of exposure to emotional trauma on grey matter (GM) volumes in adolescent females. METHODS: We explored GM volumes in non-clinical females aged 12-17 years who had been exposed to either higher (HET; N = 75) or minimal (MET; N = 127) emotional trauma. High-resolution T1-weighted structural images were analysed with an optimised FSL-VBM protocol. The General Linear Model was run on HET versus MET with continuous age as an interaction. Mean GM volumes were extracted from significant corrected age interaction statistical maps and scrutinised with SPSS®. RESULTS: We observed greater HET*age than MET*age interactions (corrected p-value = 0.0002), in 4 separate bilateral cortical regions associated with mood disorders. Scrutiny of these regions showed significant GM volume enlargements in the early adolescent HET group (p = 0.017) and reductions in the late adolescent HET group (p < 0.0001). Notably, there were no differences in middle adolescence (p > 0.05). LIMITATIONS: Causality cannot be inferred from this cross-sectional study and the onset of trauma cannot be determined using retrospective measures. CONCLUSIONS: Whilst GM volumes diminish from early adolescence onwards, our results show that HET impacts this brain development, perhaps first via unstable adaptative mechanisms, followed by maladaptive processes in late adolescence. This suggests that compromises of emotional and cognitive self-regulation in mood disorders may underpin the structural abnormalities observed across multiple brain regions in these teenage girls.

Seeking a deeper understanding of 'distributed health literacy': A systematic review.

BACKGROUND: Previous research suggests that it would be useful to view health literacy as a set of 'distributed competencies', which can be found dispersed through the individual's social network, rather than an exclusively individual attribute. However, to date there is no focused exploration of how distributed health literacy has been defined, conceptualized or assessed in the peer-reviewed literature. AIMS: This systematic review aimed to explore: (1) definitions and conceptual models of distributed health literacy that are available from the peer-reviewed literature; and (2) how distributed health literacy has been measured in empirical research. METHODS: We searched MEDLINE, Embase, CINAHL, PsycInfo, Scopus, ERIC and Web of Science using truncated versions of the keywords 'literacy' and 'distributed' (within five words' distance). We collated the definitions and conceptual models of distributed health literacy, and report on how health literacy has been measured in empirical research studies. Findings related to distributed health literacy from included manuscripts were synthesized using thematic synthesis. RESULTS: Of the 642 studies screened, 10 were included in this systematic review. The majority were empirical manuscripts reporting on qualitative research in one of five countries, with two reviews, one conceptual analysis and one quantitative study. Edwards' definition of distributed health literacy, which emphasizes the health literacy abilities, skills and practices of others that contribute to an individual's level of health literacy was widely applied in a variety of clinical and geographical settings. However, we did not identify any quantitative instruments which directly measured distributed health literacy. There was significant variability in questions used to explore the concept qualitatively, and discrepancies across studies in regard to (a) what constitutes distributed health literacy and what does not (e.g., general social support), and (b) the relationship between distributed health literacy and other constructs (e.g., public health literacy). CONCLUSION: Although there is a widely applied definition of distributed health literacy, our review revealed that the research space would benefit from the development of the concept, both theoretically for example via conceptual distinctions between distributed health literacy and other types of social support, and empirically for example through the development of a quantitative measurement instrument. PATIENT OR PUBLIC CONTRIBUTION: This paper is a systematic review and did not involve patients or the public.

Clinician-patient-family decision-making and health literacy in adolescents and young adults with cancer and their families: A systematic review of qualitative studies.

OBJECTIVE: Engaging in shared decision-making may be particularly difficult for adolescents and young adults with cancer (AYAs), possibly because of lower levels of health literacy. Family members of AYAs are likely to support decision-making about their healthcare by contributing to health literacy skills/practices; however, the nature of this process is unclear. This systematic review synthesized qualitative studies that explored the process of decision-making and characterized how AYA healthcare information is shared, from the perspective of the AYA and their family members. METHODS: Electronic searches of EMBASE, MEDLINE, PsycINFO, and CINAHL were conducted in May 2018. Peer-reviewed studies discussing the decision-making process in AYAs and/or their families were eligible for inclusion. Findings were analyzed thematically using Framework analysis. RESULTS: Seven thousand two hundred seventy-three studies were screened, and 14 eligible studies were included. The synthesized themes aligned with the Supported Health Literacy Pathway model3 in that AYAs draw on their family members' knowledge, skills, and practices to generate informed options and make shared decisions. Families of AYAs were found to be involved throughout all stages of decision-making. The use of health literacy skills was also found to be distributed in families, such that family members of AYAs mediate access to knowledge and use of health information in the decision-making process. CONCLUSIONS: Our findings suggest that health literacy is a dynamic and transactional process and provide clinicians, researchers, and other stakeholders with a framework to foster AYA engagement in decision-making.

The effects of childhood trauma on adolescent hippocampal subfields.

OBJECTIVE: Mood disorders are more common among girls and typically emerge during adolescence. The precise reasons for this are unknown, but among the many mechanisms implicated are stress-induced hippocampal structural changes during this developmental stage. The hippocampus is a complex structure comprised of subfields that develop differentially and respond variably to stress and childhood adversity, both of which are risk factors for mood disorders. To better understand vulnerability to mood disorders, we investigated a cohort of adolescent girls and determined volumetric changes in their hippocampal subfields to elucidate the potential effects of childhood trauma. METHODS: Of the 229 participants, 201 girls (aged 12-17 years) fulfilled our analysis inclusion criteria. Of these, 76 had been exposed to higher emotional trauma (emotional abuse or neglect). The girls underwent high-resolution structural magnetic resonance imaging scans, and hippocampal subfield volumes were measured using FreeSurfer. We compared hippocampal subfield volumes in those exposed to higher emotional trauma and those exposed to minimal emotional trauma, at three time-points of adolescent development: early (12-13 years), mid (14-15 years) and late (16-17 years). RESULTS: Mid-adolescent girls exposed to higher emotional trauma had significantly smaller left CA3 volumes than minimal emotional trauma girls ( p = 0.028). Within the minimal emotional trauma group, mid-adolescents had significantly larger left CA3 volumes than early ( p = 0.034) and late ( p = 0.036) adolescents. Within the higher emotional trauma group, early adolescents had significantly larger left CA3 volumes than late adolescents ( p = 0.036). CONCLUSION: In our exploratory study, we observed higher emotional trauma-induced volume changes in the left CA3 hippocampal subfield, which varied depending on age, and may ultimately produce deficits in behavioural, cognitive and emotional processes. We propose that these changes (1) may provide a mechanism through which vulnerability to mood disorders may be increased in adolescent girls, and (2) may signal the best times to implement targeted prevention interventions.

Effect of stress gene-by-environment interactions on hippocampal volumes and cortisol secretion in adolescent girls.

OBJECTIVE: Adolescence is a time of increased susceptibility to environmental stress and mood disorders, and girls are particularly at risk. Genes interacting with the environment (G × E) are implicated in hypothalamic-pituitary-adrenal axis dysregulation, hippocampal volume changes and risk or resilience to mood disorders. In this study, we assessed the effects of stress system G × E interactions on hippocampal volumes and cortisol secretion in adolescent girls. METHODS: We recruited 229 girls aged 12-18 years, and scans were obtained from 202 girls. Of these, 76 had been exposed to higher emotional trauma (abuse or neglect). Hippocampal volumes were measured using Freesurfer and high-resolution structural magnetic resonance imaging scans. Saliva samples were collected for measurement of cortisol levels and genotyping of stress system genes: FKBP5, NR3C1 (both N = 194) and NR3C2 ( N = 193). RESULTS: Among girls with the 'G' allelic variant of the NR3C1 gene, those who had been exposed to higher emotional trauma had significantly smaller left hippocampal volumes ( N = 44; mean = 4069.58 mm3, standard deviation = 376.99) than girls who had been exposed to minimal emotional trauma with the same allelic variant ( N = 69; mean = 4222.34 mm3, standard deviation = 366.74). CONCLUSION: In healthy adolescents, interactions between emotional trauma and the 'protective' NR3C1 'GG' variant seem to induce reductions in left hippocampal volumes. These G × E interactions suggest that vulnerability to mood disorders is perhaps driven by reduced 'protection' that may be specific to emotional trauma. This novel but preliminary evidence has implications for targeted prevention of mood disorders and prospective multimodal neuroimaging and longitudinal studies are now needed to investigate this possibility.

The Lithium Battery: assessing the neurocognitive profile of lithium in bipolar disorder.

OBJECTIVE: The aim of the present study was to characterize the neurocognitive effects of lithium in bipolar disorder to inform clinical and research approaches for further investigation. METHODS: Key words pertaining to neurocognition in bipolar disorder and lithium treatment were used to search recognized databases to identify relevant literature. The authors also retrieved gray literature (e.g., book chapters) known to them and examined pertinent articles from bibliographies. RESULTS: A limited number of studies have examined the effects of lithium on neurocognition in bipolar disorder and, although in some domains a consistent picture emerges, in many domains the findings are mixed. Lithium administration appears to reshape key components of neurocognition - in particular, psychomotor speed, verbal memory, and verbal fluency. Notably, it has a sophisticated neurocognitive profile, such that while lithium impairs neurocognition across some domains, it seemingly preserves others - possibly those vulnerable to the effects of bipolar disorder. Furthermore, its effects are likely to be direct and indirect (via mood, for example) and cumulative with duration of treatment. Disentangling the components of neurocognition modulated by lithium in the context of a fluctuating and complex illness such as bipolar disorder is a significant challenge but one that therefore demands a stratified and systematic approach, such as that provided by the Lithium Battery. CONCLUSIONS: In order to delineate the effects of lithium therapy on neurocognition in bipolar disorder within both research and clinical practice, a greater understanding and measurement of the relatively stable neurocognitive components is needed to examine those that indeed change with lithium treatment. In order to achieve this, we propose a Lithium Battery-Clinical and a Lithium Battery-Research that can be applied to these respective settings.

Irritability and mood symptoms in adolescent girls: Trait anxiety and emotion dysregulation as mediators.

BACKGROUND: Irritability is a common symptom in youth that is thought to be predictive of mood disorders. Its effects on mood are likely to be age-dependent, with direct and indirect mediators. We assessed age-related effects and mediators of irritability in adolescent girls with subthreshold depressive and manic symptoms. METHODS: We analysed the irritability item from the Mood Disorder Questionnaire in 3 cohorts of girls aged 12-18years (N=229); 12-13years (N=82); 14-15years (N=68); and 16-18years (N=79). They also completed mood, anxiety and emotion regulation questionnaires. MANOVA, correlations and bootstrapped mediation analyses were performed with SPSS®v25 and Hayes Processv3.5®. RESULTS: Overall, irritable girls had higher depressive and manic symptoms, trait anxiety and emotion dysregulation than those who were not irritable. Significantly higher rates of irritability were observed in mid-adolescents (aged 14-15years; p = 0.001). Notably, irritability exerted effects on depressive symptoms via trait anxiety, non-acceptance of emotions and dysregulation in emotion clarity throughout adolescence. However, irritability directly exerted effects on manic symptoms in mid-adolescence but in older adolescents, their relationship was indirect via impulse control dysregulation. LIMITATIONS: The cross-sectional design and non-clinical sample limit generalisability of our findings. CONCLUSIONS: Irritability is involved in subthreshold depressive symptoms, via trait anxiety and perceptual emotion dysregulation. On the other hand, irritability is directly and indirectly associated with subthreshold manic symptoms via dysregulated impulse control depending on age. Therefore, screening for irritability, trait anxiety and emotion dysregulation throughout adolescence may facilitate the early detection of subthreshold depressive and manic symptoms, and the implementation of preventive strategies.

Interactions of OXTR rs53576 and emotional trauma on hippocampal volumes and perceived social support in adolescent girls.

Oxytocin (OXT) is a neuropeptide involved in social behaviour and is sensitive to environmental influences to alter individual vulnerability or resilience to stress resulting in both negative and positive outcomes. The effects of the OXT receptor (OXTR) single nucleotide polymorphism (SNP) rs53576 on hippocampal and amygdala structure and functions in adults are differentially associated with susceptibility to adversity and social behaviours, but this evidence is lacking in healthy adolescents. Adolescence is a developmental period characterised by neurobiological and psychosocial changes resulting in higher susceptibility to mood disorders, particularly among girls. As the brain is highly plastic at this stage, to understand psychosocial and emotional development, clarity of the interactions between rs53576 and adversity on hippocampal and amygdala volumes and social behaviours is needed. In this study, we investigated the interactions between rs53576 and emotional trauma (ET) exposure on hippocampal and amygdala volumes of adolescent girls, and associations with parenting style, perceived social support and bullying behaviour. Based on an unbiased and corrected analytical approach, we found smaller left hippocampal volumes in higher (hET) compared to minimally (mET) exposed AA homozygotes, but no differences in G allele carriers nor in the amygdala. Within the mET AA group, larger volumes were associated with peer perceived social support, but in their hET counterparts, smaller volumes were associated with familial perceived social support. This evidence supports an important role for the hippocampus in social behaviours but extends current knowledge to suggest that hippocampal social behavioural features are contextually dependent on rs53576.

The Structure of the FACT-Cog v3 in Cancer Patients, Students, and Older Adults.

CONTEXT: The Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) version 3 questionnaire is designed to assess perceived cognitive function and impact on quality of life in cancer patients. OBJECTIVES: We examined the factor structure of the FACT-Cog version 3 in samples of cancer patients, older adults, and students. METHODS: Data from three populations were sourced. Cancer patient data (N = 158) came from two studies, one evaluating a web-based cognitive training program, and the other evaluating symptoms in patients receiving chemotherapy. The older adult sample (N = 477) was commercial brain training users in the general population. The student sample (N = 154) came from a study examining the relation between cognitive test performance and perceived cognitive function. RESULTS: The patient sample conformed to the traditional four-factor structure (impairments, abilities, noticeability, and quality of life), with some support for separating the broad impairment/ability factors into specific cognitive domains. The older adult sample was best described using both impairments/abilities and specific cognitive domains. The student sample suggested two impairment/ability factors but separation of concentration/acuity and memory/verbal impairment items. CONCLUSION: The FACT-Cog can be used in populations other than cancer patients, with modifications to the scoring system. Even when used with cancer patients, it is worth considering scoring specific cognitive domains separately.

The use of lithium for the treatment of bipolar disorder: Recommendations from clinical practice guidelines.

BACKGROUND: Lithium is an effective mood stabilizer that is used principally for the management of bipolar disorder (BD). Its administration is complex and often requires sophisticated management and assiduous monitoring. When considering the use of lithium therapy for bipolar disorder, clinicians are advised to refer to recommendations outlined in clinical practice guidelines (CPGs); but because of varying emphases placed by different international CPGs, recommendations addressing the practical use of lithium lack consistency. METHOD: In order to inform clinicians of optimal lithium therapy for bipolar disorder, we compared and synthesized recommendations for the treatment of bipolar disorder made by recognized CPGs internationally. We conducted a search of the literature and extracted guidance across multiple clinical issues, including clinical indications, disorder subtypes, additional uses, special populations, practical aspects, and side effects. RESULTS: Collectively, CPGs consider lithium most robustly as a first-line intervention for maintenance treatment of bipolar disorder and strongly for the treatment of mania, with relatively modest support for the management of acute bipolar depression. Additionally, there is consensus across the CPGs that lithium tangibly reduces the risk of suicide. Generally, CPGs provide guidance on the many facets of initiating and maintaining patients on lithium therapy, but individually the CPGs varied in terms of depth and practical guidance they provide across these areas. However, consensus was established across many key areas of practice such as the ideal lithium plasma concentration for maintenance and monitoring (0.6-0.8mmol/L), along with the need for regular monitoring of renal and endocrine function. However, with more complex aspects (e.g., atypical presentations) and in special populations (e.g., youth; pregnancy and post-partum; older adults), guidance varied considerably and clear consensus recommendations were more difficult to achieve. In younger adults desirable plasma lithium levels of 0.6-0.8mmol/L can perhaps be achieved with comparatively lower doses and in the very elderly it may be prudent to target lower plasma levels in the first instance. These are important practical points for consideration that, along with many others offered throughout the article, should assist clinicians in dissecting the more complex aspects of management with greater precision. LIMITATIONS: This review was limited to CPGs written in English. CPGs are themselves limited by reliance on evidence that often has little resemblance to real-world presentations. An important area that is not sufficiently addressed in the CPGs is clear guidance on the cessation of lithium therapy. CONCLUSIONS: Further research is needed on many aspects of lithium therapy and this alongside existing knowledge needs to be used more consistently to inform CPGs, which should also incorporate empirical evidence and clinical experience. The recommendations in this paper provide a useful synthesis of guidance available currently.