Peripartum depression and anxiety as an integrative cross domain target for psychiatric preventative measures

Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety. Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety

Child DNA methylation in a randomized controlled trial of a video-feedback intervention to promote positive parenting and sensitive discipline (VIPP-SD)

A major modifiable risk factor for behavioural difficulties is harsh and insensitive parenting, and it has been hypothesised that the biological mechanism by which parenting influences child behaviour is via changes in the child’s DNA methylation. We attempted to, in part, address the hypothesis that parenting is associated with child DNA methylation and, in turn, behaviour. Primary caregivers of young children with behavioural difficulties (children aged 12-36 months) were randomised to receive Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) (n=151), or usual care (n=149). Child buccal samples were collected at a 2-year post-randomisation follow up (children aged 3-5 years, VIPP-SD group n=106, usual care group n=117) and were assessed for DNA methylation at the NR3C1, FKBP5 and OXYR genes. Child behaviour was assessed at baseline, post-intervention and 2-years post-randomisation using the Preschool Parental Account of Children’s Symptoms (PPACS). We examined group differences in DNA methylation, associations of DNA methylation with behaviour, and sex differences. For the NR3C1 and OXYR genes, there were no group differences, sex differences, or associations of DNA methylation with child behaviour, though all non-significant findings were in the hypothesised direction. For FKBP5 DNA methylation, there was a significant interaction between group and sex, such that males in the usual care group had higher DNA methylation than females, but in the intervention group females had higher DNA methylation than males. However, FKBP5 DNA methylation was not associated with behaviour in males or females. We provide the first evidence from a randomised controlled trial focused on improving parenting for sex-specific changes in child DNA methylation at a key gene involved in stress reactivity and psychopathology. This study adds to our understanding of causal mechanisms linking parenting with child behaviour, which is important to developing targeted interventions. A key limitation is that child DNA methylation was only assessed at one time point, so we were unable to assess change in DNA methylation over time. However, we demonstrate that is possible to collect and analyse DNA samples from families with young children receiving parenting interventions in the community, providing impetus for further research on this topic

Child DNA methylation in a randomised controlled trial of a video-feedback intervention to promote positive parenting and sensitive discipline (VIPP-SD)

Peer reviewed: TrueIntroductionA major modifiable risk factor for behavioural difficulties is harsh and insensitive parenting, and it has been hypothesised that the biological mechanism by which parenting influences child behaviour is via changes in the child's DNA methylation. We attempted to, in part, address the hypothesis that parenting is associated with child DNA methylation and, in turn, behaviour.MethodsPrimary caregivers of young children with behavioural difficulties (children aged 12–36 months) were randomised to receive a video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) (n = 151), or usual care (n = 149). Child buccal samples were collected at a 2-year post-randomisation follow up (children aged 3–5 years, VIPP-SD group n = 106, usual care group n = 117) and were assessed for DNA methylation at the NR3C1, FKBP5 and OXYR genes. Child behaviour was assessed at baseline, post-intervention and 2-years post-randomisation using the Preschool Parental Account of Children's Symptoms (PPACS). We examined group differences in DNA methylation, associations of DNA methylation with behaviour, and sex differences.ResultsFor the NR3C1 and OXYR genes, there were no group differences, sex differences, or associations of DNA methylation with child behaviour, though all non-significant findings were in the hypothesised direction. For FKBP5 DNA methylation, there was a significant interaction between group and sex, such that males in the usual care group had higher DNA methylation than females, but in the intervention group females had higher DNA methylation than males. However, FKBP5 DNA methylation was not associated with behaviour in males or females.DiscussionWe provide the first evidence from a randomised controlled trial focused on improving parenting for sex-specific changes in child DNA methylation at a key gene involved in stress reactivity and psychopathology. This study adds to our understanding of causal mechanisms linking parenting with child behaviour, which is important for developing targeted interventions. A key limitation is that child DNA methylation was only assessed at one time point, so we were unable to assess change in DNA methylation over time. However, we demonstrate that is possible to collect and analyse DNA samples from families with young children receiving parenting interventions in the community, providing impetus for further research on this topic.</jats:sec

Chemical Control of Correlated Metals as Transparent Conductors

Correlated metallic transition metal oxides offer a route to thin film transparent conductors that is distinct from the degenerate doping of broadband wide gap semiconductors. In a correlated metal transparent conductor, interelectron repulsion shifts the plasma frequency out of the visible region to enhance optical transmission, while the high carrier density of a metal retains sufficient conductivity. By exploiting control of the filling, position, and width of the bands derived from the B site transition metal in ABO3 perovskite oxide films, it is shown that pulsed laser deposition-grown films of cubic SrMoO3 and orthorhombic CaMoO3 based on the second transition series cation 4d2 Mo4+ have superior transparent conductor properties to the first transition series 3d1 V4+-based SrVO3. The increased carrier concentration offered by the greater bandfilling in the molybdates gives higher conductivity while retaining sufficient correlation to keep the plasma edge below the visible region. The reduced binding energy of the n = 4 frontier orbitals in the second transition series materials shifts the energies of oxide 2p to metal nd transitions into the near-ultraviolet to enhance visible transparency. The A site size-driven rotation of MoO6 octahedra in CaMoO3 optimizes the balance between Q3 plasma frequency and conductivity for transparent conductor performance

Image1_Child DNA methylation in a randomised controlled trial of a video-feedback intervention to promote positive parenting and sensitive discipline (VIPP-SD).jpeg

IntroductionA major modifiable risk factor for behavioural difficulties is harsh and insensitive parenting, and it has been hypothesised that the biological mechanism by which parenting influences child behaviour is via changes in the child's DNA methylation. We attempted to, in part, address the hypothesis that parenting is associated with child DNA methylation and, in turn, behaviour.MethodsPrimary caregivers of young children with behavioural difficulties (children aged 12–36 months) were randomised to receive a video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) (n = 151), or usual care (n = 149). Child buccal samples were collected at a 2-year post-randomisation follow up (children aged 3–5 years, VIPP-SD group n = 106, usual care group n = 117) and were assessed for DNA methylation at the NR3C1, FKBP5 and OXYR genes. Child behaviour was assessed at baseline, post-intervention and 2-years post-randomisation using the Preschool Parental Account of Children's Symptoms (PPACS). We examined group differences in DNA methylation, associations of DNA methylation with behaviour, and sex differences.ResultsFor the NR3C1 and OXYR genes, there were no group differences, sex differences, or associations of DNA methylation with child behaviour, though all non-significant findings were in the hypothesised direction. For FKBP5 DNA methylation, there was a significant interaction between group and sex, such that males in the usual care group had higher DNA methylation than females, but in the intervention group females had higher DNA methylation than males. However, FKBP5 DNA methylation was not associated with behaviour in males or females.DiscussionWe provide the first evidence from a randomised controlled trial focused on improving parenting for sex-specific changes in child DNA methylation at a key gene involved in stress reactivity and psychopathology. This study adds to our understanding of causal mechanisms linking parenting with child behaviour, which is important for developing targeted interventions. A key limitation is that child DNA methylation was only assessed at one time point, so we were unable to assess change in DNA methylation over time. However, we demonstrate that is possible to collect and analyse DNA samples from families with young children receiving parenting interventions in the community, providing impetus for further research on this topic.</p

Table1_Child DNA methylation in a randomised controlled trial of a video-feedback intervention to promote positive parenting and sensitive discipline (VIPP-SD).docx

IntroductionA major modifiable risk factor for behavioural difficulties is harsh and insensitive parenting, and it has been hypothesised that the biological mechanism by which parenting influences child behaviour is via changes in the child's DNA methylation. We attempted to, in part, address the hypothesis that parenting is associated with child DNA methylation and, in turn, behaviour.MethodsPrimary caregivers of young children with behavioural difficulties (children aged 12–36 months) were randomised to receive a video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) (n = 151), or usual care (n = 149). Child buccal samples were collected at a 2-year post-randomisation follow up (children aged 3–5 years, VIPP-SD group n = 106, usual care group n = 117) and were assessed for DNA methylation at the NR3C1, FKBP5 and OXYR genes. Child behaviour was assessed at baseline, post-intervention and 2-years post-randomisation using the Preschool Parental Account of Children's Symptoms (PPACS). We examined group differences in DNA methylation, associations of DNA methylation with behaviour, and sex differences.ResultsFor the NR3C1 and OXYR genes, there were no group differences, sex differences, or associations of DNA methylation with child behaviour, though all non-significant findings were in the hypothesised direction. For FKBP5 DNA methylation, there was a significant interaction between group and sex, such that males in the usual care group had higher DNA methylation than females, but in the intervention group females had higher DNA methylation than males. However, FKBP5 DNA methylation was not associated with behaviour in males or females.DiscussionWe provide the first evidence from a randomised controlled trial focused on improving parenting for sex-specific changes in child DNA methylation at a key gene involved in stress reactivity and psychopathology. This study adds to our understanding of causal mechanisms linking parenting with child behaviour, which is important for developing targeted interventions. A key limitation is that child DNA methylation was only assessed at one time point, so we were unable to assess change in DNA methylation over time. However, we demonstrate that is possible to collect and analyse DNA samples from families with young children receiving parenting interventions in the community, providing impetus for further research on this topic.</p

Maternal High-Fat Diet Alters Methylation and Gene Expression of Dopamine and Opioid-Related Genes

Maternal obesity during pregnancy increases the risk of obesity in the offspring. Obesity, arising from an imbalance of energy intake and expenditure, can be driven by the ingestion of palatable [high fat (HF), high sugar], energy-dense foods. Dopamine and opioid circuitry are neural substrates associated with reward that can affect animals’ preference for palatable foods. Using a mouse model, the long-term effect of maternal consumption of a HF diet on dopamine and opioid gene expression within the mesocorticolimbic reward circuitry and hypothalamus of the offspring was investigated. Mice from dams fed a HF diet during pregnancy and lactation showed an increased preference for sucrose and fat. Gene expression, measured using quantitative real-time PCR, revealed a significant approximately 3- to 10-fold up-regulation of dopamine reuptake transporter (DAT) in the ventral tegmental area, nucleus accumbens, and prefrontal cortex and a down-regulation of DAT in the hypothalamus. Additionally, expression of both μ-opioid receptor (MOR) and preproenkephalin (PENK) was increased in nucleus accumbens, prefrontal cortex, and hypothalamus of mice from dams that consumed the HF diet. Epigenetic mechanisms have been associated with long-term programming of gene expression after various in utero insults. We observed global and gene-specific (DAT, MOR, and PENK) promoter DNA hypomethylation in the brains of offspring from dams that consumed the HF diet. These data demonstrate that maternal consumption of a HF diet can change the offsprings’ epigenetic marks (DNA hypomethylation) in association with long-term alterations in gene expression (dopamine and opioids) and behavior (preference for palatable foods)