Associating Multimodal Neuroimaging Abnormalities With the Transcriptome and Neurotransmitter Signatures in Schizophrenia

Schizophrenia Bulletin, Journal Year: 2023, Volume and Issue: 49(6), P. 1554 - 1567

Published: Aug. 22, 2023

Abstract Background and Hypothesis Schizophrenia is a multidimensional disease. This study proposes new research framework that combines multimodal meta-analysis genetic/molecular architecture to solve the consistency in neuroimaging biomarkers of schizophrenia whether these link molecular genetics. Study Design We systematically searched Web Science, PubMed, BrainMap for amplitude low-frequency fluctuations (ALFF) or fractional ALFF, regional homogeneity, cerebral blood flow, voxel-based morphometry analysis studies investigating schizophrenia. The pooled-modality, single-modality, illness duration-dependent meta-analyses were performed using activation likelihood estimation algorithm. Subsequently, Spearman correlation partial least squares regression analyses conducted assess relationship between identified reliable convergent patterns multimodality neurotransmitter/transcriptome, prior imaging brain-wide gene expression. Results In total, 203 experiments comprising 10 613 patients 461 healthy controls included. Multimodal showed brain regions significant convergence mainly distributed frontotemporal cortex, anterior cingulate insula, thalamus, striatum, hippocampus. Interestingly, illness-duration subgroups aberrant functional structural evolutionary patterns: Lines from striatum cortical core networks extensive subcortical regions. we found robust abnormalities associated with multiple neurobiological abnormalities, such as dopaminergic, glutamatergic, serotonergic, GABAergic systems. Conclusions work links transcriptome/neurotransmitters signatures underlying disease effects schizophrenia, which provides novel insight into understanding pathophysiology targeted treatments.

Language: Английский

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Neural circuit-selective, multiplexed pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 8, 2024

Selective manipulation of neural circuits using optogenetics and chemogenetics holds great translational potential but requires genetic access to neurons. Here, we demonstrate a general framework for identifying tool-independent, pharmacological strategies circuit-selective modulation. We developed an economically accessible calcium imaging-based approach large-scale scans endogenous receptor-mediated activity. As testbed this approach, used the mouse locus coeruleus due combination its widespread, modular efferent circuitry wide variety endogenously expressed GPCRs. Using machine learning-based action deconvolution retrograde tracing, identified agonist cocktail that selectively inhibits medial prefrontal cortex-projecting

Language: Английский

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Apathy in Alzheimer’s disease: A neurocircuitry based perspective

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101891 - 101891

Published: March 5, 2023

Language: Английский

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Hippocampal perineuronal net degradation identifies prefrontal and striatal circuits involved in schizophrenia-like changes in marmosets

Science Advances, Journal Year: 2025, Volume and Issue: 11(16)

Published: April 18, 2025

In schizophrenia, anterior hippocampus (aHipp) overactivity is associated with orbitofrontal cortex (OFC) dysfunction, but the contribution to symptomatology unknown. rodents, degradation of hippocampal perineuronal net (PNN) replicates this overactivity, uncertainty over rodent/human prefrontal homology limits translation humans. Here, we test hypothesis that aHipp PNN in a species human-like cortex, marmoset, alters aHipp-striatal and aHipp-OFC circuitry. Microdialysis [ 18 F]-fluoro- l -dihydroxyphenylalanine positron emission tomography identified increased dopamine synthesis associative striatum, not nucleus accumbens, as seen elevated noradrenaline OFC. Behaviorally, activity was marmoset version amphetamine-induced test, impaired probabilistic discrimination learning an OFC/striatum-dependent task computational modeling suggests due loss goal-directed behavior. Together, these findings demonstrate primate PNNs sufficient induce striatal dysfunction consistent observed humans schizophrenia.

Language: Английский

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Neuroendocrine characterization into schizophrenia: norepinephrine and melatonin as promising biomarkers

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: May 1, 2025

Although brain-derived neurotrophic factor (BDNF)has garnered extensive attention as a neuroendocrine marker in schizophrenia (SZ), its clinical utility remains limite due to inconsistent findings. To address this gap, serum samples were collected from 24 female patients with SZ and 25 healthy controls. The metabolic profiling was performed using gas chromatography-mass spectrometry (GC-MS) liquid (LC-MS) capture abroad range of metabolites. Our results revealed that BDNF is not robust discriminatory biomarker. Marked differences profiles identified between individuals. GC-MS analysis significant 79 metabolites; while the LC-MS 419 significantly differential Functional reveals these metabolites predominantly contribute neuro-related processes. findings demonstrate norepinephrine melatonin, two additional compounds, are elevated compared Notably, their higher areas under curve (AUC) values highlight potential more reliable biomarkers for SZ. This study offers valuable insights into altered patterns establishes melatonin promising biomarkers, underscoring diagnostic value role regulation mental disorders.

Language: Английский

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Ketamine for psychotic depression: An overview of the glutamatergic system and ketamine's mechanisms associated with antidepressant and psychotomimetic effects

Psychiatry Research, Journal Year: 2021, Volume and Issue: 306, P. 114231 - 114231

Published: Oct. 11, 2021

Language: Английский

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Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: March 1, 2021

Background: The locus coeruleus (LC) is a nucleus in the human brainstem with variety of noradrenaline-driven functions involved cognition, emotions, and perception. Dementia Lewy bodies (DLB) constitutes neurodegenerative disease involving deposits alpha-synuclein, first appearing brainstem. goal this narrative review to delineate relationship between expression psychiatric symptoms as an early-onset DLB degeneration LC's noradrenaline system. Methods: We searched PubMed for relevant articles concerning LC prodromal review. rely on McKeith criteria DLB. Results: found four studies that document neuronal loss, other hints neurodegeneration patients Furthermore, we reviewed theories how degenerated system contributes DLB's phenotype. hypothesized anxiety, hallucinations, delusions, depressive might occur due noradrenergic neurons entailing consecutive altered transmission projection areas. Conclusions: cause non-motor manifestation DLB, affected earlier by than are dopaminergic structures such substantia nigra, which impaired later course.

Language: Английский

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The interaction between first-episode drug-naïve schizophrenia and age based on gray matter volume and its molecular analysis: a multimodal magnetic resonance imaging study

Psychopharmacology, Journal Year: 2023, Volume and Issue: 240(4), P. 813 - 826

Published: Jan. 31, 2023

Language: Английский

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Maternal Immune Activation Induces Cortical Catecholaminergic Hypofunction and Cognitive Impairments in Offspring

Journal of Neuroimmune Pharmacology, Journal Year: 2023, Volume and Issue: 18(3), P. 348 - 365

Published: May 20, 2023

Abstract Background Impairment of specific cognitive domains in schizophrenia has been associated with prefrontal cortex (PFC) catecholaminergic deficits. Among other factors, prenatal exposure to infections represents an environmental risk factor for development adulthood. However, it remains largely unknown whether the infection-induced changes brain may be concrete switches a particular neurochemical circuit, and therefore, if they could alter behavioral functions. Methods In vitro vivo evaluation PFC systems was performed offspring from mice undergoing maternal immune activation (MIA). The status also evaluated. Prenatal viral infection mimicked by polyriboinosinic-polyribocytidylic acid (poly(I:C)) administration pregnant dams (7.5 mg/kg i.p., gestational day 9.5) consequences were evaluated adult offspring. Results MIA-treated showed disrupted recognition memory novel object task ( t = 2.30, p 0.031). This poly(I:C)-based group displayed decreased extracellular dopamine (DA) concentrations compared controls 3.17, 0.0068). Potassium-evoked release DA noradrenaline (NA) impaired poly(I:C) (DA: F [10,90] 43.33, < 0.0001; tr [1,90] 1.224, 0.2972; i 5.916, n 11); (NA: 36.27, 1.841, 0.208; 8.686, 11). same way, amphetamine‐evoked NA [8,328] 22.01, [1,328] 4.507, 0.040; 2.319, 0.020; 43); 52.07; 4.322; 0.044; [8,398] 5.727; 43). catecholamine imbalance accompanied increased D 1 2 receptor expression 2.64, 0.011 3.55, 0.0009; respectively), whereas tyrosine hydroxylase, tissue content, transporter (DAT/NET) function unaltered. Conclusions MIA induces presynaptic hypofunction impairment. model reproduces phenotypes reported opportunity study impairment this disorder.

Language: Английский

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Structural and functional characterization of the locus coeruleus in young and late middle-aged individuals

Frontiers in Neuroimaging, Journal Year: 2023, Volume and Issue: 2

Published: June 21, 2023

The brainstem locus coeruleus (LC) influences a broad range of brain processes, including cognition. so-called LC contrast is an accepted marker the integrity that consists local hyperintensity on specific Magnetic Resonance Imaging (MRI) structural images. small size has, however, rendered its functional characterization difficult in humans, aging. A full and characteristics healthy young late middle-aged individuals needed to determine potential roles different medical conditions. Here, we wanted whether activation mismatch negativity task changes aging response was associated contrast.We used Ultra-High Field (UHF) 7-Tesla MRI (fMRI) record during auditory oddball 53 volunteers, 34 younger (age: 22.15y ± 3.27; 29 women) 19 61.05y 5.3; 14 individuals.Whole-brain analyses confirmed responses typical cortical subcortical regions previously with negativity. When focusing brainstem, found significant rostral part probability mask generated based individual Although bilateral, more extensive left LC. Individual activity not significantly between individuals. Importantly, while higher older individuals, contrast.These findings may suggest age-related alterations be related response. results further remain stable aged 20 70.

Language: Английский

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