Salmonella, Shigella, Shiga toxin–producing Escherichia coli (STEC), and Listeria monocytogenes were obtained from laboratory surveillance data. These data were supplemented with epidemiological information on the suspected source of illness, collected for cases identified within whole genome sequencing clusters. Incidence rate ratios were calculated for each pathogen. All data were compared with a prepandemic reference period. Decreases in the number of reported cases in 2020 compared with the previous 5-year period were noted for Salmonella, Shigella, Escherichia coli O157, and non-O157 STEC. Reported number of cases for L. monocytogenes in 2020 remained similar to those of the previous 5-year period. There was a considerable decline (59.9%) in the number of cases associated with international travel compared with a 10% decline in the number of domestic cases. Comparison of reported incidence rates of clustered versus sporadic cases for each pathogen showed little variation. This study represents the first formal assessment of the impact of COVID-19 on reported enteric diseases in Canada. Reported case counts across several pathogens saw notable declines in 2020 compared with prepandemic levels, with restrictions on international travel playing a key role. Additional research is needed to understand how limitations on social gatherings, lock downs, and other public health measures have impacted enteric diseases.The aim of this study was to describe the impact of the COVID-19 pandemic on reported cases and clusters of select enteric diseases in Canada, for the period of March 2020 to December 2020. Weekly counts of laboratory confirmed cases of  In March 2020, when the pandemic was first declared by the World Health Organization , Shigella, Salmonella, and Listeria monocytogenes. In addition, this study aims to further explore the possible mechanisms for changes in reported enteric illness rates, including the impacts of changes to health care seeking behavior and restrictions on international travel.Clear trends in enteric disease surveillance have been documented in many countries, however, the impact of the COVID-19 pandemic on enteric diseases in Canada has yet to be formally assessed. This study is the first to describe the impact of the COVID-19 pandemic on enteric cases and clusters in Canada, for the period of March 2020 to December 2020, for Shigella, Salmonella, and L. monocytogenes. Provincial public health laboratories across Canada send NESP weekly summaries of the number of enteric isolates from human patients that they have received for testing and/or confirmation.The National Enteric Surveillance Program (NESP) collects and reports the number of key laboratory-confirmed enteric pathogens in Canada on a weekly basis. This program has been conducted since April 1997, through collaborations between the Public Health Agency of Canada (PHAC) and provincial public health laboratories. Timely surveillance and analysis occur for 14 enteric pathogens, including STEC, E. coli cases are included in the study, and how isolates are sequenced and placed into clusters, are included in Efforts are made to ensure that multiple isolates from a single case are removed, but it is possible there are duplicates in the data set. To improve readability, for the remainder of this article, the term “case” will be used instead of isolate. The data received are aggregated by province and pathogen. Further details on the enteric disease surveillance system that this study is based on, including clarifying which At the federal level, whole genome sequencing (WGS) data from PulseNet Canada are reviewed weekly by a team of epidemiologists within the PHAC to identify clusters that require further investigation to determine the vehicle of infection.Clusters are classified as being (1) multijurisdictional, if there are human cases located in two or more provinces or territories or human cases in one province or territory and internationally or (2) single jurisdictional, if all human cases in the cluster are from one province or territory. Cases that do not group within 10 whole genome multi locus sequence typing (wgMLST) alleles of a multijurisdictional or single-jurisdictional cluster are considered sporadic cases. The wgMLST typing method was chosen for use as the results were shown to be highly congruent with the available epidemiological data during validation studies  were calculated comparing rates in 2020 with those of an appropriate reference period. These calculations were conducted for each pathogen overall, by cluster classification, and by cluster categorization. To analyze the impact of COVID-19 more accurately, the period analyzed for these calculations was restricted to epidemiological weeks 12–52. This period was chosen as public health measures in Canada began to be implemented in week 12 of 2020, as can be observed in the spike in the stringency index.For overall case counts, the reference period was the equivalent weeks from a 5-year timespan from 2015 to 2019. For all cluster-based analyses, the reference period was the equivalent weeks from a 2-year timespan from 2018 to 2019 as prospective WGS was initiated in Canada beginning in 2017/2018. Details on the calculation for the person time at risk for the IRR are detailed in the Compared with the average number of cases reported by the provincial public health laboratories in the previous 5 years (9053), there was a 33% reduction in the total number of cases of enteric pathogens reported nationally in 2020 (6054). Results specific to each pathogen are shown in Escherichia coli O157, Shigella, and Salmonella all had more than half the reported cases in 2020 associated with a single or multijurisdictional cluster, compared with non-O157 STEC and Listeria that both had ∼20% of cases associated with a cluster. Comparing the proportions of cases in clusters or sporadic cases between 2019 and 2020 showed little change. The most notable differences observed between 2019 and 2020 were the proportion of cases added to multijurisdictional clusters of non-O157 STEC, Shigella, and L. monocytogenes.The estimated proportion of cases associated with single or multijurisdictional clusters compared with sporadic cases varied considerably based on pathogen . EscheriIn Canada, the number of reported cases associated with a multijurisdictional cluster linked to international travel typically follows a seasonal pattern with the highest number of cases in the winter months (January to March), however, travel cases are reported throughout the year. In 2020, there was a sharp decline in the number of reported cases associated with a travel cluster following the government directive to avoid all nonessential international travel .Salmonella Newport associated with red onions in the summer of 2020 . When examining trends in the IRRs across pathogens  are generally similar in value . This is not the case for cluster categorization, where for each pathogen the IRRs for domestic clusters and travel clusters are not similar . For the three pathogens wherein both domestic and travel IRRs could be calculated, the travel clusters consistently had the lower IRR, suggesting there was a greater reduction in reported travel cases compared with domestic cases in 2020.The total count of reported cases of enteric illness in Canada declined in 2020 compared with historical averages, and was the lowest total count in 23 years of monitoring enteric illness at the national level. Similar declines in reported enteric illness incidence in 2020 were observed in other countries including the United States that observed a 26% decrease in reported enteric illness incidence in 2020   are believed to be acquired through person-to-person transmission based on expert elicitation, whereas the other pathogens included in this study have substantially lower proportions of cases attributed to that transmission route (7.3–13.2%)  was the lack of variation of these IRRs within pathogens. As previously mentioned, there are numerous ways in which the public health measures could have impacted exposure to enteric pathogens. The cluster classification analysis was thought to be one means of providing some evidence into these impacts.For example, if the IRRs of the sporadic classification were found to be consistently lower than the other classifications, it could suggest that proportionally more cases were being acquired from isolated incidents such as improper food safety practices in a home, as opposed to larger outbreaks that could be associated with a food establishment. However, this was not our finding. There was relatively little variation in the IRRs between cluster classifications, suggesting that the public health measures impacted exposures that spanned the various cluster classifications.The largest reduction observed across all analyses conducted was the decline in cases added to multijurisdictional clusters that were associated with international travel. This finding is not surprising given that the government of Canada implemented substantial restrictions on international travel and advised Canadians to avoid travel outside the country in March of 2020  (Public Health Agency of Canada, Comparing the proportional reductions observed in the reported national enteric incidence rates in 2020 with the proportion of cases reported to FoodNet Canada that were classified as being associated with international travel in 2019 showed similar percentages (Escherichia coli O157 associated with romaine lettuce, import requirements were implemented for romaine lettuce originating from parts of California between October 7 and December 31, 2020, likely contributing to the reduced number of reported Escherichia coli O157 cases observed over the same time period (Government of Canada, It is important to highlight that some of the trends seen in this study may be impacted by non-COVID-19–related factors. For example, as a result of previous outbreaks of Salmonella and Escherichia coli O157 cases are most representative of the true nationally reported incidence of disease compared with other pathogens. In contrast, although efforts are made to minimize over-reporting of organisms, this may occur due to the submission of multiple specimens from a single patient.There are some limitations to note while considering the study presented here. First, the number of cases reported nationally may be a subset of laboratory isolations and, therefore, may not be reflective of the true incidence of reported disease at the national level. Within NESP, Second, efforts were made to use reference periods that were as robust as possible, however, due to Canada's transition to prospective WGS in 2017/2018, only a 2-year reference period was available for the cluster analysis. In comparison, the case-level analysis used a more robust 5-year reference period. Third, as already mentioned, other notable trends in enteric disease in Canada co-occurred with the COVID-19 pandemic and should be taken into consideration when interpreting the findings presented here. Lastly, a limitation of this study, and many like it, is the difficulty teasing apart the impacts of COVID-19 on enteric disease trends.Although the stringency index was used as a proxy of all public health measures, we were not able to deduce the unique impacts of each public health measure, with the notable exception of international travel restrictions. We also were not able to deduce the unique impact of other COVID-19–related behavior changes, such as changes in health care seeking behaviors and hand washing. It is likely that the trends seen in this study are a result of a combination of COVID-19–related factors, and that the relative influence of each likely varied over time and geography.The findings of this study demonstrate that reported enteric illnesses in Canada were significantly impacted by the COVID-19 pandemic. Furthermore, analyzing the patterns observed in the reported incidence rates of enteric illnesses in 2020 provided evidence to support possible mechanisms that could have caused the changes to reported incidence rates, including changes to health care seeking behavior and international travel restrictions. This information can also be useful in understanding other pathogens that may not have enhanced surveillance data.For example, if future research corroborates the findings of this study, and evidence shows that the majority of the decline in most pathogens was the result of the near full cessation of international travel, pathogens that have annual count data before and during the pandemic could possibly estimate the proportion of cases that were associated with international travel, by examining the decline in cases during the pandemic. Continued research into the impacts of the COVID-19 pandemic and associated public health measures on enteric illnesses may provide evidence to inform future policies and interventions aimed at reducing the burden of enteric illnesses in Canada.


Background: Insomnia is the perception of inadequate, insufficient or non-restorative sleep. Of all sleep-related disorders, insomnia is the most common. It is important to remember that the sleep–wake cycle also plays a central role in the genesis of anxiety and depression. The aim of our study is to evaluate the association between sleep disturbances and anxiety and depression in a group of workers of both sexes who perform night shift work. Methods: Information on sleep disorders was collected by administering the Insomnia Severity Index (ISI) questionnaire. Statistical analysis was conducted using the Chi-square test to assess whether there were any differences between sex for those who were healthy or who were diagnosed with psychiatric disorders. Results: The results showed that there was a good percentage of subjects with insomnia problems, impairing normal daily activities and promoting the onset of fatigue, daytime sleepiness, cognitive performance deficits and mood disorders. Conclusion: We highlighted how anxious and depressive anxiety disorders are more pronounced in people who suffer from altered sleep–wake rhythms. Further research in this direction could prove to be fundamental for understanding the genesis of the onset of other disorders as well. Insomnia is the perception of inadequate, insufficient or non-restorative sleep. Of all sleep-related disorders, insomnia is the most common, with estimates ranging from 30 to 35 per cent; and the prevalence of chronic or severe insomnia is estimated at 10 to 15 per cent .Gender, age and life style affect the onset of sleep disorders: it has been observed, for example, that nicotine-dependent individuals have a greater chance of developing this disorder  and thatIn particular, it has been observed that women have a higher rate of insomnia than men and that these disorders increase with age .It has been observed that there is a correlation between insomnia and hypersomnia and certain systemic diseases. Sleep-disordered individuals have a significantly higher risk of developing cardiovascular diseases such as hypertension, cardiac and cerebral ischemic episodes and psychiatric diseases, among others . The latInsomnia is a very common condition among people suffering from depression . While aDepression can promote the genesis of sleep–wake rhythm disturbances that, in turn, may contribute to the exacerbation of the disorder . For somThe presence of insomnia in depression is, in most cases, associated with a more severe depressive picture. Different research has shown that people with insomnia have a three times greater risk of developing a major depressive episode than those with good sleep quality.Certain work activities also seem to influence the onset of pathologies related to the alteration of the sleep–wake cycle ,15,16,17Although the importance of stress as a pathogenetic factor of various psychosomatic diseases has been recognised since the first half of the last century, it is only in the last few decades that the deepening of knowledge in the fields of neurochemistry, neuroendocrinology and immunology have made it possible to understand and interpret, to a large extent, the variations in the specific mechanisms underlying pathologies induced by an excess of adverse stimuli ,22.Adaptive responses to stress can be quantitatively and qualitatively different, depending on the personality and experiences of the individual, his or her biorhythms and the intrinsic characteristics of stressors, such as regularity, predictability, avoidance, duration and intensity, as well as different environmental factors.On the basis of the above premises, the aim of our pilot study is to assess the association between sleep disorders and psychiatric disorders, specifically anxiety and depression, in a group of workers of both sexes performing different work activities involving night shifts for at least 50 nights per year in order to evaluate possible effective interventions in preventing these disorders.A sample of workers working night shifts for at least 50 nights per year was selected from a private practice of Occupational Medicine in Palermo. This cross-sectional study was conducted from January to September 2022. The selected population initially consisted of 523 (100%) persons of both sexes working in different occupations .Authorisation to participate in this study was given by the employer and/or the company human resources department. Of these, 47 (8.99%) declined to participate; consequently, the study initially recruited 476 workers (91.01%). All participants were informed about the purpose of the research and signed the informed consent before participating. Respondents were asked not to mention their name or the name of their organisation in the questionnaire to ensure privacy and anonymity.At the first visit, an in-depth anamnesis was conducted on all the workers, including an interview with a neurology specialist, which allowed us to make the differential diagnosis of sleep disorders and to confirm the possible clinical diagnosis of anxious and/or anxious depressive state through the analysis of the documentation submitted.In addition, the entire sample was subjected to a thorough physical examination, including the assessment of anthropometric  and cardiovascular (blood pressure and electrocardiogram) parameters.At the end of the medical evaluation, 27 subjects were excluded from the study because at the time of the research they were taking drugs that could affect sleep quality, different from those used for the possible treatment of anxiety and depression. Finally, a further 36 subjects were not included due to different causes: body mass index greater than 32, dysmetabolic diseases, treatment with antineoplastic drugs, immunosuppressants or corticosteroids.In the end, our sample consisted of 413 adults, 222 males and 191 females (M/F ratio 1.2).All data were managed according to the Italian law for the protection of privacy . A multidisciplinary team of health experts collected and analysed the data obtained through the questionnaire administered on sleep disturbance and also verified the presence or absence of anxiety disorders or depression through the patients’ careful medical history.The collection of information on sleep disturbances was carried out through the administration of the Insomnia Severity Index (ISI) questionnaire, a valuable tool for understanding the nature, severity and impact of insomnia . The timData analysis was conducted with the aid of the GraphPadPrism 8.01 statistical software package . All data were analysed for normal distribution using the D’Agostino and Pearson omnibus normality test in order to determine which was the best statistical test to apply for the analysis of our data.Since our data were not normally distributed, we chose to apply the nonparametric Chi-square test in order to check whether the frequency of the values obtained from our surveys were significantly different from the frequencies obtained with the theoretical distribution. The Chi-square test was performed to assess whether there were any differences in the scores obtained from the Insomnia Severity Index test between subjects of different sexes and between those who were healthy or diagnosed with psychiatric pathologies at the time of their medical history. The degree of correlation between insomnia in general and the presence of anxiety and depressive disorders was also assessed through the odds ratio (OR).A descriptive data analysis was also conducted to determine the degree of insomnia in both the subjects with psychiatric illnesses and the rest of the study population.The analysis of the data from the ISI test revealed that, within the population under evaluation, there are different subjects who suffer from insomnia. Specifically, the results obtained through descriptive data analysis revealed that 292  have no insomnia problems, 67  have subthreshold insomnia, 43  have moderate insomnia and 11  were found to have severe insomnia problems.Furthermore, based on the results obtained on the entire population, we asked what the differences were within the male and female sample regarding insomnia-related problems A,B.2 = 0.2829 z = 0.5319 p = 0.5948), moderate  or severe insomnia , between male and female subjects.In order to understand whether there were differences in the severity of insomnia between male and female subjects, we conducted the Chi-square test, taking into consideration the degree of insomnia obtained from the analysis of the data obtained from the ISI. The analysis of the data did not reveal any significant difference in the number of subjects with subthreshold sleep (χ2 = 44.84 z = 6.696 p < 0.0001) and anxious/depressive disorder (χ2 = 43.94 z = 6.629 p < 0.0001), compared to those with a diagnosis of anxiety and anxious/depressive disorder but no insomnia problem  and male (26.57%) subjects with insomnia problems. In particular, analysis of the Insomnia Severity Index returned an evident prevalence of subjects with subthreshold and moderate insomnia compared to those with severe insomnia among both female and male subjects. Furthermore, subjects suffering from insomnia disorders showed a greater likelihood of developing anxiety or anxiety–depressive disorder.These data are in agreement with various studies that show that the presence of sleep disorders is capable of compromising normal daily activities and promoting the onset of fatigue, daytime sleepiness, deficits in cognitive performance and mood disorders . In addiTotal sleep loss amplifies activity within the ‘fear network’, which includes the limbic system, influencing the evaluation of emotional experiences that may result in promoting the onset of anxious behaviour ,30. SleeSeveral substances that balance the sleep/wake state are also implicated in the emotional regulation underlying the genesis of anxiety and depression, including γ-aminobutyric acid (GABA) and serotonin (5HT). Specifically, a deficiency of GABAergic activity in the occipital cortex of patients with sleep disorders has been reported to be consistent with the hyperexcitation pattern in insomnia . SimilarGABA is known to modulate the firing of the locus coeruleus (LC), a nucleus composed mainly of noradrenergic neurons located in the brainstem bridge, implicated as a component of the neuronal network and able to modulate the sleep–wake state ,39. IncrAnother neurotransmitter important in the regulation of different physiological functions, including sleep and mood, is 5HT ,44,45. INumerous studies have shown how dysregulation of the circadian system can favour the genesis of different depressive symptoms ,49,50. OThe above could further corroborate the data obtained from our research in that the reduction of sleep hours could lead to an under-regulation of 5HT levels, which, in turn, would favour the onset of mood disorders such as anxiety–depressive disorder.Although this pilot study provides an overview of how insomnia correlates with the genesis of anxiety–depressive disorders, it has several limitations. Even if the number of subjects enrolled in our study is sufficient to diagnose the presence or absence of insomnia, the number of participants diagnosed with psychiatric disorders is not sufficient to draw definitive conclusions; in this regard, we are collecting additional data to enlarge the sample. In addition, it would be desirable to carry out direct assessments of the diagnosis of anxiety and anxious depressive disorders in patients with previous insomnia problems in order to be able to investigate the influence of reduced sleep hours on the onset of psychiatric disorders.In conclusion, in this pilot study, we have highlighted how anxious and depressive anxiety disorders are more present in people who suffer from altered sleep–wake rhythms, such as in those who carry out their work activities during the night hours. In particular, the presence of psychiatric disorders is not only directly related to insomnia, but also proportional to its degree of severity.It is not infrequent, in fact, that we may be faced with particularly heavy and demanding conditions that disturb the normal homeostatic balance and the ability to cyclically adapt one’s circadian rhythms to those of work. This imbalance could therefore promote a desynchronisation of the sleep/wake cycle, increasing susceptibility to various disorders of the psycho-emotional sphere.The further development of our pilot study and the future understanding of the exact mechanisms by which reduced sleep hours of workers periodically working night shifts may predispose them to the onset of psychiatric disorders, such as anxiety and depression, could provide valuable prevention and support tools.Our work therefore provides a basis on how different therapeutic interventions can be undertaken in the future.Numerous studies have in this respect highlighted the effectiveness of cognitive restructuring and behavioural activation techniques in the treatment of both depression and insomnia ,55.Further studies on its efficacy could make this psychological support a useful tool for those who, subjected to shift work, manifest precursor symptoms of insomnia and depression, also providing new basic results for understanding the genesis of the onset of other pathologies, apparently less important, but which may act in a concausal role on the efficiency of work performance.Furthermore, it would be essential to provide recommendations about habits and practices that can improve the quality and quantity of sleep of the workers. These sleep hygiene recommendations can help workers improve the quality and quantity of their sleep, which can positively impact their daily functioning, mood and overall well-being.


The debate surrounding the brain disease model and the associated questioning of the relevance of animal models is polarizing the field of addiction, and tends to widen the gap between preclinical research and addiction medicine. Here, we aimed at bridging this gap by establishing a dialog between a preclinical researcher and a clinician in addiction medicine. Our objective was to evaluate animal models and the neuroscientific conceptualization of addiction in light of alcohol or drug dependence and treatment in patients struggling with an addiction. We sought to determine how preclinical research influenced addiction medicine over past decades, and reciprocally, what can preclinical researchers learn from addiction medicine that could lead to more effective approaches. In this dialog, we talk about the co-evolution of addiction concepts and treatments from neuroscientific and medical perspectives. This dialog illustrates the reciprocal influences and mutual enrichment between the two disciplines and reveals that, although preclinical research might not produce new pharmacotherapies, it does shape the theoretical conceptualization of addiction and could thereby contribute to the implementation of therapeutic approaches. YV: The relevance of animal models of alcohol, tobacco, and substance use disorder (referred to as addiction hereafter) is being increasingly questioned . NotablyHowever, the influence of the BDMA worldwide, dominating thinking and practice and driven by the neuroscience of addiction, highlights the importance of preclinical research in affecting societal attitudes toward addiction. Preclinical research may not have led to major breakthrough in the development of new pharmacotherapies, but it has generated neurobiological theories that have significantly shaped our conception of addiction with many clinical and societal implications (for better or for worse). My goal here is not to advocate for or against the BDMA, a topic already extensively covered in the literature , 4, 9–11YV: The current neuroscientific conceptualization of addiction is the result of several decades of preclinical research on the brain mechanisms underlying loss of control over drug  use in animal models of addiction. Much of the progress in preclinical research on addiction emerged in the ’60s from the development of intravenous drug self-administration techniques in monkeys  and ratsBuilding on these multiple models, different theories posit that transition to addiction results from a disruption of brain reward circuits Box  with: anBOX 1 Animal models of addictionAnimal models of addiction: Preclinical research employs models consisting in mimicking key symptoms of addiction in animals based on diagnostic criteria of the DSM. Most models employ self-administration paradigms in which animals press on a lever or poke their nose into an aperture to earn the drug reward before screening in different tests.The 3-criteria model consists in measuring (1) the motivation for the drug, (2) the persistence in drug-seeking when the drug is not available and (3) the resistance to punishment [nishment . AnimalsThe extinction-reinstatement model is more specifically designed to assess relapse [ relapse . FollowiThe extended access and intermittent access models manipulate pattern of drug self-administration to reproduce an escalation of consumption [sumption , 85. In Choice models assess the preference for the drug at the expense of alternative activities [tivities . In thesValidation of animal models: Animal models are validated based on three criteria; (1) face validity, (2) predictive validity and (3) construct validity. Face validity is defined as the similarity of what is observed in the animal model vs. what is observed in the human disease. Predictive validity is mainly defined as the ability of the model to correctly predict treatment effects on the human disease. Construct validity refers to the similarity between the mechanisms used in the model to induce de disease phenotype and the disease etiology in human.Reverse translation: The concept of reverse translation was recently proposed by Venniro et al. [o et al.  and consBOX 2 Neurobiological theories of addictionThe opponent-process theory [s theory —This theThe incentive-sensitization theory [n theory —In this The aberrant learning theory [g theory —this theThe habit theory [t theory —This theNeurobiological theories of addiction: Multiple theories of addiction have been proposed over the past decades to describe brain alterations accompanying the development of addiction. Among them, the most influential theories include:JBD: In the ’60s and ’70s, the clinical approach to addictions was dominated by Alcoholics Anonymous (AA) and Narcotics Anonymous (NA), who consider loss of control and automaticity as landmarks of addiction. AA and NA are built on the belief that individuals are powerless over alcohol and drugs and need the help of a Higher Power to restore control over consumption , 39.The If addiction is conceptualized as a brain disease, characterized by compulsive drug use and a defect of free-will, the logical consequence is that individuals do not have the ability or the responsibility to change. It suggests that external pressures should impose change. In the ’70s, there was a very strong belief that the remission of an addiction was possible only through abstinence, even when the affected individual did not agree . TreatmeClinical research with experimental treatments testing confrontational counseling styles, including various types of constraint and pressure, became very popular. However, despite this popularity, the efficacy of these approaches has not been conclusive , 44. A sIn summary, my impression is that the compulsive account of addiction described in the BDMA appeared to justify that individuals had no responsibility for the occurrence and maintenance of their addictions. However, evidence in my daily practice suggests otherwise. In fact, my patients do not behave like automatons compelled to consume alcohol or drugs, but can instead exert some degree of control over their consumption.YV: There is currently no satisfying evidence of a complete loss of control over drug use in preclinical research. The illusion of compulsion, as defined by an absence of free-will , may havThese findings suggest that drug-seeking can be considered as a voluntary goal-directed behavior, sensitive to changes in environmental contingencies such as the dose, the price, the delay or the availability of alternative rewards. Thus, theories of addiction viewing maladaptive habits and compulsions as central concepts in the etiology of this disorder are now being questioned in both clinical and preclinical literature , 60. InsPreclinical findings from choice experiments reveal the fundamental role of environmental contingencies on drug use and contribute to the critic of the brain disease model of addiction, which focus on drug-induced brain alterations while minimizing socio-economic and environmental factors.JBD: Transposed to humans, the “Rat Park” and choice experiments suggest that there is a strong influence of external factors in the induction and maintenance of addictions, and that drug use in addicted patient may continue as a result of a lack of rewarding alternatives. These findings also suggest that remission of addiction in humans is possible when the environment offers interesting alternatives to drug use. There is a large body of research on humans suggesting that the motivation to stop using alcohol or drugs results from the anticipated benefits. For example, in contingency management experiments Box , subjectIn my experience, contingency management strategies are rarely used to treat addiction. Besides the practical difficulty of implementing them in outpatient settings, part of the problem resides in the fact that, although addiction can be conceived as a disorder of choice, the choice to use or to abstain from using drugs is hard. In my opinion, patients with addictions are prone to strong ambivalence, which is a cardinal feature of addiction.Ambivalence is characterized by vacillation between the desire to use alcohol or drugs, on the one hand, and regrets when suffering the adverse consequences, on the other hand. In contrast to animals, humans with addictions can verbalize to some degree the feelings and thoughts they experience at different moments in the history of their addiction. In the beginning, subjects do not fight against their progressively increasing consumption. They tend to justify it cognitively . During this period, consumption is part of a routine, the adverse effects are subtle and the motivation to use alcohol or drugs dominates. As the addiction progresses, the desire for drugs becomes stronger in parallel with the increasing costs experienced . Therefore, an internal conflict emerges from the opposition between the desire to use and accompanying negative consequences, which finally results in an ambivalence between using or stopping, as expressed by a patient:« I like to drink. When I don’t have my drink, I miss it and it’s all I can think about. But sometimes I think I should stop. I can’t stand feeling like this, it’s like I have no control. But drinking helps me to relax, it makes it easier for me to talk to people. I don’t know what to do, I feel stuck. I want to, but it’s driving me crazy»In the example above, the patient manifests this ambivalence, with immediate advantages of using and not getting into treatment, opposed to the delayed costs of doing it. The ambivalence of using fluctuates rapidly during the day, depending on the level of intoxication or symptoms of withdrawal. Typically, the decision to stop and get into treatment is associated with symptoms of withdrawal, while the decision to use typically follows craving. Therefore, the ambivalence could be illustrated by sinusoidal waves with varying amplitudes and periods. In the above case, we observe that the period of the sinusoidal wave is very short, since the patient expresses in the same sentence that he both wants and does not want to use or to stop using alcohol. Therefore, although addiction can be conceived as a disorder of choice where the drug is preferred over alternative activities, it is probably more precise to conceive of addiction as arising from conflicting decisions resulting in an internal fight, and experienced as feelings of ambivalence.BOX 3 Addiction treatmentsPharmacotherapies—Most effective pharmacotherapies consist in reducing craving and include naltrexin and nalmefen for alcohol dependence or varenicline for nicotine dependence. Other pharmacological tools include agonist treatments for opiate and nicotine dependence, aimed at reducing withdrawal symptoms. Notably, methadone or buprenorphine are used for opiate dependance. For tobacco use disorder, nicotine replacement therapy  can be used to alleviate withdrawal symptoms.Psychotherapies—Most popular and well documented evidence-based efficacy treatment include contingency management, cognitive and behavioral therapies and motivational interviewing. Contingency management consists in ‘reinforcing’, or rewarding individuals with voucher, for evidence of positive behavioral changes  to reinforce abstinence. Cognitive and behavioral therapy consists in teaching behavioral strategies to help patients (1) learning to recognize and evaluate one’s distortions in thinking, (2) gaining a better understanding of one’s own behavior and motivation, (3) developing problem-solving skills to cope with difficult situations or (4) learning to develop a greater sense of confidence is one’s own abilities. Finally, motivational interviewing is a counseling method that consists in enhancing patients’ motivation to change. The therapeutic hypothesis is that patients need to hear themself talking about changing behavior  and confront their own behavior to personal values to have enough motivation to change. In contrast to cognitive and behavioral therapy, the therapist doesn’t teach patient behavioral strategies to avoid craving and relapses but guides the patient in his/her elaboration of reasons to change.Social support—For successful treatment of addiction, pharmacotherapies and psychotherapies are often combined with different forms of social support including group therapy, community-based organization, alcoholics anonymous or narcotic anonymous, or support from friends and family.Available treatments for addiction can be subdivided into three categories:YV: In fact, the opposition between brain reward circuits and the prefrontal executive system has been suggested to underlie compulsive drug use in many neurobiological theories of addiction , 34, 37.Ambivalence refers to the simultaneous existence of contradictory feelings and attitudes, where individuals feel torn between two alternatives (drug vs. nondrug reward or using vs. not using). In the choice model presented in Fig. This double dissociation between delay and valence is related to the concept of delay discounting. Delay discounting refers to the fact that the value of a delayed reinforcer  is discounted compared to an immediate reinforcer. Principles of behavioral economics involving the process of delay discounting can provide an explanation for inconsistent choices, impulsivity and ambivalent feelings observed in addiction. Thus, as illustrated in Fig. Subcortical regions including the mesolimbic circuit, the striatum and the amygdala, are involved in reward processing and emotion regulation. These regions will contribute to associate subjective value and emotion to each option (using or not using). Notably, emotions of positive and negative valence are encoded in the amygdala , 69 and Importantly, although brain alterations induced by repeated drug exposure are likely involved in the development and maintenance of addiction, they are not required to explain ambivalence in the choice model presented here. Instead, it seems that short-term positive effects of drug and consideration of long-term negative consequences, combined with the anticipation of long-term benefits of abstinence, are responsible for ambivalent feelings.JBD: Yes, indeed. This is one of the principles of Motivational Interviewing (MI) Box , which rThe therapeutic hypothesis of motivational interviewing is that patients need to hear themselves voicing the advantages of change and to encounter their own behavior and personal values in order to develop enough motivation to change. The therapists avoid confrontation and do not force abstinence , nor do they prematurely teach behavioral strategies to avoid craving and relapse . Instead, they act as a guide, eliciting patient aspirations and strengths, listening to them in the spirit of acceptance and non-judgment, and supporting their autonomy in decision-making. Research indicates that MI technical skills are associated with a higher proportion of change talk, which is predictive of actual change in behavior .It is worth noting that the principles of MI imply that the patients have some ability and therefore some responsibility to change. When the moral perspective on addictions was predominant, the AA/NA philosophy and the brain disease model issued from neurosciences developed a symmetrical counterargument, pointing out the limitation or absence of responsibility to change in individuals suffering from addictions. Currently, a more balanced perspective on the treatment of addiction is possible, in which some degree of autonomy coexists with the ability and responsibility to change. This brings a positive therapeutic perspective, but also has important moral implications. Responsibility to change carries the risk that the person feels guilty for not changing, thus complicating the interactions with significant others and health care providers. In turn, those trying to help someone suffering from addiction, because of this responsibility and ability, might adopt MI non-adherent and counterproductive attitudes such as pressure, threats or constraints. MI therefore requires not only empathy, acceptance and autonomy support from the provider, but also, simultaneous acceptance that the person is responsible for deciding to change, or not.To conclude our discussion, I think that a better understanding of the physiological processes explaining ambivalence, and, more generally, the mechanisms underlying addiction, is essential for clinicians in allowing them to provide “gentle” psychoeducation to patients. It also permits patients to better understand their ability to resist the strong pathophysiological processes underlying addiction.YV: Our dialog reveals that while neurobiological theories of addiction informed us on the mechanisms responsible for the development of addiction, the medicine of addiction can enlighten preclinical research on the reality of drug use in addicted individuals and the interventions most effective at promoting remission. Therefore, this exchange allowed me to more fully comprehend the reciprocal influences and mutual enrichment between the preclinical research and addiction medicine. Furthermore, through this dialog, I learned about the motivational interviewing approach, which has aroused my interest in the cognitive and neurobiological bases of ambivalence, a topic largely overlooked in preclinical research on addiction. Perhaps this could be explained by the fact that non-human animals cannot report their feelings, as can humans. However, in my opinion, the progress already made in our understanding of decision-making and delay-discounting processes using animal models can be extended to the investigation of ambivalence. We can infer from their behavior whether rodents deliberate  or couldTwo years ago, Field and Kersbergen published an opinion article questioning the relevance of animal models of addiction . The autRegarding the poor predictive validity of animal models, it is worth pointing out that preclinical models have contributed to identifying several pharmacotherapies such as varenicline and buprenorphine , 79 Box. This beWith respect to the popular preclinical conceptualization of addiction as a disorder of compulsion arising from the brain disease model, we do not consider this as a limit of preclinical research. While the compulsive account of addiction appeared to justify that individuals had no responsibility for the occurrence and maintenance of their addictions, this belief was already in place in addiction medicine, when the brain disease model was first introduced in 1997 . IronicaMoving forward, we believe that more discussion and collaboration between preclinical researchers and clinicians is required to take into account the complexity of drug use in humans suffering from addiction when modeling this disorder, or at least some of its key symptoms, in non-human animals. On the other hand, preclinical research on the cognitive and neurobiological mechanisms underlying addiction can guide psychotherapies and help clinicians in understanding the nature of patients’ internal conflicts, which can in turn be explained to the patients. Through this dialog, we realized that although we share the same concepts and terminology, clinicians and preclinical researchers do not assign the same meaning to these concepts . Thus, to improve translational utility of animal model and treatments, the future direction we suggest is to promote exchange between the two disciplines through (1) training  (2) international conferences on translational psychiatry  and (3) funding of translational research with collaboration between preclinical and clinical researchers. The disconnection between preclinical research and addiction medicine could partly result from the “rodent-centric” preclinical view of addiction, at the foundation of the BDMA. Thus, future training and research directions should absolutely include preclinical and clinical studies from numerous species, including non-human primates.


Management of rectal cancer has become more complex with multimodality therapy (neoadjuvant chemoradiotherapy and surgery) and this has led to the need to organize multidisciplinary teams. The aim of this study was to report on the planning, implementation and evaluation of an integrated care pathway for neoadjuvant treatment of middle and lower rectal cancer. This was a cross-sectional post-implementation study that was carried out at a public university cancer center. The Framework for Program Evaluation in Public Health of the Centers for Disease Control and Prevention (CDC) was used to identify resources and activities; link results from activities and outcomes with expected goals; and originate indicators and outcome measurements. The logic model identified four activities: stakeholders’ engagement, clinical pathway development, information technology improvements and training programs; and three categories of outcomes: access to care, effectiveness and organizational outcomes. The measurements involved 218 patients, among whom 66.3% had their first consultation within 15 days after admission; 75.2% underwent surgery < 14 weeks after the end of neoadjuvant treatment and 72.7% completed the treatment in < 189 days. There was 100% adherence to the protocol for the regimen of 5-fluorouracil and leucovorin. The logic model was useful for evaluating the implementation of the integrated care pathways and for identifying measurements to be made in future outcome studies. Colorectal cancer is the third leading type of cancer worldwide, accounting for about 1,200,000 new cases and 600,000 deaths annually.About 25% of occurrences of colorectal cancer are located in the rectum. Over the last few decades, there have been major achievements in rectal cancer treatments, with the introduction of neoadjuvant therapy and total mesorectal excision for surgical removal of the tumor. Today, the treatment for middle and lower rectal cancer consists of three phases: first, the staging phase based on colonoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) scans; followed by a second phase of neoadjuvant therapy with concomitant chemotherapy and radiotherapy (nCRT). The last phase is the surgery, including total mesorectal excision.Integrated care pathways (ICPs) have been adopted into oncology practice as a tool for enhancing both quality and value by limiting undesirable variability and reducing cost, while providing the optimal course of care for a patient’s specific diagnosis.In the present study, an ICP for neoadjuvant treatment of middle and lower rectal cancer was implemented at a public university cancer center with about 10,000 new cancer patients per year, across the state of São Paulo, Brazil. The planning and implantation of the ICP involved participation by medical oncologists, gastrointestinal surgeons, radiation oncologists, endoscopists, radiologists, pathologists, anesthesiologists, physicians, nurses, nutritionists, social workers, psychologists and physiotherapists. This multidisciplinary team standardized practices and constructed a flowchart outlining the sequence and timing of consultations, staging procedures, nCRT and surgery .In order to report on the experience of implementing this ICP, a program logic model was used to inform the planning and development of the evaluation process. Logic models are defined as pictures of the way in which planners think their program is going to work. They comprise the theory and assumptions underlying the program.,,Logic models originate from the field of program evaluation and are diagrams that convey relationships between contextual factors, inputs, processes, program activities and intended outcomes.They have been used in a variety of fields,As far as we know, no studies on ICPs for neoadjuvant treatment of middle and lower rectal cancer, with analysis using program logic modelling, had previously been conducted. Furthermore, standardization of treatment for this type of cancer at our institution was not an easy task: there had been complaints about delays in radiotherapy, examinations and surgery; time interval measurements between the phases of treatment were unknown; and there were difficulties in managing all the steps of the forms of rectal cancer care that were in use.The aim of this study was to report on the planning, implementation and evaluation of an ICP for rectal cancer treatment, using a logic model.This is a cross-sectional post-implementation study reporting the implementation of an administrative and healthcare program of cancer care at the Cancer Institute of the State of São Paulo , São Paulo, Brazil, 2011-2013. A program logic model approach was adopted with the aim of designing an evaluation that would focus on relevant healthcare outcomes  and factors that were involved in achieving these outcomes, using the CDC’s Framework for Program Evaluation in Public Health.In the present study, the development of the logic model began with a review of the literature. This identified thinking, policy and research relating to colorectal cancer treatment and the role of ICPs in the delivery of care, both in Brazil and in other countries. It also involved a review of policy and program documents and one-to-one interviews with a sample of six managers and thirteen healthcare professionals involved in the development and delivery of the ICP. This phase resulted in identification of program goals, objectives and inputs.The inputs were listed as the service users (patients included in the care pathway) and the resources (human resources and facilities) that were needed to carry out activities .The next phase involved identification of all the activities (services or interventions) that were developed as requirements for fulfilling the implementation goals. The direct results from the activities (outputs) were linked to expected goals, which originated indicators and measurements for evaluating pathway outcomes . The resAll consecutive patients with middle or lower rectal cancer who were admitted to the public university cancer center between May 2011 and December 2013 were evaluated. These patients were named the ICP group (ICPg). Patients who had undergone prior treatment, those who had not undergone nCRT treatment and those who presented metastatic disease at diagnosis were excluded.A single database in Microsoft Excel was built up, using information extracted from the following electronic healthcare records: Tasy system , Laserfiche document scanning system , Mosaiq radiation therapy system  and the hospital cancer registry (HCR). The following information was obtained: the date when the patient was included in the ICPg, the date of the first medical consultation, the start and end dates of nCRT and the date of the surgery.Statistical analyses were performed using the Statistical Package for the Social Sciences, version 18.0 for Windows . Qualitative variables were shown as counts and percentages. Means, medians, standard deviations and 95% confidence intervals (95% CI) were calculated for quantitative variables. The significance level adopted for all statistical tests was 5%.This study was approved by the Research Ethics Committee of the University of São Paulo , under protocol no. 126/14, on May 9, 2014.The clinical staff and the administrative team were the stakeholders in developing the ICP. They were the people with an interest in the results from the evaluation and were the intended users of its findings. A board of medical oncologists, surgeons, radiation oncologists, radiologists, pathologists, clinicians and anesthesiologists was assembled with the aim of reviewing the neoadjuvant treatment protocol for middle and lower rectal cancer. Multidisciplinary meetings were held under the leadership of the board to discuss treatment steps and intervals between phases.2 of 5-fluorouracil and 20 mg/m2 of leucovorin, intravenously, on days D1-D5) was delivered in two courses during the first and fifth weeks of radiotherapy. The surgery, with total mesorectal excision, consisted of open resection (ORR), laparoscopic resection (LRR) or abdominoperineal resection (APR) of the rectum and sigmoid.The clinical protocol consisted of radiotherapy, with 5,040 cGy delivered in 28 fractions , over a five-week period. Concomitant chemotherapy  or patients who had completed the pathway: doctors and/or the regulation sector staff could proceed with deactivation of the flagging.A training program was developed in order to introduce the ICP step-by-step to the administrative sectors. Outpatient reception sectors were systematically trained to use the reports, with the aim of ensuring correct scheduling of medical consultations and tests.The regulation sector staff was trained to flag eligible patients who had been identified by the medical teams through screening the documentation of patients who had been referred to the hospital.The information technology sector developed a training manual for flag deactivation. This manual was presented at medical meetings and has been made available via e-mail to medical oncologists and surgeons.ICP is an administrative and care milestone that combines administrative support with care needs in order to ensure multidisciplinary care. Implementation of a clinical pathway within daily practice is challenging, especially in public hospitals with high demand and limited resources.Regarding pathway implantation, the initial activity of engaging stakeholders showed that there was a need to standardize and disseminate the clinical pathway between the various medical specialties and find solutions to ensure that the treatment steps were achieved. Previously, referral to another team or to the next stage was done only after the end of the preceding stage. Some adaptations were made because of a lack of time resources: for example, the medical oncologists prescribed chemotherapy until chemoradiotherapy sessions started to be scheduled, because of difficulties in coordinating the sessions. Scheduling the surgery at the right time after neoadjuvant treatment was also a challenge.,,,In this regard, the National Comprehensive Cancer Network, through its clinical practice guidelines for oncology, advocates a multidisciplinary approach involving oncologists, gastroenterologists, surgeons, radiation oncologists and radiologists.To develop the clinical pathway, administrative support was necessary to ensure that the flowchart design defined by the medical teams within daily practice was implemented. The care teams  raised any critical issues and needs that had to be resolved.Regarding inputs and activities, communication problems between the teams were a barrier that needed to be overcome. The gap between the care team and the administrative team is an aggravating factor: on one hand, the care team perceives the administrative team to be a bureaucratic control sector focused exclusively on productivity; on the other hand, the administrative team perceives the care professionals to be technical experts who excessively request supplementary tests and resources without having any management experience. Data in the literature have demonstrated that there is a need for evaluation studies on clinical pathways, in order to check the proposed interventions, behavioral changes and context, and to identify the critical success factors.Flagging (i.e. stamps that were placed on the regulatory documentation) and shared spreadsheets were simple solutions that were developed to enable communication between the stakeholders. Another critical point was the need to rationalize resources and processes. Previously, a diversity of diagnostic tests had been requested by doctors and there had been delays in issuing imaging examination reports. Through defining staging tests and interval deadlines, rational use of resources became possible.The training program was especially necessary because of the high turnover rate in the outpatient reception sector. Several meetings were held during the implementation of the ICP: between medical teams, between medical and care teams and between care and administrative teams. These interactions brought the various professionals together and facilitated mutual understanding of their respective attributions, thus placing value on the importance of each professional within the strands of the clinical pathway.Finally, regarding outputs and outcomes, it has been pointed out in the literature that there is a lack of indicator descriptions for colorectal cancer protocols. Ludt et al.In this study, the indicators showed opportunities for improvement. Specific studies and actions are needed in order to increase the percentage of patients with ranges of values for these indicators that are within the targets.Management of middle and lower rectal cancer has become complex with the multimodality therapy of nCRT and surgery. This has led to a need to monitor access to all phases of the treatment. Eldin et al. showed that there were difficulties in relation to adherence to treatment guidelines among stage II/III rectal cancer patients in Alberta, Canada, because of lack of access to medical oncologists among patients, and the distance from these patients’ homes.In relation to effectiveness of care, there is no agreement regarding the impact on overall survival of multimodal treatment for rectal cancer. Wiegering et al. reported that increased use of neoadjuvant therapy and total mesorectal excision led to improvement of overall survival.The organizational outcome indicators selected in the present study were related to resource use and cost evaluation. Although use of integrated care pathways has been correlated with improvement to the quality of care, cost reduction and optimization of resource allocation,Figure 4) were not evaluated separately. Furthermore, since the purpose of the study was to analyze an ICP implementation process, outcomes before and after the intervention were not compared. Secondly, it might be argued that a wider group of participants could have been included to reflect differences in views among participants from similar backgrounds. Although the proposal to evaluate ICPs for rectal cancer treatment came from a hospital/university joint research network and members of this network formed the research team, inclusion of a wider group of stakeholders in the process generated further ownership and support for the subsequent evaluation. Thus, we believe that this exercise was conducted among a reasonably coherent group of stakeholders, across the range of roles involved in rectal cancer treatment.Some limitations of the present study can be highlighted. Firstly, early and later outcomes , effectiveness of care  and organizational outcomes (resource use).Implementation of an ICP for rectal cancer treatment, analyzed by means of a logic model approach, was feasible and informed the design of this complex intervention for evaluation of rectal cancer care.


Psychological distress reached historically high levels in 2020, but why, and why were there pronounced age differences? We address these questions using a relatively novel, multipronged approach, part narrative review and part new data analyses. We first updated previous analyses of national surveys that showed distress was increasing in the US and Australia through 2017 and then re-analyzed data from the UK, comparing periods with and without lockdowns. We also analyzed the effects of age and personality on distress in the US during the pandemic. Results showed distress levels and age differences in distress were still increasing through 2019 in the US, UK, and Australia. The effects of lockdowns in 2020 revealed the roles of social deprivation and fear of infection. Finally, age-related differences in emotional stability accounted for the observed age differences in distress. These findings reveal the limitations of analyses comparing pre-pandemic and pandemic periods without accounting for ongoing trends. They also suggest that differences in personality traits such as emotional stability modulate responses to stressors. This could explain age and individual differences in both increases and decreases in distress in response to changes in the level of stressors such as those occurring prior to and during the COVID-19 pandemic. But in many respects, it was simply revelatory. It revealed things that were already there, things that have been under the hood, waiting for something to come along and pull the curtain back.”(Curt Thompson)https://www.nytimes.com/2022/10/09/opinion/burnout-friends-isolation.html, accessed on 9 October 2022).Quoted in the Tish Harrison Warren newsletter for Times subscribers, What if Burnout Is Less About Work and More About Isolation? New York Times, 9 October 2022.  in keeping with the missions of these surveys. Here we bring their results together to be examined and compared using the same analytic approach. Unfortunately, however, the pandemic led to disruptions in some of the consistency that is one of the greatest strengths of national surveys. Indeed, the NSDUH collected data in only the first and fourth quarters of 2020, and the timing of HILDA, which collects data biennially, was such that no data were collected during the first six months of the pandemic in Australia.Our second major goal was to examine changes in distress levels throughout the first year of the pandemic. The one national survey that did collect data continuously throughout 2020 was the United Kingdom Household Longitudinal Survey (UKHLS), albeit with significant changes in procedure and smaller samples. Importantly, the UK underwent two national lockdown periods during that year, and thus the UKHLS data, in addition to allowing us to assess the generality of the trends observed in pre-pandemic data from the NSDUH and HILDA, provided a unique opportunity to examine the effects of social deprivation on distress during the pandemic.Given the pronounced age differences in psychological distress and in the size of the changes in distress levels observed in all three national surveys analyzed here, our third major goal was to examine the extent to which these changes reflected various pandemic stressors and personality traits. Whereas previous efforts to explain age-related differences in psychological distress have tended to focus on why distress has increased so markedly in adolescents and younger adults , the prThus, our fourth and final goal concerned the implications of age and individual differences in personality traits for interpretation of the national survey data. At issue was the form of a model that might describe the pattern revealed by trend analyses. More specifically, regardless of whether distress increased or decreased over time, the degree to which adults’ distress levels changed was inversely related to their age—the exact opposite of what one might have expected based on age differences in the risk of severe negative consequences from infection with the SARS-CoV-2 virus. Two conceptual models are considered, an additive model and a modulatory model in which trait scores predict the degree to which individuals are affected by external stressors. The pattern in the national survey data is considered in light of the predictions of the additive and modulatory models.Taken together, the present investigation focused on four questions regarding recent changes in the level of distress. The first question was whether the increasing trend both in psychological distress and in the size of age differences in distress continued right up through 2019, the year before the COVID-19 pandemic began. The second question concerned how much of the distress during the first year of the pandemic role was due to mandated lockdowns and again, whether age differences changed when the overall level of distress increased and decreased over that time period. Finally, the third and fourth questions were whether individual and age differences in psychological distress might be explained by differences in personality traits such as emotional stability, and whether the role of such traits, both before and during the pandemic, was more accurately described by an additive model or one in which traits played a modulatory or interactive role.In order to answer our first question, we began by following up on Twenge et al. , analyziNext, we followed up on Butterworth et al. , analyziAlthough the NSDUH and HILDA use very similar questionnaires, the K-6 and the K-10 (which is a longer version of the K-6 ), they dThe distress measures used by the two surveys are similar, but the procedures they follow are quite different. Despite these differences and the fact that the samples came from two different countries, Butterworth et al.  reportedThe NSDUH reports psychological distress data for three adult age groups: participants whose ages when they were tested were 18–25 and 26–49, as well as those 50 and older. Distress was assessed using the Kessler-6 (K-6). As its name suggests, the annual NSDUH reports summarize current levels of drug use and health-related psychological measures. The summary data for each adult age group were reanalyzed here and fitted with quadratic functions whose parameters allow extrapolation of the functions to predict survey responses in 2020.In contrast to the NSDUH, which surveys a different sample every year, the HILDA is a panel study that contacts members of the same households every other year. Like the NSDUH, which has used the K-6 in its present form to assess psychological distress since 2008, the Hilda has used the K-10 to assess psychological distress since 2007. The two scales differ in that the K-6 is a six-item questionnaire with four items related to depressive symptoms  and two related to anxiety symptoms  whereas the K-10 adds another question related to anxiety and three more related to depression.Although the published analyses of the HILDA provide data for six age groups, for the present purposes these data were averaged to yield three age groups similar to those used by NSDUH to facilitate comparison. Unfortunately, the HILDA survey did not conduct interviews from the beginning of February until August in 2020—the first six months of the pandemic in Australia—irrevocably complicating any efforts to compare observed and predicted distress levels to assess the effects of the pandemic.R2s for the NSDUH percentages from the 18–25-year-old and 26–49-year-old groups were 0.985 and 0.892, respectively. Moreover, linear fits to the percentages from the last five years before the pandemic (2015–2019) revealed significant increases in distress for both groups . Notably, the annual rate of increase for the 18–25-year-old group was 1.29 percentage points per year and the rate for the 26–49-year-old group was only 0.44 points annually, whereas no significant change in psychological distress was observed in those 50 years of age and older (p > 0.35), and the R2 was only 0.285  is an ongoing panel survey that, prior to the COVID-19 pandemic, collected data from more than 40,000 households using mainly face-to-face interviews. Rather than basing analyses on the percentages of participants meeting specific distress criteria such as those reported in the periodic, publicly available reports of the NSDUH and HILDA surveys, the analyses of the UKHLS reported here were based on raw data available from the UK Data Service repository. Having access to the raw data made it possible to construct age groups in exactly the same way as that done with the NSDUH and to calculate and analyze the means for each age group in the same way.The data from the 2008–2019 period were collected following the usual UKHLS procedures. During the last week in April of 2020, the first year of the pandemic, members of households that had participated in either of the two most recent waves of UKHLS data collection were invited to complete the first wave of the COVID-19 web survey if they were 16 or older. They also were asked to complete follow-up surveys online, initially every month and then every other month throughout 2020.As in previous years, the 12-item General Health Questionnaire (GHQ-12) was used to measure psychological distress in 2020. Data were analyzed here using the actual scores for each participant, coded in the way recommended by the developers of the test, and using the same age groups as with the NSDUH in order to facilitate comparisons of the data from the US and UK. It should be noted, however, that testing for the UKHLS was undertaken online rather than face-to-face. Moreover, sample sizes in 2020 were less than half of those in 2019 and varied considerably both between age groups and from wave to wave. As with the NSDUH, the considerable differences in procedure between 2019 and 2020 suggest that statistical comparisons may be inappropriate.Examination of Finally, because measures of distress on the GHQ-12 were available from both before and after the pandemic began, we calculated what the level of distress would have been in the absence of a pandemic if the increasing trend simply continued from 2019 to 2020. As with the NSDUH extrapolations, this was done using the parameter estimates for each age groups’ best-fitting quadratic function  or longitudinal/panel (UKHLS and HILDA) survey designs, and regardless of whether they used the shorter (NSDUH) or longer (HILDA) versions of the Kessler distress questionnaire or a completed different questionnaire, the GHQ-12 (UKHLS). Similar trends were also observed regardless of whether the data analyzed here were reported in terms of the percentages of participants who did or did not exceed some threshold for serious or clinically relevant distress or whether, as in the case of the UKHLS, the raw questionnaire data were analyzed.Despite all these differences, including different samples of participants from three different countries, the data from all waves collected since 2007 or 2008 are well described by quadratic trends, with little or no change up until about 2015, followed by almost linear increases from around 2015 to 2019, the year before the pandemic. Finally, regression analyses of the data from the last five waves prior to the pandemic revealed that not only were younger participants consistently more distressed than middle-aged ones, but in each case, psychological distress increased at more than twice the rate for the younger groups compared to the older ones.Taken together, these results suggest that even though there is still no consensus as to what had been causing distress levels to increase prior to the pandemic, whatever the stressors were, people’s sensitivity to them clearly decreased with age. Importantly, although adolescents and young adults may have been the most sensitive, distress in middle-aged and older adults appears to have increased roughly in synchrony, albeit not to the same extent.In order to facilitate comparisons of the US with Australia and the UK, we used age groupings similar to the NSDUH groups in our analyses. However, these groupings obscured evidence of pre-pandemic increases in psychological distress in younger older adults. In this regard, it should be noted that the percentage of Britons aged 55–69 whose distress was “clinically significant” on the UKHLS increased progressively from 14.8% to 17.0% between 2014–2015 and 2018–2019 and the percentage of Australians aged 55–64 who reported “serious psychological distress” on the HILDA increased from 14.9% in 2015 to 18.5% in 2019. In addition to providing comparative information on pre-pandemic trends in psychological distress, we believe that these age-related differences in distress, taken together with the age-related differences in the rates at which distress increased, are major clues as to the mechanism(s) underlying age and individual differences in people’s responses to stressors under many circumstances, and not just when people’s health and well-being is threatened by a pandemic. Importantly, these results suggest that although it may be extremely useful to group participants for purposes of statistical analyses, there may in fact be one or more age-sensitive traits, and that looking for the causes of distress in different age groups separately may preclude discovering the source(s) of an underlying continuous variation in sensitivity.Pierce et al.  and NiedA major strength of the NSDUH, HILDA, and UKHLS has been each survey’s consistent methodology. In order to examine the time course of the pandemic in greater detail, however, the UKHLS asked for volunteers to undergo repeated online testing, initially once per month and then changing to once every two months, and then even less frequently. The size of the resulting sample was approximately half that of the usual sample, and that fact, taken together with the special recruitment, the online testing, and the frequently repeated tests, are the kinds of procedural changes that call for caution in interpreting the results of statistical comparisons.Visual comparisons, nevertheless, provide important information regarding the effects of the pandemic. For example, the timing of observed changes in distress in 2020 coincided with the beginning and ending of periods of government-ordered lockdowns in the UK . The firFurther evidence of the effects of lockdowns on psychological distress comes from Australia where a surge in infections in the state of Victoria led to a lockdown in that state alone. Notably, equivalent levels of distress were observed in Victoria and other states prior to the lockdown, suggesting that the different states did not differ appreciably with respect to ongoing trends in psychological distress. During the period when lockdown was in effect in Victoria, however, symptoms of both anxiety and depression were significantly higher than in other states ,27. In aIt may be recalled that, in the US, most states also had issued stay-at-home orders by the beginning of April 2020, the point at which distress peaked in the US according to a study by Daly and Robinson . These rAlthough the increasing trends in psychological distress from the three national surveys just reviewed suggest that studies that simply compare distress levels prior to and during the first year of the COVID-19 pandemic likely overestimate the effects of the pandemic, that does not mean that events associated with the pandemic did not lead to significant increases in anxiety and depression. Rather, changes in distress levels during the pandemic, notably those associated with the lockdowns in the UK, Australia, New Zealand, and Germany , suggestWe recently hypothesized that social deprivation has been a major cause of psychological distress during the COVID-19 pandemic ,30. We hdifferential distress hypothesis: Social deprivation is a major source of the psychological distress associated with the pandemic [These findings, taken together with the observed effects of lockdowns, strongly support the fundamental assumption of the pandemic ,30. The r = 0.528, p < 0.001) with distress  was coron Scale . Multiplon Scale ). A reduR2 of 0.434 indicates that the model is a good fit to the data, the model provides little insight into why distress is negatively correlated with age. In contrast, the analyses in this part of our investigation, the third, which we conducted to address our final pair of questions, do appear to provide such insightAlthough we had collected three IPIP NEO personality measures from our sample of over 800 participants, two of which  increased significantly with age, our focus at the time was on social deprivation and associated consequences of psychological distress rather than on its causes . As a reAs described in detail in Myerson et al. , 852 MTuOne might expect that Emotional Stability (the flip side of Neuroticism) would predict psychological distress in the current situation because it measures both reactivity to negative events and how prone a person is to negative emotional states such as anxiety, depression, and anger . ConMoreover, when both Age and Stability were included in the model, the coefficient for Age was not significant . Taken tR2s indicate that a model that includes Stability as a predictor of distress is clearly better than an analogous one that instead includes Conscientiousness as a predictor. Indeed, a similar protective effect of Stability was observed in Germany during the pandemic [The AICc is particularly useful in situations like the present one where the models to be compared are not nested. In the present case, the AICc values and pandemic . It woulpandemic ).To say that Stability affects psychological distress, however, does not address the question of how it affects distress. Consider, for example, two conceptual models of the effect of an external stressor on an individual’s level of psychological distress, an additive model and what we have termed a modulatory model:Now imagine that we measured a person’s distress at two points in time, one before and the other after a change in the magnitude of the stressor. Assuming that the initial magnitude of the stressor was not zero, both models predict that the individual’s initial level of psychological distress would depend on their emotional stability, with more stable individuals being less distressed than less stable individuals. The models differ, however, in the effect of a change in the stressor. According to the additive model, the degree to which psychological distress will change when the stressor changes will be independent of a person’s emotional stability. In contrast, the modulatory model predicts that the degree to which distress will change is inversely related to the emotional stability of the individual. More stable individuals will change less, and less stable individuals will change more. Importantly, this prediction holds regardless of whether the stressor increases or decreases in magnitude: If the stressor increases, the distress of more stable individuals will increase less than the distress felt by less stable individuals, whereas, if the stressor decreases, more stable individuals will show smaller decreases in distress than less stable individuals.Notably, the effects of lockdowns on the level of psychological distress in the UK during the first year of the COVID-19 pandemic are consistent with the predictions of the modulatory model see , as are Both the additive model and the modulatory model predict that increases in a stressor such as the social deprivation caused by a lockdown will increase distress and that those who are less emotionally stable will experience greater distress at all levels of Stress. However, the additive model predicts that psychological distress will increase to the same extent regardless of a person’s or group’s Emotional Stability, whereas the modulatory model predicts that lower Stability will be associated with greater increases in distress.It should be recalled that, in the UK, younger individuals showed larger decreases on average than older individuals when the first lockdown there ended and again showed larger increases when the second lockdown began. Because younger adults are known to be less emotionally stable than older adults, these results are clearly more consistent with the modulatory model than with the additive model. The fact that the initiation and termination of lockdowns were in response to increases and decreases, respectively, in the risk of COVID-19 infection, does not change the predictions or weaken the evidence for the modulatory model, although it does make it difficult to separate the effects of social deprivation and concerns regarding the likelihood of infection.We would note, moreover, that gender differences also provide a test of the modulatory hypothesis. Women are known to score lower on Emotional Stability and higher on measures of both depression and anxiety. Thus, like younger adults, women would be predicted to show larger increases in both depression and anxiety when lockdowns go into effect, and in fact this was the case for the UKHLS pandemic data reported by Pierce et al.  and the Although we would argue that the increases during lockdowns also reflected ongoing trends, the data are clearly consistent with a modulatory role for Stability. With respect to the ongoing trends, moreover, according to the UKHLS data reported by Pierce et al. , femalesSome stressors, of course, may have greater effects than others, and Stability may play a larger role in modulating the contribution of some stressors than it does with respect to other stressors. Moreover, although we have focused on Emotional Stability here because its definition implies a modulatory role, other measures  that change with age could, in principle, also play a modulatory role.We posed four questions at the outset of this paper. First, we asked whether the increasing trend both in psychological distress and in the size of age differences in distress continued right up through 2019, the year before the COVID-19 pandemic began. We answered this question by updating national survey data. After updating the data, analyses clearly revealed that the COVID-19 pandemic was preceded by a period of increasing psychological distress in the U.S., Australia, and the U.K., and that younger adults were the most affected and older adults the least. Notably, although young adults showed the largest increases in distress, increases were observed in adults of all ages.Second, we asked how much of the distress during the first year of the pandemic was due to mandated lockdowns and again, whether age differences changed when the overall level of distress increased and decreased over that time period. Although a precise, quantitative characterization is not possible because of procedural changes in these national surveys, we were able to address our second question based on evidence showing that lockdowns were responsible for increased distress in the U.S, Australia, and the U.K.The data from the U.K. provide the most detailed picture and indicate that younger, middle-aged, and older adults were all affected, but that the size of changes, both increases when a lockdown was imposed and decreases when it was lifted, were, again, largest for the younger adults and smallest for the older adults. We found that when the first U.K. lockdown was lifted, the level of distress level in each age group decreased to approximately the level predicted based on the increasing pre-pandemic trend. These results raise the possibility that most, if not all, of the increase in distress at the beginning of 2020 was due to social deprivation, but the fact that the lockdown was due to the high rates of infection with the SARS-CoV-2 precludes a definitive test of this possibility.Our third and fourth questions concerned whether individual and age differences in psychological distress might be explained by differences in personality traits such as Emotional Stability. Our answer to these questions is based on the entire pattern of individual and age-related differences analyzed here. Specifically, we postulate that individuals’ sensitivity to stressors decreases with age, and that this sensitivity modulates the size of changes in distress as the level of stressors changes. By definition, the psychological trait of Emotional Stability is the kind of individual attribute that could play such a modulating role because it increases with age, suggesting that stressors would have less and less of an effect as one gets older. Thus, it predicts both the pattern of age differences in distress levels as well as the age differences in the rates of change in distress that were observed both before and during the pandemic.Emotional Stability also shows significant gender differences that are consistent with the gender differences in distress levels and in the size of changes in distress observed in our analyses. Notably, however, some other personality traits  also show both age and gender differences and thus represent possible alternative modulating factors, although of course, more than one trait may be playing a role here. Further analyses and more data will be needed, but the approach described here appears to us to be a promising one.Currently, social deprivation appears to play an important role not only in distress levels but also in mitigation behaviors and vaccination decisions, interfering with the former while facilitating the latter ,30. StilAll this, moreover, comes on the heels of increases in distress indicative of an international mental health pandemic that preceded the COVID-19 pandemic, at least in English-speaking countries. Taken together, the pre-pandemic increases followed by those associated with the pandemic may have created a “perfect storm” of psychological distress, at least during mandated lockdowns. As a result, there is clearly a lot at stake in estimating levels of psychological distress and the extent to which changes reflect the current pandemic, as well as in the ability to predict future distress levels.The present findings highlight the extent to which on-going trends must be considered as well as the likelihood that failure to do so may lead to overestimating the effect of the pandemic, per se. Still, it is likely that even after taking ongoing trends into account, distress levels really did increase somewhat because of the pandemic ,38, in lFinally, our analysis of previously unreported personality measures from the recent study by Myerson et al.  suggests