From nature versus nurture, via nature and nurture, to gene x environment interaction in mental disorders

It is now generally accepted that complex mental disorders are the results of interplay between genetic and environmental factors. This holds out the prospect that by studying G x E interplay we can explain individual variation in vulnerability and resilience to environmental hazards in the development of mental disorders. Furthermore studying G x E findings may give insights in neurobiological mechanisms of psychiatric disorder and so improve individualized treatment and potentially prevention. In this paper, we provide an overview of the state of field with regard to G x E in mental disorders. Strategies for G x E research are introduced. G x E findings from selected mental disorders with onset in childhood or adolescence are reviewed [such as depressive disorders, attention-deficit/hyperactivity disorder (ADHD), obesity, schizophrenia and substance use disorders]. Early seminal studies provided evidence for G x E in the pathogenesis of depression implicating 5-HTTLPR, and conduct problems implicating MAOA. Since then G x E effects have been seen across a wide range of mental disorders (e.g., ADHD, anxiety, schizophrenia, substance abuse disorder) implicating a wide range of measured genes and measured environments (e.g., pre-, peri- and postnatal influences of both a physical and a social nature). To date few of these G x E effects have been sufficiently replicated. Indeed meta-analyses have raised doubts about the robustness of even the most well studied findings. In future we need larger, sufficiently powered studies that include a detailed and sophisticated characterization of both phenotype and the environmental risk.

Impaired performance on the rapid visual information processing task (RVIP) could be an endophenotype of schizophrenia

The aim of the present study was to investigate whether healthy first-degree relatives of schizophrenia patients show reduced sensitivity performance, higher intra-individual variability (IIV) in reaction time (RT), and a steeper decline in sensitivity over time in a sustained attention task. Healthy first-degree relatives of schizophrenia patients (n=23) and healthy control subjects (n=46) without a family history of schizophrenia performed a demanding version of the Rapid Visual Information Processing task (RVIP). RTs, hits, false alarms, and the sensitivity index A' were assessed. The relatives were significantly less sensitive, tended to have higher IIV in RT, but sustained the impaired level of sensitivity over time. Impaired performance on the RVIP is a possible endophenotype for schizophrenia. Higher IIV in RT, apparently caused by impaired context representations, might result in fluctuations in control and lead to more frequent attentional lapses.

A field study on characteristics and diversity of gene expression in the liver of dairy cows during the transition period

Metabolic and endocrine adaptations to support milk production during the transition period vary between individual cows. This variation between cows to adapt to lactation may have a genetic basis. The present field study was carried out to determine hepatic adaptations occurring from late pregnancy through early lactation by measuring mRNA abundance of candidate genes in dairy cows on-farm. Additionally, the objective was to observe the diversity in inter-individual variation for the candidate genes that may give indications where individual adaptations at a molecular level can be found. This study was carried out on-farm including 232 dairy cows (parity >3) from 64 farms in Switzerland. Blood and liver samples were collected on d 20+/-7 before parturition, on d 24+/-2, and on d 89+/-4 after parturition. Blood plasma was assayed for concentrations of glucose, nonesterified fatty acids, beta-hydroxybutyrate, cholesterol, triglycerides, urea, albumin, protein, insulin, insulin-like growth factor-1, leptin, 3,5,3'-triiodothyronine, and thyroxine. Liver samples were obtained at the same time points and were measured for mRNA abundance of 26 candidate genes encoding enzymes and nuclear receptors involved in gluconeogenesis, fatty acid beta-oxidation, fatty acid and triglyceride synthesis, ketogenesis, citric acid cycle, cholesterol synthesis, and the urea cycle. The cows in the present study experienced a marked metabolic load in early lactation, as presented by changes in plasma metabolites and hormones, and responded accordingly with upregulation and downregulation of almost all candidate genes involved in metabolic processes in the liver. The observed inter-individual variation for the candidate genes, which was highest for acetyl-CoA-carboxylase and glycerol-3-phosphate dehydrogenase 2, should be further investigated to unravel the regulation at molecular level for optimal adaptive performance in dairy cows.

Age-modulated association between prefrontal NAA and the BDNF gene

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of psychiatric and neurological disorders and in the mechanisms of antidepressant pharmacotherapy. Psychiatric and neurological conditions have also been associated with reduced brain levels of N-acetyl-aspartate (NAA), which has been used as a putative marker of neural integrity. However, few studies have explored the relationship between BDNF polymorphisms and NAA levels directly. Here, we present data from a single-voxel proton magnetic resonance spectroscopy study of 64 individuals and explore the relationship between BDNF polymorphisms and prefrontal NAA level. Our results indicate an association between a single nucleotide polymorphism (SNP) within BDNF, known as rs1519480, and reduced NAA level (p = 0.023). NAA levels were further predicted by age and Asian ancestry. There was a significant rs1519480 × age interaction on NAA level (p = 0.031). Specifically, the effect of rs1519480 on NAA level became significant at age ⩾34.17 yr. NAA level decreased with advancing age for genotype TT (p = 0.001) but not for genotype CT (p = 0.82) or CC (p = 0.34). Additional in silico analysis of 142 post-mortem brain samples revealed an association between the same SNP and reduced BDNF mRNA expression in the prefrontal cortex. The rs1519480 SNP influences BDNF mRNA expression and has an impact on prefrontal NAA level over time. This genetic mechanism may contribute to inter-individual variation in cognitive performance seen during normal ageing, as well as contributing to the risk for developing psychiatric and neurological conditions.

Pineal calcification in Alzheimer's disease: an in vivo study using computed tomography

Melatonin has been postulated to have diverse properties, acting as an antioxidant, a neuroprotector, or a stabilizer within the circadian timing system, and is thus thought to be involved in the aging process and Alzheimer's disease (AD). We used computed tomography to determine the degree of pineal calcification (DOC), an intra-individual melatonin deficit marker, as well as the size of uncalcified pineal tissue, in 279 consecutive memory clinic outpatients (AD: 155; other dementia: 25; mild cognitive impairment: 33; depression: 66) and 37 age-matched controls. The size of uncalcified pineal tissue in patients with AD (mean 0.15 cm(2) [S.D. 0.24]) was significantly smaller than in patients with other types of dementia (0.26 [0.34]; P=0.038), with depression (0.28 [0.34]; P=0.005), or in controls (0.25 [0.31]; P=0.027). Additionally, the DOC in patients with AD (mean 76.2% [S.D. 26.6]) was significantly higher than in patients with other types of dementia (63.7 [34.7]; P=0.042), with depression (60.5 [33.8]; P=0.001), or in controls (64.5 [30.6]; P=0.021). These two findings may reflect two different aspects of melatonin in AD. On the one hand, the absolute amount of melatonin excretion capability, as indicated by uncalcified pineal volume, refers to the antioxidant properties of melatonin. On the other hand, the relative reduction in melatonin production capability in the individual, as indicated by DOC, refers to the circadian properties of melatonin.

Support for the predictions of the pollinator-mediated stabilizing selection hypothesis

Aims Floral traits are frequency used in traditional plant systematics because Of their assumed constancy. One potential reason for the apparent constancy of flower size is that effective pollen transfer between flowers depends oil the accuracy of the physical fit between the flower and pollinator. Therefore, dowels are likely to he under stronger stabilizing selection for uniform size than vegetative plant parts. Moreover, as predicted by the pollinator-mediated stabilizing selection (PMSS) hypothesis, all accurate fit between flowers and their pollinators is likely to he more important for specialized pollination systems as found in many species with bilaterally symmetric (zygomorphic) flowers than for species, with radially symmetric (actinomorphic) flowers. Methods In a comparative study of 15 zygomorphic and 13 actinomorphic species ill Switzerland, we tested whether variation in flower size, among and within individuals, is smaller than variation ill leaf size and whether variation in flower size is smaller ill zygomorphic compared to actinomorphic species. Important findings Indeed, variation ill leaf length was significantly larger than variation in flower length and width. Within-individual variation ill flower and leaf sizes did not differ significantly between zygomorphic and actinomorphic species. In line with the predictions of the PMSS, among-individual variation ill flower length and flower width was significantly smaller for zygomorphic species than for actinomorphic species, while the two groups did not differ in leaf length variation. This suggests that plants with zygomorphic flowers have undergone stronger selection for uniform flowers than plants with actinomorphic flowers. This supports that the uniformity of flowers compared to vegetative structures within species, as already observed in traditional plant systematics, is, at least in part, a consequence of the requirement for effective pollination.

A test of genetic association among male nuptial coloration, female mating preference, and male aggression bias within a polymorphic population of cichlid fish

Both inter- and intrasexual selection have been implicated in the origin and maintenance of species-rich taxa with diverse sexual traits. Simultaneous disruptive selection by female mate choice and male-male competition can, in theory, lead to speciation without geographical isolation if both act on the same male trait. Female mate choice can generate discontinuities in gene flow, while male-male competition can generate negative frequency-dependent selection stabilizing the male trait polymorphism. Speciation may be facilitated when mating preference and/or aggression bias are physically linked to the trait they operate on. We tested for genetic associations among female mating preference, male aggression bias and male coloration in the Lake Victoria cichlid Pundamilia. We crossed females from a phenotypically variable population with males from both extreme ends of the phenotype distribution in the same population (blue or red). Male offspring of a red sire were significantly redder than males of a blue sire, indicating that intra-population variation in male coloration is heritable. We tested mating preferences of female offspring and aggression biases of male offspring using binary choice tests. There was no evidence for associations at the family level between female mating preferences and coloration of sires, but dam identity had a significant effect on female mate preference. Sons of the red sire directed significantly more aggression to red than blue males, whereas sons of the blue sire did not show any bias. There was a positive correlation among individuals between male aggression bias and body coloration, possibly due to pleiotropy or physical linkage, which could facilitate the maintenance of color polymorphism.

Fixed and Flexible: Coexistence of Obligate and Facultative Migratory Strategies in a Freshwater Fish

Migration is an important event in many animal life histories, but the degree to which individual animals participate in seasonal migrations often varies within populations. The powerful ecological and evolutionary consequences of such partial migration are now well documented, but the underlying mechanisms are still heavily debated. One potential mechanism of partial migration is between-individual variation in body condition, where animals in poor condition cannot pay the costs of migration and hence adopt a resident strategy. However, underlying intrinsic traits may overrule such environmental influence, dictating individual consistency in migratory patterns. Unfortunately, field tests of individual consistency compared to the importance of individual condition on migratory propensity are rare. Here we analyse 6 years of field data on roach migration, gathered by tagging almost 3000 individual fish and monitoring their seasonal migrations over extended periods of time. Our aims were to provide a field test of the role of condition in wild fish for migratory decisions, and also to assess individual consistency in migratory tendency. Our analyses reveal that (1) migratory strategy, in terms of migration/residency, is highly consistent within individuals over time and (2) there is a positive relationship between condition and the probability of migration, but only in individuals that adopt a migratory strategy at some point during their lives. However, life-long residents do not differ in condition to migrants, hence body condition is only a good predictor of migratory tendency in fish with migratory phenotypes and not a more general determinant of migratory tendency for the population. As resident individuals can achieve very high body condition and still remain resident, we suggest that our data provides some of the first field evidence to show that both facultative and obligate strategies can co-exist within populations of migratory animals.

The role of learning-related dopamine signals in addiction vulnerability

Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signaling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical, and experimental accounts of phasic dopamine signaling, with implications for the role of learning-related dopamine signaling in addiction and related disorders. We describe the theoretical and behavioral characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction.

The quiet eye and tasks demands: Do tougher shots need a quieter eye?

The Quiet Eye (QE; Vickers 1996) has been shown to underpin successful performance, differentiating both expertise (inter-individual) and proficiency (intra-individual), with experts and successful attempts characterised by longer QE durations. The QE is proposed to reflect the time needed to organise and fine tune the parameters of movement (e.g. force and direction). In order to examine this prediction and build upon previous research we experimentally manipulated the difficulty of a golf putting task; we hypothesised that if the QE is related to motor programming then a more difficult task should be associated with longer QE durations. 33 golfers (M age= 21.16, SD= 3.98) with an average handicap of 6.5 (SD= 6.02) performed putts in 4 conditions of increasing difficulty. We manipulated the length of the golf putt (short-4ft, long-8ft) and the contact point of the putter head (large-1.7cm, small-0.5cm,) giving increasingly difficult putting conditions of short-large [1], short-small [2], long-large [3] and long-small [4]. We measured performance (radial error from hole in cm) and QE (in ms) for 10 putts in each condition. A repeated measures ANOVA was performed on the performance and QE data. The performance data suggest that we were successful in increasing the difficulty of the task (F (3,93) = 26.46. p = .000), with the best performance in condition [1] (8.57cm), followed by [2] (9.10cm) followed by [3] (16.11cm) and finally the worst performance was in condition [4] (23.40cm). The QE data suggest that, in keeping with our hypothesis, the QE was lengthened as task difficulty increased (F (3,87) = 11.91, p = .043). The QE was shortest in condition [1] (1787.85ms) and increased to condition [2] (1939.78ms) and condition [3] (2076.51ms), with the longest QE in condition [4] (2164.08ms). More detailed analysis of the QE reveal that it was the proportion of the QE that occurred before movement initiation (pre-QE) which increased with shot difficulty, rather than the proportion that occurred during the swing (Online-QE; see Vine et al., 2013). Results support the notion that more complex tasks are associated with a longer QE duration, specifically participants appear to spend longer fixating the target prior to movement. This likely reflects the time needed to process visual information gathered in a pre-performance routine, to inhibit external distraction, and to pre-programme the increasingly difficult parameters of the movement. Vickers, J.N. (1996). Visual control when aiming at a far target. Journal of Experimental Psychology: Human Perception and Performance, 22, 342-354. Vine, S.J. et al. (2013). Quiet eye and choking: Online control breaks down at the point of performance failure. Medicine and Science in Sports and Exercise, 45, 1988-1994.

A neural marker of costly punishment behavior

Human readiness to incur personal costs to punish norm violators is a key force in the maintenance of social norms. The willingness to punish is, however, characterized by vast individual heterogeneity that is poorly understood. In fact, this heterogeneity has so far defied explanations in terms of individual-level demographic or psychological variables. Here, we use resting electroencephalography, a stable measure of individual differences in cortical activity, to show that a highly specific neural marker--baseline cortical activity in the right prefrontal cortex--predicts individuals' punishment behavior. The analysis of task-independent individual variation in cortical baseline activity provides a new window into the neurobiology of decision making by bringing dispositional neural markers to the forefront of the analysis.

Objective assessment of patient compliance with removable orthodontic appliances: a cross-sectional cohort study.

OBJECTIVE To assess objectively patient compliance with removable orthodontic appliances and the effect of possible influential factors. MATERIALS AND METHODS Wearing times of 45 White patients were recorded with the aid of the TheraMon microsensor. Patient compliance was assessed relative to wear prescription and other parameters, such as age and sex. RESULTS There was high individual variation in most measured variables and in all groups/subgroups. During a median observation period of 186 days (range, 55-318 days) the actual wear time was 9.0 h/d (range, 0.0-16.0 h/d) and did not differ between distinct prescriptions (P = .49). Eight patients wore their appliances less than 2 h/d, and six of them did not wear their appliances at all. Overall, the median wear per day relative to prescription was 62.5% (range, 0.0-89.3%) for the 14 h/d and 112.5% (range, 0.0-200.0%) for the 8 h/d prescription wear (P = .01) groups. There was a strong negative correlation of age (median: 12.5 years) with the daily percentage of actual wear time per day relative to wear prescription (14 h/d prescription: n = 21, rho = -0.61, P = .00; 8 h/d prescription: n = 24, rho = -0.73, P = .00), while sex did not exert a significant influence on compliance (P = .58). CONCLUSIONS Despite the fact that patients and parents were informed about wear time recording, compliance was insufficient with regard to functional treatment (14 h/d prescription), while it was sufficient for retention purposes (8 h/d prescription). Objective measures are necessary to assess compliance with removable orthodontic appliances since patient compliance is a highly variable issue.

The pharmacokinetics of dexmedetomidine administered as a constant rate infusion in horses.

Dexmedetomidine, the most selective α2 -adrenoceptor agonist in clinical use, is increasingly being used in both conscious and anaesthetized horses; however, the pharmacokinetics and sedative effects of this drug administered alone as an infusion are not previously described in horses. Seven horses received an infusion of 8 μg dexmedetomidine/kg/h for 150 min, venous blood samples were collected, and dexmedetomidine concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analyzed using noncompartmental pharmacokinetic analysis. Sedation was scored as the distance from the lower lip of the horse to the ground measured in centimetre. The harmonic mean (SD) plasma elimination half-life (Lambda z half-life) for dexmedetomidine was 20.9 (5.1) min, clearance (Cl) was 0.3 (0.20) L/min/kg, and volume of distribution at steady-state (Vdss ) was 13.7 (7.9) L/kg. There was a considerable individual variation in the concentration of dexmedetomidine vs. time profile. The level of sedation covaried with the plasma concentration of dexmedetomidine. This implies that for clinical use of dexmedetomidine constant rate infusion in conscious horses, infusion rates can be easily adjusted to effect, and this is preferable to an infusion at a predetermined value.

Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values.

The Career Satisfaction Scale: Longitudinal measurement invariance and latent growth analysis

The present research analyses the adequacy of the widely used Career Satisfaction Scale (CSS; Greenhaus, Parasuraman, & Wormley, 1990) for measuring change over time. We used data of a sample of 1,273 professionals over a 5-year time period. First, we tested longitudinal measurement invariance of the CSS. Second, we analysed changes in career satisfaction by means of multiple indicator latent growth modelling (MLGM). Results revealed that the CSS can be reliably used in mean change analyses. Altogether, career satisfaction was relatively stable over time; however, we found significant variance in intra-individual growth trajectories and a negative correlation between the initial level of and changes in career satisfaction. Professionals who were initially highly satisfied became less satisfied over time. Theoretical and practical implications with respect to the construct of career satisfaction and its development over time (i.e., alpha, beta, and gamma change) are discussed.