Journal: Molecular Psychiatry

Abbreviation

Mol. Psychiatry

Publisher

Nature

Journal Volumes

ISSN

1359-4184
1476-5578

Description

Filters

Reset filters

Search Results

Publications1 - 10 of 39
  • Reconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry
    Item type: Review Article
    Notter, Tina; Coughlin, Jennifer; Sawa, Akira; et al. (2018)
    Molecular Psychiatry
  • The autism brain imaging data exchange: Towards a large-scale evaluation of the intrinsic brain architecture in autism
    Item type: Journal Article
    Di Martino, Adriana; Yan, Chaogan G.; Li, Qingyang; et al. (2014)
    Molecular Psychiatry
  • Dysfunction of ventral tegmental area GABA neurons causes mania-like behavior
    Item type: Journal Article
    Yu, Xiao; Ba, Wei; Zhao, Guangchao; et al. (2021)
    Molecular Psychiatry
    The ventral tegmental area (VTA), an important source of dopamine, regulates goal- and reward-directed and social behaviors, wakefulness, and sleep. Hyperactivation of dopamine neurons generates behavioral pathologies. But any roles of non-dopamine VTA neurons in psychiatric illness have been little explored. Lesioning or chemogenetically inhibiting VTA GABAergic (VTA(Vgat)) neurons generated persistent wakefulness with mania-like qualities: locomotor activity was increased; sensitivity to D-amphetamine was heightened; immobility times decreased on the tail suspension and forced swim tests; and sucrose preference increased. Furthermore, after sleep deprivation, mice with lesioned VTA(Vgat)neurons did not catch up on lost sleep, even though they were starting from a sleep-deprived baseline, suggesting that sleep homeostasis was bypassed. The mania-like behaviors, including the sleep loss, were reversed by valproate, and re-emerged when treatment was stopped. Lithium salts and lamotrigine, however, had no effect. Low doses of diazepam partially reduced the hyperlocomotion and fully recovered the immobility time during tail suspension. The mania like-behaviors mostly depended on dopamine, because giving D1/D2/D3 receptor antagonists reduced these behaviors, but also partially on VTA(Vgat)projections to the lateral hypothalamus (LH). Optically or chemogenetically inhibiting VTA(Vgat)terminals in the LH elevated locomotion and decreased immobility time during the tail suspension and forced swimming tests. VTA(Vgat)neurons help set an animal's (and perhaps human's) mental and physical activity levels. Inputs inhibiting VTA(Vgat)neurons intensify wakefulness (increased activity, enhanced alertness and motivation), qualities useful for acute survival. In the extreme, however, decreased or failed inhibition from VTA(Vgat)neurons produces mania-like qualities (hyperactivity, hedonia, decreased sleep).
  • Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes
    Item type: Journal Article
    Zerbi, Valerio; Pagani, Marco; Markicevic, Marija; et al. (2021)
    Molecular Psychiatry
    Autism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy and relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation of fMRI-based connectivity in the mouse, in which specific ASD-relevant mutations can be isolated and modeled minimizing environmental contributions. By performing brain-wide connectivity mapping across 16 mouse mutants, we show that different ASD-associated etiologies cause a broad spectrum of connectional abnormalities in which diverse, often diverging, connectivity signatures are recognizable. Despite this heterogeneity, the identified connectivity alterations could be classified into four subtypes characterized by discrete signatures of network dysfunction. Our findings show that etiological variability is a key determinant of connectivity heterogeneity in ASD, hence reconciling conflicting findings in clinical populations. The identification of etiologically-relevant connectivity subtypes could improve diagnostic label accuracy in the non-syndromic ASD population and paves the way for personalized treatment approaches.
  • Activin tunes GABAergic neurotransmission and modulates anxiety-like behavior
    Item type: Journal Article
    Zheng, F.; Adelsberger, H.; Müller, M.; et al. (2008)
    Molecular Psychiatry
  • Models of persecutory delusions: a mechanistic insight into the early stages of psychosis
    Item type: Journal Article
    Diaconescu, Andreea O.; Hauke, Daniel J.; Borgwardt, Stefan (2019)
    Molecular Psychiatry
  • Behavioral, neuroanatomical, and molecular correlates of resilience and susceptibility to maternal immune activation
    Item type: Journal Article
    Müller, Flavia S.; Scarborough, Joseph; Schalbetter, Sina M.; et al. (2021)
    Molecular Psychiatry
    Infectious or noninfectious maternal immune activation (MIA) is an environmental risk factor for psychiatric and neurological disorders with neurodevelopmental etiologies. Whilst there is increasing evidence for significant health consequences, the effects of MIA on the offspring appear to be variable. Here, we aimed to identify and characterize subgroups of isogenic mouse offspring exposed to identical MIA, which was induced in C57BL6/N mice by administration of the viral mimetic, poly(I:C), on gestation day 12. Cluster analysis of behavioral data obtained from a first cohort containing >150 MIA and control offspring revealed that MIA offspring could be stratified into distinct subgroups that were characterized by the presence or absence of multiple behavioral dysfunctions. The two subgroups also differed in terms of their transcriptional profiles in cortical and subcortical brain regions and brain networks of structural covariance, as measured by ex vivo structural magnetic resonance imaging (MRI). In a second, independent cohort containing 50 MIA and control offspring, we identified a subgroup of MIA offspring that displayed elevated peripheral production of innate inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in adulthood. This subgroup also showed significant impairments in social approach behavior and sensorimotor gating, whereas MIA offspring with a low inflammatory cytokine status did not. Taken together, our results highlight the existence of subgroups of MIA-exposed offspring that show dissociable behavioral, transcriptional, brain network, and immunological profiles even under conditions of genetic homogeneity. These data have relevance for advancing our understanding of the variable neurodevelopmental effects induced by MIA and for biomarker-guided approaches in preclinical psychiatric research.
  • Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma
    Item type: Journal Article
    Gapp, Katharina; van Steenwyk, Gretchen; Germain, Pierre-Luc; et al. (2020)
    Molecular Psychiatry
    Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we show that alterations in long RNA in sperm contribute to the inheritance of specific trauma symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal trauma recapitulates the effects on food intake, glucose response to insulin and risk-taking in adulthood whereas the small RNA fraction alters body weight and behavioural despair. Alterations in long RNA are maintained after fertilization, suggesting a direct link between sperm and embryo RNA.
  • Imaging microglia activity in schizophrenia Microglia and schizophrenia: where next?
    Item type: Other Journal Item
    Notter, Tina; Meyer, Urs (2017)
    Molecular Psychiatry
  • Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings
    Item type: Review Article
    Smigielski, Lukasz; Jagannath, Vinita; Rössler, Wulf; et al. (2020)
    Molecular Psychiatry
    Schizophrenia and other psychotic disorders are highly debilitating psychiatric conditions that lack a clear etiology and exhibit polygenic inheritance underlain by pleiotropic genes. The prevailing explanation points to the interplay between predisposing genes and environmental exposure. Accumulated evidence suggests that epigenetic regulation of the genome may mediate dynamic gene–environment interactions at the molecular level by modulating the expression of psychiatric phenotypes through transcription factors. This systematic review summarizes the current knowledge linking schizophrenia and other psychotic disorders to epigenetics, based on PubMed and Web of Science database searches conducted according to the PRISMA guidelines. Three groups of mechanisms in case–control studies of human tissue (i.e., postmortem brain and bio-fluids) were considered: DNA methylation, histone modifications, and non-coding miRNAs. From the initial pool of 3,204 records, 152 studies met our inclusion criteria (11,815/11,528, 233/219, and 2,091/1,827 cases/controls for each group, respectively). Many of the findings revealed associations with epigenetic modulations of genes regulating neurotransmission, neurodevelopment, and immune function, as well as differential miRNA expression (e.g., upregulated miR-34a, miR-7, and miR-181b). Overall, actual evidence moderately supports an association between epigenetics and schizophrenia and other psychotic disorders. However, heterogeneous results and cross-tissue extrapolations call for future work. Integrating epigenetics into systems biology may critically enhance research on psychosis and thus our understanding of the disorder. This may have implications for psychiatry in risk stratification, early recognition, diagnostics, precision medicine, and other interventional approaches targeting epigenetic fingerprints.
Publications1 - 10 of 39