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Epistatic effects between gene variants of 5-HTTLPR (L=long, S=short), MAOA-VNTR (L=long, S=short), and BDNF Val/Met have been found with regard to behaviour in experimental animals as well as indicated in human samples in relation to neuroticism and depression. In the present study we studied epistatic effects of the above gene variations in an interaction with environmental adversity on adolescent criminality.
Family maltreatment, sexual abuse and criminality were measured by self-reports in a Swedish adolescent population-based sample (n=1819). Genomic DNA was isolated from saliva and used for genotyping of the BDNF, the 5-HTT and MAOA genes.
BDNF genotype showed a main effect on adolescent criminality. BDNF also showed a two-way interaction with 5- HTT and Family maltreatment. 5HTT showed two-way interactions with MAOA and Family maltreatment. MAOA also showed a two-way interaction with Family maltreatment. Significant three-way interactions were found for; BDNF-5-HTT-Family maltreatment; BDNF-MAOA-Family maltreatment; BDNF-MAOA-Sexual abuse; and 5HTT-MAOA-Family maltreatment. Significant four-way (G*G*G*E) interactions were found for BDNF-5-HTT-MAOA-Family maltreatment and BDNF-5-HTTMAOA- Sexual abuse, respectively.
Boys showed a stronger effect of environmental adversity compared to girls. However, there were no significant sex-gene interactions. Furthermore, the two most genotypically divergent groups, according to expression levels, showed the highest criminality scores (MAOA-LL + 5-HTT-LL + BDNF Val-Val vs. MAOA S/LS + 5-HTT-S/LS + BDNF Val-Met/Met-Met), when exposed to environmental adversity.
There are significant epistatic effects between 5-HTT, MAOA and BDNF genotypes and environmental adversity for criminal behavior. Two distinct “types” can be recognized with regard to genotype.
The candidate gene-environment interaction (cG × E) research field in psychiatry has traditionally been dominated by the diathesis–stress framework, where certain genotypes are assumed to confer increased risk for adverse outcomes in a stressful environment. In later years, theories of differential susceptibility or biological sensitivity have been presented, suggesting that cGs that interact with environmental events do not exclusively confer a risk for behavioural or psychiatric disorders but rather seem to alter the sensitivity to both positive and negative environmental influences.
The present study investigates the susceptibility properties of the 5HTTLPR gene in relation to depressive symptoms and delinquency in two separate adolescent community samples: n = 1457, collected in 2006; and n = 191, collected in 2001.
Two-, three- and four-way interactions between the 5HTTLPR, positive family environment, negative family environment, and sex were found in relation to both depressive symptoms and delinquency. However, the susceptibility properties of the 5HTTLPR gene were distinctly less pronounced in relation to depressive symptoms.
If the assumption that the 5HTTLPR gene induces differential susceptibility to both positive and negative environmental influences is correct, the previous failures to measure and control for positive environmental factors might be a possible explanation for former inconsistent findings within the research field.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Adolescence is a period of increasing demands in independent social functioning where parenting style may have an impact on social anxiety. A context-dependent effect of oxytocin on human social behavior has been suggested, however research on the gene coding for oxytocin (OXT) has mostly been reported without considering contextual factors.
This study investigated interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents.
The study group consisted of 1359 adolescents. Two single nucleotide polymorphisms located near OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires.
Significant joint effects in line with the differential susceptibility framework were observed for rs4813625 with parenting style. The levels of social anxiety among C allele carriers were conditional on the level of supportive parenting style whereas homozygote G carriers’ levels of social anxiety were unaffected by supportive parenting style. The nature of the interactions between rs2770378 and parenting style was in line with the diatheses-stress model. However, associations of rs2770378 and parenting style with social anxiety became nonsignificant in nonlinear models.
The study provides preliminary evidence for a modifying effect of supportive parenting style on the relationship between rs4813625 and social anxiety symptoms in adolescents, independent of sex. The findings may be interpreted from the perspective of the social salience hypotheses of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe–safe social context dimension.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
To understand parent and child relations researchers have used three bipolar dimensions (warmth and rejection, structure and chaos, autonomy support, and coercion). These dimensions are not necessarily bipolar but could work as unipolar dimensions. The Parents as Social Context Questionnaire (PASCQ) has been used in parenting studies but needs to be further investigated in different populations to ensure the validity and reliability of the scale. The present study explored the structures of and provided evidence regarding validity and reliability of the PASCQ. This study aimed to examine whether the Swedish version of the PASCQ is a reliable questionnaire when measuring the six dimension of parenting. The participants consisted of 1634 adolescents (58.6% females) born in 1997 (52%) and 1999. Factor analyses were conducted to investigate whether the Swedish scale generated six dimensions. Regression analyses were conducted to measure the different factors and spearman correlations between dimensions were conducted. The analysis indicates that the PASCQ consists of five dimensions, however rejection (negative) and warmth (positive) loaded on the same dimension and are referred to as two separate factors, making the questionnaire consistent of six dimensions. All items had a factor score >0.4 and loaded in a coherent manner. Therefore, the PASCQ can be used to assess six dimensions of parenting styles. The PASCQ Swedish version can be used as a measure of parenting styles in a Swedish population. Further research is necessary to evaluate the validity and reliability in other samples as well.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We re-analyzed OJ287 in 120 Very Long Baseline Array (VLBA, MOJAVE) observations (at 15 GHz) covering the time span between Apr. 1995 and Apr. 2017. We find that the radio jet motion over the sky is consistent with a precessing and nutating jet source. The variability of the radio flux-density can be explained by Doppler beaming due to a change in the viewing angle. We suggest that part of the optical emission is due to synchrotron emission related to the jet radiation. We find a strikingly similar scaling for the timescales for precession and nutation as indicated for SS433 with a factor of roughly 50 times longer in OJ287.
Blazar OJ287 exhibits large thermal flares at least twice every 12 years. The times of these flares have been predicted successfully using the model of a quasi-Keplerian eccentric black hole binary where the secondary impacts the accretion disk of the primary, creating the thermal flares. New measurements of the historical light curve have been combined with the observations of the 2015 November/December flare to identify the impact record since year 1886, and to constrain the orbit of the binary. The orbital solution shows that the binary period, now 12.062 years, is decreasing at the rate of 36 days per century. This corresponds to an energy loss to gravitational waves that is 6.5 ± 4 % less than the rate predicted by the standard quadrupolar gravitational wave (GW) emission. We show that the difference is due to higher order gravitational radiation reaction terms that include the dominant order tail contributions.
In unipolar depressed patients participating in trials on antidepressants, we investigated if illness characteristics at baseline could predict conversion to bipolar disorder.
A long-term register-based follow-up study of 290 unipolar depressed patients with a mean age of 50.8 years (SD = 11.9) participating in three randomized trials on antidepressants conducted in the period 1985–1994. The independent effects of explanatory variables were examined by applying Cox regression analyses.
The overall risk of conversion was 20.7%, with a mean follow-up time of 15.2 years per patient. The risk of conversion was associated with an increasing number of previous depressive episodes at baseline, [HR 1.18, 95% CI (1.10–1.26)]. No association with gender, age, age at first depressive episode, duration of baseline episode, subtype of depression or any of the investigated HAM-D subscales included was found.
The patients were followed-up through the Danish Psychiatric Central Research Register, which resulted in inherent limitations such as possible misclassification of outcome.
In a sample of middle-aged hospitalized unipolar depressed patients participating in trials on antidepressants, the risk of conversion was associated with the number of previous depressive episodes. Therefore, this study emphasizes that unipolar depressed patients experiencing a relatively high number of recurrences should be followed more closely, or at least be informed about the possible increased risk of conversion.
Obsessive–compulsive disorder (OCD) is a chronic psychiatric disorder leading to considerable distress and disability. Therapies are effective in a majority of paediatric patients, however, many only get partial response. It is therefore important to study the underlying pathophysiology of the disorder.
1H magnetic resonance spectroscopy (MRS) was used to study the concentration of brain metabolites in four different locations (cingulate gyrus and sulcus, occipital cortex, thalamus and right caudate nucleus). Treatment-naive children and adolescents with OCD (13 subjects) were compared with a group of healthy age- and gender-matched subjects (11 subjects). Multivariate analyses were performed on the concentration values.
No separation between controls and patients was found. However, a correlation between metabolite concentrations and symptom severity as measured with the Children’s Yale-Brown Obsessive–Compulsive Scale (CY-BOCS) was found. Strongest was the correlation with the CY-BOCS obsession subscore and aspartate and choline in the caudate nucleus (positively correlated with obsessions), lipids at 2 and 0.9 ppm in thalamus, and occipital glutamate+glutamine, N-acetylaspartate and myo-inosytol (negatively correlated with obsessions).
The observed correlations between 1H MRS and CY-BOCS in treatment-naive patients further supports an occipital involvement in OCD. The results are consistent with our previous study on adult OCD patients. The 1H MRS data were not supportive of a separation between the patient and control groups.
We present the most up-to-date and complete multi-wavelength correlation analysis on luminosity properties of TeV BL Lacs. Correlation function (power law or linear) parameters are calculated based on linear regression method. Using the lower energy luminosities of a sample of 182 non-TeV BL Lacs and the generated functions, minimum level of VHE gamma-ray emission was calculated for each non-TeV BL Lacs. This multi wavelength prediction method gives us a list of best candidates to be observed with current generation of Imaging Air Cherenkov Telescopes.
The blazar QSO B0218+357 is the first gravitationally lensed blazar detected in the very high energy (VHE, E > 100 GeV) gamma-ray spectral range (Ahnen et al. 2016). It is gravitationally lensed by the intervening galaxy B0218+357G (zl = 0.68466 ± 0.00004, Carilli et al. 1993), which splits the blazar emission into two components, spatially indistinguishable by gamma-ray instruments, but separated by a 10-12 days delay. In July 2014 a flare from QSO B0218+357 was observed by the Fermi-LAT (Large Area Telescope, Atwood et al. 2009, Ackermann et al. 2012), and followed-up by the MAGIC (Major Atmospheric Gamma Imaging Cherenkov) telescopes, a stereoscopic system of two 17m Imaging Atmospheric Cherenkov Telescopes located on La Palma, Canary Islands (Aleksić et al. 2016a, 2016b), during the expected time of arrival of the delayed component of the emission. MAGIC could not observe the leading image due to the Full Moon. The MAGIC and Fermi-LAT observations were accompanied by optical data from KVA telescope at La Palma, and X-ray observations by Swift-XRT (Fig. 1 left). Variability in gamma-rays was of the order of one day, while no variability correlated with gamma-rays was observed at lower energies. The flux ratio of the leading to trailing image in HE gamma-rays was larger than in the flare of QSO B0218+357 observed by Fermi-LAT in 2012 (Cheung et al. 2014). Changes in the observed flux ratio can be caused by gravitational microlensing on individual stars in the host galaxy (Neronov et al. 2015), or by other compact objects like for ex. clumps in giant molecular clouds (Sitarek & Bednarek 2016).
Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation.
A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed.
The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow.
Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression.
Gametocytes are the specialized form of Plasmodium parasites that are responsible for human-to-mosquito transmission of malaria. Transmission of gametocytes is highly effective, but represents a biomass bottleneck for the parasite that has stimulated interest in strategies targeting the transmission stages separately from those responsible for clinical disease. Studying targets of naturally acquired immunity against transmission-stage parasites may reveal opportunities for novel transmission reducing interventions, particularly the development of a transmission blocking vaccine (TBV). In this review, we summarize the current knowledge on immunity against the transmission stages of Plasmodium. This includes immune responses against epitopes on the gametocyte-infected erythrocyte surface during gametocyte development, as well as epitopes present upon gametocyte activation in the mosquito midgut. We present an analysis of historical data on transmission reducing immunity (TRI), as analysed in mosquito feeding assays, and its correlation with natural recognition of sexual stage specific proteins Pfs48/45 and Pfs230. Although high antibody titres towards either one of these proteins is associated with TRI, the presence of additional, novel targets is anticipated. In conclusion, the identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocyte stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.
In this paper the feasibility to extract the proportion of pigs located in different areas of a pig pen by advanced image analysis technique is explored and discussed for possible applications. For example, pigs generally locate themselves in the wet dunging area at high ambient temperatures in order to avoid heat stress, as wetting the body surface is the major path to dissipate the heat by evaporation. Thus, the portion of pigs in the dunging area and resting area, respectively, could be used as an indicator of failure of controlling the climate in the pig environment as pigs are not supposed to rest in the dunging area. The computer vision methodology utilizes a learning based segmentation approach using several features extracted from the image. The learning based approach applied is based on extended state-of-the-art features in combination with a structured prediction framework based on a logistic regression solver using elastic net regularization. In addition, the method is able to produce a probability per pixel rather than form a hard decision. This overcomes some of the limitations found in a setup using grey-scale information only. The pig pen is a difficult imaging environment because of challenging lighting conditions like shadows, poor lighting and poor contrast between pig and background. In order to test practical conditions, a pen containing nine young pigs was filmed from a top view perspective by an Axis M3006 camera with a resolution of 640×480 in three, 10-min sessions under different lighting conditions. The results indicate that a learning based method improves, in comparison with greyscale methods, the possibility to reliable identify proportions of pigs in different areas of the pen. Pigs with a changed behaviour (location) in the pen may indicate changed climate conditions. Changed individual behaviour may also indicate inferior health or acute illness.
Attentional impairment is a core cognitive feature of major depressive disorder (MDD) and bipolar disorder (BD). However, little is known of the characteristics of response time (RT) distributions from attentional tasks. This is crucial to furthering our understanding of the profile and extent of cognitive intra-individual variability (IIV) in mood disorders.
A computerized sustained attention task was administered to 138 healthy controls and 158 patients with a mood disorder: 86 euthymic BD, 33 depressed BD and 39 medication-free MDD patients. Measures of IIV, including individual standard deviation (iSD) and coefficient of variation (CoV), were derived for each participant. Ex-Gaussian (and Vincentile) analyses were used to characterize the RT distributions into three components: mu and sigma (mean and standard deviation of the Gaussian portion of the distribution) and tau (the ‘slow tail’ of the distribution).
Compared with healthy controls, iSD was increased significantly in all patient samples. Due to minimal changes in average RT, CoV was only increased significantly in BD depressed patients. Ex-Gaussian modelling indicated a significant increase in tau in euthymic BD [Cohen's d = 0.39, 95% confidence interval (CI) 0.09–0.69, p = 0.011], and both sigma (d = 0.57, 95% CI 0.07–1.05, p = 0.025) and tau (d = 1.14, 95% CI 0.60–1.64, p < 0.0001) in depressed BD. The mu parameter did not differ from controls.
Increased cognitive variability may be a core feature of mood disorders. This is the first demonstration of differences in attentional RT distribution parameters between MDD and BD, and BD depression and euthymia. These data highlight the utility of applying measures of IIV to characterize neurocognitive variability and the great potential for future application.
We explore the connection between the black hole mass and its relativistic jet for a sample of radio-loud AGN (z < 1), in which the relativistic jet parameters are well estimated by means of long term monitoring with the 14m Metsähovi millimeter wave telescope and the Very Long Base-line Array (VLBA). NIR host galaxy images taken with the NOTCam on the Nordic Optical Telescope (NOT) and retrieved from the 2MASS all-sky survey allowed us to perform a detailed surface brightness decomposition of the host galaxies in our sample and to estimate reliable black hole masses via their bulge luminosities. We present early results on the correlations between black hole mass and the relativistic jet parameters. Our preliminary results suggest that the more massive the black hole is, the faster and the more luminous jet it produces.
We examined whether conversion to dementia can be predicted by self-reported olfactory impairment and/or by an inability to identify odors. Common forms of dementia involve an impaired sense of smell, and poor olfactory performance predicts cognitive decline among the elderly. We followed a sample of 1529 participants, who were within a normal range of overall cognitive function at baseline, over a 10-year period during which 159 were classified as having a dementia disorder. Dementia conversion was predicted from demographic variables, Mini-Mental State Examination score, and olfactory assessments. Self-reported olfactory impairment emerged as an independent predictor of dementia. After adjusting for effects of other predictors, individuals who rated their olfactory sensitivity as “worse than normal” were more likely to convert to dementia than those who reported normal olfactory sensitivity (odds ratio [OR] = 2.17; 95% confidence interval [CI] [1.40, 3.37]). Additionally, low scores on an odor identification test also predicted conversion to dementia (OR per 1 point increase = 0.89; 95% CI [0.81, 0.98]), but these two effects were additive. We suggest that assessing subjective olfactory complaints might supplement other assessments when evaluating the risk of conversion to dementia. Future studies should investigate which combination of olfactory assessments is most useful in predicting dementia conversion. (JINS, 2014, 20, 1–9)
This study examines if lactase non-persistent (LNP) children and adolescents differ from those who are lactase persistent (LP) as regards milk avoidance and Ca intake. We also studied potential differences in anthropometric features related to obesity, and examined if milk avoidance is associated with lactase-persistence status. Additionally, we aimed to determine if heterozygous subjects showed an intermediary phenotype as regards Ca intake. Furthermore, we tested if LP and LNP influence vitamin D intake. The European Youth Heart Study is an ongoing international, multi-centre cohort study primarily designed to address CVD risk factors. Children (n 298, mean age 9·6 years) and adolescents (n 386, mean age 15·6 years) belonging to the Swedish part of the European Youth Heart Study were genotyped for the LCT-13910 C > T polymorphism. Mendelian randomisation was used. Milk avoidance was significantly more common in LNP adolescents (OR 3·2; 95% CI 1·5, 7·3). LP subjects had higher milk consumption (P < 0·001). Accordingly, energy consumption derived from milk and Ca intake was lower in LNP (P < 0·05 and P < 0·001, respectively). Heterozygous subjects did not show an intermediary phenotype concerning milk consumption. LP or LNP status did not affect vitamin D intake or anthropometric variables. LNP in children and adolescents is associated with reduced intake of milk and some milk-product-related nutritional components, in particular Ca. This reduced intake did not affect the studied anthropometric variables, indicators of body fat or estimated vitamin D intake. However, independently of genotype, age and sex, daily vitamin D intake was below the recommended intakes. Milk avoidance among adolescents but not children was associated with LNP.