Loneliness and health: An umbrella review

Nima Rezaei; Amene Saghazadeh

doi:10.4103/hm.hm_51_22

REVIEW ARTICLE

Year : 2022 | Volume : 6 | Issue : 4 | Page : 242-253

Loneliness and health: An umbrella review

Nima Rezaei¹, Amene Saghazadeh²
¹ Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences; Department of Immunology, School of Medicine, Tehran University of Medical Sciences; Metacognition Interest Group, Universal Scientific Education and Research Network, Tehran, Iran
² Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences; Systematic Review and Meta-Analysis Expert Group, Universal Scientific Education and Research Network, Tehran, Iran

Date of Submission	02-Oct-2022
Date of Acceptance	11-Nov-2022
Date of Web Publication	16-Dec-2022

Correspondence Address:
Prof. Nima Rezaei
Children's Medical Center Hospital, Dr. Qarib Street, Keshavarz Blvd, Tehran 14194
Iran

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/hm.hm_51_22

Abstract

Loneliness has been associated with different health outcomes in the following domains: general health, well-being, physical health, mental health, sleep, and cognitive function. However, the most significant associations fall into mental health- and well-being-related outcomes. Moreover, loneliness is an identified risk factor for all-cause mortality. This article overviews the systematic and meta-analytic studies, which have investigated epidemiology and etiology, associated medical and neuropsychiatric conditions, and interventions for loneliness. Meta-analyses have associated higher levels/prevalence of loneliness with pathological conditions, including physical (cardiovascular diseases, obesity, and cancer) and mental health conditions (dementia, cognitive impairment, depression, anxiety, suicide, substance abuse, frailty, and addiction). Furthermore, loneliness commonly occurs to people during particular physiological conditions, for example, childhood, adulthood, elderly, pregnancy, and taking care of others. Moreover, young adults commonly experience transient loneliness. For all these pathological/physiological conditions, COVID-19 has been confirmed as a loneliness-worsening condition. Genetic background, in addition to environmental factors, plays a role in the etiology of loneliness. Biomarkers mainly include neural correlates, including aberrations in the structure/function of cognitive or emotional control-related brain regions, inflammatory correlates, and anthropometric measures. The current interventions for loneliness alleviation are mostly focused on older people, for whom the evidence derived from systematic or meta-analytic studies shows none-to-moderate benefits and substantial heterogeneity across studies. The evidence is not adequate to conclude about the effectiveness of interventions in youth. In addition to the need for pathology- and population-specific interventions for loneliness reduction/prevention, there is a need to survey loneliness longitudinally to examine the causality of loneliness-health associations.

Keywords: Association, health, intervention, loneliness, mental health

How to cite this article:
Rezaei N, Saghazadeh A. Loneliness and health: An umbrella review. Heart Mind 2022;6:242-53

How to cite this URL:
Rezaei N, Saghazadeh A. Loneliness and health: An umbrella review. Heart Mind [serial online] 2022 [cited 2023 May 31];6:242-53. Available from: http://www.heartmindjournal.org/text.asp?2022/6/4/242/363953

Introduction

Since 2020, researchers have been increasingly acknowledging that people are lonely. This acknowledgment occurred amid the COVID-19 pandemic when man chose to use social isolation and physical distancing as non-pharmacological measures to contain the disease transmission. This choice was the only option given that, at that time, no vaccine had been developed; however, whether we were ready to manage its expense – loneliness – that inevitably penetrated throughout our homes – the warmest places we had were suddenly turned into the coldest places we had ever experienced.

This article briefly reviews the epidemiology and etiology, associated medical and neuropsychiatric conditions, and interventions for loneliness.

Methods

To prepare this review article as concisely as to meet the guidelines of the special issue in which the article appears, we searched for and selected among high-quality evidence of systematic review and meta-analysis studies published in PubMed through September 23, 2022. The results of these studies are narrated below [Table 1].

Table 1: Sytematic review with/without meta-analysis studies included in the review

Click here to view

Epidemiology

Older adults are the main focus of meta-analyses of loneliness prevalence due to their specific susceptibility to loneliness. Gardiner et al. conducted a meta-analysis of 13 studies of loneliness among older people who lived in residential and nursing care homes.^[1] They highlighted large variations in loneliness prevalence across studies: 31%–100% for moderate loneliness and 9%–81% for severe loneliness. Gardiner et al.'s study reported the prevalence of loneliness by severity: the mean prevalence was estimated at about 61% and 35% for moderate and severe loneliness, respectively. These rates are much higher than those estimated by Chawla et al. through a meta-analysis of 39 studies of high-income countries: the pooled prevalence was about 26% and 8% for moderate and severe loneliness, respectively.^[2] Besides the living condition, culture might also affect the prevalence of loneliness. For example, in Latin America, the pooled prevalence of loneliness was between 25% and 32%; in India, it was about 18%; and in China, it was about 4%.^[3] Compared to older adults, the ranges of loneliness prevalence are much narrower among adolescents and young and middle-aged adults. A recently published meta-analysis of data from 106 countries and territories estimated the prevalence of loneliness to vary between about 9% and 14%, with South Eastern Asia and the Eastern Mediterranean region as the least and most affected World Health Organization-defined regions.^[4] For young, middle-aged, and older adults, the ranges were 2.9%–7.5%, 2.7%–9.6%, and 5.2%–21.3%, respectively, and Northern Europe and Eastern Europe were the least and most affected regions for all age categories of adults.

A meta-analysis of longitudinal studies provides evidence that loneliness scores peaked in May 2020, especially in North America.^[5] It is an expected finding, given that the COVID-19 pandemic dominated early 2020. The duration of social isolation and physical distancing is another factor that will potentially impact the prevalence of loneliness. A meta-analysis of 30 studies has recently shown that the prevalence of loneliness was higher among older adults 3 months after the COVID pandemic than during the first 3 months of the pandemic.^[6] Furthermore, for children and adolescents aged 24 years or less, this review^[7] confirms that loneliness has increased during the COVID-19 pandemic compared to before the pandemic. In 4–19-year-old children and adolescents, a pooled estimate of 5% for loneliness prevalence during the pandemic has been reported.^[8]

To treat the heterogeneity in reporting loneliness prevalence, there is a need for:

Standardized loneliness concept and definition across cultures; and
Valid and reliable tool for distinguishing moderate from severe loneliness.

To reduce the burden of loneliness in low-income countries and residential and nursing care homes, there is a need for:

An international collaboration to transfer services to susceptible places; and
Then a regional management system to monitor the equable allocation of services.

In a review of 114 studies, the association of loneliness with health outcomes has been investigated.^[9] Loneliness has been associated with different health outcomes in the following domains: general health, well-being, physical health, mental health, sleep, and cognitive function. However, the most significant associations fall into mental health-related and well-being-related outcomes. Moreover, based on a meta-analysis of more than 77,000 people, loneliness is an identified risk factor for all-cause mortality among both male and female subjects.^[10]

Etiology

No need to emphasize the extent to which environmental factors are important in determining whether one is lonely or not. In addition to environmental factors, a few genetic factors have been identified.^[11] Neural correlates of loneliness are, however, of the highest interest. Different neuroimaging tools, for example, computed tomography (CT), diffusion tensor imaging, positron emission tomography, single-photon emission CT, and functional magnetic resonance imaging, could correlate loneliness with both aberrations in the structure and function of specific brain regions, mainly the prefrontal cortex, insula, amygdala, and hippocampus. These regions are mainly recognized for their role in cognitive and emotional control.^[12] Biomarkers for loneliness also include tau and amyloid, two Alzheimer's disease-related proteins; interleukin 6, a pro-inflammatory cytokine;^[12],[13] anthropometric measures.^[14] Totally, the current evidence orients thoughts to consider loneliness as a neuro-immune-metabolic syndrome.^[14],[15] This orientation is understandable given the association of loneliness with increased risk of neurocognitive disorders, mainly dementia, as well as with odds of developing physical health conditions which are known to be underpinned by chronic inflammation and metabolic changes, i.e., obesity and cardiovascular diseases (CVD).

Chronic Diseases

Loneliness commonly occurs in chronic conditions, including CVD and metabolic disorders. Despite this, interventions effectively targeting chronic disease-related loneliness are lacking, calling for well-designed controlled studies to address whether loneliness treatment can help improve health in chronic conditions.^[16]

Cardiovascular health

Loneliness affects acute physiological responses, including cardiac responses.^[17] Meta-analyses correlate poor social relationships with an increase of about 30% in the risk of each chronic heart disease and stroke.^[18] However, it seems that this association varies across populations and countries. For example, a meta-analysis of studies in Hispanic/Latin adults has confirmed the positive correlation between loneliness and CVD and metabolic disorders and added that loneliness, in general, correlates with comorbidities.^[19] This contrasts with a meta-analysis of studies in Australia and New Zealand, where no such significant association could be found in both adjusted and nonadjusted analyses.^[20] Further meta-analyses are required to map the associations across regions and countries worldwide.

In addition, loneliness after heart failure is detrimental and might lead to an increase in the risk of readmission. A meta-analysis of longitudinal studies has estimated that during an average of almost 1 year after heart failure, social isolation correlates with a more than 50% increased risk of readmission.^[21] Despite this significant fact, a recently published systematic review of 21 studies has underlined that the current interventions are ineffective in reducing loneliness in people with chronic heart failure and their caregivers.^[22] These findings call for a future line of research focused on interventions targeting loneliness during the critical period of post-heart failure.

Obesity

Obese people commonly report self-stigmatization. In particular, obese children and adolescents are among vulnerable populations to cyberbullying and also to the negative effects of the pandemic on health.^[8],[23] Individual studies correlate school closure during the pandemic with loneliness, body mass index, and obesity.^[24] However, there have been, in general, published a small number of studies investigating the association between loneliness and obesity, and the published results are inconsistent,^[25] so the issue largely remains unanswered until further studies, especially follow-up studies, examine this association and its casualty and potential sources of heterogeneity, i.e., culture and gender.

Cancer

Cancer therapy affects functioning in many aspects, especially social and psychological aspects. A systematic review of breast cancer survivors shows that younger women are more likely to feel lonely and socially isolated.^[26] A meta-analysis of 15 studies estimates that loneliness is, on average, to a moderate degree in cancer patients.^[27] Of note, none of the cancer-related factors, type, stage, etc., appear to affect the severity of loneliness, but the time-since-diagnosis of cancer, i.e., the longer the time the patients are aware of their disease, the higher the loneliness is severe.^[27] However, being unmarried and the unmet need for psychosocial support also positively correlate with loneliness severity in cancer patients.^[27] Cancer survivors are, therefore, a vulnerable population to experience “loss” unless close support is provided, encouraging them to participate actively in social gatherings, drinking, and eating.^[28] Despite these pieces of evidence, the health-care system is less able to provide patients with cancer access to effective interventions for loneliness alleviation.^[29]

Neuropsychological Health

Dementia

Meta-analyses findings are mixed, showing no and positive associations between loneliness and dementia risk.^{[30],[31],[32],[33]} However, most agree with a positive association and estimate the risk ratios between 1.26 and 1.58.^[30],[31] Particularly among older people, those with loneliness are at a higher risk of developing dementia than those without loneliness.^[33]

Cognitive impairment

Increased loneliness has been associated with decreased memory function and cognitive function.^[34],[35] Meta-analyses show that the effect of loneliness on memory function is exacerbated when it is combined with social isolation.^[34] Different domains of cognitive function, including general and global cognitive function and recall (immediate and delayed), might be influenced by loneliness.^[35] Of note, loneliness contributes as a risk factor to the development of minor depression in people with mild cognitive impairment, among whom nearly one per five develop minor depression.^[36]

Depression

Many studies have included both loneliness and depression in their review or analysis; however, less is paid to exploring the association between these two factors. A meta-analysis of 88 studies involving more than 40,000 people reports a moderate effect of loneliness on depressive symptoms.^[37] Particularly, in the elderly, a meta-analysis of longitudinal studies confirms the contribution of loneliness to the later development of depression, with odds ratios (ORs), estimated up to about 18.^[38] As well in children and adolescents, this effect is confirmed through a review of longitudinal studies measuring loneliness at the study entry and following depressive symptoms later in time between 3 months and 9 years.^[39]

There are meta-analyses of studies focusing on the effect of loneliness on depression during the COVID-19 pandemic. Depression peaked on May 20 and co-occurred with the peak of loneliness.^[5] Through a meta-analysis of 33 studies with a total of more than 131,000 people included, social restrictions have been found to increase both loneliness and depressive symptoms.^[40] In children and adolescents of 4–19 years (n = 65,508), the pooled depression prevalence was estimated at around 23% during the COVID-19 pandemic.^[8] The significant association between loneliness and depression in older people of 60 years or more is also confirmed through a meta-analysis of 11 studies.^[41]

From the few meta-analyses, it is possible to conclude that loneliness makes individuals susceptible to depression development in both young and older populations and in both pandemic and nonpandemic conditions.

Anxiety

Children and adolescents are one of the most documented populations in anxiety literature, possibly due to that the harm anxiety disorders might bring about to this special population would potentially influence their academic achievement, and later in time, this would be reflected in the rates of employment and therefore, job and life satisfaction and well-being. Both cross-sectional and longitudinal studies provide evidence that loneliness might make children and adolescents susceptible to developing anxiety symptoms.^[39],[42] On the other hand, those with anxiety disorders also report loneliness more than their counterparts without anxiety disorders.^[43] Like depression and loneliness, anxiety increased after the COVID-19 pandemic and peaked in May 2020.^[5] A meta-analysis of all studies estimates the anxiety prevalence amid the pandemic at around 20.7%.^[44] In children and adolescents, there was particularly a slightly increased prevalence (about 28%).^[8] In summary, a devastating loop governs loneliness and anxiety association. Interventions are required to target this loop, especially in young people and during the pandemic condition.

Suicide

Suicidal ideation and behavior highly correlate with loneliness. This correlation has been confirmed in reviews of studies of older people, especially older people who are long-term care residents and older people who have depression.^[45],[46] A pooled analysis of almost 63,000 individuals estimates that between 19 and 65 per 100,000 older people self-harm.^[47] Older people who harm themselves express a few motivations, and loneliness is one of them, along with aging, perceived burdensomeness, and loss of control. Furthermore, a meta-analysis of 22 studies confirms loneliness as a predictor of suicidal ideation and behavior and shows that depression has a mediatory effect on this correlation and that women, older people, and adolescents aged 16–20 years are the most susceptible populations.^[48] In a meta-analysis of studies on children and adolescents, loneliness has been affirmed as a risk factor for cyberbullying, which is, in turn, a risk factor for suicidal behavior and self-harm.^[23]

Another era paving the way for these two modern pandemics, loneliness, and suicide, to synergistically exacerbate each other effect was the COVID-19 pandemic, a third pandemic. Studies have identified loneliness as a risk factor for suicidal ideation during the COVID-19 pandemic.^[49],[50] However, the effect sizes derived from a meta-analysis of studies involving more than 70,000 people and investigating the contribution of lockdowns to loneliness and suicide are not significant.^[51] This implies the potential role of the people's resilience in combatting the negative effects of lockdown.

Another line of research noteworthy mentioning here is that loneliness and suicidal thoughts are commonly reported as the motivation for frequently calling Helplines in frequent callers.^[52] The efforts are necessary to target the pathology behind frequently calling, i.e., loneliness and suicidal thoughts, instead of investing in reducing/blocking these calls. Helpline responders should care that these frequent callers even have not had a person to call them to speak with. Responsible managers must provide suitable and adequate services for these responders to be effectively patient at their posts.

Frailty

Frailty is not a unidimensional concept but involves social, physical, and other aspects. Instruments used for social frailty, in turn, include different measurements related to social activities, networks, and support, as well as loneliness.^[53] When investigating the causes behind emergency department-seeking behavior in older people, three categories of risk factors were identified: predisposing, enabling, and health-related factors, where loneliness is a predisposing factor and frailty is a health factor.^[54] A meta-analysis comparing loneliness scores between older people of three physical frailty severity categories could correlate the highest loneliness scores with the highest frailty.^[55] Furthermore, through a meta-analysis of two longitudinal studies that provided baseline loneliness scores and frailty at follow-up,^[55] it could be possible to conclude that the more one is lonely, the higher the odds they have of becoming physically frail. These lines show the importance of loneliness interventions in older people, especially those who are long-term care residents,^[45] for frailty prevention.

Substance use

Loneliness commonly occurs in people with substance use disorders (SUDs). Loneliness and substance use are both risk factors contributing to poor mental health, self-harm, and suicidal behaviors. Their contribution to these negative outcomes has been reported in all age groups, for example, children, adolescents, adults, and the elderly.^[23],[46] However, the most critical population being affected is the elderly: elderly men are, due to their specific age group, predisposed to loneliness, and SUDs are the most mental health issues after mood disorders in this group;^[56],[57] older women living with HIV are, due to the stigmatization, prone to loneliness, and frequently report SUDs.^[58] Interventions to reduce/prevent loneliness are therefore required to apply to vulnerable non-SUD populations to prevent SUDs and also to SUD populations not to add loneliness to the negative influence of SUDs. Despite these facts, no specific measurement and effective intervention for loneliness in people with SUDs has been made available.^[59]

Addiction to social media use, gaming, and the internet

Social media, the Internet, and games have unlimited uses, for example, being connected to and communicating with other people, sharing information, searching to prepare assignments, and having fun; however, there is a determined expectation for using them – meeting the actual needs. When being online on different social media and gaming become addictive behaviors, the observation of concurrent mental health issues exceeds our expectations. Loneliness is not an exception. Meta-analyses have associated loneliness with problematic social media use, addiction to Facebook, gaming disorder, and internet addiction.^{[60],[61],[62],[63]} In the era of gaming, meta-analyses show inconsistent results; participation in video games, in particular, correlates with loneliness in this meta-analysis;^[64] however, in another meta-analysis, playing video games, in particular, augmented reality and online multiplayer games, showed an inverse effect, i.e., it was found to alleviate loneliness.^[65] The difference between these two analyses is that the latter, not the former, included studies exclusively conducted in the COVID-19 pandemic world, where the stress and pressure are different from previous and might cause ambiguities to the sense we called loneliness previously, and the current measurements of loneliness seem to not work well, differentiating loneliness and many other intertwined concepts.

Interventions

Loneliness interventions are different, and their one-by-one inclusion is not possible due to space limitations here. At a glance, older people are the most critical target group of loneliness interventions, if not the largest. On the other hand, nowadays, digital technologies constitute one of the main categories of loneliness interventions. We are, therefore, to overview interventions for these specific categories.

Older people

Systematic reviews published in recent years (between 2015 and 2020) could gather 15–18 loneliness interventions for older people, in general, or specifically for those who live in long-term care homes.^[66],[67] This situation is, of course, better than what was in the 2000s, when there was a very paucity of effective interventions, as declared in a systematic review.^[68] Despite advances in the number, the effectiveness of these interventions is variable, and systematic reviews could not even address this variability: in a systematic review of 18 interventions, more than 40% of interventions (10/18) appeared not effective,^[66] whereas another systematic review of 15 interventions, the proportion of unsuccessful interventions decreased to <20% (2/15).^[67] The former review also highlights that individually delivered interventions might be abler to alleviate loneliness/social isolation than interventions delivered at the group level than those with a mixed mode of delivery (100% vs. 54.5% vs. 25%).^[66] The latter review included solely studies of people living in long-term care homes and underlined three interventions as the best ones, which include laughter therapy, horticulture therapy, and reminiscence therapy.^[67]

Which level of intervention delivery is more effective appears to rely on the cultural background. As mentioned above, the individual interventions appear better in a systematic review of studies irrespective of their country of residence.^[66] In addition, in a systematic review of 13 randomized controlled trials, the superiority of individual interventions was confirmed, along with addressing whether remotely delivered interventions can help older people alleviate loneliness as the primary objective.^[69] Effect sizes ranging from -1.01 to -0.32 derived from overall and subgroup meta-analyses have indicated that remotely delivered interventions could significantly contribute to loneliness reduction and that the significance of this contribution depends on the media type, intervention strategy, format, and participant status of living.^[69] In the subgroup analysis by format, the response, i.e., loneliness reduction, to individual-based interventions was significant.^[69] In contrast, a systematic review of 34 studies on older people in China confirms the efficacy of interventions to reduce loneliness with an estimated effect size of about 0.84 and adds that group-based interventions work better in this context.^[70]

Social networking sites' usage

In the era of social networking site (SNS) usage and in line with the fact that social media offer online support, individual studies included in the review^[71] report that online social support could alleviate loneliness. On the other hand, numerous meta-analyses investigating the association between SNS use and loneliness have shown paradoxical findings. The most recent one, including 82 studies and more than 48,000 participants, shows a direct association between SNS and loneliness.^[72] This is consistent with the other meta-analysis of 67 studies, including almost 20,000 subjects: SNS usage time correlates, though weakly, with loneliness.^[73] In contrast, two meta-analyses that included a subset of studies – one included studies of older people^[74] and the other included studies of people with depression and anxiety^[75] – have found a reverse association, indicating that SNS usage is related to loneliness improvement. Whether this finding is a biased estimation lying in the small number of included studies or is a correct estimation and its difference compared to the two general meta-analyses of all studies might be then attributed to the specific population of included studies. The implication of the latter hypothesis is that vulnerable populations might benefit from SNS, which along with the former hypothesis, warrants further research.

Digital technologies

Digital technologies have been frequently used as interventions for loneliness in older people. The investigated technologies mainly included assistive technologies for communication, such as information communication technologies (ICT), robot, videoconferencing equipment, devices for people with speech impairment, and miscellaneous.^[76] These assistive devices, which have been shown to be welcomed by both older people with and without communication-affecting conditions, can enhance the capability of older people to communicate and reduce social isolation through different mechanisms. For example, ICT provides a positive way of connecting to the outside world, being socially supported, speaking about self-interests and following them, and therefore improving self-confidence.^[77] Unfortunately, technologies seem to not operate well in real-life yet. In qualitative reviews, most of the included individual studies report positive effects of these technologies and related interventions on reducing social isolation and loneliness and increasing well-being.^[78],[79] However, some studies show that these effects are at most short-term, and also studies that show no such effect or even show a negative effect.^[77]

To pool the inconsistent results, meta-analyses have been conducted on studies of different focuses: older adults with or without dementia and older adults with dementia, and have shown no effect of digital technologies in general or specifically ICT on loneliness at 3–6 months after the intervention administration, which at least took 3 months, was completed.^{[80],[81],[82]} However, the available studies suffer from low quality, with less than ten randomized-controlled trials have been made available to date, calling for further well-designed studies to address the issue. Furthermore, meta-analyses are being conducted on studies of older adults who are long-term care residents in general and specifically older adults who are long-term care residents during the COVID-19 pandemic, with protocols available here^[83],[84] but results unavailable when preparing this article.

In addition to older people, digital technology interventions for loneliness apply to other populations like young adults.^[85] More interesting is, however, the application of these technologies for the primary objective of education. Importantly, the COVID-19 pandemic has caused a shift in teaching and learning platforms to be more remote and computerized than before.^[86] When offering such technologies in the era of higher education, the consideration of a very threat is crucial to prevent loneliness. Higher education people are young adults with the need to connect to others, attend to the community, and interact with their teacher/supervisor – the needs that might be principal more than education and should be taken seriously by digital technologies designers and implementers.

Place-based interventions

These interventions have been of interest for mental health improvement, interestingly, loneliness. They mainly include community facilities, green spaces, and housing regeneration. A general systematic review has declared that these interventions would be helpful with no noticeable harm.^[87] A meta-analysis of 22 studies has recently been published, specifically examining the effects of green spaces on loneliness-related measures.^[88] Of 132 examined associations, about 70% agree with green spaces' protective effect against loneliness. In this meta-analysis, an integrated narrative synthesis was also performed, revealing that loneliness mediates the positive influence of green spaces on well-being and that different factors at different levels, including individual, relationship, and collective levels, play a role in determining the efficacy of green spaces.

Conclusion

Due to limited space, it was not possible to deal with all issues surrounding loneliness and health. Some of those unaddressed issues are briefed as follows:

Youth-specific interventions

It is, in general, thought that youth are more likely to experience transient loneliness rather than chronic loneliness. For this, interventions for loneliness reduction in youth mostly target those who are known as high-risk populations, for example, being diagnosed with a medical condition.^[89],[90] But what about those, even not substantial, youth populations with chronic loneliness? How much could this population serve the world if they were not lonely? Interventions are necessary to not leave the youth alone with loneliness – to save all of them with equity successfully.

Pandemic-specific interventions

During COVID-19, yoga, meditation, and mindfulness-based interventions were frequently proposed to fight the negative impact of related restrictions on loneliness.^[91],[92] Moreover, the power of arts, including painting, dancing, and music were pronounced for children and adolescents, whose many needs were unmet due to school closure.^[93] Despite all of these alternative options, it took a long for many community people to cope with huge stress like COVID-19. The reason is clear: we were not prepared, so we could not be competent to take care of ourselves. The lack of competency caused people to experience the peak of loneliness and other mental disorders, as reviewed in the text of the manuscript. Pandemic-specific interventions are, therefore, necessary, as well.

Behind the scenes-specific interventions

Informal caregivers are those who remain faithful in taking care of their dears behind the scenes, while are not observable to other people, and they are very susceptible to loneliness. In particular, informal caregivers of older men, patients with cancer, and chronic heart failure report high levels of loneliness.^{[22],[94],[95],[96],[97]} As reviewed in,^[22] behavioral interventions mostly failed to rescue this population from loneliness, indicating the need for interventions to target what we call it faithfulness-associated loneliness specifically.

Miscellaneous

loneliness is concerning in other special populations, including people with intellectual and neurodevelopmental disorders, such as autism, people with psychosis, pregnant women, and people with visual and hearing problems.^{[42],[98],[99],[100],[101],[102],[103],[104],[105]} These people also need interventions.

Social support, social prescribing, and peer support are at the top of treatment strategies used in loneliness interventions. Social robots and pets and robots/animals-based interventions are among the modern protocols becoming increasingly popular in the literature.^{[106],[107],[108],[109],[110],[111]} However, the failure of these interventions to confer benefit to all people in the long-term implies that the pathology of loneliness is probably variable, and this variability makes loneliness complex up to that it is, on some occasions, difficult to suppose it as a state. Indeed, we are facing a condition that is evolving in resistance to therapy. This calls for the need for personalized medicine of loneliness to rejuvenate many senses, from the sense of purpose, belonging, and meaning to affiliation and connectedness, which will be otherwise missed.

In addition to the population-specific social barriers, there are barriers affecting socialization dynamics in the general population, including poverty, racism, and discriminatory gender norms, to name a few. To briefly exemplify the devastating feedback loop between only one of such barriers and loneliness, suppose poverty. Poverty is a state of socioeconomic deprivation characterized by the presence of multiple obstacles to communal living, including but not limited to food insecurity, health disparities, and housing instability, all of which disadvantage both children and adults in a variety of ways, academically, educationally, socially, and economically. Therefore, addressing loneliness on a societal scale will require an integrated scientific approach that takes into account all these factors simultaneously and efficiently.

Ethical statement

The ethical statement is not applicable for this article.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Gardiner C, Laud P, Heaton T, Gott M. What is the prevalence of loneliness amongst older people living in residential and nursing care homes? A systematic review and meta-analysis. Age Ageing 2020;49:748-57.
2.	Chawla K, Kunonga TP, Stow D, Barker R, Craig D, Hanratty B. Prevalence of loneliness amongst older people in high-income countries: A systematic review and meta-analysis. PLoS One 2021;16:e0255088.
3.	Gao Q, Prina AM, Prince M, Acosta D, Luisa Sosa A, Guerra M, et al. Loneliness among older adults in latin America, China, and India: Prevalence, correlates and association with mortality. Int J Public Health 2021;66:604449.
4.	Surkalim DL, Luo M, Eres R, Gebel K, van Buskirk J, Bauman A, et al. The prevalence of loneliness across 113 countries: Systematic review and meta-analysis. BMJ 2022;376:e067068.
5.	Cénat JM, Farahi SM, Dalexis RD, Darius WP, Bekarkhanechi FM, Poisson H, et al. The global evolution of mental health problems during the COVID-19 pandemic: A systematic review and meta-analysis of longitudinal studies. J Affect Disord 2022;315:70-95.
6.	Su Y, Rao W, Li M, Caron G, D'Arcy C, Meng X. Prevalence of loneliness and social isolation among older adults during the COVID-19 pandemic: A systematic review and meta-analysis. International Psychogeriatrics, 1-13. doi:10.1017/S1041610222000199.
7.	Kauhanen L, Wan Mohd Yunus WM, Lempinen L, Peltonen K, Gyllenberg D, Mishina K, et al. A systematic review of the mental health changes of children and young people before and during the COVID-19 pandemic. Eur Child Adolesc Psychiatry (2022). https://doi.org/10.1007/s00787-022-02060-0.
8.	Theberath M, Bauer D, Chen W, Salinas M, Mohabbat AB, Yang J, et al. Effects of COVID-19 pandemic on mental health of children and adolescents: A systematic review of survey studies. SAGE Open Med 2022;10:20503121221086712.
9.	Park C, Majeed A, Gill H, Tamura J, Ho RC, Mansur RB, et al. The effect of loneliness on distinct health outcomes: A Comprehensive review and meta-analysis. Psychiatry Res 2020;294:113514.
10.	Rico-Uribe LA, Caballero FF, Martín-María N, Cabello M, Ayuso-Mateos JL, Miret M. Association of loneliness with all-cause mortality: A meta-analysis. PLoS One 2018;13:e0190033.
11.	Jami ES, Hammerschlag AR, Ip HF, Allegrini AG, Benyamin B, Border R, et al. Genome-wide association meta-analysis of childhood and adolescent internalizing symptoms. J Am Acad Child Adolesc Psychiatry 2022;61:934-45.
12.	Lam JA, Murray ER, Yu KE, Ramsey M, Nguyen TT, Mishra J, et al. Neurobiology of loneliness: A systematic review. Neuropsychopharmacology 2021;46:1873-87.
13.	Smith KJ, Gavey S, RIddell NE, Kontari P, Victor C. The association between loneliness, social isolation and inflammation: A systematic review and meta-analysis. Neurosci Biobehav Rev 2020;112:519-41.
14.	Pourriyahi H, Yazdanpanah N, Saghazadeh A, Rezaei N. Loneliness: An immunometabolic syndrome. Int J Environ Res Public Health 2021;18:12162.
15.	Pourriyahi H, Saghazadeh A, Rezaei N. Altered immunoemotional regulatory system in COVID-19: From the origins to opportunities. J Neuroimmunol 2021;356:577578.
16.	Petitte T, Mallow J, Barnes E, Petrone A, Barr T, Theeke L. A systematic review of loneliness and common chronic physical conditions in adults. Open Psychol J 2015;8:113-32.
17.	Brown EG, Gallagher S, Creaven AM. Loneliness and acute stress reactivity: A systematic review of psychophysiological studies. Psychophysiology 2018;55:e13031.
18.	Valtorta NK, Kanaan M, Gilbody S, Ronzi S, Hanratty B. Loneliness and social isolation as risk factors for coronary heart disease and stroke: Systematic review and meta-analysis of longitudinal observational studies. Heart 2016;102:1009-16.
19.	Tibiriçá L, Jester DJ, Jeste DV. A systematic review of loneliness and social isolation among Hispanic/Latinx older adults in the United States. Psychiatry Res 2022;313:114568.
20.	Freak-Poli R, Phyo AZ, Hu J, Barker SF. Are social isolation, lack of social support or loneliness risk factors for cardiovascular disease in Australia and New Zealand? A systematic review and meta-analysis. Health Promot J Austr 2022;33 Suppl 1:278-315.
21.	Heidari Gorji MA, Fatahian A, Farsavian A. The impact of perceived and objective social isolation on hospital readmission in patients with heart failure: A systematic review and meta-analysis of observational studies. Gen Hosp Psychiatry 2019;60:27-36.
22.	Suthershinii G, Tan WA, Lee AR, Chen MZ. Behavioral interventions for the patient-caregiver unit in patients with chronic heart failure: A systematic review of caregiver outcomes. J Multidiscip Healthc 2022;15:921-39.
23.	Dorol-Beauroy-Eustache O, Mishara BL. Systematic review of risk and protective factors for suicidal and self-harm behaviors among children and adolescents involved with cyberbullying. Prev Med 2021;152:106684.
24.	Chaabane S, Doraiswamy S, Chaabna K, Mamtani R, Cheema S. The impact of COVID-19 school closure on child and adolescent health: A rapid systematic review. Children (Basel) 2021;8:415.
25.	Hajek A, Kretzler B, König HH. The association between obesity and social isolation as well as loneliness in the adult population: A systematic review. Diabetes Metab Syndr Obes 2021;14:2765-73.
26.	Campbell-Enns H, Woodgate R. The psychosocial experiences of women with breast cancer across the lifespan: A systematic review protocol. JBI Database System Rev Implement Rep 2015;13:112-21.
27.	Deckx L, van den Akker M, Buntinx F. Risk factors for loneliness in patients with cancer: A systematic literature review and meta-analysis. Eur J Oncol Nurs 2014;18:466-77.
28.	Dornan M, Semple C, Moorhead A, McCaughan E. A qualitative systematic review of the social eating and drinking experiences of patients following treatment for head and neck cancer. Support Care Cancer 2021;29:4899-909.
29.	McElfresh JJ, Skiba MB, Segrin CG, Badger TA, Crane TE, Crist JD, et al. Interventions for loneliness among adult cancer survivors: A systematic review and meta-analysis. J Psychosoc Oncol 2021;39:509-33.
30.	Lara E, Martín-María N, De la Torre-Luque A, Koyanagi A, Vancampfort D, Izquierdo A, et al. Does loneliness contribute to mild cognitive impairment and dementia? A systematic review and meta-analysis of longitudinal studies. Ageing Res Rev 2019;52:7-16.
31.	Kuiper JS, Zuidersma M, Oude Voshaar RC, Zuidema SU, van den Heuvel ER, Stolk RP, et al. Social relationships and risk of dementia: A systematic review and meta-analysis of longitudinal cohort studies. Ageing Res Rev 2015;22:39-57.
32.	Penninkilampi R, Casey AN, Singh MF, Brodaty H. The association between social engagement, loneliness, and risk of dementia: A systematic review and meta-analysis. J Alzheimers Dis 2018;66:1619-33.
33.	Lazzari C, Rabottini M. COVID-19, loneliness, social isolation and risk of dementia in older people: A systematic review and meta-analysis of the relevant literature. Int J Psychiatry Clin Pract 2022;26:196-207.
34.	Kang JW, Oremus M. Examining the combined effects of social isolation and loneliness on memory: A systematic review. Arch Gerontol Geriatr 2022;104:104801.
35.	Boss L, Kang DH, Branson S. Loneliness and cognitive function in the older adult: A systematic review. Int Psychogeriatr 2015;27:541-53.
36.	Polyakova M, Sonnabend N, Sander C, Mergl R, Schroeter ML, Schroeder J, et al. Prevalence of minor depression in elderly persons with and without mild cognitive impairment: A systematic review. J Affect Disord 2014;152-154:28-38.
37.	Erzen E, Çikrikci Ö. The effect of loneliness on depression: A meta-analysis. Int J Soc Psychiatry 2018;64:427-35.
38.	Van As BA, Imbimbo E, Franceschi A, Menesini E, Nocentini A. The longitudinal association between loneliness and depressive symptoms in the elderly: A systematic review. Int Psychogeriatr 2022;34:657-69.
39.	Loades ME, Chatburn E, Higson-Sweeney N, Reynolds S, Shafran R, Brigden A, et al. Rapid systematic review: The impact of social isolation and loneliness on the mental health of children and adolescents in the context of COVID-19. J Am Acad Child Adolesc Psychiatry 2020;59:1218-39.e3.
40.	Knox L, Karantzas GC, Romano D, Feeney JA, Simpson JA. One year on: What we have learned about the psychological effects of COVID-19 social restrictions: A meta-analysis. Curr Opin Psychol 2022;46:101315.
41.	Ciuffreda G, Cabanillas-Barea S, Carrasco-Uribarren A, Albarova-Corral MI, Argüello-Espinosa MI, Marcén-Román Y. Factors associated with depression and anxiety in adults ≥60 years old during the COVID-19 pandemic: A systematic review. Int J Environ Res Public Health 2021;18:11859.
42.	Hards E, Loades ME, Higson-Sweeney N, Shafran R, Serafimova T, Brigden A, et al. Loneliness and mental health in children and adolescents with pre-existing mental health problems: A rapid systematic review. Br J Clin Psychol 2022;61:313-34.
43.	de Lijster JM, Dieleman GC, Utens EM, Dierckx B, Wierenga M, Verhulst FC, et al. Social and academic functioning in adolescents with anxiety disorders: A systematic review. J Affect Disord 2018;230:108-17.
44.	Leung CM, Ho MK, Bharwani AA, Cogo-Moreira H, Wang Y, Chow MS, et al. Mental disorders following COVID-19 and other epidemics: A systematic review and meta-analysis. Transl Psychiatry 2022;12:205.
45.	Lapane KL, Lim E, McPhillips E, Barooah A, Yuan Y, Dube CE. Health effects of loneliness and social isolation in older adults living in congregate long term care settings: A systematic review of quantitative and qualitative evidence. Arch Gerontol Geriatr 2022;102:104728.
46.	Fernandez-Rodrigues V, Sanchez-Carro Y, Lagunas LN, Rico-Uribe LA, Pemau A, Diaz-Carracedo P, et al. Risk factors for suicidal behaviour in late-life depression: A systematic review. World J Psychiatry 2022;12:187-203.
47.	Troya MI, Babatunde O, Polidano K, Bartlam B, McCloskey E, Dikomitis L, et al. Self-harm in older adults: Systematic review. Br J Psychiatry 2019;214:186-200.
48.	McClelland H, Evans JJ, Nowland R, Ferguson E, O'Connor RC. Loneliness as a predictor of suicidal ideation and behaviour: A systematic review and meta-analysis of prospective studies. J Affect Disord 2020;274:880-96.
49.	Farooq S, Tunmore J, Wajid Ali M, Ayub M. Suicide, self-harm and suicidal ideation during COVID-19: A systematic review. Psychiatry Res 2021;306:114228.
50.	Dos Santos ER, Silva de Paula JL, Tardieux FM, Costa-E-Silva VN, Lal A, Leite AF. Association between COVID-19 and anxiety during social isolation: A systematic review. World J Clin Cases 2021;9:7433-44.
51.	Prati G, Mancini AD. The psychological impact of COVID-19 pandemic lockdowns: A review and meta-analysis of longitudinal studies and natural experiments. Psychol Med 2021;51:201-11.
52.	Mishara BL, Côté LP, Dargis L. Systematic review of research and interventions with frequent callers to suicide prevention helplines and crisis centers. Crisis 2022; [doi: 10.1027/0227-5910/a000838].
53.	Bessa B, Ribeiro O, Coelho T. Assessing the social dimension of frailty in old age: A systematic review. Arch Gerontol Geriatr 2018;78:101-13.
54.	Tang XR, Pek PP, Siddiqui FJ, Malhotra R, Kwan YH, Tiah L, et al. Determinants of emergency department utilisation by older adults in Singapore: A systematic review. Ann Acad Med Singap 2022;51:170-9.
55.	Kojima G, Taniguchi Y, Aoyama R, Tanabe M. Associations between loneliness and physical frailty in community-dwelling older adults: A systematic review and meta-analysis. Ageing Res Rev 2022;81:101705.
56.	Boumans J, van de Mheen D, Crutzen R, Dupont H, Bovens R, Rozema A. Understanding how and why alcohol interventions prevent and reduce problematic alcohol consumption among older adults: A systematic review. Int J Environ Res Public Health 2022;19:3188.
57.	Ribeiro GC, Vieira WA, Herval ÁM, Rodrigues RP, Agostini BA, Flores-Mir C, et al. Prevalence of mental disorders among elderly men: A systematic review and meta-analysis. Sao Paulo Med J 2020;138:190-200.
58.	Rubtsova AA, Kempf MC, Taylor TN, Konkle-Parker D, Wingood GM, Holstad MM. Healthy aging in older women living with HIV infection: A systematic review of psychosocial factors. Curr HIV/AIDS Rep 2017;14:17-30.
59.	Ingram I, Kelly PJ, Deane FP, Baker AL, Goh MC, Raftery DK, et al. Loneliness among people with substance use problems: A narrative systematic review. Drug Alcohol Rev 2020;39:447-83.
60.	Rajesh T, Rangaiah B. Relationship between personality traits and facebook addiction: A meta-analysis. Heliyon 2022;8:e10315.
61.	Yoon S, Yang Y, Ro E, Ahn WY, Kim J, Shin SH, et al. Reliability, and convergent and discriminant validity of gaming disorder scales: A meta-analysis. Front Psychol 2021;12:764209.
62.	Mozafar Saadati H, Mirzaei H, Okhovat B, Khodamoradi F. Association between internet addiction and loneliness across the world: A meta-analysis and systematic review. SSM Popul Health 2021;16:100948.
63.	Huang C. A meta-analysis of the problematic social media use and mental health. Int J Soc Psychiatry 2022;68:12-33.
64.	Luo Y, Moosbrugger M, Smith DM, France TJ, Ma J, Xiao J. Is increased video game participation associated with reduced sense of loneliness? A systematic review and meta-analysis. Front Public Health 2022;10:898338.
65.	Pallavicini F, Pepe A, Mantovani F. The effects of playing video games on stress, anxiety, depression, loneliness, and gaming disorder during the early stages of the COVID-19 pandemic: PRISMA systematic review. Cyberpsychol Behav Soc Netw 2022;25:334-54.
66.	Poscia A, Stojanovic J, La Milia DI, Duplaga M, Grysztar M, Moscato U, et al. Interventions targeting loneliness and social isolation among the older people: An update systematic review. Exp Gerontol 2018;102:133-44.
67.	Quan NG, Lohman MC, Resciniti NV, Friedman DB. A systematic review of interventions for loneliness among older adults living in long-term care facilities. Aging Ment Health 2020;24:1945-55.
68.	Sander R. Preventing social isolation and loneliness among older people: A systematic review of health promotion interventions. Nurs Older People 2005;17:40.
69.	Fu Z, Yan M, Meng C. The effectiveness of remote delivered intervention for loneliness reduction in older adults: A systematic review and meta-analysis. Front Psychol 2022;13:935544.
70.	Li J, Zhou X, Wang Q. Interventions to reduce loneliness among Chinese older adults: A network meta-analysis of randomized controlled trials and quasi-experimental studies. Appl Psychol Health Well Being 2022; [doi: 10.1111/aphw. 12375].
71.	Zhou Z, Cheng Q. Relationship between online social support and adolescents' mental health: A systematic review and meta-analysis. J Adolesc 2022;94:281-92.
72.	Zhang L, Li C, Zhou T, Li Q, Gu C. Social networking site use and loneliness: A meta-analysis. J Psychol 2022;156:492-511.
73.	Huang C. Time spent on social network sites and psychological well-being: A meta-analysis. Cyberpsychol Behav Soc Netw 2017;20:346-54.
74.	Wiwatkunupakarn N, Pateekhum C, Aramrat C, Jirapornchaoren W, Pinyopornpanish K, Angkurawaranon C. Social networking site usage: A systematic review of its relationship with social isolation, loneliness, and depression among older adults. Aging Ment Health 2022;26:1318-26.
75.	Seabrook EM, Kern ML, Rickard NS. Social networking sites, depression, and anxiety: A systematic review. JMIR Ment Health 2016;3:e50.
76.	Pedrozo Campos Antunes T, Souza Bulle de Oliveira A, Hudec R, Brusque Crocetta T, Ferreira de Lima Antão JY, de Almeida Barbosa RT, et al. Assistive technology for communication of older adults: A systematic review. Aging Ment Health 2019;23:417-27.
77.	Chen YR, Schulz PJ. The effect of information communication technology interventions on reducing social isolation in the elderly: A systematic review. J Med Internet Res 2016;18:e18.
78.	Ibarra F, Baez M, Cernuzzi L, Casati F. A systematic review on technology-supported interventions to improve old-age social wellbeing: Loneliness, social isolation, and connectedness. J Healthc Eng 2020;2020:2036842.
79.	Rai HK, Kernaghan D, Schoonmade L, Egan K, Pot AM. Digital technologies to prevent social isolation and loneliness in dementia: A systematic review. J Alzheimers Dis 2022; [doi: 10.3233/JAD-220438].
80.	Jin W, Liu Y, Yuan S, Bai R, Li X, Bai Z. The effectiveness of technology-based interventions for reducing loneliness in older adults: A systematic review and meta-analysis of randomized controlled trials. Front Psychol 2021;12:711030.
81.	Heins P, Boots LM, Koh WQ, Neven A, Verhey FR, de Vugt ME. The effects of technological interventions on social participation of community-dwelling older adults with and without dementia: A systematic review. J Clin Med 2021;10:2308.
82.	Shah SG, Nogueras D, van Woerden HC, Kiparoglou V. Evaluation of the effectiveness of digital technology interventions to reduce loneliness in older adults: Systematic review and meta-analysis. J Med Internet Res 2021;23:e24712.
83.	Macdonald M, Weeks L, Moody E, Martin-Misener R, Iduye D, States C, et al. Experiences of residents in long-term-care homes with socially assistive technologies and the effectiveness of these technologies: A mixed methods systematic review protocol. JBI Evid Synth 2022; [doi: 10.11124/JBIES-21-00409].
84.	Beogo I, Sia D, Tchouaket Nguemeleu E, Zhao J, Gagnon MP, Etowa J. Strengthening social capital to address isolation and loneliness in long-term care facilities during the COVID-19 pandemic: Protocol for a systematic review of research on information and communication technologies. JMIR Res Protoc 2022;11:e36269.
85.	Shah SG, Nogueras D, van Woerden H, Kiparoglou V. Effectiveness of digital technology interventions to reduce loneliness in adults: A protocol for a systematic review and meta-analysis. BMJ Open 2019;9:e032455.
86.	Hehir E, Zeller M, Luckhurst J, Chandler T. Developing student connectedness under remote learning using digital resources: A systematic review. Educ Inf Technol (Dordr) 2021;26:6531-48.
87.	Hsueh YC, Batchelor R, Liebmann M, Dhanani A, Vaughan L, Fett AK, et al. A systematic review of studies describing the effectiveness, acceptability, and potential harms of place-based interventions to address loneliness and mental health problems. Int J Environ Res Public Health 2022;19:4766.
88.	Astell-Burt T, Hartig T, Putra IG, Walsan R, Dendup T, Feng X. Green space and loneliness: A systematic review with theoretical and methodological guidance for future research. Sci Total Environ 2022;847:157521.
89.	Eccles AM, Qualter P. Review: Alleviating loneliness in young people – A meta-analysis of interventions. Child Adolesc Ment Health 2021;26:17-33.
90.	Osborn T, Weatherburn P, French RS. Interventions to address loneliness and social isolation in young people: A systematic review of the evidence on acceptability and effectiveness. J Adolesc 2021;93:53-79.
91.	Bursky M, Kosuri M, Walsh Carson K, Babad S, Iskhakova A, Nikulina V. The utility of meditation and mindfulness-based interventions in the time of COVID-19: A theoretical proposition and systematic review of the relevant prison, quarantine and lockdown literature. Psychol Rep 2021;332941211048734.
92.	Kuru Alici N, Arikan Dönmez A. A systematic review of the effect of laughter yoga on physical function and psychosocial outcomes in older adults. Complement Ther Clin Pract 2020;41:101252.
93.	Rezaei N, Vahed A, Ziaei H, Bashari N, Afkham SA, Bahrami F, et al. Health and Art (HEART): Integrating science and art to fight COVID-19. Adv Exp Med Biol 2021;1318:937-64.
94.	Fee A, McIlfatrick S, Ryan A. Examining the support needs of older male spousal caregivers of people with a long-term condition: A systematic review of the literature. Int J Older People Nurs 2020;15:e12318.
95.	Hajek A, Kretzler B, König HH. Informal caregiving, loneliness and social isolation: A systematic review. Int J Environ Res Public Health 2021;18:12101.
96.	Hajek A, Kretzler B, König HH. Informal caregiving for adults, loneliness and social isolation: A study protocol for a systematic review. BMJ Open 2021;11:e044902.
97.	Piil K, Nordentoft S, Larsen A, Jarden M. Bereaved caregivers of patients with high-grade glioma: A systematic review. BMJ Support Palliat Care 2019;9:26-33.
98.	Umagami K, Remington A, Lloyd-Evans B, Davies J, Crane L. Loneliness in autistic adults: A systematic review. Autism 2022;26:2117-35.
99.	Alexandra P, Angela H, Ali A. Loneliness in people with intellectual and developmental disorders across the lifespan: A systematic review of prevalence and interventions. J Appl Res Intellect Disabil 2018;31:643-58.
100.	Isaacs NZ, Andipatin MG. A systematic review regarding women's emotional and psychological experiences of high-risk pregnancies. BMC Psychol 2020;8:45.
101.	Chau AK, Zhu C, So SH. Loneliness and the psychosis continuum: A meta-analysis on positive psychotic experiences and a meta-analysis on negative psychotic experiences. Int Rev Psychiatry 2019;31:471-90.
102.	Lim MH, Gleeson JF, Alvarez-Jimenez M, Penn DL. Loneliness in psychosis: A systematic review. Soc Psychiatry Psychiatr Epidemiol 2018;53:221-38.
103.	van der Aa HP, Margrain TH, van Rens GH, Heymans MW, van Nispen RM. Psychosocial interventions to improve mental health in adults with vision impairment: Systematic review and meta-analysis. Ophthalmic Physiol Opt 2016;36:584-606.
104.	Shukla A, Harper M, Pedersen E, Goman A, Suen JJ, Price C, et al. Hearing loss, loneliness, and social isolation: A systematic review. Otolaryngol Head Neck Surg 2020;162:622-33.
105.	Smith IC, White SW. Socio-emotional determinants of depressive symptoms in adolescents and adults with autism spectrum disorder: A systematic review. Autism 2020;24:995-1010.
106.	Abbott R, Orr N, McGill P, Whear R, Bethel A, Garside R, et al. How do “robopets” impact the health and well-being of residents in care homes? A systematic review of qualitative and quantitative evidence. Int J Older People Nurs 2019;14:e12239.
107.	Bemelmans R, Gelderblom GJ, Jonker P, de Witte L. Socially assistive robots in elderly care: A systematic review into effects and effectiveness. J Am Med Dir Assoc 2012;13:114-20.e1.
108.	Pu L, Moyle W, Jones C, Todorovic M. The effectiveness of social robots for older adults: A systematic review and meta-analysis of randomized controlled studies. Gerontologist 2019;59:e37-51.
109.	Jain B, Syed S, Hafford-Letchfield T, O'Farrell-Pearce S. Dog-assisted interventions and outcomes for older adults in residential long-term care facilities: A systematic review and meta-analysis. Int J Older People Nurs 2020;15:e12320.
110.	Clements H, Valentin S, Jenkins N, Rankin J, Baker JS, Gee N, et al. The effects of interacting with fish in aquariums on human health and well-being: A systematic review. PLoS One 2019;14:e0220524.
111.	Purewal R, Christley R, Kordas K, Joinson C, Meints K, Gee N, et al. Companion animals and child/adolescent development: A systematic review of the evidence. Int J Environ Res Public Health 2017;14:234.