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In the UK, broiler chickens are normally slaughtered at about six weeks of age when they weigh approximately 2.2 kg; this contrasts with the growth of an ‘unimproved’ traditional strain of bird such as a White Sussex, which would weigh about 800 g at the same age. Lameness, characterised by abnormal gait, posture and impaired walking ability, can be prevalent in these rapidly growing birds and has been highlighted as a major welfare concern. It is during the later stages of rearing, when the bird is becoming heavy and may be achieving weight gains of over 50 g per day, that lameness begins to have an economic and welfare impact on the flock and to compromise the behaviour of large numbers of birds. A study was carried out to identify potential differences in the expression of genes between groups of lame and normal broiler chickens using subtraction hybridisation. The first group comprised lame birds with measurable gait abnormalities, and the second group comprised sound (not lame) birds. Both populations came from within the same flock. After extraction of mRNA and creation of cDNA, subtractive hybridisation was performed to eliminate genetic sequences common to both populations. The resultant DNA was separated and presented for sequence data analysis and comparison with a large sequence database. Some examples of the subtracted sequences detected are given, and the potential significance of these sequence differences at the individual and group level is discussed.
Some children are more affected by specific family environments than others, as a function of differences in their genetic make-up. However, longitudinal studies of genetic moderation of parenting effects during early childhood have not been conducted. We examined developmental profiles of child behavior problems between 18 months and age 8 in a longitudinal parent–offspring sample of 361 adopted children. In toddlerhood (18 months), observed structured parenting indexed parental guidance in service of task goals. Biological parent psychopathology served as an index of genetic influences on children’s behavior problems. Four profiles of child behavior problems were identified: low stable (11%), average stable (50%), higher stable (29%), and high increasing (11%). A multinominal logistic regression analysis indicated a genetically moderated effect of structured parenting, such that for children whose biological mother had higher psychopathology, the odds of the child being in the low stable group increased as structured parenting increased. Conversely, for children whose biological mother had lower psychopathology, the odds of being in the low stable group was reduced when structured parenting increased. Results suggest that increasing structured parenting is an effective strategy for children at higher genetic risk for psychopathology, but may be detrimental for those at lower genetic risk.
The behavioral issues experienced by individuals with Prader-Willi Syndrome (PWS) can be both surprising and overwhelming to clinicians and caregivers. Despite the distress and dysfunction posed by them, there are very few resources available to address these neuropsychiatric problems. This invaluable guidebook helps to identify and address the spectrum of behavioral issues faced by individuals with PWS. Written by a psychiatrist with unique expertise in the management of patients with this condition, this easy-to-read book explores practical details that will aid any clinician or caregiver. Chapters offer vivid case examples and clear guidance on both the behavioral and pharmacological management of issues such as anxiety, skin-picking, ADHD, disruptive behavior (including non-suicidal self-harm), mood disorders (including depression and bipolar disorder), and psychosis. Neuro-behavioral Manifestations of Prader-Willi Syndrome serves as an essential and practical companion for any caregiver or healthcare professional providing care to people with PWS.
A moderate to high alcohol consumption is associated with a lower risk of cardiovascular disease (CVD) mortality in comparison with low consumption. The mechanisms underlying this association are not clear and have been suggested to be caused by residual confounding. The main objective of this study was to separate the familial and individual risk for CVD mortality and all-cause mortality related to alcohol consumption. This will be done by estimating the risk for CVD mortality and all-cause mortality in twin pairs discordant for alcohol consumption.
Alcohol consumption was assessed at two time points using self-report questionnaires in the Norwegian Twin Registry. Data on CVD mortality was obtained from the Norwegian Cause of Death Registry. Exposure–outcome associations for all-cause mortality and mortality due to other causes than CVD were estimated for comparison.
Coming from a family with moderate to high alcohol consumption was protective against cardiovascular death (HR = 0.54, 95% CI 0.65–0.83). Moderate and high alcohol consumption levels were associated with a slightly increased risk of CVD mortality at the individual level (HR = 1.33, 95% CI 1.02–1.73). There was no association between alcohol consumption and all-cause mortality both at the familial nor at the individual level.
The protective association of moderate to high alcohol consumption with a lower risk of CVD mortality was accounted for by familial factors in this study of twins. Early life genetic and environmental familial factors may mask an absence of health effect of moderate to high alcohol consumption on cardiovascular mortality.
Previous research has shown that self-reports of the amount of social support are heritable. Using the Kessler perceived social support (KPSS) measure, we explored sex differences in the genetic and environmental contributions to individual differences. We did this separately for subscales that captured the perceived support from different members of the network (spouse, twin, children, parents, relatives, friends and confidant). Our sample comprised 7059 male, female and opposite-sex twin pairs aged 18−95 years from the Australian Twin Registry. We found tentative support for different genetic mechanisms in males and females for support from friends and the average KPSS score of all subscales, but otherwise, there are no sex differences. For each subscale alone, the additive genetic (A) and unique environment (E) effects were significant. By contrast, the covariation among the subscales was explained — in roughly equal parts — by A, E and the common environment, with effects of different support constellations plausibly accounting for the latter. A single genetic and common environment factor accounted for between half and three-quarters of the variance across the subscales in both males and females, suggesting little heterogeneity in the genetic and environmental etiology of the different support sources.
Anguillicoloides crassus is an invasive nematode parasite of the critically endangered European eel, Anguilla anguilla, and possibly one of the primary drivers of eel population collapse, impacting many features of eel physiology and life history. Early detection of the parasite is vital to limit the spread of A. crassus, to assess its potential impact on spawning biomass. However accurate diagnosis of infection could only be achieved via necropsy. To support eel fisheries management we developed a rapid, non-lethal, minimally invasive and in situ DNA-based method to infer the presence of the parasite in the swim bladder. Screening of 131 wild eels was undertaken between 2017 and 2019 in Ireland and UK to validate the procedure. DNA extractions and PCR were conducted using both a Qiagen Stool kit and in situ using Whatman qualitative filter paper No1 and a miniPCR DNA Discovery-System™. Primers were specifically designed to target the cytochrome oxidase mtDNA gene region and in situ extraction and amplification takes approximately 3 h for up to 16 individuals. Our in-situ diagnostic procedure demonstrated positive predictive values at 96% and negative predictive values at 87% by comparison to necropsy data. Our method could be a valuable tool in the hands of fisheries managers to enable infection control and help protect this iconic but critically endangered species.
Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5−36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.
Polygenic risk scores (PRSs) capture genetic vulnerability to psychiatric conditions. However, PRSs are often associated with multiple mental health problems in children, complicating their use in research and clinical practice. The current study is the first to systematically test which PRSs associate broadly with all forms of childhood psychopathology, and which PRSs are more specific to one or a handful of forms of psychopathology.
The sample consisted of 4717 unrelated children (mean age = 9.92, s.d. = 0.62; 47.1% female; all European ancestry). Psychopathology was conceptualized hierarchically as empirically derived general factor (p-factor) and five specific factors: externalizing, internalizing, neurodevelopmental, somatoform, and detachment. Partial correlations explored associations between psychopathology factors and 22 psychopathology-related PRSs. Regressions tested which level of the psychopathology hierarchy was most strongly associated with each PRS.
Thirteen PRSs were significantly associated with the general factor, most prominently Chronic Multisite Pain-PRS (r = 0.098), ADHD-PRS (r = 0.079), and Depression-PRS (r = 0.078). After adjusting for the general factor, Depression-PRS, Neuroticism-PRS, PTSD-PRS, Insomnia-PRS, Chronic Back Pain-PRS, and Autism-PRS were not associated with lower order factors. Conversely, several externalizing PRSs, including Adventurousness-PRS and Disinhibition-PRS, remained associated with the externalizing factor (|r| = 0.040–0.058). The ADHD-PRS remained uniquely associated with the neurodevelopmental factor (r = 062).
PRSs developed to predict vulnerability to emotional difficulties and chronic pain generally captured genetic risk for all forms of childhood psychopathology. PRSs developed to predict vulnerability to externalizing difficulties, e.g. disinhibition, tended to be more specific in predicting behavioral problems. The results may inform translation of existing PRSs to pediatric research and future clinical practice.
Genetic counselling has been defined as the process of helping people “understand and adapt to medical, psychosocial, and familial aspects of genetic conditions.” It can also help patients and families deal with stigma and understand the significance of possible genetic findings. Psychiatric genetic counselling (PGC) is an emerging field aimed to help people with a personal or family history of psychiatric illnesses such as schizophrenia, bipolar disorder, or neuropsychiatric conditions, to understand genetic etiological mechanisms as a critical component. Counselling strategies are used to identify and adapt to psychological and familial consequences of the conditions and to reduce stigma surrounding the psychiatric illness. A recent survey showed that PGC is still not routinely offered and usually only discussed at the initiative of the patient, e.g. if they ask about the possibility of “hereditary" illness, or if a caregiver during a session for another indication, identifies the family history. If a monogenetic or chromosomal cause is identified, the genetic counselling follows a more traditional path, but if, on the other hand, the cause is complex, the counselling will not be as clearcut. It will then focus on explaining risk for disease with quite uncertain riskscores as no causative genetic change is identified. Although genetic testing most often cannot be offered and individual risk scores based on genetic markers cannot be given, there is still great value for patients and their relatives in PGC. Studies have shown that the effect of PGC is an increase of empowerment and a reduction of stigma.
Epilepsy is a disorder of recurrent unprovoked (or reflex) seizures; the key to diagnosing epilepsy is estimating the risk of recurrence. Epilepsy may be diagnosed if a patient has two or more seizures at least 24 hours apart, a first-time seizure with factors that increase the risk of recurrence, or an epilepsy syndrome. When determining the type of epilepsy, first identify the seizure type(s), then the corresponding epilepsy type. Consider if the epilepsy is potentially syndromic or nonsyndromic. Consider the underlying etiology (structural, genetic, infectious, immune, or metabolic). Focal epilepsies may be classified based on their region of onset, that is, frontal, temporal (mesial/lateral), parietal, occipital, or insular. Ictal and interictal EEG findings vary with the type of focal epilepsy.
Recent studies suggest that close-range blast exposure (CBE), regardless of acute concussive symptoms, may have negative long-term effects on brain health and cognition; however, these effects are highly variable across individuals. One potential genetic risk factor that may impact recovery and explain the heterogeneity of blast injury’s long-term cognitive outcomes is the inheritance of an apolipoprotein (APOE) ε4 allele, a well-known genetic risk factor for Alzheimer’s disease. We hypothesized that APOE ε4 carrier status would moderate the impact of CBE on long-term cognitive outcomes.
To test this hypothesis, we examined 488 post-9/11 veterans who completed assessments of neuropsychological functioning, psychiatric diagnoses, history of blast exposure, military and non-military mild traumatic brain injuries (mTBIs), and available APOE genotypes. We separately examined the effects of CBE on attention, memory, and executive functioning in individuals with and without the APOE ε4 allele.
As predicted, we observed a differential impact of CBE status on cognition as a function of APOE ε4 status, in which CBE ε4 carriers displayed significantly worse neuropsychological performance, specifically in the domain of memory. These results persisted after adjusting for clinical, demographic, and genetic factors and were not observed when examining other neurotrauma variables (i.e., lifetime or military mTBI, distant blast exposure), though these variables displayed similar trends.
These results suggest APOE ε4 carriers are more vulnerable to the impact of CBE on cognition and highlight the importance of considering genetic risk when studying cognitive effects of neurotrauma.
LMNA mutations cause a variety of inherited diseases referred to as laminopathies which are associated with a wide spectrum of disease phenotypes, ranging from skeletal muscle disease, pre-mature ageing, metabolic disorders, and cardiac abnormalities. We present a case of a 14-year-old boy with dilated cardiomyopathy induced by the LMNA mutation (p. R429C) and described its electrocardiogram and imaging features.
Childhood adversity appears to sensitize youth to stress, increasing depression risk following stressful life events occurring throughout the lifespan. Some evidence suggests hypothalamic–pituitary–adrenal (HPA) axis-related and serotonergic genetic variation moderates this effect, in a “gene-by-environment-by-environment” interaction (G × E × E). However, prior research has tested single genetic variants, limiting power. The current study uses a multilocus genetic profile score (MGPS) approach to capture polygenic risk relevant to HPA axis and serotonergic functioning. Adolescents (N = 241, Mage = 15.90) completed contextual-threat-based interviews assessing childhood adversity and acute life events, and diagnostic interviews assessing depression. Established MGPSs indexed genetic variation linked to HPA axis (10 single nucleotide polymorphisms [SNPs]) and serotonergic (five SNPs) functioning. Results showed significant MGPS × Childhood Adversity × Recent Life Stress interactions predicting depression for both HPA axis and serotonergic MGPSs, with both risk scores predicting stronger Childhood Adversity × Recent Stress interactions. Serotonergic genetic risk specifically predicted sensitization to major interpersonal stressors. The serotonergic MGPS G × E × E was re-tested in an independent replication sample of early adolescent girls, with comparable results. Findings support the notion that genetic variation linked to these two neurobiological symptoms alters stress sensitization, and that gene-by-environment (G × E) interactions may be qualified by environmental exposures occurring at different points in development.
This chapter focuses on the Partition of India along religious lines, and on the shifting of the emotional locus of belonging from where one actually lives to Pakistan, which is seen as simultaneously hostile and territory that one is not prepared to surrender. The author reflects on the continuation of the Partition rhetoric through the aggressive and criminal sundering of couples who marry across community barriers.
Background – Ecstasy is a recreational drug with an anecdotal reputation for safety. However, reports of adverse effects and fatalities have increased in the medical and popular press.
Method – Literature search and review.
Results – Acute Ecstasy toxicity does not appear to be due to overdose and cannot be solely attributed to the nature of the usual ambient environment. Adverse effects include hyperthermia, seizures, cardiac arrhythmias, hepatotoxicity, hyponatraemia and many psychiatric disorders. Ecstasy causes serotonergic neurotoxicity in the brains of animals at doses close to those used by humans, but its long-term effect on the human brain is unknown.
Conclusion – Ecstasy toxicity should be considered in the differential diagnosis of a variety of medical and psychiatric conditions. Given its popularity, both the acute and the potential long-term effects are a cause for concern.
The concept of deficit schizophrenia is regarded as one of the most promising attempts to reduce heterogeneity within schizophrenia. This paper summarizes the clinical, neurocognitive, brain imaging and electrophysiological correlates of this subtype of schizophrenia. Attempts to identify genetic and non-genetic risk factors are reviewed. Methodological limitations of studies supporting the efficacy of atypical antipsychotics in the treatment of the syndrome are highlighted. Two decades of research on deficit schizophrenia have failed to prove that it represents the extreme end of a severity continuum in schizophrenia, while some findings support the claim that it may be a separate disease entity.
As no genetic study has been made in deficit patients, characterized by enduring and primary negative symptoms, the aim of the study was to test the involvement of a familial factor in deficit syndrome. The results in 71 schizophrenic patients showed less familial factors but a greater weight in heritage of schizophrenia in deficit than in nondeficit patients.
Several studies have affirmed the existence of a strong and complex genetic component in the determination of psychotic disorders. However, the genetic architecture of these disorders remains poorly understood. GWAS studies conducted over the past decade have identified some associations to low effect, and the major part of this heritability remains unexplained, thus calling into question the hypothesis of “common disease – common variant” for model involving a large number of rare variants. Family studies of extended pedigrees selected from geographical isolate can be a powerful approach in identifying rare genetic variants of complex diseases such as psychotic disorders. Here, we studied four multigenerational families in which co-exist psychotic and mood disorders and a high rate of consanguinity, identified in the northwest of Algeria. This case-control study aimed to characterize new rare genetic variants responsible for psychosis. These families have received complete clinical and genealogical investigations, genome wide analysis that were performed in the laboratory of medical genetics in the university hospital of Geneva. A genome wide research CNVs using Agilent Human Genome CGH Microarray Kit 44 K, covering 45 subjects including 20 patients and in a control population of 55 individuals. Three CNVs that had never been reported to date have been identified in one of four families and validated by two techniques. It is the dup 4q26, and 16q23.1 del del21q21. These CNVs are transmitted by either parent line, suggesting a cumulative effect on the risk of psychotic disorders. Further analyzes using pan-genomic linkage analysis using GWAS chip (Illumina Human 660 W-Quad v1.0 Breadchip) and complete WES (by GAIIx Illumina/HiSeq 2000) were performed in some related individuals to search other mutations may explain the appearance of the phenotype in this population.
Consanguinity is usually defined as the result of a sexual reproduction between two related individuals. It can also refer to populations sharing at least one common ancestor, as those who live within isolates or within communities practicing endogamy. Second or higher order related couples and their offspring represent more than 10% of the current world population. The highest levels of consanguinity are found in the Southern and Eastern shores of the Mediterranean Basin, and the most concerned region extends from the southern shore of the Mediterranean Sea to Southeast Asia through Middle-East, Gulf and India. In Maghreb countries, consanguineous marriages are wide-spread. The rates for this practice vary from 23% in Morocco to 60% in Tunisia, with highest rates being found in rural areas. In Algeria, consanguineous marriages represent more than 38% of all marriages. Large scale migrations from South countries to North countries in the second half of the twentieth century had legal impact on migrants for these specific unions. As a consequence, controversies have been rising in the United States and the United Kingdom especially when a fast decrease of inter-related individuals unions seems unlikely. Consanguinity certainly increases the risk of autosomal recessive pathology, but what about mental pathologies with complex and polygenic heredity? The necessity of an awareness of the genetic risks of consanguinity is as essential in countries where inter-cousin unions are culturally encouraged as among migrant populations in Europe.