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Biology subjects

Rohde, L. A.

Publications and source records attributed to Rohde, L. A..

5 recordsLinked to original sources

Reproducible Brain Charts: An open data resource for mapping brain development and its associations with mental health

Major mental disorders are increasingly understood as disorders of brain development. Large and heterogeneous samples are required to define generalizable links between brain development and psychopathology. To this end, we introduce the Reproducible Brain Charts (RBC), an open data resource that integrates data from 5 large studies of brain development in youth from three continents (N=6,346; 45% Female). Confirmatory bifactor models were used to create harmonized psychiatric phenotypes that capture major dimensions of psychopathology. Following rigorous quality assurance, neuroimaging data were carefully curated and processed using consistent pipelines in a reproducible manner with DataLad, the Configurable Pipeline for the Analysis of Connectomes (C-PAC), and FreeSurfer. Initial analyses of RBC data emphasize the benefit of careful quality assurance and data harmonization in delineating developmental effects and associations with psychopathology. Critically, all RBC data - including harmonized psychiatric phenotypes, unprocessed images, and fully processed imaging derivatives - are openly shared without a data use agreement via the International Neuroimaging Data-sharing Initiative. Together, RBC facilitates large-scale, reproducible, and generalizable research in developmental and psychiatric neuroscience.

neuroscience↗

Cell-autonomous generation of the wave pattern within the vertebrate segmentation clock

Rhythmic and sequential segmentation of the growing vertebrate body relies on the segmentation clock, a multi-cellular oscillating genetic network. The clock is visible as tissue-level kinematic waves of gene expression that travel through the pre-somitic mesoderm (PSM) and arrest at the position of each forming segment. Here we test how this hallmark wave pattern is driven by culturing single maturing PSM cells. We compare their cell-autonomous oscillatory and arrest dynamics to those we observe in the embryo at cellular resolution, finding similarity in the relative slowing of oscillations and arrest in concert with differentiation. This shows that cell-extrinsic signals are not required by the cells to instruct the developmental program underlying the wave pattern. We show that a cell-autonomous timing activity initiates during cell exit from the tailbud, then runs down in the anterior-ward cell flow in the PSM, thereby using elapsed time to provide positional information to the clock. Exogenous FGF lengthens the duration of the cell-intrinsic timer, indicating extrinsic factors in the embryo may regulate the segmentation clock via the timer. In sum, our work suggests that a noisy cell-autonomous, intrinsic timer drives the slowing and arrest of oscillations underlying the wave pattern, while extrinsic factors in the embryo tune this timers duration and precision. This is a new insight into the balance of cell-intrinsic and -extrinsic mechanisms driving tissue patterning in development.

developmental biology↗

Cross-sectional and longitudinal associations of threat and deprivation on cognition, emotional processing and psychopathology in children and adolescents

BackgroundExposure to childhood adversity has been consistently associated with poor developmental outcomes, but it is unclear whether these associations vary across different forms of adversity. We examined cross-sectional and longitudinal associations between two types of adversity--threat and deprivation--with cognition, emotional processing, and psychopathology in a middle-income country. MethodsThe sample consisted of 2,511 children and adolescents (6-17 years old) from the Brazilian High-Risk Cohort for Psychiatric Disorders. Parent reports on childhood adversity were used to construct threat and deprivation latent constructs. Psychopathology was measured by the CBCL which generated a measure of general psychopathology (the "p" factor). Executive function (EF) and attention orienting toward angry faces were assessed using cognitive tasks. All measures were acquired at two time-points 3-years apart. Cross-lagged panel models were estimated to evaluate longitudinal associations. ResultsPsychopathology was associated with threat and deprivation cross-sectionally, and higher levels of threat and deprivation predicted increases in general psychopathology at follow-up. For EF, worse performance was more strongly associated with deprivation than threat at baseline, and only with deprivation at follow-up. Deprivation was associated with attention orienting away from angry faces cross-sectionally, but neither form of adversity was associated with changes over time in attention bias. ConclusionBoth types of adversity are associated with current and future psychopathology and with current, but not future, EF. Threat was more strongly linked to higher psychopathology, whereas deprivation was more strongly linked to lower EF. Lack of longitudinal associations between deprivation and EF mean reverse causality cannot be excluded.

neuroscience↗

Disentangling unity from diversity in developmental psychopathology

Developmental psychopathology has been a fruitful space for the investigation of the validity of multidimensionality. Nonetheless, previous studies in the field have not tested a model with a fine-grained division within the internalizing and externalizing spectra that also accounts for the contribution of a general psychopathology factor. The aim of this study is to test the validity and reliability of a theoretically-driven bifactor model with one general dimension and ten specific dimensions of psychopathology: fear, somatic complaints, distressful thoughts, low mood, low motivation/energy, inattention-hyperactivity, temper loss, aggression, noncompliance, and low concern for others. Our study evaluated 2,511 children aged 6-14 years-old from the Brazilian High-Risk Cohort for Psychiatric Disorders. There was support for the model in terms of its fit to the data, reliability, and external validity. Our findings highlight the potential of combined fine-grained approaches with models disentangling unity from diversity in developmental psychopathology.

animal behavior and cognition↗

Genome wide meta-analysis identifies genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders.

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed a meta-analysis of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders identifying three groups of inter-related disorders. We detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning in the second trimester prenatally, and play prominent roles in a suite of neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

genomics↗