Single-nucleotide polymorphisms (SNPs) in CACNA1C, the α1C subunit of the voltage-gated L-type calcium channel Cav1.2, rank among the most consistent and replicable genetics findings in psychiatry and have been associated with schizophrenia, bipolar disorder and major depression. However, genetic variants of complex diseases often only confer a marginal increase in disease risk, which is additionally influenced by the environment. Here we show that embryonic deletion of Cacna1c in forebrain glutamatergic neurons promotes the manifestation of endophenotypes related to psychiatric disorders including cognitive decline, impaired synaptic plasticity, reduced sociability, hyperactivity and increased anxiety. Additional analyses revealed that depletion of Cacna1c during embryonic development also increases the susceptibility to chronic stress, which suggest that Cav1.2 interacts with the environment to shape disease vulnerability. Remarkably, this was not observed when Cacna1c was deleted in glutamatergic neurons during adulthood, where the later deletion even improved cognitive flexibility, strengthened synaptic plasticity and induced stress resilience. In a parallel gene × environment design in humans, we additionally demonstrate that SNPs in CACNA1C significantly interact with adverse life events to alter the risk to develop symptoms of psychiatric disorders. Overall, our results further validate Cacna1c as a cross-disorder risk gene in mice and humans, and additionally suggest a differential role for Cav1.2 during development and adulthood in shaping cognition, sociability, emotional behavior and stress susceptibility. This may prompt the consideration for pharmacological manipulation of Cav1.2 in neuropsychiatric disorders with developmental and/or stress-related origins.

Neddylation is a ubiquitylation-like pathway that controls cell cycle and proliferation by covalently conjugating Nedd8 to specific targets. However, its role in neurons, nonreplicating postmitotic cells, remains unexplored. Here we report that Nedd8 conjugation increased during postnatal brain development and is active in mature synapses, where many proteins are neddylated. We show that neddylation controls spine development during neuronal maturation and spine stability in mature neurons. We found that neddylated PSD-95 was present in spines and that neddylation on Lys202 of PSD-95 is required for the proactive role of the scaffolding protein in spine maturation and synaptic transmission. Finally, we developed Nae1(CamKIIα-CreERT2) mice, in which neddylation is conditionally ablated in adult excitatory forebrain neurons. These mice showed synaptic loss, impaired neurotransmission and severe cognitive deficits. In summary, our results establish neddylation as an active post-translational modification in the synapse regulating the maturation, stability and function of dendritic spines.

The Study of Personality Architecture and Dynamics (SPeADy) is a German research project that aims to investigate the sources of interindividual differences in intraindividual personality development. The main focus lies in the dynamic interplay between more stable core characteristics and more environmentally malleable surface characteristics, as well as between personality and life experiences over time. SPeADy includes a twin family study encompassing data from 1962 individuals (age: 14–94) of 682 families, including 570 complete twin pairs (plus 1 triplet set), 327 parents, 236 spouses and 145 children of twins. Data collection started in 2016 and data from the first wave are currently obtainable as open source. Available data comprise a broad range of personality variables, such as personality trait constructs, motives, interests, values, moral foundations, religiosity and self-related concepts. For the currently ongoing second wave of data collection, we added retrospective reports on major life events. Special features of this genetically informative study are the extended twin family data and its longitudinal design. Three assessment waves in 2 years’ intervals are planned until 2022. In this article, we briefly describe the design and contents of the SPeADy twin family study as well as some recent findings, future plans and open science issues.

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Abstract. This study was designed to provide detailed estimates of genetic and environmental sources of variance in the HEXACO personality traits. For this purpose, we analyzed data from a German extended twin family study including 573 pairs of twins as well as 208 mothers, 119 fathers, 228 spouses, and 143 offspring of twins. All participants provided self-reports on the HEXACO-60. Extended twin family analyses using structural equation modeling (SEM) yielded that additive and nonadditive genetic influences accounted for about 50% of the variance in personality traits. The remaining variance was primarily due to individual-specific environmental sources and random measurement error. Spousal similarity in Openness was attributable to assortative mating, whereas spousal similarity in Honesty-Humility was attributable to environmental circumstances, partly due to a shared social background and spouse-specific effects. Our analyses yielded specifics for different personality traits. However, transmission of trait similarity from one generation to the next was primarily genetic.

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This study examined sojourners' long-term personality trait changes over five years, extending previous research on immediate sojourn effects. A sample of German students (N = 1095) was surveyed thrice (T1-T3) over the course of an academic year. Sojourners (n = 498) lived abroad shortly after T1 for one or two semesters; stayers (n = 597) remained in their home country. Five years after T1, we surveyed the same participants (n = 441, 40.3%) again (T4). Beyond substantial selection effects, latent neighbour-change models revealed that small differences between sojourners' and stayers' openness, agreeableness, and neuroticism changes occurred early after sojourn-induced contextual change. Model estimates suggested sustained sojourn effects on openness and neuroticism changes thereafter and a reversed effect on agreeableness change after return. Because of reduced power and low accuracy at T4, these estimates were not statistically significant. Based on model comparison analyses, however, we could rule out reversed effects for openness and accentuated effects for agreeableness and neuroticism as least likely. Moreover, separating short-term and long-term sojourners revealed no substantial differences, but recurring sojourn experiences tended to play a role in sustaining differences. We discuss implications for future studies on patterns of sojourn effects on personality trait changes.