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Levels of serotonin in the body are regulated by the serotonin transporters (SERT), which are predominantly located on the presynaptic terminals of serotonin-containing neurons. Alterations in the density of SERT have been implicated in the pathophysiology of many neuropsychiatric disorders.
To evaluate 123-I mZIENT (2(S)-[(S)-2b-carbomethoxy-3b-[3′-((Z)-2-iodoethenyl)phenyl]nortropane), a novel radiopharmaceutical for imaging SERT. The bio-distribution of the radiopharmaceutical in humans was investigated and dosimetry performed.
The study includes three healthy volunteers and three patients receiving SSRIs. Whole body images obtained on a gamma camera at 10 minutes, 1, 2, 3, 6, 24 and 48 hours post administration. Dosimetry was performed. ROIs were drawn over the brain, heart, kidneys, liver, lungs, salivary glands, spleen, thyroid and intestines. Blood was sampled at 5, 15, & 30 minutes and 1, 2, 3, 6, 24 and 48 hours post administration. Urine was collected at 1, 2, 3, 4, 6, 24 and 48 hours. Brain SPECT images were obtained using a neuroSPECT scanner at 4 hours, evaluated visually and analysed using ROI analysis.
High quality SPECT images can be obtained after 100–150 MBq 123-ImZEINT. Regional brain uptake was observed in midbrain and basal ganglia in healthy volunteers, consistent with the known distribution of SERT. Biodistribution images demonstrated highest uptake in the lungs, brain, liver and intestines. The effective dose was within range of other commonly used ligands and is acceptable for clinical imaging.
123-ImZIENT is a promising agent for imaging SERT in humans with acceptable dosimetry.
Although neuroimaging studies suggest brain regional abnormalities in depressive disorders, it remains unclear whether abnormalities are present at illness onset or reflect disease progression.
We hypothesized that cerebral variations were present in adolescents with subthreshold depression known to be at high risk for later full-blown depression.
We examined brain structural and diffusion-weighted magnetic resonance images of adolescents with subthreshold depression.
The participants were extracted from the European IMAGEN study cohort of healthy adolescents recruited at age 14. Subthreshold depression was defined as a distinct period of abnormally depressed or irritable mood, or loss of interest, plus two or more depressive symptoms but without diagnosis of Major Depressive Episode. Comparisons were performed between adolescents meeting these criteria and control adolescents within the T1-weighted imaging modality (118 and 475 adolescents respectively) using voxel-based morphometry and the diffusion tensor imaging modality (89 ad 422 adolescents respectively) using tract-based spatial statistics. Whole brain analyses were performed with a statistical threshold set to p< 0.05 corrected for multiple comparisons.
Compared with controls, adolescents with subthreshold depression had smaller gray matter volume in caudate nuclei, medial frontal and cingulate cortices; smaller white matter volume in anterior limb of internal capsules, left forceps minor and right cingulum; and lower fractional anisotropy and higher radial diffusivity in the genu of corpus callosum.
The findings suggest that adolescents with subthreshold depression have volumetric and microstructural gray and white matter changes in the emotion regulation frontal-striatal-limbic network.
A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
In recent years, researchers have been working towards creating a standard conceptual framework of food parenting. To understand how parents’ reports correspond with the proposed model, the current study examined parents’ reports of their feeding behaviours in the context of a newly established framework of food parenting.
Cross-sectional, with a two-week follow-up for a subset of the sample. Participants completed a quantitative and qualitative survey to assess food parenting. The survey included items from common food parenting instruments to measure the constructs posited in the framework. Exploratory factor analyses were conducted to ascertain which items related most closely to one another and factors were mapped on to existing constructs.
Parents of children aged 2·5–7 years (n 496). Of these, 122 completed a two-week follow-up.
Analyses revealed eleven aspects of Structure (monitoring; distraction; family presence; meal/snack schedule; unstructured practices; healthy/unhealthy food availability; food preparation; healthy/unhealthy modelling; rules), ten aspects of Coercive Control (pressure to eat; using food to control emotions; food incentives to eat; food incentives to behave; non-food incentives to eat; restriction for health/weight; covert restriction; clean plate; harsh coercion) and seven aspects of Autonomy Promotion (praise; encouragement; nutrition education; child involvement; negotiation; responsive feeding; repeated offering). Content validity, assessed via parents’ open-ended explanations of their responses, was high, and test–retest reliability was moderate to high. Structure and Autonomy Promoting food parenting were highly positively correlated.
In general, parents’ responses provided support for the model, but suggested some amendments and refinements.
Previous research has shown that problematic parent–child, peer, and romantic partner relationships are associated with an increased likelihood for major depressive disorder (MDD). Less research has evaluated the developmental unfolding of how these interpersonal relationship features are both an antecedent versus a consequence of MDD symptoms from adolescence through young adulthood. These gaps were evaluated using a large community sample (N = 1,127; 54% female, 96% white) via a developmental cascade model. Results showed support for significant antecedent effects, as greater parent–child relationship problems at ages 11 and 17 predicted rank-order increases in MDD symptoms at ages 14 and 20. Supporting a developmental cascade of problematic social relationships, greater parent–child relationship problems at ages 11 and 14 also predicted greater subsequent rank-order increases in antisocial peer affiliation at ages 14 and 17. Greater affiliation to antisocial peers at age 20 predicted greater rank-order increases in romantic relationship problems at age 24, which in turn predicted greater MDD symptoms at age 29. Cross-effects were generally small (βs ≤ .16), illustrating other factors may be relevant to the development or consequences of MDD. Nonetheless, findings support the importance of efforts to strengthen social support networks to offset risk as well as potentially treat depression.
Diet manipulation and genetic selection are two important mitigation strategies for reducing enteric methane (CH4) emissions from ruminant livestock. The aim of this study was to assess whether the diurnal pattern of CH4 emissions from individual dairy cows changes over time when cows are fed on diets varying in forage composition. Emissions of CH4 from 36 cows were measured during milking in an automatic (robotic) milking station in three consecutive feeding periods, for a total of 84 days. In Periods 1 and 2, the 36 cows were fed a high-forage partial mixed ration (PMR) containing 75% forage, with either a high grass silage or high maize silage content. In Period 3, cows were fed a commercial PMR containing 69% forage. Cows were offered PMR ad libitum plus concentrates during milking and CH4 emitted by individual cows was sampled during 8662 milkings. A linear mixed model was used to assess differences among cows, feeding periods and time of day. Considerable variation was observed among cows in daily mean and diurnal patterns of CH4 emissions. On average, cows produced less CH4 when fed on the commercial PMR in feeding Period 3 than when the same cows were fed on high-forage diets in feeding Periods 1 and 2. The average diurnal pattern for CH4 emissions did not significantly change between feeding periods and as lactation progressed. Emissions of CH4 were positively associated with dry matter (DM) intake and forage DM intake. It is concluded that if the management of feed allocation remains constant then the diurnal pattern of CH4 emissions from dairy cows will not necessarily alter over time. A change in diet composition may bring about an increase or decrease in absolute emissions over a 24-h period without significantly changing the diurnal pattern unless management of feed allocation changes. These findings are important for CH4 monitoring techniques that involve taking measurements over short periods within a day rather than complete 24-h observations.
Children with poor mental health often struggle at school. The relationship between childhood psychiatric disorder and exclusion from school has not been frequently studied, but both are associated with poor adult outcomes. We undertook a secondary analysis of the British Child and Adolescent Mental Health Surveys from 2004 and its follow-up in 2007 to explore the relationship between exclusion from school and psychopathology. We predicted poorer mental health among those excluded.
Psychopathology was measured using the Strengths and Difficulties Questionnaire, while psychiatric disorder was assessed using the Development and Well-Being Assessment and applying Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV) criteria. Exclusion from school and socio-demographic characteristics were reported by parents. Multi-variable regression models were used to examine the impact of individual factors on exclusion from school or psychological distress.
Exclusion from school was commoner among boys, secondary school pupils and those living in socio-economically deprived circumstances. Poor general health and learning disability among children and poor parental mental health were also associated with exclusion. There were consistently high levels of psychological distress among those who had experienced exclusion at baseline and follow-up.
We detected a bi-directional association between psychological distress and exclusion. Efforts to identify and support children who struggle with school may therefore prevent both future exclusion and future psychiatric disorder.
The identification of the factors that influence the persistence of psychiatric disorder may assist practitioners to focus on young people who are particularly prone to poor outcomes, but population-based samples of sufficient size are rare.
This secondary analysis combined data from two large, population-based cross-sectional surveys in Great Britain (1999 and 2004) and their respective follow-ups (2002 and 2007), to study homotypic persistence among the 998 school-age children with psychiatric disorder at baseline. Psychiatric disorder was measured using the Development and Well-Being Assessment applying DSM-IV criteria. Factors relating to the child, family, and the severity and type of psychopathology at baseline were analysed using logistic regression.
Approximately 50% of children with at least one psychiatric disorder were assigned the same diagnostic grouping at 3-year follow-up. Persistent attention-deficit/hyperactivity disorder and anxiety were predicted by poor peer relationship scores. Persistent conduct disorder was predicted by intellectual disability, rented housing, large family size, poor family function and by severer baseline psychopathology scores.
Homotypic persistence was predicted by different factors for different groups of psychiatric disorders. Experimental research in clinical samples should explore whether these factors also influence response to interventions.
Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression.
We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery–Asberg Depression Rating Scale – Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point.
The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period.
The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.
Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents.
Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography.
Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups.
High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.
Methane (CH4) emissions by dairy cows vary with feed intake and diet composition. Even when fed on the same diet at the same intake, however, variation between cows in CH4 emissions can be substantial. The extent of variation in CH4 emissions among dairy cows on commercial farms is unknown, but developments in methodology now permit quantification of CH4 emissions by individual cows under commercial conditions. The aim of this research was to assess variation among cows in emissions of eructed CH4 during milking on commercial dairy farms. Enteric CH4 emissions from 1964 individual cows across 21 farms were measured for at least 7 days/cow using CH4 analysers at robotic milking stations. Cows were predominantly of Holstein Friesian breed and remained on the same feeding systems during sampling. Effects of explanatory variables on average CH4 emissions per individual cow were assessed by fitting a linear mixed model. Significant effects were found for week of lactation, daily milk yield and farm. The effect of milk yield on CH4 emissions varied among farms. Considerable variation in CH4 emissions was observed among cows after adjusting for fixed and random effects, with the CV ranging from 22% to 67% within farms. This study confirms that enteric CH4 emissions vary among cows on commercial farms, suggesting that there is considerable scope for selecting individual cows and management systems with reduced emissions.
Turkey has the youngest population in Europe with about 25 million people aged below 19 years and Turkish-speaking people comprise the biggest migrant group in Europe with 2.5 million people dispersed in different countries, but conducting epidemiologic surveys on Turkish people is challenging due to the lack of a suitable diagnostic tool. The Development and Well-Being Assessment (DAWBA) is one of the most widely used diagnostic interviews in child and adolescent psychiatry. In this study, we aimed at translating the DAWBA into Turkish and then examined its validity and reliability.
The validity of the Turkish version was examined in clinical (n = 50) and community (n = 104) samples. The interrater reliability was also evaluated on 20 cases.
The translation method used in the study achieved semantic, conceptual, content, technical, item and criterion equivalence between the Turkish and original forms. The validity of the Turkish DAWBA was good or excellent for different diagnostic categories (κ: 0.43–0.84); the interrater reliability was also excellent (κ: 0.85–1).
The Turkish DAWBA may be useful for future prevalence studies in Turkey. European clinicians and researchers who work with Turkish-speaking families can use the online Turkish DAWBA to gather structured information from Turkish-speaking informants and review the answers in their own language.