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Cigarette smoking has a major impact on global health and morbidity, and positron emission tomographic research has provided evidence for reduced inflammation in the human brain associated with cigarette smoking. Given the consequences of inflammatory dysfunction for health, the question of whether cigarette smoking affects neuroinflammation warrants further investigation. The goal of this project therefore was to validate and extend evidence of hypoinflammation related to smoking, and to examine the potential contribution of inflammation to clinical features of smoking. Using magnetic resonance spectroscopy, we measured levels of neurometabolites that are putative neuroinflammatory markers. N-acetyl compounds (N-acetylaspartate + N-acetylaspartylglutamate), glutamate, creatine, choline-compounds (phosphocholine + glycerophosphocholine), and myo-inositol, have all been linked to neuroinflammation, but they have not been examined as such with respect to smoking. We tested whether people who smoke cigarettes have brain levels of these metabolites consistent with decreased neuroinflammation, and whether clinical features of smoking are associated with levels of these metabolites. The dorsal anterior cingulate cortex was chosen as the region-of-interest because of previous evidence linking it to smoking and related states. Fifty-four adults who smoked daily maintained overnight smoking abstinence before testing and were compared with 37 nonsmoking participants. Among the smoking participants, we tested for associations of metabolite levels with tobacco dependence, smoking history, craving, and withdrawal. Levels of N-acetyl compounds and glutamate were higher, whereas levels of creatine and choline compounds were lower in the smoking group as compared with the nonsmoking group. In the smoking group, glutamate and creatine levels correlated negatively with tobacco dependence, and creatine correlated negatively with lifetime smoking, but none of the metabolite levels correlated with craving or withdrawal. The findings indicate a link between smoking and a hypoinflammatory state in the brain, specifically in the dorsal anterior cingulate cortex. Smoking may thereby increase vulnerability to infection and brain injury.

BackgroundCigarette craving, which can negatively impact smoking cessation, is reportedly stronger in women than in men when they initiate abstinence from smoking. Identifying approaches to counteract craving in people of different sexes may facilitate the development of personalized treatments for Tobacco Use Disorder, which disproportionately affects women. Because cigarette craving is associated with nicotine dependence and structure of the insula, this study addressed whether a person's sex influences these associations.MethodsThe research participants (n = 99, 48 women) reported daily cigarette smoking and provided self-reports of nicotine dependence. After overnight abstinence from smoking, they underwent structural magnetic resonance imaging scanning to determine cortical thickness of the left and right anterior circular insular sulcus, and self-rated their cigarette craving before and after their first cigarette of the day.ResultsWomen reported stronger craving than men irrespective of smoking condition (i.e., pre- and post-smoking) (P = .048), and smoking reduced craving irrespective of sex (P

Research using rodent models has established a relationship between the steroid hormone estrogen and dopamine function, by revealing changes throughout the estrous cycle and by directly manipulating neuroendocrine signaling through ovariectomy and administration of estrogen. However, a direct link between estrogen levels and dopamine signaling had not been established in humans. The goal of this study, therefore, was to assess the relationship between circulating 17β-estradiol and dopamine signaling in the human brain by testing for a relationship between two proxies for these variables: peripheral 17β-estradiol and striatal dopamine D2-type receptor availability, measured with [18F]fallypride and positron emission tomography (PET). Sixteen (23-45 years of age) women were tested on 2 days of the menstrual cycle estimated prospectively to occur during (a) the early follicular phase, when estrogen levels are near their nadir, and (b) the periovulatory phase, when estrogen levels peak. PET scans with [18F]fallypride were performed on these 2 days, and serum 17β-estradiol was measured using radioimmunoassay. Dopamine D2-type receptor availability did not differ significantly in the whole striatum or the caudate, putamen, or accumbens subregions during the high-estrogen vs. the low-estrogen phases of the menstrual cycle. We conclude that circulating estrogen levels do not affect dopamine D2-type receptor availability in the human striatum although other indices of dopaminergic function may be affected.

Gonadal hormones influence neuronal organization and plasticity. Yet the consequences of altering their concentrations by administering contraceptive agents, which are used by most reproductive-age women in the United States, are unclear. Cross-sectional studies have found both larger and smaller cortical regions alongside a variety of mood alterations in women who use oral contraceptive pills (OCPs) compared to naturally-cycling women. The goal of this study, therefore, was to determine whether there is an effect of OCPs on MRI measures of prefrontal cortical brain structure that may influence regulation of mood. We performed a double-blind, placebo-controlled, randomized crossover study comparing effects of OCPs (0.15 mg levonorgestrel + 0.30 μg ethinyl estradiol) vs placebo (N = 26) on MRI measures of prefrontal cortical thickness and on mood, as indicated by self-report on the Daily Record of Severity of Problems, which also includes one item related to somatic symptoms. MRI measures that reflect cortical thickness were smaller bilaterally in the pars triangularis and in the pars opercularis and frontal pole of the right hemisphere during the OCP arm vs. placebo. Only the effect in the right pars triangularis survived multiple comparisons correction. Right pars triangularis MRI measures of cortical thickness were not related to mood symptoms, but negatively correlated across conditions with severity of somatic symptoms on the DSRP. The somatic symptoms and MRI measures may be independently related to the actions of steroid hormones in OCPs, with OCPs simultaneously inducing both more effects on MRI measures of cortical thickness and somatic symptoms.

Purpose of reviewThe goal was to review recent (1/2015-2/2020) evidence of impulsivity as a feature of substance use disorders or use of substances (alcohol, cannabis, nicotine, opioids, stimulants) in males compared to females in terms of: a) impulsivity in substance-using groups (or substance-using compared to control groups), and b) relationship between impulsivity and substance use behavior, clinical severity, or treatment outcomes.Recent findingsOf 361 papers identified by the searches, 69 met inclusion criteria, and 39 were highlighted for considering sex/gender in relation to impulsivity in substance-using populations. Taken together, findings supported higher impulsivity in males and females who use substances, relative to controls; and higher impulsivity was linked with more substance use/severity in both sex/genders. There were mixed findings regarding male versus female differences in impulsivity among individuals who use substances, or in the magnitude of the relationship between impulsivity and substance use severity.SummaryThe current body of evidence does not point to a consistent sex/gender difference in the role of impulsivity within and across substance use disorders. Impulsivity is a clinically-relevant construct for male and female individuals who use substances, across a range of substances.

BackgroundPremenstrual dysphoric disorder (PMDD) is an understudied, debilitating disorder of women. Given evidence for prefrontal cortical and limbic dysfunction in PMDD, we compared intrinsic connectivity of the executive control network (ECN), default mode network (DMN), and amygdala in women with PMDD vs. controls.MethodsThirty-six women (18 PMDD, 18 control) participated in fMRI during the follicular and luteal phases of the menstrual cycle. At each time, resting-state functional connectivity was evaluated both before and after participants performed an emotion regulation task. The ECN was identified using independent components analysis, and connectivity of left and right amygdala seeds was also evaluated.ResultsNonparametric permutation testing identified a cluster in the left middle temporal gyrus (MTG) with significantly stronger connectivity to the left ECN in women with PMDD vs. controls in all four fMRI sessions. Women with PMDD exhibited no difference in functional connectivity between menstrual cycle phases. Amygdala connectivity did not differ between the groups but differed significantly with menstrual phase, with left amygdala connectivity to cingulate cortex being significantly stronger during the follicular vs. luteal phase. Right amygdala connectivity to the middle frontal gyrus was also stronger during the follicular vs. luteal phase, with no group differences. These findings suggest that women with PMDD have different intrinsic network dynamics in the left executive control network compared to healthy controls.

Mesolimbic dopaminergic function influences addiction through effects on reinforcement learning, decision-making, and impulsivity. This review covers sex differences in dopaminergic neurochemistry, their hormonal and genetic determinants, and how differences in dopaminergic tone interact with sex and/or ovarian hormone status to affect cognitive functions. Findings from research on cigarette smoking reveal sex differences in striatal and midbrain dopamine D2-type receptor availability and striatal dopamine release that suggest mechanisms of nicotine dependence, and stronger subjective responses to nicotine and efficacy of nicotine replacement therapies in male smokers than in their female counterparts. Opportunities exist to extend such efforts in studies of how sex and hormone status influence other addictions.

BackgroundDifficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD.MethodsOn the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle.ResultsWomen with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants.ConclusionsDuring the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.

RationalePolicies that establish a standard for reduced nicotine content in cigarettes can decrease the prevalence of smoking in the USA. Cigarettes with nicotine yields as low as 0.05 mg produce substantial occupancy of nicotinic acetylcholine receptors (26%), but women and men respond differently to these cigarettes.ObjectiveThis study aimed to measure responses to smoking cigarettes that varied widely in nicotine yields, investigating whether sex differences in the effects on craving, withdrawal, and affect would be observed at even lower nicotine yields than previously studied, and in young smokers.MethodsOvernight abstinent young smokers (23 men, 23 women, mean age 22.18) provided self-reports of craving, withdrawal, and affect before and after smoking cigarettes with yields of 0.027, 0.110, 0.231, or 0.763 mg nicotine, and evaluated characteristics of each cigarette.ResultsCompared to abstinent young men, abstinent young women reported greater negative affect, psychological withdrawal, and sedation, all of which were relieved equally by all cigarettes. Men but not women reported greater craving reduction, perceived nicotine content, and cigarette liking with increasing nicotine dose.ConclusionsMen may experience less smoking-related relief of craving, and enjoy cigarettes less, if nicotine yields are reduced to very low levels. Conversely, women respond equally well to cigarettes with nicotine yields as low as 0.027 mg as to cigarettes with nicotine yields 28-fold higher (0.763 mg). These differences are relevant for policy regarding reduced nicotine in cigarettes and may influence the efficacy and acceptability of reduced-nicotine cigarettes as smoking cessation aids.

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to

Women differ from men in smoking-related behaviors, among them a greater difficulty in quitting smoking. Unlike female smokers, male smokers have lower striatal dopamine D2-type receptor availability (binding potential, BPND) than nonsmokers and exhibit greater smoking-induced striatal dopamine release. Because dopamine D2-type autoreceptors in the midbrain influence striatal dopamine release, a function that has been linked to addiction, we tested for sex differences in midbrain dopamine D2-type receptor BPND and in relationships between midbrain BPND, nicotine dependence and striatal dopamine D2-type receptor BPND. Positron emission tomography was used with [18F]fallypride to measure BPND in a midbrain region, encompassing the substantia nigra and ventral tegmental area, in 18 daily smokers (7 women, 11 men) and 19 nonsmokers (10 women, 9 men). A significant sex-by-group interaction reflected greater midbrain BPND in female but not male smokers than in corresponding nonsmokers (F1, 32=5.089, p=0.03). Midbrain BPND was positively correlated with BPND in the caudate nucleus and putamen in nonsmokers and female smokers but not in male smokers and with nicotine dependence in female but not in male smokers. Striatal BPND was correlated negatively with nicotine dependence and smoking exposure. These findings extend observations on dopamine D2-type receptors in smokers and suggest a sex difference in how midbrain dopamine D2-type autoreceptors influence nicotine dependence.

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.

The amygdala is a highly interconnected region of the brain that is critically important to emotional processing and affective networks. Previous studies have shown that the response of the amygdala to emotionally arousing stimuli can be modulated by sex hormones. Because oral contraceptive pills dramatically lower circulating sex hormone levels with potent analogs of those hormones, we performed a functional magnetic resonance imaging experiment to measure amygdala reactivity in response to emotional stimuli in women using oral contraceptives, and compared their amygdala reactivity with that of naturally cycling women. Here, we show that women who use oral contraceptive pills have significantly decreased bilateral amygdala reactivity in response to negatively valenced, emotionally arousing stimuli compared with naturally cycling women. We suggest that by modulating amygdala reactivity, oral contraceptive pills may influence behaviors that have previously been shown to be amygdala dependent-in particular, emotional memory.

Oral contraceptive pills (OCs), which are used to prevent pregnancy by the majority of women in the United States, contain steroid hormones that may affect the brain's structure and function. In this investigation, we tested the hypothesis that OC use is associated with differences in brain structure using a hypothesis-driven, surface-based approach. In 90 women, (44 OC users, 46 naturally-cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. Further investigations are needed to determine if cortical thinning in these regions are associated with behavioral changes, and also to identify whether OC use is causally or only indirectly related to these changes in brain morphology.

At rest, brain activity can be characterized not by an absence of organized activity but instead by spatially and temporally correlated patterns of activity. In this experiment, we investigated whether and to what extent resting state functional connectivity is modulated by sex hormones in women, both across the menstrual cycle and when altered by oral contraceptive pills. Sex hormones have been shown to have important effects on task-related activity, but few studies have investigated the extent to which they can influence the behavior of functional networks at rest. These hormones are dramatically altered by the use of hormonal contraception, which is used by approximately 100 million women worldwide. However, potential cognitive side effects of hormonal contraception have been given little attention. Here, we collected resting state data for naturally-cycling women (n=45) and women using combined oral contraceptive pills (n=46) and evaluated the differences in resting state activity between these two groups using independent component analysis. We found that in the default mode network and in a network associated with executive control, resting state dynamics were altered both by the menstrual cycle and by oral contraceptive use. Specifically, the connectivity of the left angular gyrus, the left middle frontal gyrus, and the anterior cingulate cortex were different between groups. Because the anterior cingulate cortex and left middle frontal gyrus are important for higher-order cognitive and emotional processing, including conflict monitoring, changes in the relationship of these structures to the functional networks with which they interact may have important consequences for attention, affect, and/or emotion regulation.

Aim: The aim of this study was to evaluate the impact of the uninstructed use of a toothpaste containing herbal ayurvedic ingredients on parameters of gingival health in a cohort of periodontal aftercare patients affected by gingival inflammation compared to the use of a standard, non‐herbal toothpaste. Materials and Methods: The monocentric, randomized, double‐blinded, two‐arm parallel‐group intervention was performed in a cohort of 88 periodontal aftercare patients with clinical signs of gingival inflammation. At baseline, bleeding on probing (BoP), gingival index (GI) and Quigley–Hein plaque index (QHI) were recorded. Subsequently, the study patients were randomly provided with a herbal ayurvedic toothpaste (n = 44) or a conventional, non‐ayurvedic control toothpaste (n = 44) and without additional oral hygiene training instructed to use it 2× daily for the next 28 days. On day 28, BoP, GI and QHI were recorded again. Results: At baseline, there were no significant differences between both groups. On day 28, mean GI and BoP scores were significantly lower (p < 0.001) compared to baseline in both groups. Differences between the groups could not be verified. Mean QHI scores did not change significantly between day 0 and day 28 in both groups. Conclusions: The impact of uninstructed toothbrushing with an ayurvedic toothpaste on the manifestation of gingival inflammation in periodontal aftercare patients is not significantly different to the use of a conventional, non‐herbal toothpaste. [ABSTRACT FROM AUTHOR]

The recent identification of highly superior autobiographical memory (HSAM) raised the possibility that there may be individuals who are immune to memory distortions. We measured HSAM participants' and age- and sex-matched controls' susceptibility to false memories using several research paradigms. HSAM participants and controls were both susceptible to false recognition of nonpresented critical lure words in an associative word-list task. In a misinformation task, HSAM participants showed higher overall false memory compared with that of controls for details in a photographic slideshow. HSAM participants were equally as likely as controls to mistakenly report they had seen nonexistent footage of a plane crash. Finding false memories in a superior-memory group suggests that malleable reconstructive mechanisms may be fundamental to episodic remembering. Paradoxically, HSAM individuals may retrieve abundant and accurate autobiographical memories using fallible reconstructive processes.

Background: Postpartum depression (PPD) is a prevalent public health concern. Combustible cigarette use is associated with increased risk of PPD. While electronic cigarette (e-cigarette) use during pregnancy is linked to increased risk of depressive symptoms during pregnancy, the relationship between e-cigarette use and PPD is not well understood. We sought to examine the association of e-cigarette use with PPD. Materials and Methods: Using Pregnancy Risk Assessment Monitoring System 2016–2019 data, unadjusted and adjusted logistic regression analyses for PPD were conducted via three analyses where e-cigarette use (any vs. none) was retrospectively self-reported (1) in past 2-year, (2) prepregnancy (i.e., 3 months before pregnancy), and (3) during pregnancy (i.e., last 3 months of pregnancy). We conducted an additional past 2-year e-cigarette use analysis excluding those who used combustible cigarette and/or hookah. Covariates included age, race, ethnicity, combustible cigarette, and/or hookah use, prenatal care during the last trimester, health insurance coverage during pregnancy, physical abuse during pregnancy, income, and survey type. Results: Only unadjusted odds ratios from past 2-year e-cigarette use (1.63, 95% confidence interval [CI]: 1.42–1.87) and past 2-year e-cigarette use excluding individuals with cigarette and/or hookah use (1.78, 95% CI: 1.30–2.38) were statistically associated with PPD. No adjusted analyses were statistically significant. Conclusion: Any e-cigarette use, as compared to no use, does not appear to be an independent risk factor of PPD, though it may be a useful clinical marker of increased risk of PPD. Future studies are warranted to advance our knowledge of impact of e-cigarette use on PPD. [ABSTRACT FROM AUTHOR]