Evidence map›Paper›PMID 31563948›Full record

ArticleThe international journal of neuropsychopharmacology2020

Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association With Memory and Social Impairments and Abnormal Sensorimotor Gating.

Marquis P Vawter, Anton Schulmann, Lamees Alhassen, Wedad Alhassen, Abdul Rezzak Hamzeh, Jasmine Sakr, Lucas Pauluk, Ryan Yoshimura, Xuejie Wang, Qi Dai and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The international journal of neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Exploratory Rearing Is Governed by Hypothalamic Melanin-Concentrating Hormone Neurons According to Locus Ceruleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  5. Article
  6. Review
  7. Article
  8. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Marquis P VawterDepartment of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, CA.
Anton SchulmannDepartment of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, CA.
Lamees AlhassenDepartment of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, CA.
Wedad AlhassenDepartment of Pharmacology, School of Medicine, University of California, Irvine, CA.
Abdul Rezzak HamzehJohn Curtin School of Medical Research, Australian National University, Canberra.
Jasmine SakrDepartment of Pharmaceutical Sciences, University of California, Irvine, CA.
Lucas PaulukDepartment of Pharmacology, School of Medicine, University of California, Irvine, CA.
Ryan YoshimuraDepartment of Pharmacology, School of Medicine, University of California, Irvine, CA.
Xuejie WangDepartment of Pharmacology, School of Medicine, University of California, Irvine, CA.
Qi DaiDepartment of Pharmacology, School of Medicine, University of California, Irvine, CA.
Nayna SanatharaDepartment of Pharmacology, School of Medicine, University of California, Irvine, CA.
Olivier CivelliDepartment of Pharmacology, School of Medicine, University of California, Irvine, CA.
Amal AlachkarDepartment of Pharmaceutical Sciences, University of California, Irvine, CA.
University of California, Irvine · USAustralian National University · AUHoward Hughes Medical Institute · US

Funding

VESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHIMMING, CORBETT · 1985 to 2019
$37.9M
QUANTITATIVE ANALYSIS OF MICROVASCULAR CHANGES IN THE AGING BRAINP01AG002219 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI HAROUTUNIAN, VAHRAM · 1985 to 2009
$19.2M
White Matter Abnormalities in SchizophreniaP50MH066392 · NIMH · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BUXBAUM, JOSEPH D. · 2002 to 2012
$18.6M
Project 5: In vivo measurement of GABA transmission in healthy controls & subjectP50MH084053 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 2008 to 2012
$11.5M
International Cohort Collection for Bipolar DisorderR01MH085542 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI SMOLLER, JORDAN W · 2008 to 2012
$10.7M
NMDA Receptor Hypofunction in the Amygdala of Schizophrenia PatientsP50MH096891 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI BILKER, WARREN B. · 2012 to 2016
$10.6M
Functional Genomics of Human Brain DevelopmentP50MH106934 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD · 2014 to 2019
$7.9M
Cis-Regulatory Epigenome Mappings in SchizophreniaU01MH103392 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, SKLAR, PAMELA · 2014 to 2017
$7.6M
Molecular Profiling of SchizophreniaR01MH110921 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHESS, ANDREW J, ROUSSOS, PANAGIOTIS · 2016 to 2020
$6.9M
Transcriptional and Epigenetic Signatures of Human Brain Development and AutismU01MH103339 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD, STATE, MATTHEW W. · 2014 to 2017
$6.5M
1/2 Cell Type and Region-Specific Regulatory Networks in Human Brain Development and DisordersU01MH116488 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD · 2018 to 2022
$6.5M
Discovery and validation of neuronal enhancers as development of psychiatric disorders supplementU01MH116492 · NIMH · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GERSTEIN, MARK BENDER, WENG, ZHIPING · 2018 to 2023
$6.2M
NIA NIH HHS P01 AG002219NIA NIH HHS P50 AG005138NIDA NIH HHS HHSN271201300031CNIMH NIH HHS HHSN271201300031CNIMH NIH HHS P50 MH066392NIMH NIH HHS P50 MH084053NIMH NIH HHS P50 MH096891NIMH NIH HHS P50 MH106934NIMH NIH HHS R01 MH075916NIMH NIH HHS R01 MH080405NIMH NIH HHS R01 MH085542NIMH NIH HHS R01 MH093725NIMH NIH HHS R01 MH094714NIMH NIH HHS R01 MH097276NIMH NIH HHS R01 MH105898NIMH NIH HHS R01 MH109677NIMH NIH HHS R01 MH109715NIMH NIH HHS R01 MH109897NIMH NIH HHS R01 MH110905NIMH NIH HHS R01 MH110920NIMH NIH HHS R01 MH110921NIMH NIH HHS R01 MH110926NIMH NIH HHS R01 MH110927NIMH NIH HHS R01 MH110928NIMH NIH HHS R01 MH111721NIMH NIH HHS R01 MH117291NIMH NIH HHS R01 MH117292NIMH NIH HHS R01 MH117293NIMH NIH HHS R21 MH102791NIMH NIH HHS R21 MH103877NIMH NIH HHS R21 MH105853NIMH NIH HHS R21 MH105881NIMH NIH HHS R21 MH109956NIMH NIH HHS R37 MH057881NIMH NIH HHS R56 MH114899NIMH NIH HHS R56 MH114901NIMH NIH HHS R56 MH114911NIMH NIH HHS U01 MH103339NIMH NIH HHS U01 MH103340NIMH NIH HHS U01 MH103346NIMH NIH HHS U01 MH103365NIMH NIH HHS U01 MH103392NIMH NIH HHS U01 MH116438NIMH NIH HHS U01 MH116441NIMH NIH HHS U01 MH116442NIMH NIH HHS U01 MH116487NIMH NIH HHS U01 MH116488NIMH NIH HHS U01 MH116489NIMH NIH HHS U01 MH116492
6 · The paper itself

Abstract

backgroundEvidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide melanin concentrating hormone system in modulating emotional and cognitive functions. Genome-wide association studies revealed a potential association between the melanin concentrating hormone receptor (MCHR1) gene locus and schizophrenia, and the largest genome-wide association study conducted to date shows a credible genome-wide association.

methodsWe analyzed MCHR1 and pro-melanin concentrating hormone RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the melanin concentrating hormone system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of melanin concentrating hormone expressing neurons using a Cre-inducible diphtheria toxin system.

resultsMCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (false discovery rate (FDR) P < .05, CommonMind and PsychEncode combined datasets, n = 901) while pro-melanin concentrating hormone is below the detection threshold. MCHR1 expression decreased with aging (P = 6.6E-57) in human dorsolateral prefrontal cortex. The deletion of MCHR1 was found to lead to behavioral abnormalities mimicking schizophrenia-like phenotypes: hyperactivity, increased stereotypic and repetitive behavior, social impairment, impaired sensorimotor gating, and disrupted cognitive functions. Conditional ablation of pro-melanin concentrating hormone neurons increased repetitive behavior and produced a deficit in sensorimotor gating.

conclusionsOur study indicates that early disruption of the melanin concentrating hormone system interferes with neurodevelopmental processes, which may contribute to the pathogenesis of schizophrenia. Further neurobiological research on the developmental timing and circuits that are affected by melanin concentrating hormone may lead to a therapeutic target for early prevention of schizophrenia.

Indexed as

AdolescentAdultAgedAged, 80 and overAnimalsBehavior, AnimalChildChild, PreschoolDisease Models, AnimalFemaleFetusHumansHypothalamic HormonesInfantMaleMelaninsHypothalamic HormonesMCHR1 protein, humanMchr1 protein, mousemelanin-concentrating hormoneMelaninsPituitary HormonesReceptors, Somatostatin

Identifiers

PMID31563948
PMCPMC7442395
OpenAlexW2976108701

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.