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Article ; Online: The gut peptide neuropeptide Y and post-traumatic stress disorder.

Rasmusson, Ann M

Current opinion in endocrinology, diabetes, and obesity

2017 Volume 24, Issue 1, Page(s) 3–8

Abstract: Purpose of review: This article reviews the role of neuropeptide Y (NPY) in the pathophysiology of post-traumatic stress disorder (PTSD) and gastrointestinal disorders such as irritable bowel syndrome (IBS) with which PTSD is highly comorbid. NPY is low ...

Abstract	Purpose of review: This article reviews the role of neuropeptide Y (NPY) in the pathophysiology of post-traumatic stress disorder (PTSD) and gastrointestinal disorders such as irritable bowel syndrome (IBS) with which PTSD is highly comorbid. NPY is low in the cerebrospinal fluid and plasma of male combat veterans with PTSD and correlates negatively with sympathetic nervous system (SNS) hyperreactivity, PTSD symptoms and time to recovery. NPY regulation has not yet been evaluated in women with PTSD. Recent findings: NPY levels in bowel tissue are low in IBS with diarrhea (IBS-D) versus IBS with constipation. The density of ghrelin containing cells of the gastric oxyntic mucosa is markedly increased in IBS-D. PTSD-related SNS hyperreactivity may interact with this substrate to increase ghrelin release, which activates receptors in the lumbosacral spinal cord and basolateral amygdala to increase colonic motility and amygdala hyperreactivity, respectively. Loss of function gene polymorphisms in adrenergic α2-autoreceptors and increased corticotropin-releasing hormone, as observed in PTSD, are also thought to contribute to IBS-D. Summary: Knowledge of shared underlying NPY system-related neurobiological factors that contribute to the comorbidity of PTSD and gastrointestinal disorders may help guide research, development and prescription of targeted and more effective individualized therapeutic interventions.
Language	English
Publishing date	2017-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2272017-0
ISSN	1752-2978 ; 1752-296X
ISSN (online)	1752-2978
ISSN	1752-296X
DOI	10.1097/MED.0000000000000301
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Article ; Online: Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone.

Liang, Jennifer J / Rasmusson, Ann M

Chronic stress (Thousand Oaks, Calif.)

2018 Volume 2, Page(s) 2470547018818555

Abstract: Allopregnanolone and pregnanolone-neurosteroids synthesized from progesterone in the brain, adrenal gland, ovary and testis-have been implicated in a range of neuropsychiatric conditions including seizure disorders, post-traumatic stress disorder, major ... ...

Abstract	Allopregnanolone and pregnanolone-neurosteroids synthesized from progesterone in the brain, adrenal gland, ovary and testis-have been implicated in a range of neuropsychiatric conditions including seizure disorders, post-traumatic stress disorder, major depression, post-partum depression, pre-menstrual dysphoric disorder, chronic pain, Parkinson's disease, Alzheimer's disease, neurotrauma, and stroke. Allopregnanolone and pregnanolone equipotently facilitate the effects of gamma-amino-butyric acid (GABA) at GABA
Language	English
Publishing date	2018-12-19
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2470-5470
ISSN (online)	2470-5470
DOI	10.1177/2470547018818555
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Article ; Online: Pleiotropic endophenotypic and phenotype effects of GABAergic neurosteroid synthesis deficiency in posttraumatic stress disorder.

Rasmusson, Ann M / Novikov, Olga / Brown, Kayla D / Pinna, Graziano / Pineles, Suzanne L

Current opinion in endocrine and metabolic research

2022 Volume 25

Abstract: PTSD is associated with deficits in synthesis of progesterone metabolites such as allopregnanolone and pregnanolone that potently facilitate gamma-amino-butyric acid (GABA) effects at ... ...

Abstract	PTSD is associated with deficits in synthesis of progesterone metabolites such as allopregnanolone and pregnanolone that potently facilitate gamma-amino-butyric acid (GABA) effects at GABA
Language	English
Publishing date	2022-05-28
Publishing country	England
Document type	Journal Article
ISSN	2451-9650
ISSN (online)	2451-9650
DOI	10.1016/j.coemr.2022.100359
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Article ; Online: Neurotransmitter, Peptide, and Steroid Hormone Abnormalities in PTSD: Biological Endophenotypes Relevant to Treatment.

Rasmusson, Ann M / Pineles, Suzanne L

Current psychiatry reports

2018 Volume 20, Issue 7, Page(s) 52

Abstract: Purpose of review: This review summarizes neurotransmitter, peptide, and other neurohormone abnormalities associated with posttraumatic stress disorder (PTSD) and relevant to development of precision medicine therapeutics for PTSD.: Recent findings: ... ...

Abstract	Purpose of review: This review summarizes neurotransmitter, peptide, and other neurohormone abnormalities associated with posttraumatic stress disorder (PTSD) and relevant to development of precision medicine therapeutics for PTSD. Recent findings: As the number of molecular abnormalities associated with PTSD across a variety of subpopulations continues to grow, it becomes clear that no single abnormality characterizes all individuals with PTSD. Instead, individually variable points of molecular dysfunction occur within several different stress-responsive systems that interact to produce the clinical PTSD phenotype. Future work should focus on critical interactions among the systems that influence PTSD risk, severity, chronicity, comorbidity, and response to treatment. Effort also should be directed toward development of clinical procedures by which points of molecular dysfunction within these systems can be identified in individual patients. Some molecular abnormalities are more common than others and may serve as subpopulation biological endophenotypes for targeting of currently available and novel treatments.
MeSH term(s)	Comorbidity ; Endophenotypes ; Hormones/metabolism ; Humans ; Neuropeptides/metabolism ; Neurotransmitter Agents/metabolism ; Steroids/metabolism ; Stress Disorders, Post-Traumatic/metabolism ; Stress Disorders, Post-Traumatic/physiopathology ; Stress Disorders, Post-Traumatic/therapy
Chemical Substances	Hormones ; Neuropeptides ; Neurotransmitter Agents ; Steroids
Language	English
Publishing date	2018-07-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2055376-6
ISSN	1535-1645 ; 1523-3812
ISSN (online)	1535-1645
ISSN	1523-3812
DOI	10.1007/s11920-018-0908-9
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Article ; Online: The Impact of the Menstrual Cycle and Underlying Hormones in Anxiety and PTSD: What Do We Know and Where Do We Go From Here?

Nillni, Yael I / Rasmusson, Ann M / Paul, Emilie L / Pineles, Suzanne L

Current psychiatry reports

2021 Volume 23, Issue 2, Page(s) 8

Abstract: Purpose of review: This paper reviews the recent literature on menstrual cycle phase effects on outcomes relevant to anxiety and PTSD, discusses potential neurobiological mechanisms underlying these effects, and highlights methodological limitations ... ...

Abstract	Purpose of review: This paper reviews the recent literature on menstrual cycle phase effects on outcomes relevant to anxiety and PTSD, discusses potential neurobiological mechanisms underlying these effects, and highlights methodological limitations impeding scientific advancement. Recent findings: The menstrual cycle and its underlying hormones impact symptom expression among women with anxiety and PTSD, as well as psychophysiological and biological processes relevant to anxiety and PTSD. The most consistent findings are retrospective self-report of premenstrual exacerbation of anxiety symptoms and the protective effect of estradiol on recall of extinction learning among healthy women. Lack of rigorous methodology for assessing menstrual cycle phase and inconsistent menstrual cycle phase definitions likely contribute to other conflicting results. Further investigations that address these limitations and integrate complex interactions between menstrual cycle phase-related hormones, genetics, and psychological vulnerabilities are needed to inform personalized prevention and intervention efforts for women.
MeSH term(s)	Anxiety ; Fear ; Female ; Humans ; Menstrual Cycle ; Retrospective Studies ; Stress Disorders, Post-Traumatic/genetics
Language	English
Publishing date	2021-01-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2055376-6
ISSN	1535-1645 ; 1523-3812
ISSN (online)	1535-1645
ISSN	1523-3812
DOI	10.1007/s11920-020-01221-9
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Article ; Online: A role for deficits in GABAergic neurosteroids and their metabolites with NMDA receptor antagonist activity in the pathophysiology of posttraumatic stress disorder.

Rasmusson, Ann M / Pineles, Suzanne L / Brown, Kayla D / Pinna, Graziano

Journal of neuroendocrinology

2021 Volume 34, Issue 2, Page(s) e13062

Abstract: Trauma-focused psychotherapies show general efficacy in post-traumatic stress disorder (PTSD), although outcomes vary substantially among individuals with PTSD and many patients do not achieve clinically meaningful symptom improvement. Several factors ... ...

Abstract	Trauma-focused psychotherapies show general efficacy in post-traumatic stress disorder (PTSD), although outcomes vary substantially among individuals with PTSD and many patients do not achieve clinically meaningful symptom improvement. Several factors may contribute to poor treatment response, including genetic or environmental (e.g., stress) effects on neurobiological factors involved in learning and memory processes critical to PTSD recovery. In this review, we discuss the relationship between deficient GABAergic neurosteroid metabolites of progesterone, allopregnanolone (Allo) and pregnanolone (PA), and PTSD symptoms in men and women or PTSD-like behavioral abnormalities observed in male rodent models of PTSD. We also review the role and molecular underpinnings of learning and memory processes relevant to PTSD recovery, including extinction, extinction retention, reconsolidation of reactivated aversive memories and episodic non-aversive memory. We then discuss preclinical and clinical research that supports a role in these learning and memory processes for GABAergic neurosteroids and sulfated metabolites of Allo and PA that allosterically antagonize NMDA receptor function. Studies supporting the possible therapeutic impact of appropriately timed, acutely administered Allo or Allo analogs to facilitate extinction retention and/or block reconsolidation of aversive memories are also reviewed. Finally, we discuss important future directions for research in this area. Examining the varied and composite effects in PTSD of these metabolites of progesterone, as well as neuroactive derivatives of other parent steroids produced in the brain and the periphery, will likely enable a broadening of targets for treatment development. Defining contributions of these neuroactive steroids to common PTSD-comorbid psychiatric and medical conditions, as well as subpopulation-specific underlying dysfunctional physiological processes such as hypothalamic-pituitary-adrenal axis and immune system dysregulation, may also enable development of more effective multisystem precision medicines to prevent and treat the broader, polymorbid sequelae of extreme and chronic stress.
MeSH term(s)	Female ; Humans ; Hypothalamo-Hypophyseal System/metabolism ; Male ; Neurosteroids ; Pituitary-Adrenal System/metabolism ; Pregnanolone/therapeutic use ; Progesterone/therapeutic use ; Receptors, N-Methyl-D-Aspartate/metabolism ; Receptors, N-Methyl-D-Aspartate/therapeutic use ; Stress Disorders, Post-Traumatic/drug therapy
Chemical Substances	Neurosteroids ; Receptors, N-Methyl-D-Aspartate ; Progesterone (4G7DS2Q64Y) ; Pregnanolone (BXO86P3XXW)
Language	English
Publishing date	2021-12-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1007517-3
ISSN	1365-2826 ; 0953-8194
ISSN (online)	1365-2826
ISSN	0953-8194
DOI	10.1111/jne.13062
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Zs.A 2634: Show issues

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Article ; Online: Tobacco withdrawal-induced changes in sensorimotor filtering as a predictor of smoking lapse in trauma-exposed individuals.

Pineles, Suzanne L / Ni, Pengsheng / Pandey, Shivani / Japuntich, Sandra J / Cesare, Nina / Shor, Rachel / Carpenter, Joseph K / Gregor, Kristin / Joos, Celina M / Blumenthal, Terry D / Rasmusson, Ann M

Addictive behaviors

2023 Volume 148, Page(s) 107868

Abstract: Prepulse inhibition (PPI) is a measure of sensorimotor filtering thought to shield the processing of initial weaker auditory stimuli from interruption by a later startle response. Previous studies have shown smoking withdrawal to have a negative impact ... ...

Abstract	Prepulse inhibition (PPI) is a measure of sensorimotor filtering thought to shield the processing of initial weaker auditory stimuli from interruption by a later startle response. Previous studies have shown smoking withdrawal to have a negative impact on sensorimotor filtering, particularly in individuals with psychopathology. Because tobacco use may alleviate sensory and sensorimotor filtering deficits, we examined whether smoking withdrawal-induced changes in PPI were associated with maintenance of smoking abstinence in trauma-exposed individuals with and without PTSD who were attempting to quit smoking. Thirty-eight individuals (n = 24 with current or past PTSD; 14 trauma-exposed healthy controls) made an acute biochemically-verified smoking cessation attempt supported by 8 days of contingency management (CM) and cognitive behavioral therapy (CBT) for smoking. Participants completed a PPI task at the pre-quit baseline, 2 days post-quit, and 5 days post-quit. Post-quit changes in PPI were compared between those who remained abstinent for the first 8-days of the quit attempt and those who lapsed back to smoking. PPI changes induced by biochemically-verified smoking abstinence were associated with maintenance of abstinence across the 8-day CM/CBT-supported quit attempt. As compared to those who maintained tobacco abstinence, participants who lapsed to smoking had significantly lower PPI at 2 and 5 days post-quit relative to baseline. Thus, among trauma-exposed individuals, decreases in PPI during acute smoking cessation supported by CM/CBT are associated with lapse back to smoking. Interventions that improve PPI during early smoking abstinence may facilitate smoking cessation among such individuals who are at high risk for chronic, refractory tobacco use.
MeSH term(s)	Humans ; Smoking/therapy ; Smoking/psychology ; Tobacco Smoking ; Smoking Cessation/psychology ; Tobacco Use Disorder/psychology ; Tobacco Products
Language	English
Publishing date	2023-09-22
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	197618-7
ISSN	1873-6327 ; 0306-4603
ISSN (online)	1873-6327
ISSN	0306-4603
DOI	10.1016/j.addbeh.2023.107868
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Article: Ganaxolone improves behavioral deficits in a mouse model of post-traumatic stress disorder.

Pinna, Graziano / Rasmusson, Ann M

Frontiers in cellular neuroscience

2014 Volume 8, Page(s) 256

Abstract: Allopregnanolone and its equipotent stereoisomer, pregnanolone (together termed ALLO), are neuroactive steroids that positively and allosterically modulate the action of gamma-amino-butyric acid (GABA) at GABAA receptors. Levels of ALLO are reduced in ... ...

Abstract	Allopregnanolone and its equipotent stereoisomer, pregnanolone (together termed ALLO), are neuroactive steroids that positively and allosterically modulate the action of gamma-amino-butyric acid (GABA) at GABAA receptors. Levels of ALLO are reduced in the cerebrospinal fluid of female premenopausal patients with post-traumatic stress disorder (PTSD), a severe, neuropsychiatric condition that affects millions, yet is without a consistently effective therapy. This suggests that restoring downregulated brain ALLO levels in PTSD may be beneficial. ALLO biosynthesis is also decreased in association with the emergence of PTSD-like behaviors in socially isolated (SI) mice. Similar to PTSD patients, SI mice also exhibit changes in the frontocortical and hippocampal expression of GABAA receptor subunits, resulting in resistance to benzodiazepine-mediated sedation and anxiolysis. ALLO acts at a larger spectrum of GABAA receptor subunits than benzodiazepines, and increasing corticolimbic ALLO levels in SI mice by injecting ALLO or stimulating ALLO biosynthesis with a selective brain steroidogenic stimulant, such as S-norfluoxetine, at doses far below those that block serotonin reuptake, reduces PTSD-like behavior in these mice. This suggests that synthetic analogs of ALLO, such as ganaxolone, may also improve anxiety, aggression, and other PTSD-like behaviors in the SI mouse model. Consistent with this hypothesis, ganaxolone (3.75-30 mg/kg, s.c.) injected 60 min before testing of SI mice, induced a dose-dependent reduction in aggression toward a same-sex intruder and anxiety-like behavior in an elevated plus maze. The EC50 dose of ganaxolone used in these tests also normalized exaggerated contextual fear conditioning and, remarkably, enhanced fear extinction retention in SI mice. At these doses, ganaxolone failed to change locomotion in an open field test. Therefore, unlike benzodiazepines, ganaxolone at non-sedating concentrations appears to improve dysfunctional emotional behavior associated with deficits in ALLO in mice and may provide an alternative treatment for PTSD patients with deficits in the synthesis of ALLO. Selective serotonin reuptake inhibitors (SSRIs) are the only medications currently approved by the FDA for treatment of PTSD, although they are ineffective in a substantial proportion of PTSD patients. Hence, an ALLO analog such as ganaxolone may offer a therapeutic GABAergic alternative to SSRIs for the treatment of PTSD or other disorders in which ALLO biosynthesis may be impaired.
Language	English
Publishing date	2014-09-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2014.00256
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Article: Composite contributions of cerebrospinal fluid GABAergic neurosteroids, neuropeptide Y and interleukin-6 to PTSD symptom severity in men with PTSD.

Kim, Byung Kil / Fonda, Jennifer R / Hauger, Richard L / Pinna, Graziano / Anderson, George M / Valovski, Ivan T / Rasmusson, Ann M

Neurobiology of stress

2020 Volume 12, Page(s) 100220

Abstract: Given that multiple neurobiological systems, as well as components within these systems are impacted by stress, and may interact in additive, compensatory and synergistic ways to promote or mitigate PTSD risk, severity, and recovery, we thought that it ... ...

Abstract	Given that multiple neurobiological systems, as well as components within these systems are impacted by stress, and may interact in additive, compensatory and synergistic ways to promote or mitigate PTSD risk, severity, and recovery, we thought that it would be important to consider the
Language	English
Publishing date	2020-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2816500-7
ISSN	2352-2895
ISSN	2352-2895
DOI	10.1016/j.ynstr.2020.100220
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Article ; Online: Gender and PTSD: different pathways to a similar phenotype.

Pineles, Suzanne L / Arditte Hall, Kimberly A / Rasmusson, Ann M

Current opinion in psychology

2017 Volume 14, Page(s) 44–48

Abstract: Whereas research supports the existence of a single posttraumatic stress disorder (PTSD) phenotype across women and men, there may be important gender differences in the pathophysiology of, or mechanisms underlying, the disorder. This paper reviews ... ...

Abstract	Whereas research supports the existence of a single posttraumatic stress disorder (PTSD) phenotype across women and men, there may be important gender differences in the pathophysiology of, or mechanisms underlying, the disorder. This paper reviews recent literature on gender differences in emotional, cognitive, and neurobiological factors, and their relations with PTSD and relevant comorbidities. Key findings and limitations from both human and animal studies are discussed. Overall, more work is needed that utilizes objective measures in addition to self-report. Studies explicitly examining gender differences and those examining mechanisms within single-gender samples each have the potential to improve our understanding of gender discrepancies in PTSD and inform tailored interventions for women and men.
Language	English
Publishing date	2017-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2831565-0
ISSN	2352-2518 ; 2352-250X ; 2352-250X
ISSN (online)	2352-2518 ; 2352-250X
ISSN	2352-250X
DOI	10.1016/j.copsyc.2016.11.002
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