Bio

Bio

Neuroimaging biologist with extensive experience in clinical and preclinical multimodal molecular imaging techniques within the field of psychiatric and neurodegenerative disease research.

Honors & Awards

  • Women in Molecular Imaging Network (WIMIN) scholar award, World Molecular Imaging Society (WMIS)/World Molecular Imaging Congress (WMIC) (2020)
  • Alavi?Mandell Award, Society of Nuclear Medicine and Molecular Imaging (SNMMI) (2020)
  • Council of Early Career Investigators in Imaging (CECI2) 2020-21, Academy for Radiology Biomedical Imaging Research (2020)
  • Young investigator of the year award winner, World molecular imaging society (WMIS)/world molecular imaging congress (WMIC) (2019)
  • Women in Molecular Imaging Network (WIMIN) scholar award, World Molecular Imaging Society (WMIS)/world molecular imaging congress (WMIC) (2019)
  • Student travel stipend award, World Molecular Imaging Society (WMIS)/world molecular imaging congress (WMIC) (2019)
  • Best oral presentation, Stanford Neuroscience Forum (2019)
  • ERF-SNMMI Postdoctoral Molecular Imaging Scholar Program Grant, Education and Research Foundation for Nuclear Medicine and Molecular Imaging-SNMMI (2018-2020)
  • Institute of Population Health Postgraduate showcase prize, individual center winner, Centre of Imaging Sciences, University of Manchester (2016)
  • Bio-Imaging Institute fully funded PhD scholarship, University of Manchester (2012-2016)
  • Biotechnology and Biological Sciences Research Council fully funded MRes scholarship, BBSRC (2011-2012)

Boards, Advisory Committees, Professional Organizations

  • Member of the women in molecular imaging network (WIMIN) leadership committee, World Molecular Imaging Society (WMIS) (2017 - Present)
  • Trainee member, Stanford Radiology Diversity Committee (2018 - Present)
  • Founder, MIPS/Canary trainee council, Stanford University (2017 - Present)
  • Member and participant in mentorship program, Association for Women in Science (AWIS) (2017 - Present)
  • Member, Women in Bio (WIB) (2017 - Present)
  • Member, European Society of Molecular Imaging (ESMI) (2012 - 2016)
  • Member, British Neuroscience Association (BNA) (2011 - 2016)

Professional Education

  • Doctor of Philosophy, University of Manchester (2016)
  • Master of Science, Imperial College of Science, Technology & Medicine (2012)
  • Bachelor of Arts, University Of Dublin, Trinity College (2011)

Stanford Advisors

Contact

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Research & Scholarship

Current Research and Scholarly Interests

Research Focus:
Developing and evaluating imaging techniques to enhance understanding and diagnosis of neurological disorders. My current research focuses on imaging neuroinflammation in neurodegenerative disorders such as stroke, Alzheimer's disease and multiple sclerosis using positron emission tomography (PET) and magnetic resonance (MR) techniques.
My previous research topics include investigating the effects of childhood maltreatment and major depressive disorder on brain morphology.

Specilaities:
Neurobiology, neuroimaging, PET imaging, MRS/MRI, neuroinflammation, pre-clinical cognitive assessments, cell culture, science communication.

Lab Affiliations

Publications

All Publications

  • 11C-DPA-713 versus 18F-GE-180: A preclinical comparison of TSPO-PET tracers to visualize acute and chronic neuroinflammation in a mouse model of ischemic stroke. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Chaney, A., Cropper, H. C., Johnson, E. M., Lechtenberg, K. J., Peterson, T. C., Stevens, M. Y., Buckwalter, M. S., James, M. L. 2018

    Abstract

    Neuroinflammation plays a key role in neuronal injury following ischemic stroke. Positron emission tomography (PET) imaging of translocator protein 18 kDa (TSPO) permits longitudinal, non-invasive visualization of neuroinflammation in both pre-clinical and clinical settings. Many TSPO tracers have been developed, however it is unclear which tracer is the most sensitive and accurate for monitoring the in vivo spatiotemporal dynamics of neuroinflammation across applications. Hence, there is a need for head-to-head comparisons of promising TSPO-PET tracers across different disease states. Accordingly, the aim of this study was to directly compare two promising second-generation TSPO tracers; 11C-DPA-713 and 18F-GE-180, for the first time at acute and chronic time-points following ischemic stroke. Methods: Following distal middle cerebral artery occlusion (dMCAO) or sham surgery, mice underwent consecutive PET/CT imaging with 11C-DPA-713 and 18F-GE-180 at 2, 6, and 28 days after stroke. T2-weighted magnetic resonance (MR) images were acquired to enable delineation of ipsilateral (infarct) and contralateral brain regions of interest (ROIs). PET images were analyzed by calculating % injected dose per gram (%ID/g) in MR-guided ROIs. Standardized uptake value ratios were determined using the contralateral thalamus as a pseudo-reference region (SUVTh). Ex vivo autoradiography and immunohistochemistry were performed to verify in vivo findings. Results: Significantly increased tracer uptake was observed in the ipsilateral compared to contralateral ROI (SUVTh, 50-60 min summed data) at acute and chronic time-points using 11C-DPA-713 and 18F-GE-180. Ex vivo autoradiography confirmed in vivo findings demonstrating increased TSPO-tracer uptake in infarcted versus contralateral brain tissue. Importantly, a significant correlation was identified between microglial/macrophage activation (CD68 immunostaining) and 11C-DPA-713-PET signal, that was not evident with 18F-GE-180. No significant correlations were observed between TSPO-PET and activated astrocytes (GFAP immunostaining). Conclusion: Both 11C-DPA-713 and 18F-GE-180-PET enable detection of neuroinflammation at early and chronic time-points following cerebral ischemia in mice. 11C-DPA-713-PET reflects the extent of microglial activation in infarcted dMCAO mouse brain tissue more accurately compared to 18F-GE-180, and appears to be slightly more sensitive. These results highlight the potential of 11C-DPA-713 for tracking microglial activation in vivo after stroke, and warrants further investigation in both pre-clinical and clinical settings.

    View details for PubMedID 29976695

  • Longitudinal investigation of neuroinflammation and metabolite profiles in the APPswe ×PS1?e9 transgenic mouse model of Alzheimer's disease J Neurochem Chaney, A., Bauer, M., Bochicchio, D., Smigova, A., Kassiou, M., Davies, K. E., Williams, S. R., Boutin, H. 2017: 318?35

    Abstract

    There is increasing evidence linking neuroinflammation to many neurological disorders including Alzheimer's disease (AD); however, its exact contribution to disease manifestation and/or progression is poorly understood. Therefore, there is a need to investigate neuroinflammation in both health and disease. Here, we investigate cognitive decline, neuroinflammatory and other pathophysiological changes in the APPswe ×PS1?e9 transgenic mouse model of AD. Transgenic (TG) mice were compared to C57BL/6 wild type (WT) mice at 6, 12 and 18 months of age. Neuroinflammation was investigated by [18 F]DPA-714 positron emission tomography and myo-inositol levels using 1 H magnetic resonance spectroscopy (MRS) in vivo. Neuronal and cellular dysfunction was investigated by looking at N-acetylaspartate (NAA), choline-containing compounds, taurine and glutamate also using MRS. Cognitive decline was first observed at 12 m of age in the TG mice as assessed by working memory tests . A significant increase in [18 F]DPA-714 uptake was seen in the hippocampus and cortex of 18 m-old TG mice when compared to age-matched WT mice and 6 m-old TG mice. No overall effect of gene was seen on metabolite levels; however, a significant reduction in NAA was observed in 18 m-old TG mice when compared to WT. In addition, age resulted in a decrease in glutamate and an increase in choline levels. Therefore, we can conclude that increased neuroinflammation and cognitive decline are observed in TG animals, whereas NAA alterations occurring with age are exacerbated in the TG mice. These results support the role of neuroinflammation and metabolite alteration in AD and in ageing.

    View details for DOI 10.1111/jnc.14251

    View details for PubMedCentralID PMC5846890

  • Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer's disease rats FEBS OPEN BIO Mampay, M., Velasco-Estevez, M., Rolle, S. O., Chaney, A. M., Boutin, H., Dev, K. K., Moeendarbary, E., Sheridan, G. K. 2020

    Abstract

    In the brain, REST (Repressor Element-1 Silencing Transcription factor) is a key regulator of neuron cell-specific gene expression. Nuclear translocation of neuronal REST has been shown to be neuroprotective in a healthy ageing context. In contrast, inability to upregulate nuclear REST is thought to leave ageing neurons vulnerable to neurodegenerative stimuli, such as Alzheimer's disease (AD) pathology. Hippocampal and cortical neurons are known to be particularly susceptible to AD-associated neurodegeneration. However, REST expression has not been extensively characterised in the healthy ageing brain. Here, we examined the spatiotemporal immunolocalisation of REST in the brains of healthy ageing wild-type Fischer-344 and transgenic Alzheimer's disease rats (TgF344-AD). Nuclear expression of REST increased from 6 months to 18 months of age in the hippocampus, frontal cortex and subiculum of wild-type rats, but not in TgF344-AD rats. No changes in REST were measured in more posterior cortical regions or in the thalamus. Interestingly, levels of the presynaptic marker synaptophysin, a known gene target of REST, were lower in CA1 hippocampal neurons of 18-month TgF344-AD rats compared to 18-month wild-types, suggesting that elevated nuclear REST may protect against synapse loss in the CA1 of 18-month wild-type rats. High REST expression in ageing wild-type rats did not, however, protect against axonal loss nor against astroglial reactivity in the hippocampus. Taken together, our data confirm that changes in nuclear REST expression are context-, age- and brain region-specific. Moreover, key brain structures involved in learning and memory display elevated REST expression in healthy ageing wild-type rats but not TgF344-AD rats.

    View details for DOI 10.1002/2211-5463.13036

    View details for Web of Science ID 000594506200001

    View details for PubMedID 33185010

  • Neuroinflammation PET imaging: Current opinion and future directions. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Jain, P., Chaney, A., Carlson, M. L., Jackson, I. M., Rao, A., James, M. L. 2020

    Abstract

    Neuroinflammation is a pathological hallmark of numerous neurologic diseases. Positron emission tomography (PET) imaging enables a non-invasive means to investigate, quantify, and track the spatiotemporal dynamics of various immune cells in living subjects. Translocator protein 18 kDa (TSPO)-PET is a technique for detecting glial activation that has yielded valuable clinical data linking neuroinflammation to cognitive decline in neurodegenerative diseases and has also been used preliminarily as a therapy monitoring tool. However, considerable limitations of TSPO-PET have prompted identification of other more cell-specific and functionally relevant biomarkers. This review analyzes the clinical potential of available and emerging PET biomarkers of innate and adaptive immune responses, with mention of exciting future directions for the field.

    View details for DOI 10.2967/jnumed.119.229443

    View details for PubMedID 32620705

  • Physiological blood-brain transport is impaired with age by a shift in transcytosis. Nature Yang, A. C., Stevens, M. Y., Chen, M. B., Lee, D. P., Stahli, D., Gate, D., Contrepois, K., Chen, W., Iram, T., Zhang, L., Vest, R. T., Chaney, A., Lehallier, B., Olsson, N., du Bois, H., Hsieh, R., Cropper, H. C., Berdnik, D., Li, L., Wang, E. Y., Traber, G. M., Bertozzi, C. R., Luo, J., Snyder, M. P., Elias, J. E., Quake, S. R., James, M. L., Wyss-Coray, T. 2020

    Abstract

    The vascular interfaceof the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability1-3. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins4,5. Thus, it is unclear whether permeability to individually injected exogenous tracers-as isstandard in BBB studies-fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery.

    View details for DOI 10.1038/s41586-020-2453-z

    View details for PubMedID 32612231

  • TREM1-PET imaging of pro-inflammatory myeloid cells distinguishes active disease from remission in Multiple Sclerosis Chaney, A., Wilson, E., Jain, P., Cropper, H., Swarovski, M., Lucot, K., Vogel, H., Andreasson, K., James, M. L. SOC NUCLEAR MEDICINE INC. 2020

    View details for Web of Science ID 000568290500179

  • Visualizing innate immune activation in a mouse model of Parkinson's disease using a highly specific TREM1-PET tracer. Lucot, K., Stevens, M., Jain, P., Bonham, T., Webber, E., Klockow, J., Azevedo, E., Chaney, A., Graves, E., Montine, T., James, M. SOC NUCLEAR MEDICINE INC. 2020

    View details for Web of Science ID 000568290500016

  • Imaging activated immune response following therapeutic vaccination in an orthotopic glioma model with Zr-89-DFO-OX40 mAb PET Nobashi, T., Mayer, A., Xiao, Z., Chan, C., Chaney, A., Gambhir, S. SOC NUCLEAR MEDICINE INC. 2020

    View details for Web of Science ID 000568290500003

  • Demarcation of Sepsis-Induced Peripheral and Central Acidosis with pH-Low Insertion Cyclic (pHLIC) Peptide. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Henry, K. E., Chaney, A. M., Nagle, V. L., Cropper, H. C., Mozaffari, S., Slaybaugh, G., Parang, K., Andreev, O., Reshetnyak, Y. K., James, M. L., Lewis, J. S. 2020

    Abstract

    Acidosis is a key driver for many diseases, including cancer, sepsis, and stroke. The spatiotemporal dynamics of dysregulated pH across disease remains elusive and current diagnostic strategies do not provide localization of pH alterations. We sought to explore if PET imaging using hydrophobic cyclic peptides that partition into the cellular membrane at low extracellular pH (denoted as "pHLIC") can permit accurate in vivo visualization of acidosis. Methods: Acid-sensitive cyclic peptide c[E4W5C] pHLIC was conjugated to bifunctional maleimide-NO2A and radiolabeled with copper-64 (t = 12.7 h). C57BL/6J mice were administered LPS (15 mg/kg) or saline (vehicle) and serially imaged with [64Cu]Cu-c[E4W5C] over 24 h. Ex vivo autoradiography was performed on resected brain slices and subsequently stained with cresyl violet to enable high-resolution spatial analysis of tracer accumulation. A non- pH-sensitive cell-penetrating control peptide (c[R4W5C]) was used to confirm specificity of [64Cu]Cu-c[E4W5C]. CD11b (macrophage/microglia) and TMEM119 (microglia) immunostaining was performed to correlate extent of neuroinflammation with [64Cu]Cu-c[E4W5C] PET signal. Results: [64Cu]Cu-c[E4W5C] radiochemical yield and purity was >95% and >99% respectively, with molar activity >0.925 MBq/nmol. Significantly increased [64Cu]Cu-c[E4W5C] uptake was observed in LPS-treated mice (vs. vehicle) within peripheral tissues including blood, lungs, liver, and small intestines (P < 0.001-0.05). Additionally, there was significantly increased [64Cu]Cu-c[E4W5C] uptake in the brains of LPS-treated animals. Autoradiography confirmed increased uptake in the cerebellum, cortex, hippocampus, striatum, and hypothalamus of LPS-treated mice (vs. vehicle). Immunohistochemical (IHC) analysis revealed microglial/macrophage infiltrate, suggesting activation in brain regions containing increased tracer uptake. [64Cu]Cu-c[R4W5C] demonstrated significantly reduced uptake in the brain and periphery of LPS mice compared to the acid-mediated [64Cu]Cu-c[E4W5C] tracer. Conclusion: Here, we demonstrate that a pH-sensitive PET tracer specifically detects acidosis in regions associated with sepsis-driven pro-inflammatory responses. This study suggests that [64Cu]Cu-pHLIC is a valuable tool to noninvasively assess acidosis associated with both central and peripheral innate immune activation.

    View details for DOI 10.2967/jnumed.119.233072

    View details for PubMedID 32005774

  • Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis. Journal of neuroinflammation Stevens, M. Y., Cropper, H. C., Lucot, K. L., Chaney, A. M., Lechtenberg, K. J., Jackson, I. M., Buckwalter, M. S., James, M. L. 2020; 17 (1): 275

    Abstract

    B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE).Female C57BL/6?J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG1-125). PET imaging of naïve and EAE mice was performed 19?h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted.Radiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2?GBq/?mol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02 ± 0.092 vs. 1.68 ± 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ± 0.020 vs. 0.12 ± 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry-providing further evidence that [64Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice.CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.

    View details for DOI 10.1186/s12974-020-01880-8

    View details for PubMedID 32948198

  • Imaging the invaders: TREM1 as a novel PET imaging biomarker of peripheral infiltrating myeloid cells and potential therapeutic target in multiple sclerosis. Chaney, A., Cropper, H., Johnson, E., Stevens, M., James, M. SOC NUCLEAR MEDICINE INC. 2019

    View details for Web of Science ID 000473116801543

  • Radiolabeling and pre-clinical evaluation of a first-in-class CD19 PET Tracer for imaging B cells in multiple sclerosis Stevens, M., Cropper, H., Jackson, I., Chaney, A., Lechtenberg, K., Buckwalter, M., James, M. L. SOC NUCLEAR MEDICINE INC. 2019

    View details for Web of Science ID 000473116800129

  • Longitudinal TSPO-PET imaging of peripheral and central myeloid cells in a mouse model of complex regional pain syndrome. Pain Cropper, H. C., Johnson, E. M., Haight, E., Cordonnier, S. A., Chaney, A. M., Forman, T. E., Biswal, A., Stevens, M. Y., James, M. L., Tawfik, V. L. 2019

    Abstract

    Complex regional pain syndrome (CRPS) is a severely disabling disease characterized by pain, temperature changes, motor dysfunction and edema that most often occurs as an atypical response to a minor surgery or fracture. Inflammation involving activation and recruitment of innate immune cells, including both peripheral and central myeloid cells (i.e. macrophages and microglia, respectively), is a key feature of CRPS. However, the exact role and time-course of these cellular processes relative to the known acute and chronic phases of the disease are not fully understood. Positron emission tomography (PET) of translocator protein-18kDa (TSPO) is a method for non-invasively tracking these activated innate immune cells. Here, we reveal the temporal dynamics of peripheral and central inflammatory responses over 20 weeks in a tibial fracture/casting mouse model of CRPS through longitudinal TSPO-PET using [F]GE-180. PET tracer uptake quantification in the tibia revealed increased peripheral inflammation as early as 2 days post-fracture and lasting 7 weeks. Centralized inflammation was detected in the spinal cord and brain of fractured mice at 7 and 21 days post-injury. Spinal cord tissue immunofluorescent staining revealed TSPO expression in microglia (CD11b+) at 7 days, but was restricted mainly to endothelial cells (PECAM1+) at baseline and 7 weeks. Our data suggest early and persistent peripheral myeloid cell activation, and transient central microglial activation are limited to the acute phase of CRPS. Moreover, we show that TSPO-PET can be used to noninvasively monitor the spatiotemporal dynamics of myeloid cell activation in CRPS progression with potential to inform disease phase-specific therapeutics.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

    View details for PubMedID 31095093

  • Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes FRONTIERS IN AGING NEUROSCIENCE Velasco-Estevez, M., Mampay, M., Boutin, N., Chaney, A., Warn, P., Sharp, A., Burgess, E., Moeendarbary, E., Dev, K. K., Sheridan, G. K. 2018; 10

    View details for DOI 10.3389/fnagi.2018.00332

    View details for Web of Science ID 000447832900001

  • PET Imaging of Neuroinflammation Using [11C]DPA-713 in a Mouse Model of Ischemic Stroke. Journal of visualized experiments : JoVE Chaney, A. M., Johnson, E. M., Cropper, H. C., James, M. L. 2018

    Abstract

    Neuroinflammation is central to the pathological cascade following ischemic stroke. Non-invasive molecular imaging methods have the potential to provide critical insights into the temporal dynamics and role of certain neuroimmune interactions in stroke. Specifically, Positron Emission Tomography (PET) imaging of translocator protein 18 kDa (TSPO), a marker of activated microglia and peripheral myeloid-lineage cells, provides a means to detect and track neuroinflammation in vivo. Here, we present a method to accurately quantify neuroinflammation using [11C]N,N-Diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide ([11C]DPA-713), a promising second generation TSPO-PET radiotracer, in distal middle cerebral artery occlusion (dMCAO) compared to sham-operated mice. MRI was performed 2 days post-dMCAO surgery to confirm stroke and define the infarct location and volume. PET/Computed Tomography (CT) imaging was carried out 6 days post-dMCAO to capture the peak increase in TSPO levels following stroke. Quantitation of PET images was conducted to assess the uptake of [11C]DPA-713 in the brain and spleen of dMCAO and sham mice to assess central and peripheral levels of inflammation. In vivo [11C]DPA-713 brain uptake was confirmed using ex vivo autoradiography.

    View details for PubMedID 29985311

  • In vivo molecular imaging of neuroinflammation in Alzheimer's disease. Journal of neurochemistry Chaney, A., Williams, S. R., Boutin, H. 2018

    Abstract

    It has become increasingly evident that neuroinflammation plays a critical role in the pathophysiology of Alzheimer's disease (AD) and other neurodegenerative disorders. Increased glial cell activation is consistently reported in both rodent models of AD and in AD patients. Moreover, recent genome wide association studies have revealed multiple genes associated with inflammation and immunity are significantly associated with an increased risk of AD development (e.g. TREM2). Non-invasive in vivo detection and tracking of neuroinflammation is necessary to enhance our understanding of the contribution of neuroinflammation to the initiation and progression of AD. Importantly, accurate methods of quantifying neuroinflammation may aid early diagnosis and serve as an output for therapeutic monitoring and disease management. This review details current in vivo imaging biomarkers of neuroinflammation being explored and summarizes both pre-clinical and clinical results from molecular imaging studies investigating the role of neuroinflammation in AD, with a focus on positron emission tomography and magnetic resonance spectroscopy (MRS).

    View details for DOI 10.1111/jnc.14615

    View details for PubMedID 30339715

  • Effect of childhood maltreatment on brain structure in adult patients with major depressive disorder and healthy participants JOURNAL OF PSYCHIATRY & NEUROSCIENCE Chaney, A., Carballedo, A., Amico, F., Fagan, A., Skokauskas, N., Meaney, J., Frodl, T. 2014; 39 (1): 50-59

    Abstract

    Childhood maltreatment has been found to play a crucial role in the development of psychiatric disorders. However, whether childhood maltreatment is associated with structural brain changes described for major depressive disorder (MDD) is still a matter of debate. The aim of this study was to investigate whether patients with MDD and a history of childhood maltreatment display more structural changes than patients without childhood maltreatment or healthy controls.Patients with MDD and healthy controls with and without childhood maltreatment experience were investigated using high-resolution magnetic resonance imaging (MRI), and data were analyzed using voxel-based morphometry.We studied 37 patients with MDD and 46 controls. Grey matter volume was significantly decreased in the hippocampus and significantly increased in the dorsomedial prefrontal cortex (DMPFC) and the orbitofrontal cortex (OFC) in participants who had experienced childhood maltreatment compared with those who had not. Patients displayed smaller left OFC and left DMPFC volumes than controls. No significant difference in hippocampal volume was evident between patients with MDD and healthy controls. In regression analyses, despite effects from depression, age and sex on the DMPFC, OFC and hippocampus, childhood maltreatment was found to independently affect these regions.The retrospective assessment of childhood maltreatment; the natural problem that patients experienced more childhood maltreatment than controls; and the restrictions, owing to sample size, to investigating higher order interactions among factors are discussed as limitations.These results suggest that early childhood maltreatment is associated with brain structural changes irrespective of sex, age and a history of depression.Thus, the study highlights the importance of childhood maltreatment when investigating brain structures.

    View details for DOI 10.1503/jpn.120208

    View details for Web of Science ID 000336276300008

    View details for PubMedID 23900024

    View details for PubMedCentralID PMC3868665

  • Neural correlates of treatment outcome in major depression INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY Lisiecka, D., Meisenzahl, E., Scheuerecker, J., Schoepf, V., Whitty, P., Chaney, A., Moeller, H., Wiesmann, M., Frodl, T. 2011; 14 (4): 521-534

    Abstract

    There is a need to identify clinically useful biomarkers in major depressive disorder (MDD). In this context the functional connectivity of the orbitofrontal cortex (OFC) to other areas of the affect regulation circuit is of interest. The aim of this study was to identify neural changes during antidepressant treatment and correlates associated with the treatment outcome. In an exploratory analysis it was investigated whether functional connectivity measures moderated a response to mirtazapine and venlafaxine. Twenty-three drug-free patients with MDD were recruited from the Department of Psychiatry and Psychotherapy of the Ludwig-Maximilians University in Munich. The patients were subjected to a 4-wk randomized clinical trial with two common antidepressants, venlafaxine or mirtazapine. Functional connectivity of the OFC, derived from functional magnetic resonance imaging with an emotional face-matching task, was measured before and after the trial. Higher OFC connectivity with the left motor areas and the OFC regions prior to the trial characterized responders (p<0.05, false discovery rate). The treatment non-responders were characterized by higher OFC-cerebellum connectivity. The strength of response was positively correlated with functional coupling between left OFC and the caudate nuclei and thalami. Differences in longitudinal changes were detected between venlafaxine and mirtazapine treatment in the motor areas, cerebellum, cingulate gyrus and angular gyrus. These results indicate that OFC functional connectivity might be useful as a marker for therapy response to mirtazapine and venlafaxine and to reconstruct the differences in their mechanism of action.

    View details for DOI 10.1017/S1461145710001513

    View details for Web of Science ID 000289374500007

    View details for PubMedID 21205435

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