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Background Gliosis is common among neuropsychiatric diseases, but the relationship between gliosis and response to therapeutics targeting effects of gliosis is largely unknown. Translocator protein total distribution volume (TSPO VT), measured with positron emission tomography, mainly reflects gliosis in neuropsychiatric disease. Here, the primary objective was to determine whether TSPO VT in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) predicts reduction of depressive symptoms following open-label celecoxib administration in treatment-resistant major depressive disorder. Methods A total of 41 subjects with treatment-resistant major depressive disorder underwent one [18F]FEPPA positron emission tomography scan to measure PFC and ACC TSPO VT. Open-label oral celecoxib (200 mg, twice daily) was administered for 8 weeks. Change in symptoms was measured with the 17-item Hamilton Depression Rating Scale (HDRS). Results Cumulative mean change in HDRS scores between 0 and 8 weeks of treatment was plotted against PFC and ACC TSPO VT, showing a significant nonlinear relationship. At low TSPO VT values, there was no reduction in HDRS scores, but as TSPO VT values increased, there was a reduction in HDRS scores that then plateaued. This was modeled with a 4-parameter sigmoidal model in which PFC and ACC TSPO VT accounted for 84% and 92% of the variance, respectively. Conclusions Celecoxib administration in the presence of gliosis labeled by TSPO VT is associated with greater reduction of symptoms. Given the predictiveness of TSPO VT on symptom reduction, this personalized medicine approach of matching a marker of gliosis to medication targeting effects of gliosis should be applied in early development of novel therapeutics, in particular for treatment-resistant major depressive disorder.

Responsiveness to drug-related cues assesses drug reward in research studies. There are currently no validated visual image cues related to electronic nicotine delivery systems (ENDS), thus, this study aimed to develop and validate affective ENDS image cues.ENDS users and non-vaping individuals in the United States and Canada were recruited via Amazon MTurk. A total of 120 ENDS-related images and 56 neutral images, matched for visual similarity, were assessed. These images were either selected from public databases or were photographed by study staff. Closely adhering to the International Affective Picture System procedure, each participant rated 66 images one-by-one on dimensions of valence, arousal, dominance, and desire-to-vape where higher scores indicated greater feelings of happiness, excitement, loss of control, and desire to vape.After excluding patterned responses, the data from 926 participants (610 ENDS users, and 316 non-vaping controls) were analyzed. When viewing ENDS-related images, desire-to-vape scores were correlated with valence (r = 0.55, p 0.0005), arousal (r = 0.72, p 0.0005), and dominance (r = 0.58, p 0.0005) scores. Images that elicited greater desires to vape also elicited greater feelings of happiness and excitement, but less perceived control. Correlations between arousal and valence (r = 0.42, p 0.0005) and dominance (r = 0.71, p 0.0005) suggest that images that increased feelings of excitement also increased happiness and decreased perceived control.Correlational findings of the affective ENDS-related images were similar to those of previous studies validating collections of tobacco and alcohol picture cues, supporting the future use of these stimuli in ENDS research.

Greater activation of glia, a key component of neuroinflammation, is an important process to target in neuropsychiatric illnesses. However, the magnitude of gliosis varies across cases so low-cost predictors are needed to stratify subjects for clinical trials. Here, several such blood serum measures were assessed in relation to TSPO V(T), an index of translocator protein density, measured with positron emission tomography. Blood serum concentration of several products known to be synthesized by activated microglia (and to some extent astroglia) [prostaglandin E(2) (PGE(2)), prostaglandin F(2) alpha (PGF(2α)), and tumor necrosis factor alpha (TNF(α))], controlled by an index of peripheral inflammation [C-reactive protein (CRP)] and TSPO V(T) were measured in 3 cohorts: prefrontal cortex TSPO V(T) of 20 subjects with major depressive episodes (MDEs) from major depressive disorder (MDD); and 56 subjects with treatment resistant MDEs from MDD; and dorsal caudate TSPO V(T) of 20 subjects with obsessive-compulsive disorder. Ln(PGE(2)/CRP) and ln(TNF(α)/CRP) consistently correlated with TSPO V(T) (R(2) = 0.36 to 0.11, p = 0.0030 to p = 0.0076). Assessment of threshold serum values to predict highly elevated TSPO V(T), demonstrated that a positive predictive value (PPV) of 80% was possible while retaining 40% of participant samples and that receiver operating curves (ROC) ranged from 75 to 81%. Post-hoc selection of ln(CRP) was more predictive (R(2) = 0.23 to 0.39, p = 0.0058 to p = 0.00013; ROC > 80%). Systematic assessment of selected peripheral inflammatory markers is promising for developing low cost predictors of TSPO V(T). Marker thresholds with high PPV will improve subject stratification for clinical trials of glial targeting therapeutics.

As food addiction is being more commonly recognized within the scientific community, parallels can be drawn between it and other addictive substance use disorders, including tobacco use disorder. Given that both unhealthy diets and smoking are leading risk factors for disability and death, a greater understanding of how food addiction and tobacco use disorder overlap with one another is necessary. This narrative review aimed to highlight literature that investigated prevalence, biology, psychology, and treatment options of food addiction and tobacco use disorder. Published studies up to August 2020 and written in English were included. Using a biopsychosocial lens, each disorder was assessed together and separately, as there is emerging evidence that the two disorders can develop concurrently or sequentially within individuals. Commonalities include but are not limited to the dopaminergic neurocircuitry, gut microbiota, childhood adversity, and attachment insecurity. In addition, the authors conducted a feasibility study with the purpose of examining the association between food addiction symptoms and tobacco use disorder among individuals seeking tobacco use disorder treatment. To inform future treatment approaches, more research is necessary to identify and understand the overlap between the two disorders.

Electronic cigarettes (e-cigarettes) are potential tools for smoking cessation because they deliver nicotine and simulate smoking behaviors. The contribution of sensorimotor versus pharmacological substitution is unknown.To evaluate whether non-nicotinic e-cigarettes, used alone or with nicotine lozenges, can attenuate cigarette craving following visual cue presentation or acute (3 h post ad-lib use) abstinence in dependent daily smokers.Following overnight (12 hours) abstinence, 41 daily smokers were exposed to 4 experimental conditions on separate days: (i) tobacco cigarettes (CIG); (ii) non-nicotinic e-cigarettes with placebo lozenges (EPL); (iii) non-nicotinic e-cigarettes with 4 mg nicotine lozenge (ENL); and (iv) 4 mg nicotine lozenge (NL). Cigarette craving was assessed following presentation of neutral and smoking cues at various time points using the Brief Questionnaire of Smoking Urges (QSU-B) and visual analog scales (VAS).All experimental conditions significantly reduced participants' baseline overnight abstinence cigarette craving. ENLs and NLs attenuated smoking-cue-induced cravings to a greater extent than CIGs, where cravings were significantly higher with CIGs compared to ENLs [mean difference (MD) ± standard error (SE) in QSU-B = 3.2 ± 0.84, P = 0.002; VAS = 12.7 ± 2.7, P0.0005] and NLs [MD ± SE in QSU-B = 2.7 ± 0.92, P = 0.031; VAS = 8.1 ± 2.3, P = 0.005]. Craving responses to cues after 3 h were higher after smoking CIGs compared to ENLs [MD ± SE in QSU-B = 3.9 ± 1.4, P = 0.047; VAS = 14.1 ± 3.6, P = 0.002] and NLs [MD ± SE in QSU-B = 3.2 ± 1.1, P = 0.046; VAS = 9.7 ± 3.1, P = 0.017].Behavioral simulation of smoking with or without nicotine reduces nicotine craving. Compared to cigarettes, ENL with NL or NL alone attenuates cigarette craving over time. Future clinical trials should evaluate the combination of ENL and NL as a method for smoking reduction or cessation.NCT02108626.

Background A key component of alcohol dependence (AD), a severe form of alcohol use disorder, is the negative emotional state during withdrawal. Monoamine oxidase A (MAO-A) is an important enzyme that metabolizes monoamines and creates oxidative stress. Elevations in MAO-A level, especially in the prefrontal and anterior cingulate cortex (PFC and ACC), are associated with low mood states, including the dysphoria of early alcohol withdrawal in humans. The aim of the present study was to determine whether chronic alcohol vapor exposure causes an upregulation of MAO-A activity or level in the PFC and ACC of rodents during acute withdrawal. Methods Sprague-Dawley rats were exposed to ethanol vapor or control condition for 17 h per day for 8 weeks. MAO-A activity and protein levels were measured immediately after exposure, acute withdrawal (24 h), protracted withdrawal (4 day), and protracted abstinence (3 weeks) (n = 16/group; 8 alcohol exposed, 8 control). Results Chronic ethanol vapor exposure significantly elevated MAO-A activity and protein levels in the PFC and ACC at 24-h withdrawal (multivariate analysis of variance (MANOVA), activity: F2,13 = 3.82, p = .05, protein: F2,13 = 5.13, p = .02). There were no significant changes in MAO-A level or activity at other timepoints. Conclusions The results of this study suggest a causal relationship between acute alcohol withdrawal and elevated MAO-A levels and activity, clarifying the observation of greater MAO-A binding in human alcohol withdrawal. This has important implications for developing methods of targeting MAO-A and/or sequelae of its dysregulation in alcohol dependence.

Importance For a small percentage of obsessive-compulsive disorder (OCD) cases exhibiting additional neuropsychiatric symptoms, it was proposed that neuroinflammation occurs in the basal ganglia as an autoimmune response to infections. However, it is possible that elevated neuroinflammation, inducible by a diverse range of mechanisms, is important throughout the cortico-striato-thalamo-cortical circuit of OCD. Identifying brain inflammation is possible with the recent advance in positron emission tomography (PET) radioligands that bind to the translocator protein (TSPO). Translocator protein density increases when microglia are activated during neuroinflammation and the TSPO distribution volume (V T ) is an index of TSPO density. Objective To determine whether TSPO V T is elevated in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, dorsal putamen, and anterior cingulate cortex in OCD. Design, Setting, and Participants This case-control study was conducted at a tertiary care psychiatric hospital from May 1, 2010, to November 30, 2016. Participants with OCD (n = 20) and age-matched healthy control individuals (n = 20) underwent a fluorine F 18–labeled N -(2-(2-fluoroethoxy)benzyl)- N -(4-phenoxypyridin-3-yl)acetamide PET scan. It is a high-quality second-generation TSPO-binding PET radiotracer. All participants were drug and medication free, nonsmoking, and otherwise healthy. Main Outcomes and Measures The TSPO V T was measured in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, dorsal putamen, and anterior cingulate cortex. Compulsions were assessed with the Yale-Brown Obsessive Compulsive Scale. Results In the OCD and healthy groups, the mean (SD) ages were 27.4 (7.1) years and 27.6 (6.6) years, respectively, and 11 (55%) and 8 (40%) were women, respectively. In OCD, TSPO V T was significantly elevated in these brain regions (mean, 32%; range, 31%-36% except anterior cingulate cortex, 24%; analysis of variance, effect of diagnosis: P P = .004). Slightly lower elevations in TSPO V T (22%-29%) were present in other gray matter regions. The Yale-Brown Obsessive Compulsive Scale measure of distress associated with preventing compulsive behaviors significantly correlated with TSPO V T in the orbitofrontal cortex (uncorrected Pearson correlation r = 0.62; P = .005). Conclusions and Relevance To our knowledge, this is the first study demonstrating inflammation within the neurocircuitry of OCD. The regional distribution of elevated TSPO V T argues that the autoimmune/neuroinflammatory theories of OCD should extend beyond the basal ganglia to include the cortico-striato-thalamo-cortical circuit. Immunomodulatory therapies should be investigated in adult OCD, rather than solely childhood OCD, particularly in cases with prominent distress when preventing compulsions.