PET imaging evidence of HDAC6 suppression in the amygdala across species in PTSD.

Histone deacetylases (HDACs), typically known for regulating gene expression, also play a major role in protein regulation outside of histone modification. Emerging evidence suggests the HDACs may be novel pharmacologic targets in complex disorders such as posttraumatic stress disorder (PTSD). Histone deacetylase 6 (HDAC6) regulates microtubule function and plays a role in stress-related cortisol signaling in serotonergic regions of the brain by maintaining the nuclear translocation of glucocorticoid receptors.

Greater Neuroimmune System Deficit in Women Than Men With Alcohol Use Disorder.

Background: Women who drink are more vulnerable than men to many of the consequences of alcohol use, including alcohol-related cancers, cardiovascular disease, liver cirrhosis, and immune system dysfunction. Acute alcohol triggers neuroimmune cells including microglia-the brain's resident immune cells. Excessive activation can contribute to neuronal dysfunction and alcohol-induced neurodegeneration.

Acute Alcohol-Induced Changes Measured With Metabotropic Glutamate Receptor 5 Positron Emission Tomography.

Background: Alcohol consumption at clinically relevant doses alters brain glutamate release. However, few techniques exist to measure these changes in humans. The metabotropic glutamate receptor 5 (mGluR5) PET radioligand [C]ABP688 is sensitive to acute alcohol in rodents, possibly mediated by alcohol effects on glutamate release.

Preclinical and clinical sex differences in the effects of alcohol on measures of brain dopamine: a systematic review.

Introduction: Dopamine is involved in reward processing and plays a critical role in the development and progression of alcohol use disorder (AUD). However, little is known about the effect of sex on the relationship between dopamine and alcohol use/AUD. There is a critical need to identify the neurobiological mechanisms that contribute to sex differences in AUD to inform treatment approaches.

Neuroglia in anxiety disorders.

Anxiety disorders are some of the most prevalent in the world and are extraordinarily debilitating to many individuals, costing millions in disability. One of the most disabling is posttraumatic stress disorder (Snijders et al., 2020).

Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia.

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls.

Does seasonal variation affect the neuroimmune system? A retrospective [C]PBR28 PET study in healthy individuals.

Introduction: The neuroimmune system performs a wide range of functions in the brain and the central nervous system. The microglial translocator protein (TSPO) has an established role as a cell marker in identification of the neuroimmune system. Previously, human studies have shown TSPO differences in neuropsychiatric disorders.

Substance use and spine density: a systematic review and meta-analysis of preclinical studies.

The elucidation of synaptic density changes provides valuable insights into the underlying brain mechanisms of substance use. In preclinical studies, synaptic density markers, like spine density, are altered by substances of abuse (e.g.

Lower Dorsal Putamen D2/3 Receptor Availability and Amphetamine-Induced Dopamine Release are Related to Poorer Cognitive Function in Recently Abstinent People Who Smoke and Healthy Controls.

Introduction: In the dopamine system, the mesolimbic pathway, including the dorsal striatum, underlies the reinforcing properties of tobacco smoking, and the mesocortical pathway, including the dorsolateral prefrontal cortex (dlPFC), is critical for cognitive functioning. Dysregulated dopamine signaling has been linked to drug-seeking behaviors and cognitive deficits. The dorsal striatum and dlPFC are structurally and functionally connected and are key regions for cognitive functioning.

Imaging a putative marker of brain cortisol regulation in alcohol use disorder.

Background: Stress is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis, initiating the release of glucocorticoid hormones, such as cortisol. Alcohol consumption can lead to HPA axis dysfunction, including altered cortisol levels. Until recently, research has only been able to examine peripheral cortisol associated with alcohol use disorder (AUD) in humans.

The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications.

Rates of alcohol use disorder (AUD) are increasing in men and women and there are high rates of concurrent posttraumatic stress disorder (PTSD) and AUD. AUD and PTSD synergistically increase symptomatology and negatively affect treatment outcomes; however, there are very limited pharmacological treatments for PTSD/AUD. Neurosteroids have been implicated in the underlying neurobiological mechanisms of both PTSD and AUD and may be a target for treatment development.

Developing Researchers with Expertise in Sex as a Biological Variable through SCORE Career Enhancement Core Center Programs.

There is a critical need for interdisciplinary and translational scientists to apply sex as a biological variable (SABV) research to address knowledge gaps in the health of women. In 2018, the Office of Research on Women's Health (ORWH) partnered with several National Institute of Health (NIH) Institutes and Centers to expand the Specialized Centers of Research (SCOR) Excellence (SCORE) Programs (together referred to as SCOR/E) with an important feature-the Career Enhancement Core (CEC). The SCORE CEC mentors early career investigators to become the next generation of biomedical and behavioral researchers focused on SABV and women's health.

Imaging the brain's immune response to alcohol with [C]PBR28 TSPO Positron Emission Tomography.

In humans, the negative effects of alcohol are linked to immune dysfunction in both the periphery and the brain. Yet acute effects of alcohol on the neuroimmune system and its relationships with peripheral immune function are not fully understood. To address this gap, immune response to an alcohol challenge was measured with positron emission tomography (PET) using the radiotracer [C]PBR28, which targets the 18-kDa translocator protein, a marker sensitive to immune challenges.

Sex steroid hormone levels associated with dopamine D receptor availability in people who smoke cigarettes.

Introduction: Sex differences exist in tobacco smoking. Women have greater difficulty quitting smoking than men. Tobacco smoking is driven by the reinforcing effects of nicotine, the primary addictive component in cigarettes.

Clustering of KOR PET images separates people with AUD into distinct responses to naltrexone.

Striatal kappa opioid receptor (KOR) availability in 48 subjects with Alcohol Use Disorder (AUD) was previously found to be associated with degree of drinking following a week of naltrexone treatment (de Laat et al. Biological Psychiatry, 86(11), 864-871, 2019). The purpose of the current study was to determine if spectral clustering applied to previously acquired KOR images (with [11C]LY2795050 PET) could identify meaningful groupings of different responses to naltrexone and to assess the robustness of the finding.

Cholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[F]flubatine PET study.

The cholinergic system is a critical mediator of cognition in animals. People who smoke cigarettes exhibit cognitive deficits, especially during quit attempts. Few studies jointly examine the cholinergic system and cognition in people while trying to quit smoking.

A Role for Histone Deacetylases in the Biology and Treatment of Post-Traumatic Stress Disorder: What Do We Know and Where Do We Go from Here?

Post-traumatic stress disorder is a prevalent disorder within the USA and worldwide with a yearly diagnosis rate of 2-4% and affecting women more than men. One of the primary methods for study of this stress disorder relies on animal models as there are few noninvasive methods and few replicated peripheral biomarkers for use in humans. One area of active research in psychiatric neuroscience is the field of epigenetics - how the chemical modifications of the genetic code regulate behavior.

Lower Dopamine D2/3 Receptor Availability is Associated With Worse Verbal Learning and Memory in People Who Smoke Cigarettes.

Introduction: Tobacco smoking is a major public health burden. The mesocortical dopamine system-including the dorsolateral prefrontal cortex (dlPFC)-plays an important role in cognitive function. Dysregulated dopamine signaling in dlPFC is associated with cognitive deficits such as impairments in attention, learning, working memory, and inhibitory control.

Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers.

Immune-brain interactions influence the pathophysiology of addiction. Lipopolysaccharide (LPS)-induced systemic inflammation produces effects on reward-related brain regions and the dopamine system. We previously showed that LPS amplifies dopamine elevation induced by methylphenidate (MP), compared to placebo (PBO), in eight healthy controls.

Why language matters in alcohol research: Reducing stigma.

Background: The use of pejorative or stigmatizing language to describe individuals with alcohol and drug use disorders adversely affects treatment seeking, quality of care, and treatment outcomes. In 2015, the International Society of Addiction Journal Editors released terminology guidelines that recommended against the use of words that contribute to stigma against individuals with an addictive disorder. This study examined the use of stigmatizing language in National Institutes of Health (NIH)-funded research and reviews published by the journal, Alcoholism: Clinical and Experimental Research (ACER) from 2010 to 2020, with the goal of sharing the results with the alcohol research community to enhance awareness.

Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder.

Background: People recovering from alcohol use disorder (AUD) show altered resting brain connectivity. The metabotropic glutamate 5 (mGlu5) receptor is an important regulator of synaptic plasticity potentially linked with synchronized brain activity and a target of interest in treating AUD. The goal of this work was to assess potential relationships of brain connectivity at rest with mGlu5 receptor availability in people with AUD at two time points early in abstinence.

Nicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response.

Introduction: Tobacco smoking is a major public health burden. The first-line pharmacological treatment for tobacco smoking is nicotine replacement therapy (eg, the nicotine patch (NIC)). Nicotine acts on nicotinic-acetylcholine receptors on dopamine terminals to release dopamine in the ventral and dorsal striatum encoding reward and habit formation, respectively.

Relationships between dopamine D2/3 receptor availability and social-environmental factors in humans.

Social factors are associated with psychiatric outcomes and brain function. Relationships between local population data obtained from Social Explorer analyses of the American Community Survey (2014-2018) and dopamine D receptor (DR) availability were explored in this retrospective analysis of [C]PHNO positron emission tomography (PET) imaging data (n = 70). Larger local population size and lower percentage of the population with a bachelor's degree or higher were significantly associated with higher striatal DR availability, suggesting that living in a populous area with fewer educational resources may be accompanied by stressors with concomitant dopaminergic changes.

Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1.

BACKGROUNDInvestigations of stress dysregulation in posttraumatic stress disorder (PTSD) have focused on peripheral cortisol, but none have examined cortisol in the human brain. This study used positron emission tomography (PET) to image 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a cortisol-producing enzyme, as a putative brain cortisol marker in PTSD.METHODSSixteen individuals with PTSD and 17 healthy, trauma-exposed controls (TCs) underwent PET imaging with [18F]AS2471907, a radioligand for 11β-HSD1.