Featured
-
-
Article
| Open AccessAstrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice
The regulatory mechanism and function of astrocytic epigenetic effects on depression remain to be explored. Here, the authors show astrocytic ALKBH5 contributes to depressive-like behaviors via the m6A RNA methylation of GLT-1.
- Fang Guo
- , Jun Fan
- & Xiong Cao
-
Article
| Open AccessImmunoregulatory role of the gut microbiota in inflammatory depression
Inflammatory depression is a treatment-resistant subtype of depression. Here, the authors show that patients with inflammatory depression exhibit a disrupted microbiota, which upon FMT in mice leads to increased peripheral and central inflammatory factors, intestinal mucosal permeability, and depressive and anxiety-like behaviors. Probiotic administration ameliorates the disease phenotype.
- Penghong Liu
- , Zhifen Liu
- & Kerang Zhang
-
Article
| Open AccessWhole-exome sequencing in UK Biobank reveals rare genetic architecture for depression
Despite many common genetic variants being linked to depression, the impact of rare coding variants on depression remains largely unknown. Here, the authors perform a whole-exome sequencing study of depression, providing insights into the rare genetic architecture of depression.
- Ruoyu Tian
- , Tian Ge
- & Chia-Yen Chen
-
Article
| Open AccessHarnessing PROTAC technology to combat stress hormone receptor activation
Stress-hormone receptors are important therapeutic targets for many diseases but the currently clinically approved inhibitor lacks specificity. Here the authors present a stress hormone receptor depletion tool that differs in its mode of action making it specific in counteracting the effects of stress.
- Mahshid Gazorpak
- , Karina M. Hugentobler
- & Katharina Gapp
-
Article
| Open AccessEnhanced TARP-γ8-PSD-95 coupling in excitatory neurons contributes to the rapid antidepressant-like action of ketamine in male mice
Ketamine produces rapid antidepressant effects, but the mechanism involved is not fully understood. Here the authors show that ketamine enhances glutamatergic neurotransmission and produces rapid antidepressant-like effects though recruitment of TARP-γ8 at the postsynaptic sites in the ventral hippocampus of stressed male mice.
- Shi-Ge Xue
- , Jin-Gang He
- & Jian-Guo Chen
-
Article
| Open AccessOpposing brain signatures of sleep in task-based and resting-state conditions
The associations between sleep, depression and brain activity are not well understood. Here, the authors show patterns of brain activity associated with insomnia and depression resemble those found in people who sleep less, but only under cognitive load. At rest, these activation patterns are hyperconnected and resemble those found in longer sleepers.
- Mohamed Abdelhack
- , Peter Zhukovsky
- & Daniel Felsky
-
Article
| Open AccessMesenchymal stromal cells alleviate depressive and anxiety-like behaviors via a lung vagal-to-brain axis in male mice
Major depressive disorder is a major public health problem. Here, the authors illustrate that mesenchymal stromal cells exert antidepressant and anxiolytic effects through a pulmonary vagal→ nucleus tractus solitarius → 5-HT dorsal raphe nucleus neural pathway in murine depression models.
- Jing Huang
- , Weijun Huang
- & Andy Peng Xiang
-
Article
| Open AccessVentral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice
Ventral striatal Islands of Calleja neurons, known to regulate grooming in mice, are reported to bidirectionally mediate depression-like behaviors. Here, authors link grooming, dopamine signaling and affective behaviors via ventral striatal circuits.
- Yun-Feng Zhang
- , Jialiang Wu
- & Minghong Ma
-
Article
| Open AccessTranscriptional dissection of symptomatic profiles across the brain of men and women with depression
Recent research sheds light on sex-specific molecular changes in the brains of MDD patients, but their association with specific symptoms is still uncertain. Here, the authors revealed the existence of gene signatures underlying the expression of distinct symptom domains in the brain of men and women with depression.
- Samaneh Mansouri
- , André M. Pessoni
- & Benoit Labonté
-
Article
| Open AccessRepressed Blautia-acetate immunological axis underlies breast cancer progression promoted by chronic stress
Chronic stress can promote breast cancer progression. Here the authors show that a reduction in the levels of Blautia and its metabolite acetate contributes to chronic stress-promoted breast cancer progression, associated with decreased CD8 + T cell anti-tumor immunity.
- Ling Ye
- , Yuanlong Hou
- & Haiping Hao
-
Article
| Open AccessParsing altered gray matter morphology of depression using a framework integrating the normative model and non-negative matrix factorization
The neuroanatomical heterogeneity of depression is not well understood. Here, the authors identify four latent factors which characterise different patterns of gray matter morphology and are related to clinical symptoms.
- Shaoqiang Han
- , Qian Cui
- & Yong Zhang
-
Article
| Open AccessA dorsomedial prefrontal cortex-based dynamic functional connectivity model of rumination
Rumination, which is the tendency to dwell on negative internal states repetitively, is a well-known cognitive style associated with depression. The authors developed a predictive model of rumination and observed that the dorsomedial prefrontal cortex plays an important role in rumination.
- Jungwoo Kim
- , Jessica R. Andrews-Hanna
- & Choong-Wan Woo
-
Article
| Open AccessCell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes
Sex differences in brain transcriptomics have unknown cell type specificity. Here, authors show concordant cortical transcriptomic patterns in depression within individual cell types between sexes, but distinctly affected top cell types and genes.
- Malosree Maitra
- , Haruka Mitsuhashi
- & Corina Nagy
-
Article
| Open AccessA computational analysis of mouse behavior in the sucrose preference test
The sucrose preference test is one of the most widely used paradigms in behavioral neuroscience. Here, authors identify previously unrecognized behavioral subcomponents that can influence how it is interpreted.
- Jeroen P. H. Verharen
- , Johannes W. de Jong
- & Stephan Lammel
-
Article
| Open AccessAccelerated biological aging and risk of depression and anxiety: evidence from 424,299 UK Biobank participants
Theory indicates that biological aging may contribute to poor mental health in late life. Here, authors show advanced biological aging may represent a potential risk factor for incident depression/anxiety in midlife and older adults and a potential target for risk assessment and intervention.
- Xu Gao
- , Tong Geng
- & Tao Huang
-
Article
| Open AccessThe basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice
While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here, authors show the critical role of the BLA-ACC pathway in pain and emotional processing, and their comorbidity.
- Léa J. Becker
- , Clémentine Fillinger
- & Ipek Yalcin
-
Article
| Open AccessPlasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice
The cholinergic circuits involved in pain modulation remain poorly understood. Here, the authors show that reversal of plasticity in the ventral pallidum-basolateral amygdala cholinergic pathway relieves hyperalgesia and depression-like behaviours in a chronic pain mouse model.
- Ya-Wei Ji
- , Zi-Lin Shen
- & Cheng Xiao
-
Article
| Open AccessAssociations between mental health, blood pressure and the development of hypertension
Mental and cardiovascular health interact in complex ways. Here, the authors demonstrate an association of blood pressure with depressive symptoms, well-being, and emotion-related brain activity that may be relevant to the development of hypertension.
- H. Lina Schaare
- , Maria Blöchl
- & Arno Villringer
-
Article
| Open AccessLateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula
The mechanism underlying caffeine consumption inversely correlation with depression is unclear. Here, authors identified adenosine A2A receptor in the lateral septum mediating depressive symptoms via direct outputs to the habenula and the hypothalamus.
- Muran Wang
- , Peijun Li
- & Wei Guo
-
Article
| Open AccessRegional clozapine, ECT and lithium usage inversely associated with excess suicide rates in male adolescents
There are conflicting results on the effectiveness of pharmacologic interventions for suicide prevention in adolescence. Here, the authors show, in a retrospective registry study from Sweden during 2016–2020, that regional utilization rates of clozapine, electroconvulsive therapy and lithium in 15–19-year-olds were associated with lower excess suicide death rates in male adolescents
- Adrian E. Desai Boström
- , Peter Andersson
- & Jussi Jokinen
-
Article
| Open AccessRegional gene expression signatures are associated with sex-specific functional connectivity changes in depression
The neural substrates of depression may differ by sex. Here the authors show that depression is associated with distinct brain connectivity changes in men and in women that are explained by sex-specific transcriptomic signatures involving genes previously implicated in synapse function, immune signalling, and depression risk.
- Aleksandr Talishinsky
- , Jonathan Downar
- & Conor Liston
-
Article
| Open AccessMapping effective connectivity of human amygdala subdivisions with intracranial stimulation
The amygdala is known to be engaged in emotional and autonomic function, yet the detailed functional connectivity of the human amygdala remains unclear. Here, the authors examine effective connectivity in the amygdala of patients with epilepsy using direct focal electrical stimulation.
- Masahiro Sawada
- , Ralph Adolphs
- & Hiroyuki Oya
-
Article
| Open AccessShared mechanisms across the major psychiatric and neurodegenerative diseases
Studying the shared genetic etiology of disease can help improve diagnosis and treatment. Here, the authors find evidence for shared genetic and molecular pathophysiology between several common psychiatric and neurodegenerative diseases using results of 25 GWAS and large-scale human brain transcriptomic and proteomic sequencing.
- Thomas S. Wingo
- , Yue Liu
- & Aliza P. Wingo
-
Article
| Open AccessKetamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
Rawat et al. demonstrate that activation of adult-born immature hippocampal neurons is necessary and sufficient for the acute antidepressant effects of low-dose ketamine in mice.
- Radhika Rawat
- , Elif Tunc-Ozcan
- & John A. Kessler
-
Article
| Open AccessMidbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors
Anxiety and depression are highly comorbid, yet the distinct or shared neurobiological correlates of anxiety remain elusive. Here, Morel et al. define that the midbrain projection to the basolateral amygdala control anxiety but not depression.
- Carole Morel
- , Sarah E. Montgomery
- & Ming-Hu Han
-
Article
| Open AccessModeling assortative mating and genetic similarities between partners, siblings, and in-laws
Assortative mating could violate the assumption of random mating used in many genetic studies. Here, the authors study more than 25,000 Norwegian families to find genetic similarity between partners, siblings, and in-laws in genetic factors related to educational attainment, height, and depression.
- Fartein Ask Torvik
- , Espen Moen Eilertsen
- & Eivind Ystrom
-
Article
| Open AccessVascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue
The vascular, cellular and molecular changes underlying sex differences in mood disorders are unclear. Here, the authors show that blood-brain barrier dysfunction modulates anxiety- and depressive-like behaviors in female mice and endothelium-specific changes associated with maladaptive responses compared to resilience to stress.
- Laurence Dion-Albert
- , Alice Cadoret
- & Caroline Menard
-
Article
| Open AccessFat mass and obesity-associated protein regulates RNA methylation associated with depression-like behavior in mice
Post-transcriptional modification of RNA can contribute to regulating behavior. Here, the authors show that modulating the expression of Fto results in epitranscriptomic changes in the mouse hippocampus associated with depression-like behavior.
- Shu Liu
- , Jianbo Xiu
- & Qi Xu
-
Article
| Open AccessNeuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior
The link between tRNA modifications, protein translation, and behavior is unclear. Here, the authors show that neuronal Nsun2 deficiency results in codon-specific epitranscriptomic changes of Gly-tRNAs and proteomic changes affecting synaptic signaling and behavior in mice.
- J. Blaze
- , A. Navickas
- & S. Akbarian
-
Article
| Open AccessCortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures
The correlation between brain structural changes in major depressive disorder (MDD) and gene expression is unclear. Here, the authors explore the correlation between cell type-specific gene expression changes and cortical structural difference in individuals with major depressive disorder.
- Jiao Li
- , Jakob Seidlitz
- & Wei Liao
-
Article
| Open AccessOver-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat
Alexander et al. causally implicate over-activity in primate subgenual cingulate in affective and cardiovascular dysfunction relevant to anxiety and depression. Over-activation led to elevated activity in a stress-related network whilst decreasing activity in higher-order prefrontal cognitive regions.
- Laith Alexander
- , Christian M. Wood
- & Angela C. Roberts
-
Article
| Open AccessA phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank
Depression is correlated with many brain-related traits. Here, Shen et al. perform phenome-wide association studies of a depression polygenic risk score (PRS) and find associations with 51 behavioural and 26 neuroimaging traits which are further followed up on using Mendelian randomization and mediation analyses.
- Xueyi Shen
- , David M. Howard
- & Andrew M. McIntosh
-
Article
| Open AccessGPR56/ADGRG1 is associated with response to antidepressant treatment
It is not fully understood why some patients respond or do not respond to antidepressant treatment. Here the authors show that in the blood of individuals with depression, GPR56 expression increases in responders to antidepressant treatment, but not in non-responders.
- Raoul Belzeaux
- , Victor Gorgievski
- & Gustavo Turecki
-
Article
| Open AccessKetamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines
The authors show that a subanesthetic dose of ketamine markedly elevate calcium signals in apical dendritic spines in the mouse prefrontal cortex. This effect is driven by a local-circuit mechanism that involves the suppression of somatostatin interneurons leading to dendritic disinhibition.
- Farhan Ali
- , Danielle M. Gerhard
- & Alex C. Kwan
-
Article
| Open AccessAttenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors
Palmitoylation is a post translational modification that regulates GPCR activity. Here the authors show that palmitoylation of 5-HT1AR by the palmitoyltransferase enzyme ZDHHC21 contributes to depression-like behaviour in rodents and might be implicated in major depressive disorder.
- Nataliya Gorinski
- , Monika Bijata
- & Evgeni Ponimaskin
-
Article
| Open AccessLocus coeruleus-CA1 projections are involved in chronic depressive stress-induced hippocampal vulnerability to transient global ischaemia
Depression and transient ischaemic attacks are tightly regulated but the neural circuits underlying depression-modulated ischaemic injury are not known. Here, the authors show that the locus coeruleus-CA1 pathway is involved in depression-associated ischaemia susceptibility.
- Qian Zhang
- , Dian Xing Hu
- & Bo Tian
-
Article
| Open AccessDeep brain stimulation of the internal capsule enhances human cognitive control and prefrontal cortex function
Deep brain stimulation (DBS) is a promising treatment for psychiatric disorders, but its mechanism in relieving symptoms is unclear. Here, the authors show that DBS of ventral internal capsule/ventral striatum (VCVS) may act by enhancing prefrontal cortex oscillations that in turn enhance cognitive control.
- A. S. Widge
- , S. Zorowitz
- & D. D. Dougherty
-
Article
| Open AccessLower synaptic density is associated with depression severity and network alterations
Lowered synaptic density is believed to occur in major depressive disorder and PTSD, possibly as an effect of stress. Here, the authors use positron emission tomography (PET) to measure levels of the synaptic marker SV2A and show that SV2A density is lower in those with more severe symptoms of depression.
- Sophie E. Holmes
- , Dustin Scheinost
- & Irina Esterlis
-
Article
| Open AccessOptogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects
Ketamine exerts fast-acting anti-depressant responses. Here the authors show that dopamine D1 receptor expressing neurons in the medial prefrontal cortex contribute to these antidepressant-like effects in mice.
- Brendan D. Hare
- , Ryota Shinohara
- & Ronald S. Duman
-
Article
| Open AccessTranslational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E
Translation of mRNA contributes to neuronal function and complex behaviours, and inflammation is thought to contribute to depression. Here the authors show that mice lacking phosphorylation sites in eIF4E (eukaryotic initiation factor 4E) display anxiety- and depression-like behaviour and decreased IkBα expression; furthermore TNFα delivery to the medial prefrontal cortex induces depression-like behaviour and deficits in serotonergic transmission.
- Argel Aguilar-Valles
- , Nabila Haji
- & Nahum Sonenberg
-
Article
| Open AccessGenome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways
The UK Biobank provides data for three depression-related phenotypes. Here, Howard et al. perform a genome-association study for broad depression, probable major depressive disorder (MDD) and hospital record-coded MDD in up to 322,580 UK Biobank participants which highlights excitatory synaptic pathways.
- David M. Howard
- , Mark J. Adams
- & Andrew M. McIntosh
-
Article
| Open AccessTrkB dependent adult hippocampal progenitor differentiation mediates sustained ketamine antidepressant response
The precise mechanism for the sustained antidepressant action of ketamine is unclear. This study shows ketamine can promote neuronal differentiation via TrkB-ERK activation in mice and the sustained behavioral effect is attenuated when adult neurogenesis is blocked, but extended when it is enhanced.
- Zhenzhong Ma
- , Tong Zang
- & Luis F. Parada
-
Article
| Open AccessLimiting habenular hyperactivity ameliorates maternal separation-driven depressive-like symptoms
Early-life stress primes depression in adulthood. This study shows that early maternal separation leads to lateral habenula (LHb) hyperactivity and causes depressive-like phenotypes, the latter being reversible when LHb hyperactivity is reduced chemogenetically or through deep-brain stimulation.
- Anna Tchenio
- , Salvatore Lecca
- & Manuel Mameli
-
Article
| Open AccessSerotonin modulates a depression-like state in Drosophila responsive to lithium treatment
Features of major depressive disorder including lack of motivation, sleep disruption and cognitive deficit have been modelled in rodents. Here, the authors develop a new method to elicit a depression-like state inDrosophila, and uncover separable roles for different serotonin receptors in depression-like behaviour.
- Ariane-Saskia Ries
- , Tim Hermanns
- & Roland Strauss
-
Article
| Open AccessKCNQ channel openers reverse depressive symptoms via an active resilience mechanism
Potassium channels in the ventral tegmental area are known to regulate resilience against stress-induced depression. Here, the authors show over expression of KCNQ3 channels in VTA dopaminergic neurons or treatment with KCNQ channel openers normalizes depressive behaviours in mouse models.
- Allyson K. Friedman
- , Barbara Juarez
- & Ming-Hu Han
-
Article
| Open AccessBidirectional regulation of synaptic transmission by BRAG1/IQSEC2 and its requirement in long-term depression
BRAG1 mutations are linked to synaptic deficits and X-chromosome linked intellectual disability. Here, the authors show that BRAG1 mediates activity-dependent removal of synaptic AMPA receptors via Arf-GEF activity and PDZ interactions, and is required for maintaining AMPAR-mediated synaptic transmission.
- Joshua C. Brown
- , Amber Petersen
- & Nashaat Z. Gerges
-
Article
| Open AccessDICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression
DICER1 is required for the maturation of miRNAs which regulate expression of thousands of genes. Here the authors show significantly reduced levels of DICER1in individuals having post-traumatic stress disorder and comorbid depression suggestive of a role in the molecular mechanism of the condition.
- Aliza P. Wingo
- , Lynn M. Almli
- & Kerry J. Ressler
-
Article
| Open AccessVentral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression
Enhanced glutamatergic transmission in the nucleus accumbens (NAc) has been implicated in the pathophysiology of depression, yet the underlying source is not known. Here, the authors demonstrate a unique role for ventral hippocampal-NAc glutamatergic projections in regulating depression-like behaviour.
- Rosemary C. Bagot
- , Eric M. Parise
- & Eric J. Nestler
-
Article |
Neuroplasticity-based computerized cognitive remediation for treatment-resistant geriatric depression
As well as substantial changes in mood, geriatric depression is also characterized by executive dysfunction (ED). Morimoto et al.show that some sufferers of geriatric depression do not respond to conventional drugs, and that ED in these patients can be alleviated with computerized cognitive remediation therapy.
- Sarah Shizuko Morimoto
- , Bruce E. Wexler
- & George S. Alexopoulos