The risk for suicidal behavior (SB) is elevated in schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD), but also occurs in subjects without psychiatric diagnoses. ...Genome-wide association studies (GWAS) on SB may help to understand this risk, but have been hampered by low power due to limited sample sizes, weakly ascertained SB or a reliance on single-nucleotide protein (SNP)-by-SNP analyses. Here, we tried to mitigate such issues with polygenic risk score (PRS) association tests combined with hypothesis-driven strategies using a family-based sample of 660 trios with a well-ascertained suicide attempt (SA) outcome in the offspring (Genetic Investigation of Suicide and SA, GISS). Two complementary sources of PRS information were used. First, a PRS that was discovered and validated in the GISS SA revealed the polygenic association of SNPs in 750 neurodevelopmental genes, which was driven by the SA phenotype, rather than the major psychiatric diagnoses. Second, a PRS based on three different genome-wide association studies (on SCZ, BPD or MDD) from the Psychiatric Genomics Consortium (PGC) showed an association of the PGC-SCZ PRS in the SA subjects with and without major psychiatric diagnoses. We characterized the PGC-SCZ overlap in the SA subjects without diagnoses. The extended major histocompatibility complex region did not contribute to the overlap, but we delineated the genic overlap to neurodevelopmental genes that partially overlapped with those identified by the GISS PRS. Among the 590 SA polygenes implicated here, there were several developmentally important functions (cell adhesion/migration, small GTPase and receptor tyrosine kinase signaling), and 16 of the SA polygenes have previously been studied in SB (BDNF, CDH10, CDH12, CDH13, CDH9, CREB1, DLK1, DLK2, EFEMP1, FOXN3, IL2, LSAMP, NCAM1, nerve growth factor (NGF), NTRK2 and TBC1D1). These novel genome-wide insights, supported by two lines of evidence, suggested the importance of a polygenic neurodevelopmental etiology in SB, even in the absence of major psychiatric diagnoses.
Granice fizyki w kosmologii Sokołowski, Leszek M
Zagadnienia Filozoficzne w Nauce (Online),
12/2015, Letnik:
59, Številka:
59
Journal Article
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The message is that physics has an „outward bound” of scientific inquiry in the field of cosmology. I present it in the historical development. Physics and astronomy, developing since the seventeenth ...century, inherited from the early Greek philosophers the conception that the Universe as a whole is invariable. In nineteenth century this conception in conjunction with the conception of eternity of the Universe (being a philosophical conclusion from the conservation laws of mass and energy) gave rise to contradictions with other laws of physics indicating that cosmology is not a branch of physics since the notion of the Universe is not a physical one. Cosmology returned to physics as its important branch due to the advent of general relativity theory and the discovery of the cosmic microwave background radiation. Modern cosmology generates fundamental problems creating real limits to inquiries in physics viewed as an empirical science. The very notion of the Universe shows that the scientific method reaches there limits of its applicability. Does „to exist” mean „to be observed by someone”? Should the definition of the Universe be based on a current physical theory, e.g. on Einstein’s general relativity, giving rise to a kind of mathematical instability? Is the fashionable concept of the „multiverse” a physical one or is a purely metaphysical notion in a scientific disguise? If the Universe is unique (as we believe), is it meaningful to describe it in the framework of physics, which by its method always assumes that the number of objects it describes, is unlimited? Apart from these permanent philosophical problems there are concrete urgent problems generated by cosmology: the nature of dark matter and dark energy. These two species of „substance” appear only in cosmology and do not fit the laboratory physics; contrary to the three centuries long tradition of modern science, now cosmology inspires physics in a troublesome way. A separate class of limits to physics is generated by the theorem in general relativity that the Universe emerged from an initial curvature singularity of the spacetime. At the singularity the whole scientific inquiry breaks down. Cosmology of the very early Universe suggests that in its evolution two specific epochs took place, that of quantum gravity and an inflationary epoch. The underlying them two physical theories are incomplete and seem to be inherently untestable. Furthermore, the experimentally verifiable physics cannot explain the origin of the initial conditions determining properties of the Universe which emerged from the singularity.
surrounding problems in order to get to the very core of „the mathematicality of the matter”. First I argue that physics cannot establish whether the matter might not be subject to mathematical laws ...of nature, then I discuss two conceptions of the nature of the physical law, the dualistic and monistic one. It seems that independently of which conception is true, none of these helps to solve the problem. In conjunction with the famous Wigner’s article of 1960 on unreasonable effectivenessof mathematics in natural sciences I indicate that the problem concerns solely the inanimate matter and does not apply to living organisms. As a next inevitable step I discuss the view of mathematics as intellectual inquiries independent of the physical world, which nonetheless perfectly fit this world; in particular I briefly present the Einstein’s conception of forming physical laws. Finally I make comments on the problem which unavoidably appears in this context, namely of whether mathematical notions are discovered or freely created; I indicate (following A. Pelczar and others) that these two concepts do not exclude each other. After this journey through a collection of problems closely accompanying that of „the mathematicality of the matter” it turns out that we come back to the starting point and we are helplessly facing the Mystery.
Abstract Suicide is a major public health problem in the WHO European Region accounting for over 150,000 deaths per year. Suicidal crisis Acute intervention should start immediately in order to keep ...the patient alive. Diagnosis An underlying psychiatric disorder is present in up to 90% of people who completed suicide. Comorbidity with depression, anxiety, substance abuse and personality disorders is high. In order to achieve successful prevention of suicidality, adequate diagnostic procedures and appropriate treatment for the underlying disorder are essential. Treatment Existing evidence supports the efficacy of pharmacological treatment and cognitive behavioural therapy (CBT) in preventing suicidal behaviour. Some other psychological treatments are promising, but the supporting evidence is currently insufficient. Studies show that antidepressant treatment decreases the risk for suicidality among depressed patients. However, the risk of suicidal behaviour in depressed patients treated with antidepressants exists during the first 10–14 days of treatment, which requires careful monitoring. Short-term supplementary medication with anxiolytics and hypnotics in the case of anxiety and insomnia is recommended. Treatment with antidepressants of children and adolescents should only be given under supervision of a specialist. Long-term treatment with lithium has been shown to be effective in preventing both suicide and attempted suicide in patients with unipolar and bipolar depression. Treatment with clozapine is effective in reducing suicidal behaviour in patients with schizophrenia. Other atypical antipsychotics are promising but more evidence is required. Treatment team Multidisciplinary treatment teams including psychiatrist and other professionals such as psychologist, social worker, and occupational therapist are always preferable, as integration of pharmacological, psychological and social rehabilitation is recommended especially for patients with chronic suicidality. Family The suicidal person independently of age should always be motivated to involve family in the treatment. Social support Psychosocial treatment and support is recommended, as the majority of suicidal patients have problems with relationships, work, school and lack functioning social networks. Safety A secure home, public and hospital environment, without access to suicidal means is a necessary strategy in suicide prevention. Each treatment option, prescription of medication and discharge of the patient from hospital should be carefully evaluated against the involved risks. Training of personnel Training of general practitioners (GPs) is effective in the prevention of suicide. It improves treatment of depression and anxiety, quality of the provided care and attitudes towards suicide. Continuous training including discussions about ethical and legal issues is necessary for psychiatrists and other mental health professionals.
•Suicides are difficult to distinguish from accidents among road traffic fatalities.•Psychosocial investigations helped to identify more suicides.•Psychosocial investigations helped to resolve many ...“undetermined” causes of death.•The improved classification will help prevention of suicide deaths in road traffic.
Introduction: Suicide is the second leading cause of death in the ages 15–29 worldwide, exceeded only by road injury. However, fatalities in road traffic may be either accidents or suicides. In 2010 Sweden began efforts to separately report deaths in road traffic as either accidents or suicides. Method: Three alternative criteria defining what constitutes a fatality by suicide were introduced. After exclusion of natural deaths, fatalities were also classified on a five-level graded scale, which distinguished between accident, undetermined, and suicide. The investigations of fatalities were complemented by extended psychosocial investigations in 2012. The improvement in the classification of suicide deaths was evaluated by an intra-year 2012 comparison, as well as using the 2010–2012 period as a control to evaluate the continued use of extended psychosocial investigations during the 2013–2019 period. Results: The 2012 intra-year comparison showed a 63% increase in the number of identified suicides when using extended psychosocial investigations. The additional 14 suicides identified in 2012 were mainly attributed to a resolution of 12 “undetermined” causes of deaths. Suicides of all road fatalities increased from 5.7-6.8% in 2010–2011, to 11.2% in 2012. Over the subsequent period 2013–2019 with extended psychosocial investigations, suicides of all road fatalities averaged 10%, a 60% increase over prior years. An average of ∼9 additional suicides was identified each year during 2013–2019, which was accompanied by an annual reduction of ∼6 “undetermined” fatalities. Conclusion: The use of extended psychosocial investigations is of major importance for our knowledge about the occurrence of suicides in road traffic. Practical applications: A standardized and in-depth classification of suicide deaths is a basic prerequisite needed for the cooperation, implementation, and effect-evaluations of suicide intervention and prevention efforts, with potential to include the entire Swedish transportation system.
Genes can affect natural behavioral variation in different ways. Allelic variation causes alternative behavioral phenotypes, whereas changes in gene expression can influence the initiation of ...behavior at different ages. We show that the age-related transition by honey bees from hive work to foraging is associated with an increase in the expression of the foraging (for) gene, which encodes a guanosine 3′,5′-monophosphate (cGMP)-dependent protein kinase (PKG). cGMP treatment elevated PKG activity and caused foraging behavior. Previous research showed that allelic differences in PKG expression result in two Drosophila foraging variants. The same gene can thus exert different types of influence on a behavior.
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