Fabio Panariello,Sara Longobardi,Lorenzo Cellini,Diana De Ronchi,Anna Rita Atti

Fabio Panariello,Sara Longobardi,Lorenzo Cellini,Diana De Ronchi,Anna Rita Atti,Department of Biomedical and NeuroMotor Sciences,Institute of Psychiatry,University of Bologna,Bologna 40126,Italy

Abstract BACKGROUND The subsequent waves of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) pandemic have represented a dramatic health emergency characterized by significant consequences on mental health.Diachronic variations in the incidence rates of acute relapse of psychiatric disorders may represent significant"sentinel events" for assessing the mental health response to an unprecedented stressful event.AIM To investigate the variation in psychiatric hospitalization rates and differences in sociodemographic and clinical-psychopathological peculiarities at Bologna"Maggiore" General Hospital Psychiatric Ward (GHPW) between the first two waves SARS-CoV-2 pandemic and the same periods of the previous 3 years.The secondary purpose of the study was to suggest a diachronic response pathway to stress by reporting additional literature data on coping strategies.METHODS This observational and retrospective study collected information on admission to the GHPW at the "Maggiore" Hospital in Bologna in the index periods defined as follows:the first period between February 24,2020 and April 30,2020 (first epidemic wave) and the second period between October 8,2020,and January 7,2021 (second pandemic wave).Absolute numbers and proportion of admitted patients,their sociodemographic and clinical-psychopathological characteristics were compared with the same parameters recorded in the two same periods of the previous 3 years.No strict inclusion or exclusion criteria were provided in the data collection to collect information on all patients requiring acute psychiatric hospitalization.RESULTS During the first wave,there was a significant reduction in hospitalization rates,although there was a simultaneous increase in compulsory hospitalizations and the acute relapse of schizophrenia spectrum and other psychotic disorders.During the second wave,hospitalization rates reached those recorded during the same period of the previous 3 years,mainly due to the rise of bipolar and related disorders,depressive disorders,anxiety disorders,trauma-and stressor-related disorders and suicidal behaviors.CONCLUSION The coping strategies adopted during the first wave of the SARS-CoV-2 pandemic protected the vulnerable population from the general risk of clinical-psychopathological acute relapse,even if they increased the susceptibility to run into schizophrenia spectrum and other psychotic disorder relapses.In the medium-long term(as in the second pandemic wave),the same strategies do not play protective roles against the stress associated with the pandemic and social restriction measures.Indeed,during the second wave of the SARS-CoV-2 pandemic,an increase in total hospitalization rate,suicidal behaviors and the incidence rate of bipolar and related disorders,depressive disorders,anxiety disorders,trauma-and stressorrelated disorders was observed.

Key Words:SARS-CoV-2;Schizophrenia spectrum and other psychotic disorders;Bipolar and related disorders;Depressive disorders;Anxiety disorders,trauma-and stressorrelated disorders;Suicide behavior;Coping strategies

INTRODUCTION

In Italy,the first epidemic outbreak occurred at the end of February 2020 in Lombardy[1].The Italian government adopted several social distancing measures and limitations of social recreational and work activities at national and regional levels to contain infection spread.These measures progressively increased until the lockdown imposed by the Prime Minister’s Decree of Ministers of March 9,2020.Similarly,from the first decade of October 2020,in order to contain the spread of the second pandemic wave,the Italian Prime Minister issued another set of social distancing measures up to a level of limitation similar to the first lockdown.Details on social distancing measures during the first and second waves in Italy are reported in Table 1.

Table 1 First and second pandemic waves and social distancing measures

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related pandemic threatened the health of citizens and significantly contributed to a widespread sense of insecurity and a lessened quality of life for both individuals and entire communities[2].Such psychosocial effects on individuals (e.g.,insecurity,fear,uncertainty,confusion,isolation,and stigma) and the whole community (e.g.,school and workplace closures,the shutdown of social gathering places,suspension of economic activities,and uncertainty in health claims) may have contributed to threatening the mental health of individuals and the collective[3,4] and causing both new onsets of clinical pictures from adjustment disorders and relapses of psychiatric disorders from severe mental illness (SMI)[5-7].These consequences have already been reported in the general population[8,9],vulnerable individuals[7,10],and patients with a history of psychiatric disorders[11].Furthermore,the long-term consequences on mental health are likely to continue even after the end of the pandemic emergency,resulting,for example,from the economic burden due to the adopted social distancing measures.In epidemiological terms,it could be worse than the consequences on the mental health during the economic crisis in Italy and Greece in 2008,where a significant increase of suicidal behaviors and suicide occurred,as was well described in the literature[12,13].

The Italian mental health system is extensively community-based,and mental health care is freely available to all citizens.Besides outpatient settings,in Italy,there are nearly 318 psychiatric wards located within the general hospitals (General Hospital Psychiatric Wards [GHPWs]).Each ward contains,on average,15 beds dedicated to treating psychiatric patients in both voluntary and compulsory ways[14].The total national number of beds to take care of acute psychiatric clinical pictures is 3981,which means around 10 bedsper100000 adult population[14].Therefore,GHPWs are places of care dedicated to the hospitalization and treatment of acute psychopathological relapses that can be configured as psychiatric emergencies/urgencies.They represent a privileged observatory to survey the changes,in terms of incidence,of new-onset or acute relapse of clinical pictures related to SMIs such as those observed during the exposure to high-stress life events.For this reason,they play a crucial role during global crises that also involve mental health and represent a fundamental source of information to be collected in the early stages of a crisis,valuable both to better understand individual and collective coping strategies and to implement preventive actions and timely care[15-17].

Only a few studies[16,18] have examined and described qualitative and quantitative differences observed in the rates of urgent/emergent hospitalization within the psychiatric wards between the pre-pandemic and SARS-CoV-2 pandemic characterized by the consistent social restriction measures.Furthermore,to the best of our knowledge,no studies to date have investigated these differences during the first and second pandemic waves.

This study investigated the existence of any differences in terms of acute psychiatric relapse or new onset of psychiatric disorders observed at the GHPW of the "Maggiore"Hospital in Bologna between the first and second epidemic wave compared to the same periods of the previous 3 years by comparing the sociodemographic and clinical features.

To achieve this aim,we took into consideration:Voluntary hospitalization rates,compulsory hospitalization rates,diagnoses,and the severity of psychopathologicalclinical pictures estimated by the mental health triage (MHTS)[19,20].

Furthermore,based on our results and the collection of scientific evidence that we have collected in the literature regarding the response of individuals and communities to stressful factors and their persistence over time,we propose an opinion review to depict a hypothetical model of the diachronic response of the community to unusually stressful and unprecedented events.We hypothesize that the coping strategies and their efficacy can change over time and,depending on the individual aptitude to answer to the stress,we have generated an "elastic" model that can give reason to the different psychopathological pictures observed over time,after and during a stressful event.

MATERIALS AND METHODS

Participants

This observational and retrospective study collected information on admissions to the GHPW at the "Maggiore" Hospital in Bologna in the index periods defined as follows:the first period between February 24,2020 and April 30,2020 (first epidemic wave)and the second period between October 8,2020,and January 7,2021 (second pandemic wave).Absolute numbers and the proportion of admitted patients,their sociodemographic and clinical-psychopathological characteristics were compared with the same parameters recorded in the two same periods of the previous 3 years.No strict inclusion or exclusion criteria were provided in the data collection to collect information on all patients requiring acute psychiatric hospitalization.This study followed the last version of the Declaration of Helsinki[21].

Assessment

For each patient hospitalized in the index periods,clinical data were collected,determining the diagnosis and the level of emergency/urgency at the time of admission based on the MHTS by the Victorian Emergency Department[19,20].The MHTS is a triage scale aimed at identifying the severity level of psychopathological pictures to prioritize the intervention.It consists of a five-level scale:Level 1,the substantial danger of life to oneself and others;Level 2,violent,aggressive,probable danger of injury to oneself or others or with police escort;Level 3,very distressed or psychotic,liable to deteriorate,situational crisis,possible danger to oneself or others;Level 4,long-lasting semi-urgent mental health disorder,support agency present;and Level 5,long-standing non-acute mental health disorder,no support agency present.Patients were assessed using combined mental health and sociodemographic information.

Hospitalized patients were divided into emergent (Level 1 and 2) and urgent (Level 3,4,and 5) cases.In the hospitalized population,the incidence rate of compulsory hospitalizations was calculated [according to the Italian law (Law number 180/1978),in case of acute psychopathological distress,when patients lack insight and refuse the treatments which they need,and there are no possibilities to provide outpatient treatments,psychiatric admissions against the patient's will are possible-compulsory admissions[22].We also collected other data such as sociodemographic data (sex,age)and the length of hospitalization.Age was used as a continuous variable.Diagnoses were assessed according to the DSM 5 through the administration of the Structured Clinical Interview for the DSM 5 Clinician Version (SCID-5-CV).The SCID-5-CV is characterized by excellent reliability and high specificity,and there is evidence for its easy use in daily clinical practice[23].

Statistical analyses

Continuous data for sociodemographic and clinical variables are expressed as the mean ± SD,while categorical variables are reported as percentages.The Kolmogorov-Smirnov test was performed to verify normal distributions of continuous variables.Multiple logistic regression analyses were performed by including variables that were significant for bivariate analysis.Pearson's chi-squared test with Yates correction or thet-test for independent samples was used to compare categorical and continuous variables,respectively,between the identified subgroups.As the dependent variable,we used GHPW hospitalization during the pandemic.Odds ratio (OR) and 95%confidence interval (95%CI) were calculated to estimate the correlation between the frequencies of the hospitalization and the frequencies of independent variables.All statistical analyses were performed using the SPSS package (version 27.0,SPSS;SPSS Inc.,Chicago,IL,United States) for Windows,andP＜0.05 (two-tailed) was considered statistically significant.

RESULTS

During the first index period,we observed 47 inpatients at GHPW "Maggiore"Hospital in Bologna (84 hospitalized patients during the second index period);42.58%of the hospitalized population was female (vs43.2% during the second lockdown).The mean age was 42 + 2 (years + SD) during the first index period (vs43.9 + 1 during the second index period).The length of hospitalization was 8.8 + 3 d in the first index period and 8.5 + 2 d in the second index period.According to MHTS,85.7% of the admitted patients were classified as urgency during the first index period (80.7%during the second index period).No differences were observed between the two pandemic waves and the same periods of the previous 3 years in length of hospitalization,mean age,and sex.

A reduction in total psychiatric hospitalization number during the first lockdown of 33.49% compared to the hospitalization rate in the same period of the previous 3 years was reported (47 in 2020vs81 in 2019,68 in 2018,and 63 in 2017 for further details;Table 2).On the other hand,an increase in compulsory admissions was observed:19.7% of total admissions that occurred during the first lockdown compared to 10.1% (P＜0.01) in the same period of 2019,13.3% (P＜0.05) in 2018,and 7.2% in 2017 (P＜0.01).Consistently with these features,hospitalized patients presented a higher degree of psychopathological emergency at MHTS than in the same period of the previous 3 years (28.2%vs13.6% [P＜0.01] in 2019,25% [P＜0.05] in 2018,and 14.3% in 2017 [P＜0.01]) (Table 2).

During the first pandemic wave and related restriction measures,schizophrenia spectrum and other psychotic disorders diagnoses increased by 10% on average.As indicated in Table 2,39.5% in 2020vs32.1% in 2019 (P＜0.05),31.5% in 2018 (P＜0.05),25.1% in 2017 (P＜0.01).Anxiety disorders and trauma-and stressor-related disorders(Group C in Table 2) showed an increasing trend during the first lockdown (8% in 2020vs5.2% in 2019,5.9% in 2018,and 5.8% in 2017).Logistic regression analyses considering hospitalization at GHPW during the first pandemic wave and the estimated probability ratio (OR) was as follows:Male/female (OR=1.754;P＜0.001),self-harm behavior (OR=2.066;P＜0.001) as an independent variable (Table 3).During the second wave,hospitalization numbers increased reaching the same rate recorded during the previous 3 years (84vs89 in 2019,85 in 2018,88 in 2017) while the proportion of compulsory admissions and the level of emergency,according to the MHT,decreased to the percentages observed in the same period of the previous 3 years (Table 4).

Table 2 Absolute numbers of total admissions,proportion of emergencies,urgencies and compulsory admissions occurred during the first pandemic wave and in the same period of previous 3 years

Table 3 Multivariate logistic regression analyses:odds ratio,and 95% confidence interval for hospitalization during the first pandemic wave

Table 4 Absolute numbers of total admissions,proportion of urgencies,emergencies and compulsory admissions occurred during the second pandemic wave and in the same period of the previous 3 yr

Bipolar and related disorders,depressive disorders,anxiety disorders,and traumaand stressor-related disorders according to the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition (DSM5) were those that were statistically increased significantly during the second pandemic wave compared to the same period of the three previous years.Bipolar and related disorders and depressive disorders were 32.9% of total hospitalizationsvs28.8% (P＜0.01) in 2019,29.4% (P＜0.05) in 2018,30.1% (P＜0.05) in 2017,in the same period of the previous 3 years.The disorders belonging to anxiety disorders and trauma-and stressor-related disorders according to the DSM5 during the second pandemic wave and related restrictive measures were 9%of total hospitalizationsvs4.2% (P＜0.01) in 2019,3.7% (P＜0.01) in 2018 and 2.1% (P＜0.01) in 2017.We also observed a statistically significant increase in suicidal behavior during the second pandemic wave compared with the average recorded during the same period of the previous 3 years (20.22%vs11.10%;P＜0.01).Disorders belonging to the schizophrenia spectrum were more prevalent in the second pandemic wave(10.4%) than in the same period of the previous 3 years,albeit not statistically significant.Logistic regression analyses considering hospitalization at GHPW during the second pandemic wave and the estimated probability ratio (OR) as an independent variable was as follows:male/female (OR=1.938;P＜0.001) and suicidal behavior(OR=2.410;P＜0.001) (Table 5).

Table 5 Multivariate logistic regression analyses:odds ratio,and 95% confidence interval for hospitalization during the first pandemic wave

DISCUSSION

Our results showed that,in patients with mild and moderate mental illness,during the first wave and the adoption of the first set of measures to contain the pandemic spread,some protective factors seemed to balance and outweigh the risky ones related to the pandemic and quarantine.The total number of hospitalizations at the GHPW decreased with a relative increase in the pictures listed as a psychiatric emergency according to the MHT (codes 1 + 2).On the other hand,the acute relapse of acute psychiatric clinical pictures belonging to schizophrenic spectrum disorders has undergone a statistically significant increase during the first pandemic wave and the first social restriction measures.In the literature,other authors have already described the increase in incidence rates of psychotic clinical pictures,and this phenomenon may probably have a generalizable value in all the countries most severely affected by the SARS-CoV-2-related pandemic and which have been subject to measures to contain the spread of the virus[24-26].These preliminary data were consistent with results from other countries,such as China,where the pandemic would have originated and where the highest incidence of the first psychotic episode was reported in the months following the origin of the pandemic[27].

It can be argued that the highly stressful scenario deriving from the fear of contagion,the confinement and the reduction of freedom imposed by the restrictive measures,the fear of the future evolution of the pandemic situation,the fear of the potential economic crisis could have played a significant role in the new-onset and the exacerbation of pathologies belonging to the schizophrenia spectrum according to international literature.

Although the relationship between the pressure exerted by highly stressful events during adult life and the onset of psychosis has been poorly studied,the results of a large meta-analysis suggest that the risk of psychosis onset is three times higher in subjects exposed to highly stressful events[28].

The data relating to the increase in the onset of new psychoses recorded in our data collection during the first pandemic wave was consistent with Polliceet al[29] in 2012.They observed the same boost in first psychosis episodes in connection with the earthquake in L'Aquila in 2009,an event whose traumatic extent can be compared,in some ways,to the traumatic impact of the related SARS-CoV-2 pandemic and to the consequent deterioration of social life and which share the same cultural scenario(both the stress events and the related results happened in Italy)[29].

We hypothesized that the coping strategy could be called into question to understand better the phenomenon from a psychological point of view in the biopsychosocial perspective.

Coping is identified as a complex of strategies adopted to manage stress better and reduce the emotional impact of stress events.They have been described as emotionfocused coping strategies,problem-oriented coping strategies and avoidance-focused coping strategies.Problem-focused coping strategies are termed "positive coping" as they relate to better outcomes[30].Patients with more severe symptoms of schizophrenia are characterized by a reduced use of positive coping strategies[30].Furthermore,the severity of psychotic symptoms is inversely related to positive coping,which is related to better functional outcomes[31,32].Overall,results from the scientific literature suggest that schizophrenic patients rely on maladaptive coping strategies or have the potential to exacerbate distress.

The observation,already reported,of a global decline in the number of hospitalizations at "Maggiore" Bologna Hospital's GHPW also may be analyzed considering the theory of coping strategies.If several social factors such as the shared experience at the national level of a sense of cohesion,trust and social compassion perceived by the whole nation and the increase of the importance of informal social networks,it can also be argued that most individuals have adopted positive coping strategies.It could mean that individuals with a higher vulnerability to psychotic disorders cannot adopt on their own problem-oriented coping strategies.From the biological point of view of the biopsychosocial model of psychiatric disorders,it can be speculated that severe psychiatric pictures,including schizophrenia,bipolar disorders,and depressive disorders for which a greater etiological weight is recognized to the biological factor in the biopsychosocial model,could have been triggered by the direct neuroinvasiveness of SARS-CoV-2 or by the consequences of consequences of peripheral infection or by the subsequent inflammatory state on the central nervous system (CNS).Our group proposed a generating hypothesis that SARS-CoV-2 would demonstrate a neuroinvasive and neurotropic capacity through different anatomical pathways[33] through the angiotensin-converting enzyme-2 receptor.Possible speculation regarding the observed data is that SARS-CoV-2,through the colonization of the CNS,may act as an etiological cofactor in the exacerbation or in the onset of psychopathological pictures that recognize a more significant causal load of the biological component in the biopsychosocial model.

Further evidence of the present study suggests that in the medium to long term,such as during the adoption of restrictive measures in the second pandemic wave,there was an overall increase in the incidence of acute psychopathological relapse.Indeed,the hospitalization rate reverted to the pre-existing incidence recorded in the same periods of the previous 3 years.This feature was mainly due to the rise of Mood(bipolar and related disorders and depressive disorders) and anxiety disorders.This result suggests that positive coping strategies,in the case of the ongoing pandemic,have proven to be effective in the short-term prevention of acute mood and anxiety disorders but have lost this in the long term.Other notable data is the increase in the suicidal behavior rate.This finding can be,in part,explained considering the increase of depressive disorders incidence.

On the other hand,the impact of the stress on suicidal behavior can also be considered.Indeed,as highlighted by Monica Starkman,in a brief report on the suicide attempt rate after the terrorist attack in September 11,2001,the stress related to that unprecedented attack contributed to the statistically significant increase in the number of suicidal behaviors during the 2 years following the September 11,2001[34].Furthermore,in our study,suicidal behaviors are also strong predictors of psychiatric hospitalization during the second pandemic wave at multiple regression analysis.

CONCLUSION

The findings in this study showed that the higher incidence of hospitalizations for mood disorders and suicidal behavior must also be evaluated considering the growing and looming economic crisis due to the restrictive policy measures influencing the indicators of social well-being.Deaths from suicidal behavior increase dramatically during economic crises.In 2016,as Merzagoraet al[35],in Italy,suicides increased between 2011 and 2016,during and immediately after the severe economic crisis that began in 2008[35].Our preliminary data highlight the requirement to adopt preventive social and health policies to contain a potential "psychopathological pandemic"following the SARS-CoV-2 pandemic and invite the scientific society to pay attention to the problem.

By combining our clinical observations with the epistemological theories present in the literature[36-38],we propose an opinion hypothesis based on applying,to the phenomenon of psychological stress and coping strategies,the same laws of physics as the law by Hooke.It states that,in a mechanical system,the elastic response to a force F applied to an object is proportional to the variation of variable length (ΔL) multiplied by a specific constant of the material of which the object is composed [F=ΔL·K].In biological systems,as reported by Kültz and Somero[38],organisms represent homeostatic systems in continuous dynamic equilibrium.Stress is constantly fluctuating around the norm throughout the life history of any organism.This fluctuation can push psychological and physiological set points out of homeostasis H.

The extent of the deviation (increase or decrease in value) of the most critical(limiting) variables (ΔHc) from the homeostatic set point (Hc) determines the behavior of the system.Therefore,for biological systems,Hooke's law can be defined as [F=ΔHc·k],where k is a constant describing the phenotype of the biological system at the moment of exposure to force F and Hc represents the homeostatic norm H of most critical (limiting) physiological variables c.Our opinion is that this construct is also valid for psychological systems where homeostasis is ensured by multiple factors,including coping and stress response strategies.The challenge is to identify which biopsychological variables might be the most critical and limiting ones.These variables will depend on stress type and severity and the individual's state at the time of the stressful event.Within this theoretical hypothesis,the time factor would also play a key role.If a perturbing event acts for a time interval Δt,some psychological homeostatic set points could alter at different time points,depending on the "elastic capacity" of the same set points and the coping strategies adopted.In our case,the set point of the affective dimension would have "broken" later than that of the psychotic dimension.

Limits and perspectives of the study

The current study had several limitations.Meanwhile,it is a monocentric study and describes what happened in one of the Italian GHPWs.As such,it does not claim to draw ecumenical conclusions.Our data are consistent with what was described by other authors during the first pandemic wave.However,our study represents the first that follows diachronically,during the first and second pandemic waves,the trend of hospitalizations for acute psychiatric relapse in response to the Trauma of the pandemic and the consequent restrictive measures.The last "take-home messages" that deserve to be taken into consideration and on which to calibrate the subsequent research trajectories are the following:The severe mental illnesses have not suffered,contrary to the moderate-mild mental disorders,a contraction in terms of acute relapse,during the first SARS-CoV-2 pandemic wave.The "advantage" of moderate/mild disorders is lost during the second pandemic because the protective factors probably no longer balance the precipitating factors.The findings from the first pandemic wave suggest that mild/moderate psychopathological clinical pictures can be successfully treated in settings other than GHPWs.This key point indicates that:It is possible to reduce hospitalization rates by enhancing and customizing the offers of the community mental health care settings;it is confirmed that traumatic experiences are important causal factors of psychotic relapse in the short-term period and mood disorders relapse in the long-term period;and the suicide risk could,with every reasonable probability,become the real post-pandemic emergency in light of the emerging and consequent economic-financial crisis.

ARTICLE HIGHLIGHTS

Research background

Significant consequences on mental health characterize unprecedented events like the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.Therefore,variations in psychiatric hospitalization rates represent significant "sentinel events" for assessing the mental health response to stress.Responses to the stress may lead to new-onset or relapses of severe mental illness and suicidal behavior rates.

Research motivation

To reduce the further consequences on the mental health of the SARS-CoV-2 Pandemic by describing the repercussions of the first two waves of the pandemic on the psychiatric new-onset or relapse pictures rates.

Research objectives

The present study investigates any differences in terms of acute psychiatric relapse or new onset of psychiatric disorders observed at the General Hospital Psychiatric Ward(GHPW) at "Maggiore" Hospital in Bologna between the first and second epidemic.

Research methods

We took into consideration:Voluntary hospitalization rates,compulsory hospitalization rates,diagnoses,and the severity of psychopathological-clinical pictures estimated by the mental health triage and Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition interview.Multiple logistic regression analyses were performed to estimate the correlation between the frequencies of the hospitalization and the frequencies of the independent variables.

Research results

The total admissions rate at GHPW decreased during the first SARS-CoV-2 pandemic wave compared to the same period throughout the 3 previous years.The compulsory admission rate and acute psychotic relapse rate increased during the first SARS-CoV-2 pandemic wave in comparison with the 3 previous years.During the second SARSCoV-2 pandemic wave the total psychiatric admission rate reached the same ratio recorded during the same period of the previous 3 years.Suicidal behaviors,depressive disorders,bipolar disorders,anxiety spectrum disorders and trauma-and stressor-related disorders relapse arose among hospitalized patients during the second SARS-CoV-2 pandemic wave compared with the 3 previous years.

Research conclusions

We hypothesize that problem-focused coping strategies may be protective for the risk of acute psychopathological relapse in the short term but not in the medium-long term.

Research perspectives

The suicidal rate could arise in the future,after the first two pandemic waves therefore may be important to survey it and to adopt preventive strategies.