Updated annotation and meta-analysis of Brugia malayi transcriptomics data reveals consistent transcriptional profiles across time and space with some study-specific differences in adult female worm transcriptional profiles.

Genomics, transcriptomics, and proteomics have significantly advanced our understanding of obligately host-associated microbes, where interrogation of the biology is often limited by the complexity of the biological system and limited tools. This includes the causative agents of many neglected tropical diseases, including filarial nematodes. Therefore, numerous transcriptomics studies have been undertaken on filarial nematodes. Most of these transcriptomics studies focus on Brugia malayi, which causes lymphatic filariasis and is a laboratory model for human filarial disease. Here, we undertook a meta-analysis of the publicly available B. malayi transcriptomics data enabling the direct cross comparison of samples from almost a dozen studies. This reanalysis highlights the consistency of transcriptomics results across many different studies and experimental designs from across the globe for over a decade of research, across many different generations of a sequencing technology, library preparation protocols, and differential expression tools. Males and microfilariae across samples had similar expression profiles. However, female samples were clustered into two differential expression patterns that were significantly different from one another. Largely, we confirm previous results for all studies reanalyzed including tissue-specific gene expression and anti-Wolbachia doxycycline treatment of microfilaria. However, we did not detect previously reported differential expression upon in vitro or in vivo treatment with ivermectin, albendazole, and DEC, instead identifying a consistent lack of transcriptomic change upon exposure to these anthelminthic drugs. Updated annotation has been provided that denotes poorly supported genes including those overlapping rRNAs.

Deciphering transcript architectural complexity in bacteria and archaea.

RNA transcripts are potential therapeutic targets, yet bacterial transcripts have uncharacterized biodiversity. We developed an algorithm for transcript prediction called tp.py using it to predict transcripts (mRNA and other RNAs) in Escherichia coli K12 and E2348/69 strains (Bacteria:gamma-Proteobacteria), Listeria monocytogenes strains Scott A and RO15 (Bacteria:Firmicute), Pseudomonas aeruginosa strains SG17M and NN2 strains (Bacteria:gamma-Proteobacteria), and Haloferax volcanii (Archaea:Halobacteria). From >5 million E. coli K12 and >3 million E. coli E2348/69 newly generated Oxford Nanopore Technologies direct RNA sequencing reads, 2,487 K12 mRNAs and 1,844 E2348/69 mRNAs were predicted, with the K12 mRNAs containing more than half of the predicted E. coli K12 proteins. While the number of predicted transcripts varied by strain based on the amount of sequence data used, across all strains examined, the predicted average size of the mRNAs was 1.6-1.7 kbp, while the median size of the 5'- and 3'-untranslated regions (UTRs) were 30-90 bp. Given the lack of bacterial and archaeal transcript annotation, most predictions were of novel transcripts, but we also predicted many previously characterized mRNAs and ncRNAs, including post-transcriptionally generated transcripts and small RNAs associated with pathogenesis in the E. coli E2348/69 LEE pathogenicity islands. We predicted small transcripts in the 100-200 bp range as well as >10 kbp transcripts for all strains, with the longest transcript for two of the seven strains being the nuo operon transcript, and for another two strains it was a phage/prophage transcript. This quick, easy, and reproducible method will facilitate the presentation of transcripts, and UTR predictions alongside coding sequences and protein predictions in bacterial genome annotation as important resources for the research community.IMPORTANCEOur understanding of bacterial and archaeal genes and genomes is largely focused on proteins since there have only been limited efforts to describe bacterial/archaeal RNA diversity. This contrasts with studies on the human genome, where transcripts were sequenced prior to the release of the human genome over two decades ago. We developed software for the quick, easy, and reproducible prediction of bacterial and archaeal transcripts from Oxford Nanopore Technologies direct RNA sequencing data. These predictions are urgently needed for more accurate studies examining bacterial/archaeal gene regulation, including regulation of virulence factors, and for the development of novel RNA-based therapeutics and diagnostics to combat bacterial pathogens, like those with extreme antimicrobial resistance.

Deciphering Bacterial and Archaeal Transcriptional Dark Matter and Its Architectural Complexity.

Transcripts are potential therapeutic targets, yet bacterial transcripts remain biological dark matter with uncharacterized biodiversity. We developed and applied an algorithm to predict transcripts for Escherichia coli K12 and E2348/69 strains (Bacteria:gamma-Proteobacteria) with newly generated ONT direct RNA sequencing data while predicting transcripts for Listeria monocytogenes strains Scott A and RO15 (Bacteria:Firmicute), Pseudomonas aeruginosa strains SG17M and NN2 strains (Bacteria:gamma-Proteobacteria), and Haloferax volcanii (Archaea:Halobacteria) using publicly available data. From >5 million E. coli K12 ONT direct RNA sequencing reads, 2,484 mRNAs are predicted and contain more than half of the predicted E. coli proteins. While the number of predicted transcripts varied by strain based on the amount of sequence data used for the predictions, across all strains examined, the average size of the predicted mRNAs is 1.6-1.7 kbp while the median size of the predicted bacterial 5'- and 3'- UTRs are 30-90 bp. Given the lack of bacterial and archaeal transcript annotation, most predictions are of novel transcripts, but we also predicted many previously characterized mRNAs and ncRNAs, including post-transcriptionally generated transcripts and small RNAs associated with pathogenesis in the E. coli E2348/69 LEE pathogenicity islands. We predicted small transcripts in the 100-200 bp range as well as >10 kbp transcripts for all strains, with the longest transcript for two of the seven strains being the nuo operon transcript, and for another two strains it was a phage/prophage transcript. This quick, easy, inexpensive, and reproducible method will facilitate the presentation of operons, transcripts, and UTR predictions alongside CDS and protein predictions in bacterial genome annotation as important resources for the research community.

Dialect and gender perception in relation to the intelligibility of low-pass and high-pass filtered spontaneous speecha).

Most cues to speech intelligibility are within a narrow frequency range, with its upper limit not exceeding 4 kHz. It is still unclear whether speaker-related (indexical) information is available past this limit or how speaker characteristics are distributed at frequencies within and outside the intelligibility range. Using low-pass and high-pass filtering, we examined the perceptual salience of dialect and gender cues in both intelligible and unintelligible speech. Setting the upper frequency limit at 11 kHz, spontaneously produced unique utterances (n = 400) from 40 speakers were high-pass filtered with frequency cutoffs from 0.7 to 5.56 kHz and presented to listeners for dialect and gender identification and intelligibility evaluation. The same material and experimental procedures were used to probe perception of low-pass filtered and unmodified speech with cutoffs from 0.5 to 1.1 kHz. Applying statistical signal detection theory analyses, we found that cues to gender were well preserved at low and high frequencies and did not depend on intelligibility, and the redundancy of gender cues at higher frequencies reduced response bias. Cues to dialect were relatively strong at low and high frequencies; however, most were in intelligible speech, modulated by a differential intelligibility advantage of male and female speakers at low and high frequencies.

Web-based treatment for depression in pregnancy: a feasibility study of Mum2BMoodBooster.

BACKGROUND: Depression in pregnancy is prevalent, under-treated, and has serious impacts on the wellbeing of women and on child development. Internet programs can reach women who may not access traditional treatments due to distance, stigma or concern about taking medication. We adapted our online postnatal depression program, MumMoodBooster, for antenatal use. We aimed to trial feasibility, acceptability, and potential efficacy of the new Mum2BMoodBooster intervention with depressed pregnant women. METHODS: Twenty-seven pregnant women with Edinburgh Postnatal Depression Scale score > 11 used the program in a feasibility trial. Twenty-one had current diagnoses of major or minor depression on the Structured Clinical Interview for the DSM-IV. Assessment of symptoms occurred at screening/baseline, post-test (8 weeks post-enrollment), and at follow-up (3 months postpartum) using the Patient Health Questionnaire (PHQ-9) and the Depression Anxiety Stress Scales (DASS-21). RESULTS: In this feasibility trial, depression scores on both the PHQ-9 and the DASS-21, showed significant reductions representing large effects, with average symptom scores reduced by > 50%, and maintained in the 'minimal or no depression' range at 3 month follow-up. Anxiety scores also decreased significantly. Program usage was high with 74% of women visiting all six sessions. Program acceptability ratings were moderate to high. CONCLUSIONS: Findings paralleled the magnitude of symptom reductions seen in randomised trials of the postnatal MumMoodBooster program, suggesting that Mum2BMoodBooster is an effective treatment for depressed pregnant women. Effective internet therapies are likely to become increasingly important as the COVID-19 pandemic continues to make face-to-face access to health care problematic during 'lockdowns'.

Internet and Face-to-face Cognitive Behavioral Therapy for Postnatal Depression Compared With Treatment as Usual: Randomized Controlled Trial of MumMoodBooster.

BACKGROUND: Previous research has confirmed that symptoms of postnatal depression (PND) can be ameliorated through internet-delivered psychological interventions. Advantages of internet-delivered treatment include anonymity, convenience, and catering to women who are unable to access face-to-face (FTF) treatments. To date, no research has examined the efficacy of such interventions compared directly with FTF treatments in women clinically diagnosed with PND. OBJECTIVE: This study aims to compare the efficacy of one of the first web-based cognitive behavioral therapy (CBT) interventions (internet CBT+coach calls) for PND (MumMoodBooster [MMB]) with FTF-CBT in a randomized controlled trial (RCT). METHODS: In this study, 116 postnatal women with a Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) diagnosis of major or minor depression were randomized to MMB (39/116, 33.6%), FTF-CBT (39/116, 33.6%), or a treatment-as-usual (TAU) control condition (38/116, 32.8%). Diagnostic status was determined at baseline and at 21-week follow-up using the Structured Clinical Interview for the DSM-IV. Severity of anxiety and depressive symptoms was evaluated using the Depression Anxiety Stress Scales and the revised Beck Depression Inventory at baseline, 12-week follow-up (after treatment), and 21-week follow-up. RESULTS: Of the 116 participants, 107 (92.2%) had a diagnosis of major depression at baseline. Rates of remission from a major or minor depressive episode at 21 weeks in both the FTF-CBT and MMB groups were superior to that of the TAU group (56.6% and 47.7% less likely to be depressed, respectively) and they were not significantly different from each other. Although remission rates differed between TAU and FTF-CBT, growth models showed that, in terms of symptom reduction across time, the FTF-CBT treatment was not significantly better than TAU. By comparison, MMB was statistically superior to both TAU and FTF-CBT in reducing symptoms of depression, anxiety, and stress from baseline to the 21-week follow-up (large and moderate effect sizes). Thus, after 21 weeks, the average symptom scores for depression and anxiety of women receiving MMB were approximately half those of women in both the TAU and FTF-CBT groups. CONCLUSIONS: In this RCT, MMB was at least as effective as FTF-CBT in achieving remission from a diagnosed PND episode. MMB was superior to TAU and FTF-CBT in encouraging and maintaining reduction of symptom severity over the 21-week follow-up for depressed postnatal women. These findings replicate results of prior studies on MMB that showed clinically significant improvements in depressive symptoms, and they provide direct empirical support that internet-delivered treatment for depressed postnatal women is a viable alternative to FTF treatment. The generalizability of the results needs to be examined in future research, as RCTs of internet-based versus FTF treatments necessarily involve a subset of people who are willing to undertake either modality of treatment. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000881730; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364683&isReview=true.

Searching for the Holy Grail: A Systematic Review of Health-Related Quality of Life Measures for Active Youth.

OBJECTIVE: To identify the most suitable existing generic and condition-specific health-related quality of life (HRQoL) patient-reported outcome measures (PROMs) for active youth with and without a musculoskeletal injury, based on measurement properties, interpretability, and feasibility. DESIGN: Systematic review of clinimetrics. LITERATURE SEARCH: We searched MEDLINE, Embase, CINAHL, SPORTDiscus, PsycINFO, and Scopus from inception to April 30, 2020. STUDY SELECTION CRITERIA: Records with original data describing the evaluation of a PROM or PROM subscale in active youth (15-24 years old) with or without a musculoskeletal injury were included. Non-English studies and those including individuals with a cognitive, developmental, or systemic condition were excluded. DATA SYNTHESIS: This review was conducted according to the COSMIN user manual for systematic reviews of PROMs and the PRISMA guidelines. The COSMIN user manual guided our measurement property evaluation and interpretability and feasibility description. RESULTS: Of 6931 potential records, 21 studies were included. Eleven generic and 7 condition-specific PROMs were identified. No PROM received a final COSMIN recommendation of "A" because all lacked sufficient content validity. The 8-item Disablement in the Physically Active scale-mental summary component Short Form (DPA-MSC SF-8), Quality of Life Survey, and Functional Arm Scale for Throwers (FAST) were the most suitable existing PROMs, given their high-quality evidence for sufficient structural validity and internal consistency. CONCLUSION: No definitively robust PROM for measuring generic or condition-specific HRQoL of active youth was identified. Until one exists, we recommend the DPA-MSC SF-8, the Quality of Life Survey, or the FAST and applying mixed methods to best characterize the HRQoL of active youth. J Orthop Sports Phys Ther 2021;51(10):478-491. doi:10.2519/jospt.2021.10412.

High-Throughput Analysis of Lignin by Agarose Gel Electrophoresis.

A high-throughput agarose gel electrophoresis (AGE) analytical method has been developed to separate lignin fractions according to their molecular weight (Mw), charge, and shape. Operating conditions to effect separation of species have been evaluated along with imaging parameters. Kraft, soda (Protobind), and Organosolv lignins showed distinct differences in migration. Bands were cut, extracted, and cross-analyzed by gel permeation chromatography (GPC), 1H NMR, and pyrolysis GC/MS to confirm their identity as lignin. The band intensity was correlated with lignin concentration by running serially diluted samples and imaging each lane to produce a precise calibration curve. The AGE technique was used to monitor and compare enzymatic, bacterial, chemical, and hydrothermal lignin digestions. Each method showed changes in lignin migration and band intensities over time. Low Mw species were seen in samples collected from the anode buffer tank. Though requiring further development, the AGE method can provide structural information about the lignin and is accessible to biological and chemistry laboratories.

Sticking to It: A Scoping Review of Adherence to Exercise Therapy Interventions in Children and Adolescents With Musculoskeletal Conditions.

OBJECTIVE: To identify and categorize barriers, facilitators, and strategies to boost exercise therapy adherence in youth with musculoskeletal conditions to inform research and clinical practice. STUDY DESIGN: Scoping review. LITERATURE SEARCH: We searched MEDLINE, CINAHL, SPORTDiscus, Scopus, PEDro, and ProQuest from inception to October 1, 2019. STUDY SELECTION CRITERIA: Studies written in English, with original data featuring an adherence barrier, facilitator, or boosting strategy for exercise therapy in youth (age, 19 years or younger) with musculoskeletal conditions, were included. DATA SYNTHESIS: Arksey and O'Malley's framework and the PRISMA Extension for Scoping Reviews guided data synthesis. Study quality was assessed with the Mixed Methods Appraisal Tool. Descriptive consolidation included study and sample characteristics, exercise therapy details, and adherence measurement specifics. Inductive thematic analysis of adherence barriers, facilitators, and boosting strategies followed Braun and Clarke's 6-step guide. RESULTS: Of 5705 potentially relevant records, 41 studies, representing 2020 participants (64% girls; age range, 2-19 years) with 12 different musculoskeletal conditions and multiple exercise therapy interventions, were included. Despite poor reporting of adherence concepts, time constraints, physical environment (eg, location), and negative exercise experiences were commonly identified barriers. Social support and positive exercise experiences were frequently identified facilitators. Reinforcement, exercise program modification, and education were recurring boosting strategies, despite being infrequent barriers or facilitators. CONCLUSION: A diversity of barriers to and facilitators of exercise therapy for youth with musculoskeletal conditions were identified. Efforts to link adherence-boosting strategies to an individual's needs should be considered. Making exercise enjoyable, social, and convenient may be important to maximizing adherence in this population. J Orthop Sports Phys Ther 2020;50(9):503-515. Epub 1 Aug 2020. doi:10.2519/jospt.2020.9715.

Cognitive Behavioral Therapy for Antenatal Depression in a Pilot Randomized Controlled Trial and Effects on Neurobiological, Behavioral and Cognitive Outcomes in Offspring 3-7 Years Postpartum: A Perspective Article on Study Findings, Limitations and Future Aims.

PURPOSE OF ARTICLE: In a previous pilot randomized controlled trial including 54 pregnant women with depression, maternal mood improved after Cognitive Behavioural Therapy (CBT) compared to treatment as usual (TAU), showing medium to large effect sizes. The effect persisted up to 9 months postpartum, with infant outcomes also showing medium to large effects favoring CBT in various child domains. This perspective article summarizes the results of a follow-up that was performed approximately 5 years later in the same cohort, assessing the effects of antenatal Cognitive Behavioural Therapy for depression and anxiety on child buccal cell DNA-methylation, brain morphology, behavior and cognition. FINDINGS: Children from the CBT group had overall lower DNA-methylation compared to children from the TAU group. Mean DNA-methylation of all NR3C1 promoter-associated probes did not differ significantly between the CBT and TAU groups. Children from the CBT group had a thicker right lateral occipital cortex and lingual gyrus. In the CBT group, Voxel-Based-Morphometry analysis identified one cluster showing increased gray matter concentration in the right medial temporal lobe, and fixel-based analysis revealed reduced fiber-bundle-cross-section in the Fornix, the Optical Tract, and the Stria Terminalis. No differences were observed in full-scale IQ or Total Problems Score. When the total of hypotheses tests in this study was considered, differences in DNA-methylation and brain measurements were no longer significant. SUMMARY: Our explorative findings suggest that antenatal depression treatment decreases overall child DNA-methylation, increases cortical thickness, and decreases white matter fiber-bundle cross-section in regions involved in cognitive function and the stress response. Nevertheless, larger studies are warranted to confirm our preliminary conclusion that CBT in pregnancy alters neurobiological outcomes in children. Clinical relevance remains unclear as we found no effects of antenatal CBT on child behavior or cognition (yet).

Psychological, social and contextual factors across recovery stages following a sport-related knee injury: a scoping review.

OBJECTIVE: To explore the role of psychological, social and contextual factors across the recovery stages (ie, acute, rehabilitation or return to sport (RTS)) following a traumatic time-loss sport-related knee injury. MATERIAL AND METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and Arksey and O'Malley framework. Six databases were searched using predetermined search terms. Included studies consisted of original data written in English that identified or described a psychological, social or contextual factor related to recovery after a traumatic time-loss sport-related knee injury. Two authors independently conducted title-abstract and full-text reviews. Study quality was assessed using the Mixed Methods Appraisal Tool. Thematic analysis was undertaken. RESULTS: Of 7289 records, 77 studies representing 5540 participants (37% women, 84% anterior cruciate ligament tears, aged 14-60 years) were included. Psychological factors were investigated across all studies, while social and contextual factors were assessed in 39% and 21% of included studies, respectively. A cross-cutting concept of individualisation was present across four psychological (barriers to progress, active coping, independence and recovery expectations), two social (social support and engagement in care) and two contextual (environmental influences and sport culture) themes. Athletes report multiple barriers to recovery and valued their autonomy, having an active role in their recovery and diverse social support. CONCLUSION: Diverse psychological, social and contextual factors are present and influence all stages of recovery following a traumatic sport-related knee injury. A better understanding of these factors at the time of injury and throughout rehabilitation could assist with optimising injury management, promoting RTS, and long-term health-related quality-of-life.

Hyperpolarised 13C MRI: a new horizon for non-invasive diagnosis of aggressive breast cancer.

Hyperpolarised 13C MRI (HP-MRI) is a novel imaging technique that allows real-time analysis of metabolic pathways in vivo.1 The technology to conduct HP-MRI in humans has recently become available and is starting to be clinically applied. As knowledge of molecular biology advances, it is increasingly apparent that cancer cell metabolism is related to disease outcomes, with lactate attracting specific attention. 2 Recent reviews of breast cancer screening programs have raised concerns and increased public awareness of over treatment. The scientific community needs to shift focus from improving cancer detection alone to pursuing novel methods of distinguishing aggressive breast cancers from those which will remain indolent. HP-MRI offers the opportunity to identify aggressive tumour phenotypes and help monitor/predict therapeutic response. Here we report one of the first cases of breast cancer imaged using HP-MRI alongside correlative conventional imaging, including breast MRI.

First-in-human in vivo non-invasive assessment of intra-tumoral metabolic heterogeneity in renal cell carcinoma.

Intratumoral genetic heterogeneity and the role of metabolic reprogramming in renal cell carcinoma (RCC) have been extensively documented. However, the distribution of these metabolic changes within the tissue has not been explored. We report on the first-in-human in vivo non-invasive metabolic interrogation of RCC using hyperpolarized carbon-13 (13C) magnetic resonance imaging (HP-MRI) and describe the validation of in vivo lactate metabolic heterogeneity against multi-regional ex vivo mass spectrometry. HP-MRI provides an in vivo assessment of metabolism and provides a novel opportunity to safely and non-invasively assess cancer heterogeneity.

Brain Magnetic Resonance Imaging Findings in Children after Antenatal Maternal Depression Treatment, a Longitudinal Study Built on a Pilot Randomized Controlled Trial.

Antenatal depression is associated with an increased risk of offspring neuro-developmental disorders, potentially as a consequence of an altered brain development in utero. We hypothesized that reducing maternal depression by Cognitive Behavioral Therapy (CBT) during pregnancy may ameliorate the offspring's brain (micro)structural outcomes. 54 pregnant women with a diagnosed clinical depression were randomly allocated to CBT or Treatment as Usual (TAU), showing moderate to large depression symptom improvements after CBT. In 16 of their children (69% boys, N(TAU) = 8, N(CBT) = 8, mean age = 5.9 years, range = 3.9-7.1 years) brain Magnetic Resonance Imaging (MRI) scans were conducted. Children from the CBT group had a thicker right lateral occipital cortex (difference: 0.13 mm, 95% CI = 0.005-0.26) and lingual gyrus (difference: 0.18 mm, 95% CI = 0.01-0.34). In the CBT group, Voxel-Based Morphometry analysis identified one cluster showing increased gray matter concentration in the right medial temporal lobe at p < 0.05 uncorrected, and fixel-based analysis revealed reduced fiber-bundle cross-section in the Fornix, the Optical Tract, and the Stria Terminalis at p < 0.01 uncorrected. However, none of the results survived correction for multiple testing. Our explorative analyses provided some indication that antenatal CBT for depression may ameliorate offspring's brain (micro)structural outcomes, but the sample size was extremely small, and our results should be cautiously interpreted. Larger studies are warranted to confirm our preliminary conclusions that CBT for antenatal depression affects brain development in children.

Behavioural and cognitive outcomes following an early stress-reduction intervention for very preterm and extremely preterm infants.

BACKGROUND: The landmark findings of the Mother-Infant Transaction Program (MITP) showing improved neurodevelopment of preterm infants following parent-sensitivity training delivered in the neonatal intensive care unit have not been consistently replicated. This study evaluated an MITP-type intervention in terms of neurobehavioural development to preschool age. METHODS: A randomised controlled trial involved 123 very preterm and extremely preterm infants allocated to either a parent-sensitivity intervention (PremieStart, n = 60) or to standard care (n = 63). When children were 2 and 4.5 years corrected age, parents completed the Child Behavior Checklist (CBCL). General development was assessed at 2 years with the Bayley Scales of Infant Development (Bayley-III). At 4.5 years, cognitive functioning was assessed with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and executive functioning with the NEPSY-II. RESULTS: There were no significant between-group differences in behaviour problems at 2 or 4.5 years, general development at 2 years, or cognitive and executive functioning at 4.5 years. CONCLUSION: Advances in the quality of neonatal intensive care may mean that MITP-type interventions now have limited additional impact on preterm infants' long-term neurobehavioural outcomes. The gestational age of infants and the exact timing of intervention may also affect its efficacy.

Exploring the effect of antenatal depression treatment on children's epigenetic profiles: findings from a pilot randomized controlled trial.

BACKGROUND: Children prenatally exposed to maternal depression more often show behavioral and emotional problems compared to unexposed children, possibly through epigenetic alterations. Current evidence is largely based on animal and observational human studies. Therefore, evidence from experimental human studies is needed. In this follow-up of a small randomized controlled trial (RCT), DNA-methylation was compared between children of women who had received cognitive behavioral therapy (CBT) for antenatal depression and children of women who had received treatment as usual (TAU). Originally, 54 women were allocated to CBT or TAU. A beneficial treatment effect was found on women's mood symptoms. FINDINGS: We describe DNA methylation findings in buccal swab DNA of the 3-7-year-old children (CBT(N) = 12, TAU(N) = 11), at a genome-wide level at 770,668 CpG sites and at 729 CpG sites spanning 16 a priori selected candidate genes, including the glucocorticoid receptor (NR3C1). We additionally explored associations with women's baseline depression and anxiety symptoms and offspring DNA methylation, regardless of treatment. Children from the CBT group had overall lower DNA methylation compared to children from the TAU group (mean Ƨ = - 0.028, 95% CI - 0.035 to - 0.022). Although 68% of the promoter-associated NR3C1 probes were less methylated in the CBT group, with cg26464411 as top most differentially methylated CpG site (p = 0.038), mean DNA methylation of all NR3C1 promoter-associated probes did not differ significantly between the CBT and TAU groups (mean Ƨ = 0.002, 95%CI - 0.010 to 0.011). None of the effects survived correction for multiple testing. There were no differences in mean DNA methylation between the children born to women with more severe depression or anxiety compared to children born to women with mild symptoms of depression or anxiety at baseline (mean Ƨ (depression) = 0.0008, 95% CI - 0.007 to 0.008; mean Ƨ (anxiety) = 0.0002, 95% CI - 0.004 to 0.005). CONCLUSION: We found preliminary evidence of a possible effect of CBT during pregnancy on widespread methylation in children's genomes and a trend toward lower methylation of a CpG site previously shown by others to be linked to depression and child maltreatment. However, none of the effects survived correction for multiple testing and larger studies are warranted. TRIAL REGISTRATION: Trial registration of the original RCT: ACTRN12607000397415 . Registered on 2 August 2007.

A randomized controlled trial of 'MUMentum Pregnancy': Internet-delivered cognitive behavioral therapy program for antenatal anxiety and depression.

BACKGROUND: Anxiety and depression are common during pregnancy and associated with adverse outcomes for the mother and infant if left untreated. Despite the need to improve treatment accessibility and uptake in this population, no studies have investigated internet-delivered cognitive behavioural therapy (iCBT) for antenatal anxiety and depression. In a randomised controlled trial, we examined the efficacy and acceptability of a brief, unguided iCBT intervention - the MUMentum Pregnancy program - in pregnant women with anxiety and/or depression. METHODS: Participants meeting clinical threshold on validated self-report measures of generalised anxiety and/or depression were recruited online and randomised to iCBT (n = 43) or a treatment as usual (TAU) control (n = 44). Outcomes were assessed at baseline, post-treatment and four-week follow-up; and included anxiety, depression, psychological distress, antenatal bonding, quality of life, and treatment acceptability. RESULTS: Of the 36 women who started iCBT, 26 completed all three lessons of treatment (76% adherence rate). iCBT produced moderate to large effect size reductions for anxiety on the GAD-7 (Hedges' g = 0.76) and psychological distress on the Kessler-10 (g = 0.88) that were superior to TAU. Only small nonsignificant differences were found for depression outcomes (g = < 0.35). Participants reported that iCBT was an acceptable treatment for antenatal anxiety and/or depression. LIMITATIONS: Lack of an active control condition and long-term postpartum follow-up. CONCLUSIONS: This is the first study to evaluate brief unguided iCBT for antenatal anxiety and depression. While our findings are promising, particularly for anxiety reduction, additional RCTs are required to establish treatment efficacy.

Internet-based cognitive behavioural therapy (iCBT) for perinatal anxiety and depression versus treatment as usual: study protocol for two randomised controlled trials.

BACKGROUND: We aimed to evaluate the acceptability and efficacy of two brief, Internet-delivered cognitive behavioural therapy interventions-MUMentum Pregnancy (study 1) and MUMentum Postnatal (study 2)-in reducing maternal symptoms of anxiety, depression and overall psychological distress compared to usual care in the perinatal period. METHODS/DESIGN: Women who are pregnant (study 1) or < 12 months postpartum (study 2) with current clinically elevated symptoms of anxiety and/or depression according to validated self-report measures, will be recruited via the research arm of a not-for-profit clinical and research unit in Australia and randomised to the intervention group or treatment as usual control group. The minimum sample size for each study (alpha 0.05; power 0.80 for a g of 0.80) was identified as 50 with at least 10% more to be recruited to account for expected attrition. The co-primary outcome measures are the Patient Health Questionnaire 9-item scale and Generalised Anxiety Disorder 7-item scale to measure depression and anxiety symptom severity, respectively, and will be administered at the following primary time-points: baseline; post treatment; and at one-month follow-up. Psychological distress will be measured according to the Kessler-10 psychological distress scale at each primary time-point and will also be completed before each lesson for those in the intervention group. The total trial period nine weeks for study 1 and 11 weeks for study 2. Program efficacy will be determined using intent-to-treat mixed models. Maintenance of gains will be assessed at one-month follow-up. DISCUSSION: The current randomised controlled trial seeks to extend the literature by evaluating the efficacy of a self-help intervention for women in the perinatal period. If efficacious, the MUMentum programs have the potential to be easily disseminated via https://thiswayup.org.au/ to large numbers of women across Australia as an intervention for women screening positive for anxiety, depressive or distress symptoms during pregnancy or postpartum. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000560493 ; ACTRN12616000559415 . Registered on 2nd May 2016.