Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health

Research efforts during the past decades have provided intriguing evidence suggesting that stressful experiences during pregnancy exert long-term consequences on the future mental wellbeing of both the mother and her baby. Recent human epidemiological and animal studies indicate that stressful experiences in utero or during early life may increase the risk of neurological and psychiatric disorders, arguably via altered epigenetic regulation. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications are prone to changes in response to stressful experiences and hostile environmental factors. Altered epigenetic regulation may potentially influence fetal endocrine programming and brain development across several generations. Only recently, however, more attention has been paid to possible transgenerational effects of stress. In this review we discuss the evidence of transgenerational epigenetic inheritance of stress exposure in human studies and animal models. We highlight the complex interplay between prenatal stress exposure, associated changes in miRNA expression and DNA methylation in placenta and brain and possible links to greater risks of schizophrenia, attention deficit hyperactivity disorder, autism, anxiety- or depression-related disorders later in life. Based on existing evidence, we propose that prenatal stress, through the generation of epigenetic alterations, becomes one of the most powerful influences on mental health in later life. The consideration of ancestral and prenatal stress effects on lifetime health trajectories is critical for improving strategies that support healthy development and successful aging.     

Prevalence and risk factors of inpatient aggression by adults with intellectual disabilities and severe challenging behaviour: A long-term prospective study in two Dutch treatment facilities

Over five years, various types of aggressive incidents by 421 intellectually disabled inpatients were recorded on a daily basis, using an adapted version of the Modified Overt Aggression Scale. Stable patient characteristics (e.g., gender, intelligence, DSM IV classification at the start of treatment) and pre-treatment scores of two treatment outcome measures (e.g., Adult Behavior Checklist and Dynamic Risk Outcome Scale) were used to predict aggression during the treatment. At an overall average of one incident per patient per week, about ten times more aggression occurred on admission compared to resocialisation wards, and the 20% most aggressive individuals caused 50% of the verbal and 80% of the physical incidents. The best predictor of aggressive behaviour was aggression early in treatment, followed by coping skills deficits and impulsiveness. The relevance of the results for the treatment of aggressive behaviour and methodological issues in the recording of inpatient aggression are discussed.     

Systematic reviews of factors associated with the onset and progression of neurological conditions in humans: A methodological overview

As a component of the National Population Health Study of Neurological conditions, systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 priority neurological conditions. Between 2011 and 2013, electronic databases and grey literature sources were searched to identify systematic reviews and primary studies reporting on the onset and progression of each condition. Inclusion was restricted to studies of humans reported in English or French. Additional condition-specific eligibility criteria were also applied. Titles and abstracts were screened by one reviewer with excluded records verified by a second reviewer. Full-text reports were screened independently by two reviewers. Disagreements were resolved by consensus or third party adjudication. Systematic reviews were quality appraised using the AMSTAR criteria, with only moderate and high quality reviews considered for inclusion. Primary studies were also sought to ensure that evidence from existing systematic reviews was supplemented with recent primary study findings (i.e., those published after the most recent systematic review). Evidence from primary studies was also considered if a systematic review was unavailable or of poor quality. Data were extracted using standardized forms. Where feasible, data were extracted independently by two reviewers. Otherwise, data were extracted by a single reviewer and independent data extraction by a second reviewer was conducted for a randomly selected sample of studies. An updated search was conducted in 2016 to identify systematic reviews published since the initial search in 2011–2013. A summary of the methodology used to conduct the systematic reviews is described. Illustrative results are provided for the risk of amyotrophic lateral sclerosis in relation to occupational exposure to lead and other heavy metals     

Development of weakness in patients with chronic inflammatory demyelinating polyneuropathy and only sensory symptoms at presentation: A long-term follow-up study

This long-term follow-up study examined patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and only sensory symptoms at first presentation, with emphasis on the development of motor symptoms and long-term disability. From all CIDP patients referred to our Department between 1987 and 1995, seven had only sensory symptoms at first clinical presentation. These were investigated according to a standard protocol, including a quantified clinical neurological examination and nerve conduction studies. The mean duration of the disease before weakness developed was 3.1 years, but varied considerably (0.8–6.3 years). At follow-up, weakness developed in five patients and persisted in three of them. Five patients were not seriously incapacitated by their disease (Rankin 1 or 2), four of them being in remission now and one showing a very slow progression of disease. Two patients were moderately disabled (Rankin 3); one had severe persistent sensory ataxia and only weakness during relapses and one had stepwise progression and moderate weakness. Motor nerve conduction studies revealed that the most notable worsening in the entire group of patients was a decrease in distal compound muscle action potential amplitudes, indicating the development of distal conduction block or axonal degeneration. These findings show that CIDP with only sensory symptoms is a transient clinical stage that precedes the appearance of weakness in about 70% of patients. The long-term prognosis does not differ from that of patients with CIDP who have weakness at the beginning of the disease. Received: 3 December 1998 Received in revised form: 17 May 1999 Accepted: 2 July 1999     

单次手法和物理治疗颈型颈椎病：疼痛和关节活动的即刻及短期效果比较

背景：大量研究表明,手法治疗和物理治疗均可显著改善颈型颈椎病患者的疼痛和关节活动度,但两种治疗方式对颈型颈椎病的即刻和短期疗效比较鲜有报道。目的：比较单次手法治疗和物理治疗对颈型颈椎病患者疼痛和活动的即刻和短期疗效。 方法：颈型颈椎病患者随机分成2组,手法治疗组和物理治疗组,各接受1次治疗。采用疼痛目测类比评分法、压力疼痛阈值和关节活动范围评定患者治疗前、后10 min(即刻疗效)和治疗后第2天(短期疗效)的情况。 结果与结论：手法治疗组患者在单次治疗后的10 min和第2天疼痛目测类比评分较治疗前下降,压力疼痛阈值增加,颈椎各方向关节活动范围均增加(P < 0.05);物理治疗组患者在单次治疗后的10 min和第2天疼痛目测类比评分较治疗前均下降(P < 0.05),在治疗后第2天,颈椎左/右侧屈关节活动范围较治疗前增加(P < 0.05);在治疗后的10 min和第2天,手法治疗组患者的疼痛目测类比评分均低于物理治疗组,压力疼痛阈值均高于物理治疗组,颈椎前屈/后伸,左/右侧屈关节活动范围均大于物理治疗组(P < 0.05)。结果表明单次手法治疗对改善慢性颈痛患者疼痛目测类比评分,压力疼痛阈值和关节活动范围的即刻效果和短期效果均优于物理治疗。关键词：手法治疗;物理治疗;颈椎病;疼痛;关节活动范围