Table of Contents
EDITORIAL
From melancholia to molecular mechanisms: Bridging centuries of understanding depression 1
Julio Licinio and Ma-Li Wong
INNOVATORS & IDEAS: RISING STAR
Mateus Vidigal de Castro: Cellular and genetic determinants of healthy aging and disease resilience 4
Mateus Vidigal de Castro
INNOVATORS & IDEAS: RESEARCH LEADERS
Barbara Franke: Understanding the biological pathways from genes to altered behaviour in neurodevelopmental conditions like ADHD – paving the way for improved understanding and care in psychiatry 7
Barbara Franke
Michael Meaney: What is the biology that underlies the gene x environment interdependence that shapes brain health? 11
Michael Meaney
Peter Falkai: In order to understand the neurobiological origins of psychoses we need to understand the genetic underpinnings of brain plasticity and its modulation due to environmental risk factors 15
Peter Falkai
COMMENTARY
The salience network is functionally twice as large in depression: The first depression biomarker? 18
Katerina Palacek, Robin Carhart-Harris and Nicholas Fabiano
INVITED EXPERT REVIEW
The descriptive psychopathology of melancholia in Roubinovitch and Toulouse's 1897 monograph “La Mélancolie” 21
Kenneth S. Kendler and Virginia Justis
RESEARCH REPORT
Polygenic liability to C-reactive protein defines immunometabolic depression phenotypes and influences antidepressant therapeutic outcomes 30
Alessandro Serretti, Daniel Souery … Julien Mendlewicz
BREVIA
Shared genetic etiology between childhood cognitive function and longevity 36
W. David Hill and Ian J. Deary
Cover Art
Cover Image: Albrecht Dürer’s “Melencolia I” (1514), a landmark of Renaissance engraving, reflects the complex inner world of melancholia through its symbolic landscape. The central, winged figure, often interpreted as the personification of melancholy, sits among the unused instruments of geometry and craft, visually echoing the theme of creative inertia and the psychological paralysis later described by Roubinovitch and Toulouse in their 1897 monograph (featured in this issue, pp. 21–29). Elements like the magic square, polyhedron, and scattered tools evoke the intact yet idle intellectual abilities typical of melancholic states, paralleling contemporary psychiatric views of preserved cognition amidst motivational impairment.
Dürer’s composition, combining the body’s languor, the intellect’s stasis, and existential uncertainty (seen in the apocalyptic background), presages modern conceptions of depression as a multi-layered biopsychosocial phenomenon, connecting historical phenomenology to genomic research such as Serretti et al.‘s study of C-reactive protein polygenic scores (pp. 30–35). Early impressions of this engraving, pulled from Dürer‘s original copper plate, are held by major museums worldwide, including the Metropolitan Museum of Art (New York), the British Museum (London), the Albertina (Vienna), the National Gallery of Art (Washington, D.C.), and the Museum of Fine Arts (Budapest). Image source: Public domain.
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