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  1. Article ; Online: The association of child maltreatment and systemic inflammation in adulthood: A systematic review.

    Kerr, Daniel M / McDonald, James / Minnis, Helen

    PloS one

    2021  Volume 16, Issue 4, Page(s) e0243685

    Abstract: Introduction: Child maltreatment (CM) is associated with mental and physical health disorders in adulthood. Some studies have identified elevated markers of systemic inflammation in adult survivors of CM, and inflammation may mediate the association ... ...

    Abstract Introduction: Child maltreatment (CM) is associated with mental and physical health disorders in adulthood. Some studies have identified elevated markers of systemic inflammation in adult survivors of CM, and inflammation may mediate the association between CM and later health problems. However, there are methodological inconsistencies in studies of the association between CM and systemic inflammation and findings are conflicting. We performed a systematic review to examine the association of CM with systemic inflammation in adults.
    Methods: A pre-registered systematic review was performed following PRISMA guidelines. Medline, Embase, Scopus and PsychInfo were searched for studies of the association of CM with blood markers of inflammation in adults. Quality was assessed using the Crowe Critical Appraisal Tool. We had intended to perform a meta-analysis, but this was not possible due to variation in study design and reporting.
    Results: Forty-four articles met criteria for inclusion in the review. The most widely reported biomarkers were C-Reactive Protein (CRP) (n = 27), interleukin-6 (IL-6) (n = 24) and Tumour Necrosis Factor-alpha (TNF-a) (n = 17). Three studies were prospective (all relating to CRP) and the remainder were retrospective. 86% of studies were based in high income countries. In the prospective studies, CM was associated with elevated CRP in adulthood. Results of retrospective studies were conflicting. Methodological issues relating to the construct of CM, methods of analysis, and accounting for confounding or mediating variables (particularly Body Mass Index) may contribute to the uncertainty in the field.
    Conclusions: There is some robust evidence from prospective studies that CM is associated with elevated CRP in adulthood. We have identified significant methodological inconsistencies in the literature and have proposed measures that future researchers could employ to improve consistency across studies. Further prospective, longitudinal, research using robust and comparable measures of CM with careful consideration of confounding and mediating variables is required to bring clarity to this field.
    MeSH term(s) Adult ; Biomarkers/blood ; C-Reactive Protein/metabolism ; Child ; Child Abuse ; Female ; Humans ; Inflammation/blood ; Inflammation/psychology ; Interleukin-6/blood ; Male ; Mental Health ; Pregnancy ; Tumor Necrosis Factor-alpha/blood
    Chemical Substances Biomarkers ; IL6 protein, human ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2021-04-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0243685
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Social isolation-induced transcriptomic changes in mouse hippocampus impact the synapse and show convergence with human genetic risk for neurodevelopmental phenotypes.

    Laighneach, Aodán / Kelly, John P / Desbonnet, Lieve / Holleran, Laurena / Kerr, Daniel M / McKernan, Declan / Donohoe, Gary / Morris, Derek W

    PloS one

    2023  Volume 18, Issue 12, Page(s) e0295855

    Abstract: Early life stress (ELS) can impact brain development and is a risk factor for neurodevelopmental disorders such as schizophrenia. Post-weaning social isolation (SI) is used to model ELS in animals, using isolation stress to disrupt a normal developmental ...

    Abstract Early life stress (ELS) can impact brain development and is a risk factor for neurodevelopmental disorders such as schizophrenia. Post-weaning social isolation (SI) is used to model ELS in animals, using isolation stress to disrupt a normal developmental trajectory. We aimed to investigate how SI affects the expression of genes in mouse hippocampus and to investigate how these changes related to the genetic basis of neurodevelopmental phenotypes. BL/6J mice were exposed to post-weaning SI (PD21-25) or treated as group-housed controls (n = 7-8 per group). RNA sequencing was performed on tissue samples from the hippocampus of adult male and female mice. Four hundred and 1,215 differentially-expressed genes (DEGs) at a false discovery rate of < 0.05 were detected between SI and control samples for males and females respectively. DEGS for both males and females were significantly overrepresented in gene ontologies related to synaptic structure and function, especially the post-synapse. DEGs were enriched for common variant (SNP) heritability in humans that contributes to risk of neuropsychiatric disorders (schizophrenia, bipolar disorder) and to cognitive function. DEGs were also enriched for genes harbouring rare de novo variants that contribute to autism spectrum disorder and other developmental disorders. Finally, cell type analysis revealed populations of hippocampal astrocytes that were enriched for DEGs, indicating effects in these cell types as well as neurons. Overall, these data suggest a convergence between genes dysregulated by the SI stressor in the mouse and genes associated with neurodevelopmental disorders and cognitive phenotypes in humans.
    MeSH term(s) Adult ; Humans ; Male ; Animals ; Mice ; Female ; Autism Spectrum Disorder ; Gene Expression Profiling ; Hippocampus/metabolism ; Social Isolation ; Synapses ; Phenotype ; Risk Factors ; Human Genetics
    Language English
    Publishing date 2023-12-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0295855
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Increasing Endocannabinoid Tone Alters Anxiety-Like and Stress Coping Behaviour in Female Rats Prenatally Exposed to Valproic Acid.

    Thornton, Aoife M / Humphrey, Rachel M / Kerr, Daniel M / Finn, David P / Roche, Michelle

    Molecules (Basel, Switzerland)

    2021  Volume 26, Issue 12

    Abstract: Given the sex differences evident in the prevalence of autism, there is an increased awareness of the importance of including females in autism research to determine sexual dimorphism and sex-specific treatments. Cannabinoids and endocannabinoid ... ...

    Abstract Given the sex differences evident in the prevalence of autism, there is an increased awareness of the importance of including females in autism research to determine sexual dimorphism and sex-specific treatments. Cannabinoids and endocannabinoid modulators have been proposed as potential novel treatments for autism-related symptoms; however, few studies to date have examined if these pharmacological agents elicit sex-specific effects. The aim of the present study was to use the valproic acid (VPA) model of autism to compare the behavioural responses of male and female rats and examine the effects of increasing endocannabinoid tone on the behavioural responses of VPA-exposed female rats. These data revealed that VPA-exposed male, but not female, rats exhibit reduced social responding in the three-chamber and olfactory habituation/dishabituation (OHD) test during adolescence. In comparison, VPA-exposed female, but not male, adolescent rats exhibited anxiety-like behaviour in the elevated plus maze (EPM) and open field test (OFT). In VPA-exposed female rats, increasing 2-AG levels augmented anxiety-like behaviour in the EPM and OFT, while increasing AEA levels reduced stress coping behaviour in the swim stress test. These data highlight sexual dimorphic behaviours in the VPA model and indicate that enhancing endocannabinoid levels may exacerbate negative affective behaviour in VPA-exposed females. Thus, considerations should be paid to the possible sex-specific effects of cannabinoids for the treatment of symptoms associated with autism.
    MeSH term(s) Animals ; Anxiety/drug therapy ; Anxiety Disorders/drug therapy ; Autistic Disorder/drug therapy ; Behavior, Animal/drug effects ; Disease Models, Animal ; Endocannabinoids/pharmacology ; Female ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects/drug therapy ; Psychological Distress ; Rats ; Rats, Sprague-Dawley ; Valproic Acid/adverse effects
    Chemical Substances Endocannabinoids ; Valproic Acid (614OI1Z5WI)
    Language English
    Publishing date 2021-06-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules26123720
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Correction: The hallmarks of childhood abuse and neglect: A systematic review.

    Lang, Jason / Kerr, Daniel M / Petri-Romão, Papoula / McKee, Tracey / Smith, Helen / Wilson, Naomi / Zavrou, Marianna / Shiels, Paul / Minnis, Helen

    PloS one

    2023  Volume 18, Issue 12, Page(s) e0296550

    Abstract: This corrects the article DOI: 10.1371/journal.pone.0243639.]. ...

    Abstract [This corrects the article DOI: 10.1371/journal.pone.0243639.].
    Language English
    Publishing date 2023-12-28
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0296550
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Exacerbated LPS/GalN-Induced Liver Injury in the Stress-Sensitive Wistar Kyoto Rat Is Associated with Changes in the Endocannabinoid System.

    Killilea, Marykate / Kerr, Daniel M / Mallard, Beth M / Roche, Michelle / Wheatley, Antony M

    Molecules (Basel, Switzerland)

    2020  Volume 25, Issue 17

    Abstract: Acute liver injury (ALI) is a highly destructive and potentially life-threatening condition, exacerbated by physical and psychological stress. The endocannabinoid system plays a key role in modulating stress and hepatic function. The aim of this study ... ...

    Abstract Acute liver injury (ALI) is a highly destructive and potentially life-threatening condition, exacerbated by physical and psychological stress. The endocannabinoid system plays a key role in modulating stress and hepatic function. The aim of this study was to examine the development of acute liver injury in the genetically susceptible stress-sensitive Wistar-Kyoto (WKY) rat compared with normo-stress-sensitive Sprague Dawley (SD) rats, and associated changes in the endocannabinoid system. Administration of the hepatotoxin lipopolysaccharide/D-Galactosamine (LPS/GalN) resulted in marked liver injury in WKY, but not SD rats, with increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) plasma levels, significant histopathological changes, increased hepatic pro-inflammatory cytokine expression and caspase-3 activity and expression and reduced Glutathione (GSH) activity. Furthermore, compared to SD controls, WKY rats display increased anandamide and 2-Arachidonoylglycerol levels concurrent with decreased expression of their metabolic enzymes and a decrease in cannabinoid (CB)
    MeSH term(s) Acute Disease ; Alanine Transaminase/blood ; Animals ; Aspartate Aminotransferases/blood ; Caspase 3/metabolism ; Chemical and Drug Induced Liver Injury/blood ; Chemical and Drug Induced Liver Injury/metabolism ; Chemical and Drug Induced Liver Injury/pathology ; Endocannabinoids/blood ; Galactosamine/toxicity ; Glutamate Dehydrogenase/blood ; Glutathione/metabolism ; Lipopolysaccharides/toxicity ; Liver/metabolism ; Liver/pathology ; Male ; Rats ; Rats, Inbred WKY ; Rats, Sprague-Dawley
    Chemical Substances Endocannabinoids ; Lipopolysaccharides ; Galactosamine (7535-00-4) ; Glutamate Dehydrogenase (EC 1.4.1.2) ; Aspartate Aminotransferases (EC 2.6.1.1) ; Alanine Transaminase (EC 2.6.1.2) ; Casp3 protein, rat (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) ; Glutathione (GAN16C9B8O)
    Language English
    Publishing date 2020-08-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules25173834
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  6. Article ; Online: FAAH inhibition attenuates TLR3-mediated hyperthermia, nociceptive- and anxiety-like behaviour in female rats.

    Flannery, Lisa E / Kerr, Daniel M / Finn, David P / Roche, Michelle

    Behavioural brain research

    2018  Volume 353, Page(s) 11–20

    Abstract: Aberrant activation of toll-like receptor (TLR)s results in persistent and prolonged neuroinflammation and has been implicated in the pathogenesis and exacerbation of psychiatric and neurodegenerative disorders. TLR3 coordinates the innate immune ... ...

    Abstract Aberrant activation of toll-like receptor (TLR)s results in persistent and prolonged neuroinflammation and has been implicated in the pathogenesis and exacerbation of psychiatric and neurodegenerative disorders. TLR3 coordinates the innate immune response to viral infection and recent data have demonstrated that inhibiting fatty acid amide hydrolase (FAAH), the enzyme that primarily metabolizes anandamide, modulates TLR3-mediated neuroinflammation. However, the physiological and behavioural consequences of such modulation are unknown. The present study examined the effect of URB597, a selective FAAH inhibitor, on neuroinflammation, physiological and behavioural alterations following administration of the TLR3 agonist and viral mimetic poly I:C to female rats. URB597 attenuated TLR3-mediated fever, mechanical and cold allodynia, and anxiety-like behaviour in the elevated plus maze and open field arena. There was no effect of URB597 on TLR3-mediated decreases in body weight and no effect in the sucrose preference or forced swim tests. URB597 attenuated the TLR3-mediated increase in the expression of CD11b and CD68, markers of microglia/macrophage activation. In summary, these data demonstrate that enhancing FAAH substrate levels suppresses TLR3-mediated microglia/macrophage activation and associated changes in fever, nociceptive responding and anxiety-related behaviour. These data provide further support for FAAH as a novel therapeutic target for neuroinflammatory disorders.
    MeSH term(s) Amidohydrolases/antagonists & inhibitors ; Amidohydrolases/metabolism ; Animals ; Anxiety/drug therapy ; Anxiety/enzymology ; Benzamides/pharmacology ; Carbamates/pharmacology ; Central Nervous System Agents/pharmacology ; Enzyme Inhibitors/pharmacology ; Fever/drug therapy ; Fever/enzymology ; Hypothalamus/drug effects ; Hypothalamus/enzymology ; Inflammation/drug therapy ; Inflammation/enzymology ; Macrophages/drug effects ; Macrophages/enzymology ; Microglia/drug effects ; Microglia/enzymology ; Nociceptive Pain/drug therapy ; Nociceptive Pain/enzymology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 3/metabolism
    Chemical Substances Benzamides ; Carbamates ; Central Nervous System Agents ; Enzyme Inhibitors ; TLR3 protein, rat ; Toll-Like Receptor 3 ; cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester ; Amidohydrolases (EC 3.5.-) ; fatty-acid amide hydrolase (EC 3.5.1.-)
    Language English
    Publishing date 2018-06-25
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2018.06.030
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  7. Article ; Online: Pharmacological inhibition of fatty acid amide hydrolase attenuates social behavioural deficits in male rats prenatally exposed to valproic acid.

    Kerr, Daniel M / Gilmartin, Aoife / Roche, Michelle

    Pharmacological research

    2016  Volume 113, Issue Pt A, Page(s) 228–235

    Abstract: Autism spectrum disorders are a group of neurodevelopmental disorders characterised by impaired social interaction, deficits in communication and repetitive stereotyped behaviours. The endocannabinoid system plays an important role in modulating ... ...

    Abstract Autism spectrum disorders are a group of neurodevelopmental disorders characterised by impaired social interaction, deficits in communication and repetitive stereotyped behaviours. The endocannabinoid system plays an important role in modulating emotionality and social responding, however there have been a paucity of studies investigating this system in autistic animal models. This study investigated the effect of inhibiting fatty acid amide hydrolyase (FAAH), the anandamide catabolic enzyme, on behavioural responding in the valproic acid (VPA) rat model of autism. Male rats prenatally exposed to VPA exhibit an autistic-like behavioural phenotype exemplified as thermal hypoalgesia, reduced social and exploratory behaviour, and enhanced repetitive behaviour. Systemic administration of the FAAH inhibitor PF3845 (10mg/kg) attenuated the deficit in social behaviour observed in VPA exposed male animals without altering nociceptive, repetitive or exploratory behaviour. In comparison, female VPA exposed rats displayed enhanced repetitive and reduced exploratory behaviour, but no change in social behaviour or thermal nociceptive responding. PF3845 did not alter social, repetitive or thermal nociceptive responding, but reduced exploratory behaviour in a social context in VPA-, but not saline-, exposed females. These data indicate that FAAH inhibition elicits sexual dimorphic effects on behavioural responding in VPA exposed rodents, and support an important role for FAAH in the regulation of social behavioural deficits in autistic males.
    Language English
    Publishing date 2016-11
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1003347-6
    ISSN 1096-1186 ; 0031-6989 ; 1043-6618
    ISSN (online) 1096-1186
    ISSN 0031-6989 ; 1043-6618
    DOI 10.1016/j.phrs.2016.08.033
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  8. Article ; Online: Endocannabinoid modulation of inflammatory hyperalgesia in the IFN-α mouse model of depression.

    Fitzgibbon, Marie / Kerr, Daniel M / Henry, Rebecca J / Finn, David P / Roche, Michelle

    Brain, behavior, and immunity

    2019  Volume 82, Page(s) 372–381

    Abstract: Depression is a well-recognised effect of long-term treatment with interferon-alpha (IFN-α), a widely used treatment for chronic viral hepatitis and malignancy. In addition to the emotional disturbances, high incidences of painful symptoms such as ... ...

    Abstract Depression is a well-recognised effect of long-term treatment with interferon-alpha (IFN-α), a widely used treatment for chronic viral hepatitis and malignancy. In addition to the emotional disturbances, high incidences of painful symptoms such as headache and joint pain have also been reported following IFN-α treatment. The endocannabinoid system plays an important role in emotional and nociceptive processing, however it is unknown whether repeated IFN-α administration induces alterations in this system. The present study investigated nociceptive responding in the IFN-α-induced mouse model of depression and associated changes in the endocannabinoid system. Furthermore, the effects of modulating peripheral endocannabinoid tone on inflammatory pain-related behaviour in the IFN-α model was examined. Repeated IFN-α administration (8000 IU/g/day) to male C57/Bl6 mice increased immobility in the forced swim test and reduced sucrose preference, without altering body weight gain or locomotor activity, confirming development of the depressive-like phenotype. There was no effect of repeated IFN-α administration on latency to respond in the hot plate test on day 4 or 7 of treatment, however, formalin-evoked nociceptive behaviour was significantly increased in IFN-α treated mice following 8 days of IFN-α administration. 2-Arachidonoyl glycerol (2-AG) levels in the periaqueductal grey (PAG) and rostroventromedial medulla (RVM), and anandamide (AEA) levels in the RVM, were significantly increased in IFN-α-, but not saline-, treated mice following formalin administration. There was no change in endocannabinoid levels in the prefrontal cortex, spinal cord or paw tissue between saline- or IFNα-treated mice in the presence or absence of formalin. Furthermore, repeated IFN-α and/or formalin administration did not alter mRNA expression of genes encoding the endocannabinoid catabolic enzymes (fatty acid amide hydrolase or monoacylglycerol lipase) or endocannabinoid receptor targets (CB
    MeSH term(s) Amidohydrolases/metabolism ; Animals ; Arachidonic Acids/metabolism ; Depression/metabolism ; Endocannabinoids/metabolism ; Glycerides/metabolism ; Hyperalgesia/immunology ; Hyperalgesia/metabolism ; Interferon-alpha/metabolism ; Interferon-alpha/pharmacology ; Male ; Mice ; Monoacylglycerol Lipases/metabolism ; Nociceptors/drug effects ; Nociceptors/metabolism ; Pain/metabolism ; Pain/physiopathology ; Polyunsaturated Alkamides/metabolism
    Chemical Substances Arachidonic Acids ; Endocannabinoids ; Glycerides ; Interferon-alpha ; Polyunsaturated Alkamides ; glyceryl 2-arachidonate (8D239QDW64) ; Monoacylglycerol Lipases (EC 3.1.1.23) ; Amidohydrolases (EC 3.5.-) ; fatty-acid amide hydrolase (EC 3.5.1.-) ; anandamide (UR5G69TJKH)
    Language English
    Publishing date 2019-09-07
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2019.09.006
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  9. Article ; Online: Letter by Kerr and Lees regarding article, "country comparisons of human stroke research since 2001: a bibliometric study".

    Kerr, Daniel M / Lees, Kennedy R

    Stroke

    2012  Volume 43, Issue 5, Page(s) e52

    MeSH term(s) Biomedical Research/statistics & numerical data ; Humans ; Stroke
    Language English
    Publishing date 2012-05
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.112.653071
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  10. Article ; Online: Should thrombolysis be recommended for diabetic stroke patients?

    Kerr, Daniel M / Lees, Kennedy R

    Expert review of cardiovascular therapy

    2011  Volume 9, Issue 4, Page(s) 409–412

    MeSH term(s) Diabetes Complications/drug therapy ; Humans ; Stroke/complications ; Stroke/drug therapy ; Thrombolytic Therapy
    Language English
    Publishing date 2011-04
    Publishing country England
    Document type Editorial
    ZDB-ID 2192343-7
    ISSN 1744-8344 ; 1477-9072
    ISSN (online) 1744-8344
    ISSN 1477-9072
    DOI 10.1586/erc.11.8
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