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Neurotransmitter, Peptide, and Steroid Hormone Abnormalities in PTSD: Biological Endophenotypes Relevant to Treatment

  • Disaster Psychiatry: Trauma, PTSD, and Related Disorders (MJ Friedman, Section Editor)
  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

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.

Summary

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.

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Abbreviations

ACTH:

adrenocorticotropic hormone

ADIOL:

5-Androsten-3β,17β-diol

ALLO:

Allopregnanolone and pregnanolone

AP-1:

Activator protein 1

AUG:

Adenine-uracil-guinine

AVP:

Arginine vasopression

BBB:

Blood-brain barrier

BDNF:

Brain-derived neurotropic factor

cAMP:

Cyclic adenosine monophosphate

CpG:

Cytosine-guanine

CPT:

Cognitive processing therapy

CRH:

Corticotropin releasing hormone

CSF:

Cerebrospinal fluid

CtBP:

C-terminal binding protein

CYP2D6:

Cytochrome P450 2D6: enzyme coded by the CYP2D6 gene

CYP3A4:

Cytochrome P450 3A4: enzyme coded by the CYP3A4 gene.

DAG:

Diacyl glycerol

DHEA:

Dehydroepiandrosterone

DHEAS:

Dehydroepiandrosterone sulfate

DNA:

Deoxyribonucleic acid

DSM-5:

Diagnostic and Statistical Manual of Mental Disorders

EC50 :

Median effective dose

ER:

Estrogen receptor

ERα:

Estrogen receptor alpha

ERβ:

Estrogen receptor beta

ERE:

Estrogen response element

EMG:

Electromyographic

EPSP:

Excitatory post-synaptic potential

ERK:

Extracellular signal-related kinase

FKBP5:

FK binding protein 506

GABA:

Gamma-amino-butyric acid

GBOs:

Gamma-band oscillations

GPER:

G-protein coupled estrogen receptor 1

GCMS:

Gas chromatography-mass spectrometry

GPRCs:

G-protein coupled receptors

GR:

Glucocorticoid receptor

GRE:

Glucocorticoid response element

HPA:

Hypothalamic-pituitary-adrenal

IP3:

Inositol 1,4,5 triphosphate

LTD:

Long-term depression

LTP:

Long-term potentiation

mCPP:

Meta-chlorophenylpiperazine

MAPK:

Mitogen-activated protein kinase

MDD:

Major depressive disorder

MR:

Mineralocorticoid receptor

mRNA:

Messenger RNA

NR3C1:

Glucocorticoid receptor (GR) gene

NE:

Norepinephrine

NMDA:

N-methyl-D-aspartate

NPY:

Neuropeptide Y

OEF/OIF:

Operation Enduring Freedom/ Operation Iraqi Freedom

OR:

Odds ratio

PACAP:

Pituitary adenylate cyclase-activating polypeptide

PAC1:

Class of G-protein coupled receptors

PBMC:

Peripheral blood mononuclear cell

PE:

Prolonged Exposure

PET:

Positron emission tomography

PFC:

Prefrontal cortex

PKA:

Protein kinase A

PLC:

Phospholipase C

PTSD:

Posttraumatic stress disorder

RNA:

Ribonucleic acid

RIA:

Radioimmunoassay

VIP:

Vasoactive intestinal protein

VPAC:

Class of G-protein coupled receptors

3α-HSD:

3α-hydroxysteroid dehydrogenase

5α-DHP:

5α-dihydroprogesterone

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Authors and Affiliations

  1. National Center for PTSD, Women’s Health Science Division, Department of Veterans Affairs, 150 South Huntington Avenue, Boston, MA, 02130, USA

    Ann M. Rasmusson & Suzanne L. Pineles

  2. VA Boston Healthcare System, 150 South Huntington Avenue, Boston, MA, 02130, USA

    Ann M. Rasmusson & Suzanne L. Pineles

  3. Boston University School of Medicine, 72 E Concord St, Boston, MA, 02118, USA

    Ann M. Rasmusson & Suzanne L. Pineles

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  1. Ann M. Rasmusson
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  2. Suzanne L. Pineles
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Correspondence to Ann M. Rasmusson.

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Suzanne L. Pineles declares no conflict of interest. Ann M. Rasmusson has received personal fees from Resilience Therapeutics and Cohen Veterans Bioscience (non-profit).

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Disaster Psychiatry: Trauma, PTSD, and Related Disorders

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Rasmusson, A.M., Pineles, S.L. Neurotransmitter, Peptide, and Steroid Hormone Abnormalities in PTSD: Biological Endophenotypes Relevant to Treatment. Curr Psychiatry Rep 20, 52 (2018). https://doi.org/10.1007/s11920-018-0908-9

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  • DOI: https://doi.org/10.1007/s11920-018-0908-9

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