Multimodal smoking cessation treatment combining repetitive transcranial magnetic stimulation, cognitive behavioral therapy, and nicotine replacement in veterans with posttraumatic stress disorder: A feasibility randomized controlled trial protocol.

Tobacco-related deaths remain the leading cause of preventable death in the United States. Veterans suffering from posttraumatic stress disorder (PTSD)-about 11% of those receiving care from the Department of Veterans Affairs (VA)-have triple the risk of developing tobacco use disorder (TUD). The most efficacious strategies being used at the VA for smoking cessation only result in a 23% abstinence rate, and veterans with PTSD only achieve a 4.

Sustained overexpression of spliced X-box-binding protein-1 in neurons leads to spontaneous seizures and sudden death in mice.

The underlying etiologies of seizures are highly heterogeneous and remain incompletely understood. While studying the unfolded protein response (UPR) pathways in the brain, we unexpectedly discovered that transgenic mice (XBP1s-TG) expressing spliced X-box-binding protein-1 (Xbp1s), a key effector of UPR signaling, in forebrain excitatory neurons, rapidly develop neurologic deficits, most notably recurrent spontaneous seizures. This seizure phenotype begins around 8 days after Xbp1s transgene expression is induced in XBP1s-TG mice, and by approximately 14 days post induction, the seizures evolve into status epilepticus with nearly continuous seizure activity followed by sudden death.

Effects of sex and genotype in human APOE-targeted replacement mice on alcohol self-administration measured with the automated IntelliCage system before and after repeated mild traumatic brain injury.

Background: Few studies have examined the association between APOE genotype and alcohol use. Although some of these studies have reported outcomes associated with a history of drinking, none have examined alcohol-seeking behavior. In addition, no preclinical studies have examined alcohol use as a function of APOE genotype with or without traumatic brain injury.

Pilot Cohorts for Development of Concurrent Mobile Treatment for Alcohol and Tobacco Use Disorders.

Alcohol and tobacco are the 2 most frequently used drugs in the United States and represent the highest co-occurrence of polysubstance use. The objective of this study was to refine an intervention combining mobile contingency management with cognitive-behavioral telephone counseling for concurrent treatment of alcohol and tobacco use disorders. Two cohorts (n = 13 total, n = 5 women) of participants were enrolled, with 10/13 completing treatment and 7/13 completing the 6-month follow-up.

Multiple sources of internal calcium stores mediate ethanol-induced presynaptic inhibitory GABA release in the central nucleus of the amygdala in mice.

Rationale: Ethanol can enhance GABA release in various brain regions via presynaptic mechanisms. However, the presynaptic action of ethanol on inhibitory GABA release is still not well understood.

Objectives: Since calcium is required for neurotransmitter release from presynaptic terminals, the purpose of this study was to investigate the role of both internal and external calcium signaling in ethanol-induced enhancement of GABA release within the central amygdala nucleus (CeA) in acute brain slice preparations.

General anesthetic exposure in adolescent rats causes persistent maladaptations in cognitive and affective behaviors and neuroplasticity.

Accumulating evidence indicates that exposure to general anesthetics during infancy and childhood can cause persistent cognitive impairment, alterations in synaptic plasticity, and, to a lesser extent, increased incidence of behavioral disorders. Unfortunately, the developmental parameters of susceptibility to general anesthetics are not well understood. Adolescence is a critical developmental period wherein multiple late developing brain regions may also be vulnerable to enduring general anesthetic effects.

Patient-Informed Treatment Development of Behavioral Smoking Cessation for People With Schizophrenia.

The objective of this study was to use qualitative methodology to tailor and refine an existing smoking cessation intervention for the population of people who use cigarettes and are diagnosed with schizophrenia, schizoaffective, or psychotic disorder. Successive cohort design methodology was used to iteratively modify the treatment in response to qualitative participant, therapist, and consultant feedback on the intervention. Qualitative methodology for participant feedback included analysis of semistructured interviews with participants, visualization of app utilization data, and stakeholder feedback from study therapists and consultants.

Pilot Trial of a Combined Cognitive Processing Therapy and Smoking Cessation Treatment.

Objective/background: Posttraumatic stress disorder (PTSD) and smoking are often comorbid. Combining PTSD and smoking cessation treatments could increase access to each treatment and could provide improved rates of smoking cessation through reductions in PTSD and depressive symptoms.

Participants: Participants were veterans with current PTSD who smoked cigarettes and were willing to initiate treatment for both problems.

Mechanisms of increased hippocampal excitability in the Mashl mouse model of Na /K -ATPase dysfunction.

Objective: Na /K -ATPase dysfunction, primary (mutation) or secondary (energy crisis, neurodegenerative disease) increases neuronal excitability in the brain. To evaluate the mechanisms underlying such increased excitability we studied mice carrying the D801N mutation, the most common mutation causing human disease, specifically alternating hemiplegia of childhood (AHC) including epilepsy. Because the gene is expressed in all neurons, particularly γ-aminobutyric acid (GABA)ergic interneurons, we hypothesized that the pathophysiology would involve both pyramidal cells and interneurons and that fast-spiking interneurons, which have increased firing rates, would be most vulnerable.

Mobile contingency management as an adjunctive treatment for co-morbid cannabis use disorder and cigarette smoking.

Introduction: Cannabis is the most widely used illicit drug in the U.S. with 19.

The Post-Deployment Mental Health (PDMH) study and repository: A multi-site study of US Afghanistan and Iraq era veterans.

The United States (US) Department of Veterans Affairs (VA) Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC) Post-Deployment Mental Health (PDMH) multi-site study examines post-deployment mental health in US military Afghanistan/Iraq-era veterans. The study includes the comprehensive behavioral health characterization of over 3600 study participants and the genetic, metabolomic, neurocognitive, and neuroimaging data for many of the participants. The study design also incorporates an infrastructure for a data repository to re-contact participants for follow-up studies.

Comparative Effectiveness of an Internet-Based Smoking Cessation Intervention Versus Clinic-Based Specialty Care for Veterans.

Introduction: The primary objective of this project was to examine the effectiveness of an Internet-based smoking cessation intervention combined with a tele-health medication clinic for nicotine replacement therapy (NRT) compared to referral to clinic-based smoking cessation care.

Methods: A total of 413 patients were proactively recruited from the Durham VA Medical Center and followed for 12 months. Patients were randomized to receive either a referral to VA specialty smoking cessation care (control) or to the Internet intervention and tele-health medication clinic.

Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1 Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social defeat stress.

Opposing effects of traumatic brain injury on excitatory synaptic function in the lateral amygdala in the absence and presence of preinjury stress.

Traumatic brain injury (TBI) is a leading cause of death and disability among young adults and is highly prevalent among recently deployed military personnel. Survivors of TBI often experience cognitive and emotional deficits, suggesting that long-term effects of injury may disrupt neuronal function in critical brain regions, including the amygdala, which is involved in emotion and fear memory. Amygdala hyperexcitability has been reported in both TBI and posttraumatic stress disorder patients, yet little is known regarding the effects of combined stress and TBI on amygdala structure and function at the neuronal level.

Adolescent Intermittent Alcohol Exposure: Dysregulation of Thrombospondins and Synapse Formation are Associated with Decreased Neuronal Density in the Adult Hippocampus.

Background: Adolescent intermittent alcohol exposure (AIE) has profound effects on neuronal function. We have previously shown that AIE causes aberrant hippocampal structure and function that persists into adulthood. However, the possible contributions of astrocytes and their signaling factors remain largely unexplored.

Interaction of CRF and kappa opioid systems on GABAergic neurotransmission in the mouse central amygdala.

The corticotropin-releasing factor (CRF) and kappa-opioid receptor (KOR) systems are both implicated in stress-related behaviors and drug dependence. Although previous studies suggest that antagonism of each system blocks aspects of experimental models of drug dependence, the possible interaction between these systems at the neuronal level has not been completely examined. We used an in vitro brain slice preparation to investigate the interaction of these two peptide systems on inhibitory neurotransmission in the central nucleus of the amygdala (CeA).

Adolescent intermittent alcohol exposure: persistence of structural and functional hippocampal abnormalities into adulthood.

Background: Human adolescence is a crucial stage of neurological development during which ethanol (EtOH) consumption is often at its highest. Alcohol abuse during adolescence may render individuals at heightened risk for subsequent alcohol abuse disorders, cognitive dysfunction, or other neurological impairments by irreversibly altering long-term brain function. To test this possibility, we modeled adolescent alcohol abuse (i.

Multicomponent smoking cessation treatment including mobile contingency management in homeless veterans.

Introduction: Smoking rates are 80% among persons who are homeless, and these smokers have decreased odds of quitting smoking. Little is known about relapse rates among homeless smokers. More information is needed regarding both quit rates and innovative methods to treat smoking cessation among homeless smokers.

Presynaptic BK channels modulate ethanol-induced enhancement of GABAergic transmission in the rat central amygdala nucleus.

Large-conductance calcium-activated potassium BK channels are widely expressed in the brain and are involved in the regulation of neuronal functions such as neurotransmitter release. However, their possible role in mediating ethanol-induced GABA release is still unknown. We assessed the role of BK channels in modulating the action of ethanol on inhibitory synaptic transmission mediated via GABAA receptors in the rat central nucleus of the amygdala (CeA).

Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult human APOE targeted replacement mice.

The human apolipoprotein ε4 allele (APOE4) has been implicated as one of the strongest genetic risk factors associated with Alzheimer's disease (AD) and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE.

Altered neurotransmission in the lateral amygdala in aged human apoE4 targeted replacement mice.

The human APOE4 allele is associated with an early age of onset and increased risk of Alzheimer's disease (AD). Apolipoprotein E is secreted as part of a high-density lipoprotein-like particle by glial cells in the brain for the primary purpose of transport of lipophilic compounds involved in the maintenance of synapses. Previous studies examining synaptic integrity in the amygdala of human apoE targeted replacement (TR) mice showed a decrease in spontaneous excitatory synaptic activity, dendritic arbor, and spine density associated with apoE4 compared with apoE3 and apoE2 in adult male mice.

Long-term modulation of A-type K(+) conductances in hippocampal CA1 interneurons in rats after chronic intermittent ethanol exposure during adolescence or adulthood.

Background: Chronic alcohol use, especially exposure to alcohol during adolescence or young adulthood, is closely associated with cognitive deficits that may persist into adulthood. Therefore, it is essential to identify possible neuronal mechanisms underlying the observed deficits in learning and memory. Hippocampal interneurons play a pivotal role in regulating hippocampus-dependent learning and memory by exerting strong inhibition on excitatory pyramidal cells.

Mobile contingency management as an adjunctive smoking cessation treatment for smokers with posttraumatic stress disorder.

Introduction: Smokers with posttraumatic stress disorder (PTSD) smoke at higher prevalence rates and are more likely to relapse early in a quit attempt. Innovative methods are needed to enhance quit rates, particularly in the early quit period. Web-based contingency-management (CM) approaches have been found helpful in reducing smoking among other difficult-to-treat smoker populations but are limited by the need for computers.