The Emotional Burden of Loneliness and its Association with Mental Health Outcomes.

BACKGROUND: The present study examined, for the first time, the emotional burden of loneliness on dimensions of emotional valence and arousal, and its association with mental health outcomes. METHOD: A cross-sectional design was used, and data were collected from 503 adults across the UK with an online survey. Measures included socio-demographic characteristics, self-reported measures of loneliness and social isolation, affective ratings (i.e., valence and arousal) of loneliness experiences, and symptoms of depression and anxiety as mental health outcomes. RESULTS: The emotional burden of loneliness differed significantly across groups with differing loneliness experiences, and females scored significantly higher in the emotional burden of loneliness than males. The emotional burden of loneliness was associated with both depression and anxiety symptoms, and respectively added 4.7% and 6.2% of the variance, on top of measures of loneliness frequency and social isolation. CONCLUSIONS: Measuring the valence and arousal dimensions of loneliness experiences advances our understanding of loneliness experiences and its association with mental health outcomes. The theoretical, methodological, and practical implications of our study are discussed.

Feelings of fear, sadness, and loneliness during the COVID-19 pandemic: Findings from two studies in the UK.

During the COVID-19 pandemic, exposure to COVID-related stimuli, has been enormous. Exposure to threat-related stimuli, can have a significant impact on people's wellbeing particularly in relation to COVID-related anxiety. The present research comprises two empirical studies. In Study 1, a newly developed Emotional Stroop Task (EST) and an Image Rating Task (IRT) were used to assess, automatic and non-automatic affective responses to COVID-related words and images during the first wave of the pandemic in the UK general population. In Study 2, the same tasks were used to evaluate the affective responses of University students during the second wave of the pandemic. Additionally, loneliness and pro-social behaviours were explored in relation COVID-related anxiety in the same population. Overall, the results showed that automatic affective responses as measured by interference effects on the EST, remained unaffected during the pandemic. However, non-automatic affective responses to COVID-related images measured by the IRT, indicated that participants rated these images as more fearful sadder and higher in anger, compared to non-COVID negative images matched for arousal and negativity and this was more evident in people with high COVID-anxiety. Trait anxiety was related to higher levels of loneliness, more prosocial behaviour and higher intentions to help others, while COVID-related anxiety mediated these effects, suggesting that for high levels of trait anxiety, participants were more likely to have helped someone in need during the pandemic when their COVID-anxiety levels were low.

A specific role for serotonin in overcoming effort cost.

Serotonin is implicated in many aspects of behavioral regulation. Theoretical attempts to unify the multiple roles assigned to serotonin proposed that it regulates the impact of costs, such as delay or punishment, on action selection. Here, we show that serotonin also regulates other types of action costs such as effort. We compared behavioral performance in 58 healthy humans treated during 8 weeks with either placebo or the selective serotonin reuptake inhibitor escitalopram. The task involved trading handgrip force production against monetary benefits. Participants in the escitalopram group produced more effort and thereby achieved a higher payoff. Crucially, our computational analysis showed that this effect was underpinned by a specific reduction of effort cost, and not by any change in the weight of monetary incentives. This specific computational effect sheds new light on the physiological role of serotonin in behavioral regulation and on the clinical effect of drugs for depression. CLINICAL TRIAL REGISTRATION: ISRCTN75872983.

Better sexual acceptability of agomelatine (25 and 50 mg) compared to escitalopram (20 mg) in healthy volunteers. A 9-week, placebo-controlled study using the PRSexDQ scale.

The present double-blind, placebo-controlled study evaluates the effects of agomelatine and the selective serotonin reuptake inhibitor escitalopram on sexual dysfunction in healthy men and women. METHODS: A total of 133 healthy volunteers (67 men, 66 women) were randomly assigned to agomelatine (25 or 50 mg) or escitalopram (20 mg) or placebo for nine weeks. Sexual acceptability was evaluated by using the psychotropic-related sexual dysfunction questionnaire 5-items total score and sexual dysfunction relative to each sub-score (in 110 volunteers with sexual activity). Sexual dysfunction was evaluated at baseline and after two, five and eight weeks of treatment and one week after drug discontinuation. RESULTS: The psychotropic-related sexual dysfunction questionnaire 5-items total score was significantly lower in both agomelatine groups versus escitalopram at all visits (p < 0.01 to p < 0.0001) with no difference between agomelatine and placebo nor between both agomelatine doses. Similar results were observed after drug discontinuation. The total score was significantly higher in the escitalopram group than in the placebo group at each post-baseline visit (p < 0.01 to p < 0.001). Similar results were observed regardless of volunteers' gender. Compared to placebo, only escitalopram significantly impaired dysfunction relative to "delayed orgasm or ejaculation" (p < 0.01) and "absence of orgasm or ejaculation" (p < 0.05 to p < 0.01). The percentage of participants with a sexual dysfunction was higher in the escitalopram group than in agomelatine groups (p < 0.01 to p < 0.05) and placebo (p < 0.01). CONCLUSION: The study confirms the better sexual acceptability profile of agomelatine (25 or 50 mg) in healthy men and women, compared to escitalopram. TRIAL REGISTRATION NAME: Evaluation of the effect of agomelatine and escitalopram on emotions and motivation in healthy male and female volunteers. TRIAL REGISTRATION NUMBER: ISRCTN75872983.

Opiate agonists and antagonists modulate taste perception in opiate-maintained and recently detoxified subjects.

Heroin addicts consume large quantities of refined sugars. This study investigated the effect of opiate use and antagonism on sweet taste in opiate-maintained drug users and detoxified former chronic opiate users, using a within-subject design. Seven opiate users received methadone and seven buprenorphine maintenance. Six detoxified subjects received naltrexone. Sucrose recognition thresholds and measurements of pleasantness and intensity were determined before and four hours after 1) a single dose of methadone or buprenorphine or 2) naltrexone. Control data were taken from a cohort of healthy volunteers including smokers. All measures of sweet and salt taste perception were significantly greater in opiate users and recently detoxified subjects compared to control subjects, with the exception of sweet pleasantness, which returned to control level after detoxification. Acute methadone administration reduced salt thresholds and unpleasantness to control levels. Increased sweet thresholds and salt unpleasantness in detoxified subjects were reversed by acute opioid antagonism, returning to control levels. These results suggest that opiate use and antagonism alters taste perception. Some of the alterations reverse on detoxification (sweet pleasantness), and others can be reversed by opioid antagonism (sweet threshold, salt unpleasantness). Changes in taste perception may underlie altered consumption of refined sugars in opiate users.

Faster but not smarter: effects of caffeine and caffeine withdrawal on alertness and performance.

RATIONALE: Despite 100 years of psychopharmacological research, the extent to which caffeine consumption benefits human functioning remains unclear. OBJECTIVES: To measure the effects of overnight caffeine abstinence and caffeine administration as a function of level of habitual caffeine consumption. METHODS: Medium-high (n = 212) and non-low (n = 157) caffeine consumers completed self-report measures and computer-based tasks before (starting at 10:30 AM) and after double-blind treatment with either caffeine (100 mg, then 150 mg) or placebo. The first treatment was given at 11:15 AM and the second at 12:45 PM, with post-treatment measures repeated twice between 1:45 PM and 3:30 PM. RESULTS: Caffeine withdrawal was associated with some detrimental effects at 10:30 AM, and more severe effects, including greater sleepiness, lower mental alertness, and poorer performance on simple reaction time, choice reaction time and recognition memory tasks, later in the afternoon. Caffeine improved these measures in medium-high consumers but, apart from decreasing sleepiness, had little effect on them in non-low consumers. The failure of caffeine to increase mental alertness and improve mental performance in non-low consumers was related to a substantial caffeine-induced increase in anxiety/jitteriness that offset the benefit of decreased sleepiness. Caffeine enhanced physical performance (faster tapping speed and faster simple and choice reaction times) in both medium-high and non-low consumers. CONCLUSIONS: While caffeine benefits motor performance and tolerance develops to its tendency to increase anxiety/jitteriness, tolerance to its effects on sleepiness means that frequent consumption fails to enhance mental alertness and mental performance.

Methodological considerations in cognitive bias research: the next steps.

Field and Christiansen (2012) comment on the importance of establishing and understanding the internal reliability of measures of substance-related cognitive bias, and suggest potential reasons for the poor reliability of some task variants. We agree that the impact of using stimuli personalized to the participant on the reliability of cognitive bias tasks is worthy of systematic investigation. However, some tasks may still be inherently less reliable than others. Ultimately, this debate should be framed within the wider debate on the validity of laboratory models and methods used to assess real-world phenomena.

Internal reliability of measures of substance-related cognitive bias.

AIMS: There is growing interest in cognitive biases related to substance use, but evidence from the anxiety literature suggests that tasks commonly used to assess these may suffer from low internal reliability. We examined the internal reliability of the visual probe and modified Stroop tasks. DESIGN: Secondary analysis of visual probe and modified Stroop task data collected across seven independent studies. SETTING: Human laboratory study. PARTICIPANTS: Healthy volunteers (n=408 across seven independent studies) recruited from the general population on the basis of alcohol or tobacco use. MEASUREMENTS: Visual probe and modified Stroop task measures of substance-related cognitive bias. FINDINGS: Measures of cognitive bias for substance-related cues, as assayed by the visual probe and the modified Stroop tasks, may not be reliable. In particular, the visual probe task showed poor internal reliability, as did unblocked versions of the modified Stroop task. CONCLUSIONS: The modified Stroop task is preferable to the visual probe task as a measure of substance-related cognitive bias, on the basis of its psychometric properties. Studies using cognitive bias tasks should not assume they are reliable, and should routinely report reliability estimates where possible.

Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption.

Caffeine, a widely consumed adenosine A(1) and A(2A) receptor antagonist, is valued as a psychostimulant, but it is also anxiogenic. An association between a variant within the ADORA2A gene (rs5751876) and caffeine-induced anxiety has been reported for individuals who habitually consume little caffeine. This study investigated whether this single nucleotide polymorphism (SNP) might also affect habitual caffeine intake, and whether habitual intake might moderate the anxiogenic effect of caffeine. Participants were 162 non-/low (NL) and 217 medium/high (MH) caffeine consumers. In a randomized, double-blind, parallel groups design they rated anxiety, alertness, and headache before and after 100 mg caffeine and again after another 150 mg caffeine given 90 min later, or after placebo on both occasions. Caffeine intake was prohibited for 16 h before the first dose of caffeine/placebo. Results showed greater susceptibility to caffeine-induced anxiety, but not lower habitual caffeine intake (indeed coffee intake was higher), in the rs5751876 TT genotype group, and a reduced anxiety response in MH vs NL participants irrespective of genotype. Apart from the almost completely linked ADORA2A SNP rs3761422, no other of eight ADORA2A and seven ADORA1 SNPs studied were found to be clearly associated with effects of caffeine on anxiety, alertness, or headache. Placebo administration in MH participants decreased alertness and increased headache. Caffeine did not increase alertness in NL participants. With frequent consumption, substantial tolerance develops to the anxiogenic effect of caffeine, even in genetically susceptible individuals, but no net benefit for alertness is gained, as caffeine abstinence reduces alertness and consumption merely returns it to baseline.

Adenosine A(2A) receptor gene: evidence for association of risk variants with panic disorder and anxious personality.

Adenosine A(2A) receptors are suggested to play an important role in different brain circuits and pathways involved in anxiety reactions. A variant within the corresponding ADORA2A gene (rs5751876) increased the risk for panic disorder (PD), for elevated anxiety during challenge tests in healthy probands and for anxiety-related arousal in blood-injury phobia. These multiple effects may mirror a more general effect of the SNP on basic personality traits. In the present study we therefore aimed to replicate the original finding in a large PD sample and extend it by investigating an additional proband sample characterized for different anxiety-related personality scores. In addition, as rs5751876 is assumed not to be the disease variant itself but to be in linkage disequilibrium (LD) with the true functional polymorphism other SNPs of potentially functional relevance were identified by re-sequencing the whole gene including several newly identified regions of putative regulatory potential and analysed for their impact on PD and anxious personality. We were indeed able to replicate rs5751876 as risk factor for PD, particularly PD with agoraphobia. Rs5751876 and several other variants in high LD (rs5751862, rs2298383 and rs3761422) as well as the corresponding haplotypes were also associated with different anxiety-related personality scores (Bonferroni corrected P(all) < 0.05). Of these variants, rs2298383 shows functional potential based on in silico analyses and might therefore represent the true underlying causal variant. Our data provide further support for an important role of ADORA2A variants in the pathogenesis of anxiety disorders and anxious personality reflecting their potential as basic susceptibility factors.