DRD4-exonIII-VNTR moderates the effect of childhood adversities on emotional resilience in young-adults

Most individuals successfully maintain psychological well-being even when exposed to trauma or adversity. Emotional resilience or the ability to thrive in the face of adversity is determined by complex interactions between genetic makeup, previous exposure to stress, personality, coping style, availability of social support, etc. Recent studies have demonstrated that childhood trauma diminishes resilience in adults and affects mental health. The Dopamine receptor D4 (DRD4) exon III variable number tandem repeat (VNTR) polymorphism was reported to moderate the impact of adverse childhood environment on behaviour, mood and other health-related outcomes. In this study we investigated whether DRD4-exIII-VNTR genotype moderates the effect of childhood adversities (CA) on resilience. In a representative population sample (n = 1148) aged 30-34 years, we observed an interactive effect of DRD4 genotype and CA (β = 0.132; p = 0.003) on resilience despite no main effect of the genotype when effects of age, gender and education were controlled for. The 7-repeat allele appears to protect against the adverse effect of CA since the decline in resilience associated with increased adversity was evident only in individuals without the 7-repeat allele. Resilience was also significantly associated with approach-/avoidance-related personality measures (behavioural inhibition/activation system; BIS/BAS) measures and an interactive effect of DRD4-exIII-VNTR genotype and CA on BAS was observed. Hence it is possible that approach-related personality traits could be mediating the effect of the DRD4 gene and childhood environment interaction on resilience such that when stressors are present, the 7-repeat allele influences the development of personality in a way that provides protection against adverse outcomes.The study was supported by NHMRC of Australia Unit Grant No. 973302. DD is funded by NHMRC Capacity Building Grant No. 418020 in Population Health Research. NC is funded by NHMRC Research Fellowship No. 471501. KA is funded by NHMRC Research Fellowship No. 366756

Attention deficit/hyperactivity disorder symptoms and cognitive abilities in the late-life cohort of the PATH Through Life Study

Attention Deficit/Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder that has not been well studied in older adults. In this study we examined relationships between ADHD symptoms and cognitive ability and compared them between middle-age (MA; 48-52 years) and older-age (OA; 68-74 years) adults sampled from the same population. ADHD, mood disorder symptoms and cognitive abilities were assessed in a large population-based sample (n = 3443; 50% male). We measured current ADHD symptoms using the adult ADHD Self-Report Scale (ASRS), which we found to have the same underlying structure in both cohorts. Older adults reported significantly lower levels of ADHD symptoms and 2.2% of the OA cohort scored equal or above the ASRS cut-off score of 14 (which has been previously associated with ADHD diagnosis) compared with 6.2% of MA adults. Symptom levels were not significantly different between males and females. Using multigroup structural equation modelling we compared ADHD symptom-cognitive performance relationships between the two age groups. Generally higher ADHD symptoms were associated with poorer cognitive performance in the MA cohort. However, higher levels of inattention symptoms were associated with better verbal ability in both cohorts. Surprisingly, greater hyperactivity was associated with better task-switching abilities in older adults. In the OA cohort ADHD symptom-cognition relationships are indirect, mediated largely through the strong association between depression symptoms and cognition. Our results suggest that ADHD symptoms decrease with age and that their relationships with co-occurring mood disorders and cognitive performance also change. Although symptoms of depression are lower in older adults, they are much stronger predictors of cognitive performance and likely mediate the effect of ADHD symptoms on cognition in this age group. These results highlight the need for age-appropriate diagnosis and treatment of comorbid ADHD and mood disorders

A Population-Based Study of Attention Deficit/Hyperactivity Disorder Symptoms and Associated Impairment in Middle-Aged Adults

Attention deficit/hyperactivity disorder (ADHD) is the most prevalent childhood psychiatric condition. It frequently persists into adulthood and can have serious health and other adverse consequences. The majority of previous adult ADHD studies have focused on young adults so that relatively little is known about ADHD symptoms and their effects in mid and late life. In addition, effects of subclinical levels of attention deficit and hyperactivity have not been studied in detail. In this study we investigated ADHD symptoms and related impairment in a large population-based sample of middle-aged Australian adults (n = 2091; 47% male). Applying the WHO adult ADHD Self Report Screener (ASRS) we observed that 6.2% of participants had scores that were previously associated with ADHD diagnosis. No significant gender difference in the distribution of ASRS scores was observed. Multiple regression analyses indicated strong positive correlations between symptoms of ADHD and depression/anxiety and significant negative associations (p<0.01) with employment, financial stress, relationship quality, health and well-being measures in this age group. Importantly, associations were highly significant even when few ADHD symptoms were reported. Compared to the hyperactivity component, the inattention trait was particularly strongly associated and remained significant after controlling for depression/anxiety symptoms. Our study confirms previous findings and significantly adds to existing literature especially for an age-group that has not been well-studied. Our results suggest that ADHD symptoms continue to be associated with ill-health and functional impairment in mid-life and are, therefore, likely to be a major, previously unrecognized source of late-life morbidity with associated social and economic costs. Thus, there is a compelling need for better understanding and development of age-appropriate approaches to the diagnosis and treatment of ADHD in mid- to late-life

Lifetime cigarette smoking is associated with striatal volume measures

Nicotine, the primary addictive component of tobacco, affects the mammalian brain. Smokers’ brains have smaller cortical grey matter volumes and/or lower densities compared with non-smokers’. Differences in subcortical structures like the striatum are however, less clear. A high concentration of nicotinic receptors makes the striatum a potential target for nicotine. In addition, striatal nuclei are essential components of the reward/reinforcement pathway involved in addiction. The aim of this study was to explore the relationship between striatal nuclei (caudate, putamen and nucleus accumbens area) volumes and lifetime smoking in a large community-based sample of ‘young–old’ individuals. Brain volumes were measured using a semi-automated method in 315 participants aged 64–70 years who were selected from a larger randomly sampled cohort and who consented to a magnetic resonance imaging scan. Multiple regression analysis was used to assess the relationship between striatal volumes and cigarette smoking measures while controlling for age, sex, intracranial and total brain volumes and general physical and mental health measures. Greater lifetime use of cigarettes (measured in pack-years) was associated with smaller left nucleus accumbens area volume (P = 0.018) and larger left putamen volume (P = 0.025). Greater putaminal volume was also associated with a lower age at smoking initiation (P = 0.004). In this generally healthy cohort, lifetime use of cigarettes is significantly associated with striatal volume measures. These changes could indicate predisposing factors for nicotine addiction, or an effect of chronic nicotine exposure or a combination of both.NHMRC (National Health and Medical Research Council of Australia

DRD4-exonIII-VNTR Moderates the Effect of Childhood Adversities on Emotional Resilience in Young-Adults

Most individuals successfully maintain psychological well-being even when exposed to trauma or adversity. Emotional resilience or the ability to thrive in the face of adversity is determined by complex interactions between genetic makeup, previous exposure to stress, personality, coping style, availability of social support, etc. Recent studies have demonstrated that childhood trauma diminishes resilience in adults and affects mental health. The Dopamine receptor D4 (DRD4) exon III variable number tandem repeat (VNTR) polymorphism was reported to moderate the impact of adverse childhood environment on behaviour, mood and other health-related outcomes. In this study we investigated whether DRD4-exIII-VNTR genotype moderates the effect of childhood adversities (CA) on resilience. In a representative population sample (n = 1148) aged 30–34 years, we observed an interactive effect of DRD4 genotype and CA (β = 0.132; p = 0.003) on resilience despite no main effect of the genotype when effects of age, gender and education were controlled for. The 7-repeat allele appears to protect against the adverse effect of CA since the decline in resilience associated with increased adversity was evident only in individuals without the 7-repeat allele. Resilience was also significantly associated with approach-/avoidance-related personality measures (behavioural inhibition/activation system; BIS/BAS) measures and an interactive effect of DRD4-exIII-VNTR genotype and CA on BAS was observed. Hence it is possible that approach-related personality traits could be mediating the effect of the DRD4 gene and childhood environment interaction on resilience such that when stressors are present, the 7-repeat allele influences the development of personality in a way that provides protection against adverse outcomes

Jet modification in absence of QGP-medium: the role of multiparton interactions and color reconnection

Recent studies of high-multiplicity events in small collision systems (proton-proton and proton-lead) have drawn research interest towards the possibility of the formation of partonic medium in such systems. One of the important consequences of the formation of dense partonic medium is quenching of high-momentum final-state particles resulting in several experimental observations such as suppression in nuclear modification factor $R_{\rm AA}$, modification of jet shape observable $\rho(r)$, etc. In this work, we study $\rho(r)$ for inclusive charged-particle jets in proton-proton (pp) collisions at $\sqrt{s}$ = 13 TeV using PYTHIA 8 Monash 2013 Monte Carlo simulation and show that the color reconnection (CR) and multiparton interaction (MPI) mechanisms in PYTHIA 8 can also lead to a significant amount of modification of $\rho(r)$ in high-multiplicity events compared to minimum bias events for 10 $<p_{\rm T,\,jet}^{\rm ch}<$ 20 GeV/$c$. The enhanced gluonic contribution in high-multiplicity events is also found to play a role in the observed modification of $\rho(r)$. We notice a direct connection between the number of MPIs and the amount of modification in $\rho(r)$ - the larger the number of MPIs, the larger the amount of modification of $\rho(r)$.Comment: 14 pages, 7 figures, 1 tabl

Late Onset Alzheimer's Disease Risk Variants in Cognitive Decline: The PATH Through Life Study

Recent genome wide association studies have identified a number of single nucleotide polymorphisms associated with late onset Alzheimer’s disease (LOAD). We examined the associations of 24 LOAD risk loci, individually and collectively as a genetic risk score, with cognitive function. We used data from 1,626 non-demented older Australians of European ancestry who were examined up to four times over 12 years on tests assessing episodic memory, working memory, vocabulary, and information processing speed. Linear mixed models were generated to examine associations between genetic factors and cognitive performance. Twelve SNPs were significantly associated with baseline cognitive performance (ABCA7, MS4A4E, SORL1), linear rate of change (APOE, ABCA7, INPP5D, ZCWPW1, CELF1), or quadratic rate of change (APOE, CLU, EPHA1, HLA-DRB5, INPP5D, FERMT2). In addition, a weighted genetic risk score was associated with linear rate of change in episodic memory and information processing speed. Our results suggest that a minority of AD related SNPs may be associated with non-clinical cognitive decline. Further research is required to verify these results and to examine the effect of preclinical AD in genetic association studies of cognitive decline. The identification of LOAD risk loci associated with non-clinical cognitive performance may help in screening for individuals at greater risk of cognitive decline.The study was supported by the National Health and Medical Research Council (NHMRC) grants 973302, 179805, and 1002160, the NHMRC Dementia Collaborative Research Centres Grant CE110001029 from the Australian Research Council. DD is funded by NHMRC Project Grant No. 1043256. KJA is funded by NHMRC Research Fellowship No. 1002560

An insight into the molecular basis of salt tolerance of L-myo-inositol 1-P synthase (PcINO1) from porteresia coarctata (Roxb.) tateoka, a halophytic wild rice1

The molecular basis of salt tolerance of L-myo-inositol 1-P synthase (MIPS; EC 5.5.1.4) from Porteresia coarctata (Roxb.) Tateoka (PcINO1, AF412340) earlier reported from this laboratory, has been analyzed by in vitro mutant and hybrid generation and subsequent biochemical and biophysical studies of the recombinant proteins. A 37-amino acid stretch between Trp-174 and Ser-210 has been confirmed as the salt-tolerance determinant domain in PcINO1 both by loss or gain of salt tolerance by either deletion or by addition to salt-sensitive MIPS(s) of Oryza (OsINO1) and Brassica juncea (BjINO1). This was further verified by growth analysis under salt environment of Schizosaccharomyces pombe transformed with the various gene constructs and studies on the differential behavior of mutant and wild proteins by Trp fluorescence, aggregation, and circular dichroism spectra in the presence of salt. 4,4'-Dianilino-1,1'-binaphthyl-5,5-disulfonic acid binding experiments revealed a lower hydrophobic surface on PcINO1 than OsINO1, contributed by this 37-amino acid stretch explaining the differential behavior of OsINO1 and PcINO1 both with respect to their enzymatic functions and thermodynamic stability in high salt environment. Detailed amino acid sequence comparison and modeling studies revealed the interposition of polar and charged residues and a well-connected hydrogen-bonding network formed by Ser and Thr in this stretch of PcINO1. On the contrary, hydrophobic residues clustered in two continuous stretches in the corresponding region of OsINO1 form a strong hydrophobic patch on the surface. It is conceivable that salt-tolerant MIPS proteins may be designed out of the salt-sensitive plant MIPS proteins by replacement of the corresponding amino acid stretch by the designated 37-amino acid stretch of PcINO1

A Novel Membrane Protein-Specific Serine/Threonine Kinase: Tissue Distribution and Role in Sperm Maturation

Our recent studies have described for the first time the purification of an ectoprotein kinase to apparent homogeneity using caprine sperm as the model. Purified ectokinase (CIK) is a novel membrane protein-specific kinase that phosphorylates serine and threonine residues of ectophosphoproteins. This study, using ELISA based on ecto-CIK antibody demonstrates that ecto-CIK level is remarkably higher in the sperm membrane than in the cytosol. The epididymal sperm maturational event as well as sperm vertical velocity is associated with a significant increase in the ecto-CIK level. Ecto-CIK, the membrane protein-specific kinase, is also present in all the tissues tested and is predominantly localized in the cell membrane. Ubiquitous localization of the novel kinase on the mammalian cell membrane suggests that the kinase may play pivotal role in gamete as well as somatic cell regulation by modulating membrane biology through serine/threonine phosphorylation of specific membrane proteins located in the ectodomains