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The effects of brain serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress.

ABSTRACT: Aberrant serotonin (5-HT) signalling and exposure to early life stress have both been suggested to play a role in anxiety- and impulsivity-related behaviours. However, whether congenital 5-HT deficiency × early life stress interactions influence the development of anxiety- or impulsivity-like behaviour has not been established. Here, we examined the effects of early life maternal separation (MS) stress on anxiety-like behaviour and behavioural disinhibition, a type of impulsivity-like behaviour, in wild-type (WT) and tryptophan hydroxylase 2 (Tph2) knock-in (Tph2KI) mice, which exhibit ~60-80% reductions in the levels of brain 5-HT due to a R439H mutation in Tph2. We also investigated the effects of 5-HT deficiency and early life stress on adult hippocampal neurogenesis, plasma corticosterone levels and several signal transduction pathways in the amygdala. We demonstrate that MS slightly increases anxiety-like behaviour in WT mice and induces behavioural disinhibition in Tph2KI animals. We also demonstrate that MS leads to a slight decrease in cell proliferation within the hippocampus and potentiates corticosterone responses to acute stress, but these effects are not affected by brain 5-HT deficiency. However, we show that 5-HT deficiency leads to significant alterations in SGK-1 and GSK3? signalling and NMDA receptor expression in the amygdala in response to MS. Together, these findings support a potential role for 5-HT-dependent signalling in the amygdala in regulating the long-term effects of early life stress on anxiety-like behaviour and behavioural disinhibition.

SUBMITTER: Sachs BD

PROVIDER: S-EPMC3931011 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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The effects of brain serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress.

Sachs Benjamin D BD Rodriguiz Ramona M RM Siesser William B WB Kenan Alexander A Royer Elizabeth L EL Jacobsen Jacob P R JP Wetsel William C WC Caron Marc G MG

The international journal of neuropsychopharmacology 20130514 9

Aberrant serotonin (5-HT) signalling and exposure to early life stress have both been suggested to play a role in anxiety- and impulsivity-related behaviours. However, whether congenital 5-HT deficiency × early life stress interactions influence the development of anxiety- or impulsivity-like behaviour has not been established. Here, we examined the effects of early life maternal separation (MS) stress on anxiety-like behaviour and behavioural disinhibition, a type of impulsivity-like behaviour, ...[more]

PMID: 23672796

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Project description:BackgroundEvidence regarding longer-term psychiatric, psychological, and behavioural outcomes (for example, anxiety, mood disorders, depression, and attention disorders) following mild traumatic brain injury (mTBI) in children and adolescents has not been previously synthesized.ObjectiveTo conduct a systematic review of the available evidence examining psychiatric, psychological, and behavioural outcomes following mTBI in children and adolescents.Materials and methodsNine electronic databases were systematically searched from 1980 to August 2014. Studies selected met the following criteria: original data; study design was a randomized controlled trial, quasi-experimental design, cohort or historical cohort study, case-control study, or cross-sectional study; exposure included mTBI (including concussion); population included children and adolescents (<19 years) at the time of mTBI, as well as a comparison group (for example, healthy children, children with orthopaedic injuries); and included psychiatric, psychological, or behavioural outcomes (for example, anxiety, mood disorders, depression, attention disorders). Two authors independently assessed the quality and level of evidence with the Downs and Black (DB) criteria and Oxford Centre of Evidence-Based Medicine (OCEBM) model, respectively, for each manuscript.ResultsOf 9472 studies identified in the initial search, 30 were included and scored. Heterogeneity in methodology and injury definition precluded meta-analyses. The median methodological quality for all 30 studies, based on the DB criteria, was 15/33 (range 6 to 19). The highest level of evidence demonstrated by all reviewed studies was level 2b based on OCEBM criteria, with the majority (28/30 studies) classified at this level. Based on the literature included in this systematic review, psychological and psychiatric problems in children with a history of mTBI were found to be more prevalent when mTBI is associated with hospitalization, when assessment occurs earlier in the recovery period (that is, resolves over time), when there are multiple previous mTBIs, in individuals with preexisting psychiatric illness, when outcomes are based on retrospective recall, and when the comparison group is noninjured healthy children (as opposed to children with injuries not involving the head).ConclusionsOverall, few rigorous prospective studies have examined psychological, behavioural, and psychiatric outcomes following mTBI. In the absence of true reports of preinjury problems and when ideally comparing mild TBI to non-TBI injured controls, there is little evidence to suggest that psychological, behavioural, and/or psychiatric problems persist beyond the acute and subacute period following an mTBI in children and adolescents.

Project description:Internet-delivered exposure-based cognitive behaviour therapy (ICBT) has been shown to be effective in the treatment of severe health anxiety. The health economic effects of the treatment have, however, been insufficiently studied and no prior study has investigated the effect of ICBT compared with an active psychological treatment. The aim of the present study was to investigate the cost effectiveness of ICBT compared with internet-delivered behavioural stress management (IBSM) for adults with severe health anxiety defined as Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) hypochondriasis. ICBT was hypothesised to be the more cost-effective treatment.This was a cost-effectiveness study within the context of a randomised controlled trial conducted in a primary care/university setting. Participants from all of Sweden could apply to participate.Self-referred adults (N=158) with a principal diagnosis of DSM-IV hypochondriasis, of whom 151 (96%) provided baseline and post-treatment data.ICBT or IBSM for 12?weeks.The primary outcome was the Health Anxiety Inventory. The secondary outcome was the EQ-5D. Other secondary measures were used in the main outcome study but were not relevant for the present health economic analysis.Both treatments led to significant reductions in gross total costs, costs of healthcare visits, direct non-medical costs and costs of domestic work cutback (p=0.000-0.035). The incremental cost-effectiveness ratio (ICER) indicated that the cost of one additional case of clinically significant improvement in ICBT compared with IBSM was $2214. The cost-utility ICER, that is, the cost of one additional quality-adjusted life year, was estimated to be $10,000.ICBT is a cost-effective treatment compared with IBSM and treatment costs are offset by societal net cost reductions in a short time. A cost-benefit analysis speaks for ICBT to play an important role in increasing access to effective treatment for severe health anxiety.NCT01673035; Results.

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The effects of brain serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress.

Publications

The effects of brain serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress.

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