Esther Nederhof

Mismatch or cumulative stress: Toward an integrated hypothesis of programming effects

This paper integrates the cumulative stress hypothesis with the mismatch hypothesis, taking into account individual differences in sensitivity to programming. According to the cumulative stress hypothesis, individuals are more likely to suffer from disease as adversity accumulates. According to the mismatch hypothesis, individuals are more likely to suffer from disease if a mismatch occurs between the early programming environment and the later adult environment. These seemingly contradicting hypotheses are integrated into a new model proposing that the cumulative stress hypothesis applies to individuals who were not or only to a small extent programmed by their early environment, while the mismatch hypothesis applies to individuals who experienced strong programming effects. Evidence for the main effects of adversity as well as evidence for the interaction between adversity in early and later life is presented from human observational studies and animal models. Next, convincing evidence for individual differences in sensitivity to programming is presented. We extensively discuss how our integrated model can be tested empirically in animal models and human studies, inviting researchers to test this model. Furthermore, this integrated model should tempt clinicians and other intervenors to interpret symptoms as possible adaptations from an evolutionary biology perspective.

Differential susceptibility in youth: evidence that 5-HTTLPR x positive parenting is associated with positive affect 'for better and worse'

Positive affect has been implicated in the phenomenological experience of various psychiatric disorders, vulnerability to develop psychopathology and overall socio-emotional functioning. However, developmental influences that may contribute to positive affect have been understudied. Here, we studied youths’ 5-HTTLPR genotype and rearing environment (degree of positive and supportive parenting) to investigate the differential susceptibility hypothesis (DSH) that youth carrying short alleles of 5-HTTLPR would be more influenced and responsive to supportive and unsupportive parenting, and would exhibit higher and lower positive affect, respectively. Three independent studies tested this gene–environment interaction (GxE) in children and adolescents (age range 9–15 years; total N=1874). In study 1 (N=307; 54% girls), positive/supportive parenting was assessed via parent report, in study 2 (N=197; 58% girls) via coded observations of parent–child interactions in the laboratory and in study 3 (N=1370; 53% girls) via self report. Results from all the three studies showed that youth homozygous for the functional short allele of 5-HTTLPR were more responsive to parenting as environmental context in a ‘for better and worse’ manner. Specifically, the genetically susceptible youth (that is, S’S’ group) who experienced unsupportive, non-positive parenting exhibited low levels of positive affect, whereas higher levels of positive affect were reported by genetically susceptible youth under supportive and positive parenting conditions. These GxE findings are consistent with the DSH and may inform etiological models and interventions in developmental psychopathology focused on positive emotion, parenting and genetic susceptibility.

Psychomotor speed: Possibly a new marker for overtraining syndrome

Overtraining syndrome (OTS) is a major threat for performance and health in athletes. OTS is caused by high levels of (sport-specific) stress in combination with too little regeneration, which causes performance decrements, fatigue an possibly other symptoms. Although there is general consensus about the causes and consequences, many different terminologies have been used interchangeably.The consequences of overreaching and overtraining are divided into three categories: (i) functional overreaching (FO); (ii) non-functional overreaching (NFO); and (iii) OTS. In FO, performance decrements and fatigue are reversed within a pre-planned recovery period. FO has no negative consequences for the athlete in the long term; it might even have positive consequences. When performance does not improve and feelings of fatigue do not disappear after the recovery period, overreaching has not been functional and is thus called NFO. OTS only applies to the most severe cases. NFO and OTS could be prevented using early markers, which should be objective, not manipulable, applicable in training practice, not too demanding, affordable and should be based on a sound theoretical framework. No such markers exist up to today. It is proposed that psychomotor speed might be such a marker.OTS shows similarities with chronic fatigue syndrome and with major depression (MD). Through two meta-analyses, it is shown that psychomotor slowness is consistently present in both syndromes. This leads to the hypothesis that psychomotor speed is also reduced in athletes with OTS. Parallels between commonly used models for NFO and OTS and a threshold theory support the idea that psychomotor speed is impaired in athletes with NFO or OTS and could also be used as an early marker to prevent NFO and/or OTS.

Monitoring load, recovery and performance in young elite soccer players

Brink, MS, Nederhof, E, Visscher, C, Schmikli, SL, and Lemmink, KAPM. Monitoring load, recovery, and performance in young elite soccer players. J Strength Cond Res 24(3): 597-603, 2010-The purpose of this study was to investigate the relation between training load, recovery, and monthly field test performance in young elite soccer players to develop training guidelines to enhance performance. In a prospective, nonexperimental cohort design, 18 young elite soccer players registered training and match duration for a full competitive season by means of daily training logs. Furthermore, session rating of perceived exertion (RPE) and total quality of recovery (TQR) scores were recorded. Weekly duration (TLd), load (duration × session RPE = TLrpe), and TQR scores were calculated for 1 and 2 weeks before a monthly submaximal interval shuttle run tests to determine interval endurance capacity. Participants spent on average 394.4 ± 134.9 minutes per week on training and game play with an average session RPE of 14.4 ± 1.2 (somewhat hard) and TQR of 14.7 ± 1.3 (good recovery). Random intercept models showed that every extra hour training or game play resulted in enhanced field test performance (p < 0.05). Session RPE and TQR scores did not contribute to the prediction of performance. The duration of training and game play in the week before field test performance is most strongly related to interval endurance capacity. Therefore, coaches should focus on training duration to improve interval endurance capacity in elite soccer players. To evaluate the group and individual training response, field tests should be frequently executed and be incorporated in the training program.

Diagnosing overtraining in athletes using the two-bout exercise protocol

Objective In this work, whether a two-bout exercise protocol can be used to make an objective, immediately available distinction between non-functional over reaching (NFO) and overtraining syndrome (OTS) was studied. Design Underperforming athletes who were diagnosed with the suspicion of NFO or OTS were included in the study. Recovery of the athletes was monitored by a sports physician to retrospectively distinguish NFO from OTS. Setting Sports medicine laboratory Participants The protocol was started and completed by 10 underperforming athletes. NFO was retrospectively diagnosed in five athletes, and OTS was diagnosed in five athletes. Interventions A two-bout maximal exercise protocol was used to measure physical performance and stressinduced hormonal reactions. Main outcome measurements Exercise duration, heart rate and blood lactate concentration were measured at the end of both exercise tests. Venous concentrations cortisol, adrenocorticotrophic hormone (ACTH), prolactin and growth hormone were measured both before and after both exercise tests. Results Maximal blood lactate concentration was lower in OTS compared with NFO, while resting concentrations of cortisol, ACTH and prolactin concentrations were higher. However, sensitivity of these measures was low. The ACTH and prolactin reactions to the second exercise bout were much higher in NFO athletes compared with OTS and showed the highest sensitivity for making the distinction. Conclusions NFO might be distinguished from OTS based on ACTH and prolactin reactions to a two-bout exercise protocol. This protocol could be a useful tool for diagnosing NFO and OTS; however, more data should be collected before this test can be used as the gold standard.

Interaction Between Childhood Adversity, Brain- Derived Neurotrophic Factor val/met and Serotonin Transporter Promoter Polymorphism on Depression: The TRAILS Study

BACKGROUND The three-way interaction between the functional polymorphism in the serotonin transporter gene linked promoter region, the val66met polymorphism in the brain-derived neurotrophic factor gene, and childhood adversity in the prediction of depression in children, reported by Kaufman and colleagues in 2006, has only been confirmed in adult samples. This study examines the gene-by-gene-by-environment interaction in an adolescent sample. METHODS In a longitudinal population-based study, depression scores were assessed with the Youth Self Report at ages 11, 13.5, and 16. Pre- and perinatal adversities and childhood events were assessed in a parent interview at age 11. Long-term difficulties until age 11 were assessed with a parent questionnaire at age 13.5. Blood or buccal cells were collected for genotyping at age 16. The study included 1096 complete data sets. RESULTS Depression score over the three measurements was not significantly predicted by any interaction between genotypes and childhood adversities. CONCLUSIONS We were unable to confirm the three-way interaction in a representative, population-based sample of adolescents. The large sample resulted in adequate power, which in combination with the reliability of our measures gives confidence in our findings.

Benefits of extensive recruitment effort persist during follow-ups and are consistent across age group and survey method. The TRAILS study

BackgroundExtensive recruitment effort at baseline increases representativeness of study populations by decreasing non-response and associated bias. First, it is not known to what extent increased attrition occurs during subsequent measurement waves among subjects who were hard-to-recruit at baseline and what characteristics the hard-to-recruit dropouts have compared to the hard-to-recruit retainers. Second, it is unknown whether characteristics of hard-to-recruit responders in a prospective population based cohort study are similar across age group and survey method.MethodsFirst, we compared first wave (T1) easy-to-recruit with hard-to-recruit responders of the TRacking Adolescents’ Individual Lives Survey (TRAILS), a prospective population based cohort study of Dutch (pre)adolescents (at first wave: n = 2230, mean age = 11.09 (SD 0.56), 50.8% girls), with regard to response rates at subsequent measurement waves. Second, easy-to-recruit and hard-to-recruit participants at the fourth TRAILS measurement wave (n = 1881, mean age = 19.1 (SD 0.60), 52.3% girls) were compared with fourth wave non-responders and earlier stage drop-outs on family composition, socioeconomic position (SEP), intelligence (IQ), education, sociometric status, substance use, and psychopathology.ResultsFirst, over 60% of the hard-to-recruit responders at the first wave were retained in the sample eight years later at the fourth measurement wave. Hard-to-recruit dropouts did not differ from hard-to-recruit retainers. Second, extensive recruitment efforts for the web based survey convinced a population of nineteen year olds with similar characteristics as the hard-to-recruit eleven year olds that were persuaded to participate in a school-based survey. Some characteristics associated with being hard-to-recruit (as compared to being easy-to-recruit) were more pronounced among non-responders, resembling the baseline situation (De Winter et al.2005).ConclusionsFirst, extensive recruitment effort at the first assessment wave of a prospective population based cohort study has long lasting positive effects. Second, characteristics of hard-to-recruit responders are largely consistent across age groups and survey methods.

Evidence for plasticity genotypes in a gene-gene- environment interaction: the TRAILS study

The purpose was to study how functional polymorphisms in the brain derived neurotrophic factor gene (BDNF val66met) and the serotonin transporter gene linked promotor region (5‐HTTLPR) interact with childhood adversities in predicting Effortful Control. Effortful Control refers to the ability to regulate behavior in a goal‐directed manner and is an interesting endophenotype for psychopathology because of its heritability and the association of low Effortful Control with both internalizing and externalizing problems. In a longitudinal population‐based study Effortful Control was assessed with the parent version of the Early Adolescent Temperament Questionnaire at age 11. Pregnancy and delivery adversities and childhood events were assessed in a parent interview at age 11. Long‐term difficulties until age 11 were assessed with a parent questionnaire at age 13.5. Blood or buccal cells were collected at age 16 for genotyping the rs6265 and rs25531 SNPs and the 5‐HTTLPR length polymorphism. The study included 1032 complete data sets. Effortful Control was significantly predicted by the interaction between BDNF val66met, 5‐HTTLPR and childhood events. The BDNF val66met val/val–5‐HTTLPR l′/l′ genotype was unaffected by childhood events, while having either at least one BDNF val66met met or 5‐HTTLPR s′ allele (l′/l′‐met‐carrier; l′/s′‐val/val; s′/s′‐val/val) made children sensitive to childhood events. Predictions of Effortful Control by pregnancy and delivery adversities and long‐term difficulties were largely independent of genotype. We concluded that the l′/l′‐met‐carrier, l′/s′‐val/val and the s′/s′‐val/val genotypes showed greatest plasticity while the l′/l′‐val/val genotype was unaffected by childhood events.

Stressful events and temperament change during early and middle adolescence : The TRAILS study

This project investigates how stressful events are related to deviations from normative temperament development during adolescence. Temperament traits were assessed at ages 11 and 16 years. Life–event data was captured using an interview (total n = 1197). Normative changes were found in all traits. A linear trend was found between the experience of stressful events and temperament development. Adolescents exposed to stressful events showed smaller decreases in fear and shyness, stronger decreases in effortful control and affiliation and smaller increases in high intensity pleasure. Exposure to stressful events was related to increases in frustration instead of decreases. Our results show that whereas normative development is mostly in the direction of maturation, adolescents who experienced stressful events showed less maturation of their temperament. Copyright

Family environment is associated with HPA-axis activity in adolescents: The TRAILS study

The purpose of the present study was to investigate the developmental programming part of the theory of biological sensitivity to context using family environmental factors and hypothalamus-pituitary-adrenal (HPA) axis functioning. Specifically, we investigated whether perceived parenting (Rejection and Emotional Warmth) and socio-economic status (SES) predicted basal cortisol levels and the cortisol awakening response (CAR). In a population-based cohort of 1594 adolescents (mean age=11.08, SD=0.54) we assessed salivary cortisol, SES and perceived parenting. Perceived parental Emotional Warmth showed an inverse, linear association with basal cortisol levels. In addition, there was a curvilinear relationship between SES and both basal cortisol levels and the CAR. Our findings with regard to basal cortisol levels confirmed our hypothesis: lower basal HPA-axis activity in both high and low SES families compared to intermediate SES families.