Childhood psychotic symptoms have been used as a subclinical phenotype of schizophrenia in etiological research and as a target for preventative interventions. However, recent studies have cast doubt ...on the specificity of these symptoms for schizophrenia, suggesting alternative outcomes such as anxiety and depression. Using a prospective longitudinal birth cohort we investigated whether childhood psychotic symptoms predicted a diagnosis of schizophrenia or other psychiatric disorders by 38 years of age.
Participants were drawn from a birth cohort of 1037 children from Dunedin, New Zealand, who were followed prospectively to 38 years of age (96% retention rate). Structured clinical interviews were administered at age 11 to assess psychotic symptoms and study members underwent psychiatric assessments at ages 18, 21, 26, 32 and 38 to obtain past-year DSM-III-R/IV diagnoses and self-reports of attempted suicides since adolescence.
Psychotic symptoms at age 11 predicted elevated rates of research diagnoses of schizophrenia and posttraumatic stress disorder (PTSD) and also suicide attempts by age 38, even when controlling for gender, social class and childhood psychopathology. No significant associations were found for persistent anxiety, persistent depression, mania or persistent substance dependence. Very few of the children presenting with age-11 psychotic symptoms were free from disorder by age 38.
Childhood psychotic symptoms were not specific to a diagnosis of schizophrenia in adulthood and thus future studies of early symptoms should be cautious in extrapolating findings only to this clinical disorder. However, these symptoms may be useful as a marker of adult mental health problems more broadly.
The Origins of You Belsky, Jay; Caspi, Avshalom; Moffitt, Terrie E ...
08/2020
eBook
A Marginal Revolution Best Book of the
Year After tracking the lives of thousands of
people from birth to midlife, four of the world's preeminent
psychologists reveal what they have learned about how ...humans
develop. Does temperament in childhood predict adult
personality? What role do parents play in shaping how a child
matures? Is day care bad-or good-for children? Does adolescent
delinquency forecast a life of crime? Do genes influence success in
life? Is health in adulthood shaped by childhood experiences? In
search of answers to these and similar questions, four leading
psychologists have spent their careers studying thousands of
people, observing them as they've grown up and grown older. The
result is unprecedented insight into what makes each of us who we
are. In The Origins of You , Jay Belsky, Avshalom Caspi,
Terrie Moffitt, and Richie Poulton share what they have learned
about childhood, adolescence, and adulthood, about genes and
parenting, and about vulnerability, resilience, and success. The
evidence shows that human development is not subject to ironclad
laws but instead is a matter of possibilities and
probabilities-multiple forces that together determine the direction
a life will take. A child's early years do predict who they will
become later in life, but they do so imperfectly. For example,
genes and troubled families both play a role in violent male
behavior, and, though health and heredity sometimes go hand in
hand, childhood adversity and severe bullying in adolescence can
affect even physical well-being in midlife. Painstaking and
revelatory, the discoveries in The Origins of You promise
to help schools, parents, and all people foster well-being and
ameliorate or prevent developmental problems.
Neutrophils play a critical role in cancer, with both protumor and antitumor neutrophil subpopulations reported. The antitumor neutrophil subpopulation has the capacity to kill tumor cells and limit ...metastatic spread, yet not all tumor cells are equally susceptible to neutrophil cytotoxicity. Because cells that evade neutrophils have greater chances of forming metastases, we explored the mechanism neutrophils use to kill tumor cells. Neutrophil cytotoxicity was previously shown to be mediated by secretion of H
O
We report here that neutrophil cytotoxicity is Ca
dependent and is mediated by TRPM2, a ubiquitously expressed H
O
-dependent Ca
channel. Perturbing TRPM2 expression limited tumor cell proliferation, leading to attenuated tumor growth. Concomitantly, cells expressing reduced levels of TRPM2 were protected from neutrophil cytotoxicity and seeded more efficiently in the premetastatic lung.
These findings identify the mechanism utilized by neutrophils to kill disseminated tumor cells and to limit metastatic spread.
.
Abstract
Background and Hypothesis
An existing model suggests that some brain features of relatives of people affected by psychosis can be distinguished from both the probands and a control group. ...Such findings can be interpreted as representing a compensating mechanism.
Study Design
We studied white matter features using diffusion tensor imaging in a cohort of 82 people affected by psychosis, 122 of their first-degree relatives, and 89 control subjects that were scanned between two to three times with an interval of approximately 3 years between consecutive scans. We measured both fractional anisotropy and other standard diffusivity measures such as axial diffusivity. Additionally, we calculated standard connectivity measures such as path length based on probabilistic or deterministic tractography. Finally, by averaging the values of the different measures over the two or three consecutive scans, we studied epoch-averagely the difference between these three groups.
Study Results
For several tracts and several connectivity measures, the relatives showed distinct features from both the probands and the control groups. In those cases, the relatives did not necessarily score between the probands and the control group. An aggregate analysis in the form of a group-dependent score for the different modes of the analysis (e.g., for fractional anisotropy) supported this observation.
Conclusions
We interpret these results as evidence supporting a compensation mechanism in the brain of relatives that may be related to resilience that some of them exhibit in the face of the genetic risk they have for being affected by psychosis.
Background
Adverse childhood experiences (ACEs; e.g. abuse, neglect, and parental loss) have been associated with increased risk for later‐life disease and dysfunction using adults’ retrospective ...self‐reports of ACEs. Research should test whether associations between ACEs and health outcomes are the same for prospective and retrospective ACE measures.
Methods
We estimated agreement between ACEs prospectively recorded throughout childhood (by Study staff at Study member ages 3, 5, 7, 9, 11, 13, and 15) and retrospectively recalled in adulthood (by Study members when they reached age 38), in the population‐representative Dunedin cohort (N = 1,037). We related both retrospective and prospective ACE measures to physical, mental, cognitive, and social health at midlife measured through both objective (e.g. biomarkers and neuropsychological tests) and subjective (e.g. self‐reported) means.
Results
Dunedin and U.S. Centers for Disease Control ACE distributions were similar. Retrospective and prospective measures of adversity showed moderate agreement (r = .47, p < .001; weighted Kappa = .31, 95% CI: .27–.35). Both associated with all midlife outcomes. As compared to prospective ACEs, retrospective ACEs showed stronger associations with life outcomes that were subjectively assessed, and weaker associations with life outcomes that were objectively assessed. Recalled ACEs and poor subjective outcomes were correlated regardless of whether prospectively recorded ACEs were evident. Individuals who recalled more ACEs than had been prospectively recorded were more neurotic than average, and individuals who recalled fewer ACEs than recorded were more agreeable.
Conclusions
Prospective ACE records confirm associations between childhood adversity and negative life outcomes found previously using retrospective ACE reports. However, more agreeable and neurotic dispositions may, respectively, bias retrospective ACE measures toward underestimating the impact of adversity on objectively measured life outcomes and overestimating the impact of adversity on self‐reported outcomes. Associations between personality factors and the propensity to recall adversity were extremely modest and warrant further investigation. Risk predictions based on retrospective ACE reports should utilize objective outcome measures. Where objective outcome measurements are difficult to obtain, correction factors may be warranted.
Abstract
MetaCyc (https://MetaCyc.org) is a comprehensive reference database of metabolic pathways and enzymes from all domains of life. It contains more than 2570 pathways derived from >54 000 ...publications, making it the largest curated collection of metabolic pathways. The data in MetaCyc is strictly evidence-based and richly curated, resulting in an encyclopedic reference tool for metabolism. MetaCyc is also used as a knowledge base for generating thousands of organism-specific Pathway/Genome Databases (PGDBs), which are available in the BioCyc (https://BioCyc.org) and other PGDB collections. This article provides an update on the developments in MetaCyc during the past two years, including the expansion of data and addition of new features.
Cell division in most prokaryotes is mediated by the well-studied fts genes, with FtsZ as the principal player. In many archaeal species, however, division is orchestrated differently. The ...Crenarchaeota phylum of archaea features the action of the three proteins, CdvABC. This Cdv system is a unique and less-well-studied division mechanism that merits closer inspection.
, the three Cdv proteins form a composite band that contracts concomitantly with the septum formation. Of the three Cdv proteins, CdvA is the first to be recruited to the division site, while CdvB and CdvC are thought to participate in the active part of the Cdv division machinery. Interestingly, CdvB shares homology with a family of proteins from the eukaryotic ESCRT-III complex, and CdvC is a homolog of the eukaryotic Vps4 complex. These two eukaryotic complexes are key factors in the endosomal sorting complex required for transport (ESCRT) pathway, which is responsible for various budding processes in eukaryotic cells and which participates in the final stages of division in Metazoa. There, ESCRT-III forms a contractile machinery that actively cuts the membrane, whereas Vps4, which is an ATPase, is necessary for the turnover of the ESCRT membrane-abscission polymers. In contrast to CdvB and CdvC, CdvA is unique to the archaeal Crenarchaeota and Thaumarchaeota phyla. The Crenarchaeota division mechanism has often been suggested to represent a simplified version of the ESCRT division machinery thus providing a model system to study the evolution and mechanism of cell division in higher organisms. However, there are still many open questions regarding this parallelism and the division mechanism of Crenarchaeota. Here, we review the existing data on the role of the Cdv proteins in the division process of Crenarchaeota as well as concisely review the ESCRT system in eukaryotes. We survey the similarities and differences between the division and abscission mechanisms in the two cases. We suggest that the Cdv system functions differently in archaea than ESCRT does in eukaryotes, and that, unlike the eukaryotic case, the Cdv system's main function may be related to surplus membrane invagination and cell-wall synthesis.
In this review, we evaluate four topics in the study of personality development where discernible progress has been made since 1995 (the last time the area of personality development was reviewed in ...this series). We (a) evaluate research about the structure of personality in childhood and in adulthood, with special attention to possible developmental changes in the lower-order components of broad traits; (b) summarize new directions in behavioral genetic studies of personality; (c) synthesize evidence from longitudinal studies to pinpoint where and when in the life course personality change is most likely to occur; and (d) document which personality traits influence social relationships, status attainment, and health, and the mechanisms by which these personality effects come about. In each of these four areas, we note gaps and identify priorities for further research.
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