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Article ; Online: Introduction to Special Issue: Insight Into Sex Differences in Neuropsychiatric Syndromes From Transcriptomic Analyses.

Seney, Marianne L / Nestler, Eric J

2021 Volume 91, Issue 1, Page(s) 3–5

MeSH term(s)	Alzheimer Disease ; Female ; Humans ; Male ; Neuropsychological Tests ; Sex Characteristics ; Syndrome ; Transcriptome
Language	English
Publishing date	2021-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2021.09.004
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Article ; Online: Author Correction: Sex differences in offspring risk and resilience following 11β-hydroxylase antagonism in a rodent model of maternal immune activation.

Martz, Julia / Shelton, Micah A / Geist, Laurel / Seney, Marianne L / Kentner, Amanda C

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2024

Language	English
Publishing date	2024-04-05
Publishing country	England
Document type	Published Erratum
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-024-01849-8
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Article ; Online: Reply to Karadag: does steroid increase LPS-induced sickness behaviors?

Martz, Julia / Shelton, Micah A / Geist, Laurel / Seney, Marianne L / Kentner, Amanda C

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2024

Language	English
Publishing date	2024-03-13
Publishing country	England
Document type	Letter
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-024-01839-w
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Article ; Online: Sex differences and hormonal regulation of metabotropic glutamate receptor synaptic plasticity.

Fabian, Carly B / Seney, Marianne L / Joffe, Max E

International review of neurobiology

2022 Volume 168, Page(s) 311–347

Abstract: Striking sex differences exist in presentation and incidence of several psychiatric disorders. For example, major depressive disorder is more prevalent in women than men, and women who develop alcohol use disorder progress through drinking milestones ... ...

Abstract	Striking sex differences exist in presentation and incidence of several psychiatric disorders. For example, major depressive disorder is more prevalent in women than men, and women who develop alcohol use disorder progress through drinking milestones more rapidly than men. With regards to psychiatric treatment responses, women respond more favorably to selective serotonin reuptake inhibitors than men, whereas men have better outcomes when prescribed tricyclic antidepressants. Despite such well-documented biases in incidence, presentation, and treatment response, sex as a biological variable has long been neglected in preclinical and clinical research. An emerging family of druggable targets for psychiatric diseases, metabotropic glutamate (mGlu) receptors are G-protein coupled receptors broadly distributed throughout the central nervous system. mGlu receptors confer diverse neuromodulatory actions of glutamate at the levels of synaptic plasticity, neuronal excitability, and gene transcription. In this chapter, we summarize the current preclinical and clinical evidence for sex differences in mGlu receptor function. We first highlight basal sex differences in mGlu receptor expression and function and proceed to describe how gonadal hormones, notably estradiol, regulate mGlu receptor signaling. We then describe sex-specific mechanisms by which mGlu receptors differentially modulate synaptic plasticity and behavior in basal states and models relevant for disease. Finally, we discuss human research findings and highlight areas in need of further research. Taken together, this review emphasizes how mGlu receptor function and expression can differ across sex. Gaining a more complete understanding of how sex differences in mGlu receptor function contribute to psychiatric diseases will be critical in the development of novel therapeutics that are effective in all individuals.
MeSH term(s)	Humans ; Female ; Male ; Receptors, Metabotropic Glutamate ; Depressive Disorder, Major ; Sex Characteristics ; Glutamates ; Neuronal Plasticity
Chemical Substances	Receptors, Metabotropic Glutamate ; Glutamates
Language	English
Publishing date	2022-11-11
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209876-3
ISSN	2162-5514 ; 0074-7742
ISSN (online)	2162-5514
ISSN	0074-7742
DOI	10.1016/bs.irn.2022.10.002
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Article ; Online: Critical roles for developmental hormones and genetic sex in stress-induced transcriptional changes associated with depression.

Seney, Marianne L / Logan, Ryan W

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2020 Volume 46, Issue 1, Page(s) 221–222

MeSH term(s)	Depression/genetics ; Gonadal Steroid Hormones ; Hormones ; Sex Characteristics
Chemical Substances	Gonadal Steroid Hormones ; Hormones
Language	English
Publishing date	2020-08-07
Publishing country	England
Document type	News ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-020-00792-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Large-Scale Transcriptomics Studies Provide Insight Into Sex Differences in Depression.

Seney, Marianne L / Glausier, Jill / Sibille, Etienne

Biological psychiatry

2021 Volume 91, Issue 1, Page(s) 14–24

Abstract: Major depressive disorder (MDD) is a leading cause of disability, affecting more than 300 million people worldwide. We first review the well-known sex difference in incidence of MDD, with women being twice as likely to be diagnosed as men, and briefly ... ...

Abstract	Major depressive disorder (MDD) is a leading cause of disability, affecting more than 300 million people worldwide. We first review the well-known sex difference in incidence of MDD, with women being twice as likely to be diagnosed as men, and briefly summarize how the impact of MDD varies between men and women, with sex differences in symptoms, severity, and antidepressant drug response. We then attempt to deconstruct the biological bases for MDD and discuss implications for sex differences research. Next, we review findings from human postmortem studies, both from selected candidate gene studies and from well-powered, unbiased transcriptomics studies, which suggest distinct, and possibly opposite, molecular changes in the brains of depressed men and women. We then discuss inherent challenges of research on the human postmortem brain and suggest paths forward that rely on thoughtful cohort design. Although studies indicate that circulating gonadal hormones might underlie the observed sex differences in MDD, we discuss how additional sex-specific factors, such as genetic sex and developmental exposure to gonadal hormones, may also contribute to altered vulnerability, and we highlight various nuances that we believe should be considered when determining mechanisms underlying observed sex differences. Altogether, this review highlights not only how various sex-specific factors might influence susceptibility or resilience to depression, but also how those sex-specific factors might result in divergent pathology in men and women.
MeSH term(s)	Antidepressive Agents/therapeutic use ; Depression ; Depressive Disorder, Major/drug therapy ; Depressive Disorder, Major/genetics ; Female ; Humans ; Male ; Sex Factors ; Transcriptome
Chemical Substances	Antidepressive Agents
Language	English
Publishing date	2021-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2020.12.025
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Article: Parvalbumin interneuron mGlu

Fabian, Carly B / Jordan, Nilah D / Cole, Rebecca H / Carley, Lily G / Thompson, Shannon M / Seney, Marianne L / Joffe, Max E

bioRxiv : the preprint server for biology

2024

Abstract: Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. Proper function of the prefrontal cortex (PFC) ...

Abstract	Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. Proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. Activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells. Recent rodent studies have identified notable sex differences in PV-IN activity and adaptations to experiences such as binge drinking. Here, we investigated the cellular and molecular mechanisms that underlie sex-specific regulation of PFC PV-IN function. Using whole-cell patch clamp electrophysiology and selective pharmacology, we report that PV-INs from female mice are more excitable than those from males. Moreover, we find that mGlu
Language	English
Publishing date	2024-03-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.20.567903
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Article ; Online: Sex differences in offspring risk and resilience following 11β-hydroxylase antagonism in a rodent model of maternal immune activation.

Martz, Julia / Shelton, Micah A / Geist, Laurel / Seney, Marianne L / Kentner, Amanda C

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2023

Abstract: Maternal immune activation (MIA) puts offspring at greater risk for neurodevelopmental disorders associated with impaired social behavior. While it is known that immune signaling through maternal, placental, and fetal compartments contributes to these ... ...

Abstract	Maternal immune activation (MIA) puts offspring at greater risk for neurodevelopmental disorders associated with impaired social behavior. While it is known that immune signaling through maternal, placental, and fetal compartments contributes to these phenotypical changes, it is unknown to what extent the stress response to illness is involved and how it can be harnessed for potential interventions. To this end, on gestational day 15, pregnant rat dams were administered the bacterial mimetic lipopolysaccharide (LPS; to induce MIA) alongside metyrapone, a clinically available 11β-hydroxylase (11βHSD) inhibitor used to treat hypercortisolism in pregnant, lactating, and neonatal populations. Maternal, placental, and fetal brain levels of corticosterone and placental 11βHSD enzymes type 1 and 2 were measured 3-hrs post treatment. Offspring social behaviors were evaluated across critical phases of development. MIA was associated with increased maternal, placental, and fetal brain corticosterone concentrations that were diminished with metyrapone exposure. Metyrapone protected against reductions in placental 11βHSD2 in males only, suggesting that less corticosterone was inactivated in female placentas. Behaviorally, metyrapone-exposure attenuated MIA-induced social disruptions in juvenile, adolescent, and adult males, while females were unaffected or performed worse. Metyrapone-exposure reversed MIA-induced transcriptional changes in monoamine-, glutamate-, and GABA-related genes in adult male ventral hippocampus, but not in females. Taken together, these findings illustrate that MIA-induced HPA responses act alongside the immune system to produce behavioral deficits. As a clinically available drug, the sex-specific benefits and constraints of metyrapone should be investigated further as a potential means of reducing neurodevelopmental risks due to gestational MIA.
Language	English
Publishing date	2023-11-25
Publishing country	England
Document type	Journal Article
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-023-01771-5
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Article ; Online: Sex-specific role of the circadian transcription factor NPAS2 in opioid tolerance, withdrawal and analgesia.

Puig, Stephanie / Shelton, Micah A / Barko, Kelly / Seney, Marianne L / Logan, Ryan W

Genes, brain, and behavior

2022 Volume 21, Issue 7, Page(s) e12829

Abstract: Opioids like fentanyl remain the mainstay treatment for chronic pain. Unfortunately, opioid's high dependence liability has led to the current opioid crisis, in part, because of side-effects that develop during long-term use, including analgesic ... ...

Abstract	Opioids like fentanyl remain the mainstay treatment for chronic pain. Unfortunately, opioid's high dependence liability has led to the current opioid crisis, in part, because of side-effects that develop during long-term use, including analgesic tolerance and physical dependence. Both tolerance and dependence to opioids may lead to escalation of required doses to achieve previous therapeutic efficacy. Additionally, altered sleep and circadian rhythms are common in people on opioid therapy. Opioids impact sleep and circadian rhythms, while disruptions to sleep and circadian rhythms likely mediate the effects of opioids. However, the mechanisms underlying these bidirectional relationships between circadian rhythms and opioids remain largely unknown. The circadian protein, neuronal PAS domain protein 2 (NPAS2), regulates circadian-dependent gene transcription in structure of the central nervous system that modulate opioids and pain. Here, male and female wild-type and NPAS2-deficient (NPAS2-/-) mice were used to investigate the role of NPAS2 in fentanyl analgesia, tolerance, hyperalgesia and physical dependence. Overall, thermal pain thresholds, acute analgesia and tolerance to a fixed dose of fentanyl were largely similar between wild-type and NPAS2-/- mice. However, female NPAS2-/- exhibited augmented analgesic tolerance and significantly more behavioral symptoms of physical dependence to fentanyl. Only male NPAS2-/- mice had increased fentanyl-induced hypersensitivity, when compared with wild-type males. Together, our findings suggest sex-specific effects of NPAS2 signaling in the regulation of fentanyl-induced tolerance, hyperalgesia and dependence.
MeSH term(s)	Analgesia ; Analgesics/pharmacology ; Analgesics, Opioid/pharmacology ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Drug Tolerance/genetics ; Female ; Fentanyl ; Humans ; Hyperalgesia ; Male ; Mice ; Nerve Tissue Proteins/genetics ; Pain/drug therapy ; Transcription Factors
Chemical Substances	Analgesics ; Analgesics, Opioid ; Basic Helix-Loop-Helix Transcription Factors ; NPAS2 protein, human ; Nerve Tissue Proteins ; Npas2 protein, mouse ; Transcription Factors ; Fentanyl (UF599785JZ)
Language	English
Publishing date	2022-08-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2075819-4
ISSN	1601-183X ; 1601-1848
ISSN (online)	1601-183X
ISSN	1601-1848
DOI	10.1111/gbb.12829
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Article ; Online: Twelve-hour rhythms in transcript expression within the human dorsolateral prefrontal cortex are altered in schizophrenia.

Scott, Madeline R / Zong, Wei / Ketchesin, Kyle D / Seney, Marianne L / Tseng, George C / Zhu, Bokai / McClung, Colleen A

PLoS biology

2023 Volume 21, Issue 1, Page(s) e3001688

Abstract: Twelve-hour (12 h) ultradian rhythms are a well-known phenomenon in coastal marine organisms. While 12 h cycles are observed in human behavior and physiology, no study has measured 12 h rhythms in the human brain. Here, we identify 12 h rhythms in ... ...

Abstract	Twelve-hour (12 h) ultradian rhythms are a well-known phenomenon in coastal marine organisms. While 12 h cycles are observed in human behavior and physiology, no study has measured 12 h rhythms in the human brain. Here, we identify 12 h rhythms in transcripts that either peak at sleep/wake transitions (approximately 9 AM/PM) or static times (approximately 3 PM/AM) in the dorsolateral prefrontal cortex, a region involved in cognition. Subjects with schizophrenia (SZ) lose 12 h rhythms in genes associated with the unfolded protein response and neuronal structural maintenance. Moreover, genes involved in mitochondrial function and protein translation, which normally peak at sleep/wake transitions, peak instead at static times in SZ, suggesting suboptimal timing of these essential processes.
MeSH term(s)	Humans ; Dorsolateral Prefrontal Cortex ; Schizophrenia/genetics ; Sleep ; Ultradian Rhythm ; Brain ; Prefrontal Cortex/metabolism
Language	English
Publishing date	2023-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3001688
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