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Perspect Psychol Sci. 2015 March ; 10(2): 238–249. doi:10.1177/1745691615570616.

Loneliness: Clinical Import and Interventions

Stephanie Cacioppo1,2, Angela J. Grippo3, Sarah London2,4, Luc Goossens5, and John T.
Cacioppo2,4
1Department of Psychiatry and Behavioral Neuroscience, The University of Chicago
2HPEN Laboratory, Center for Cognitive and Social Neuroscience, The University of Chicago
3Department of Psychology, Northern Illinois University
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4Department of Psychology, The University of Chicago

5School of Psychology and Child and Adolescent Development, KU Leuven – University of
Leuven

Abstract
In 1978, when the Task Panel report to the US President’s Commission on Mental Health
emphasized the importance of improving health care and easing the pain of those suffering from
emotional distress syndromes including loneliness, few anticipated that this issue would still need
to be addressed 40 years later. A meta-analysis (Masi et al., 2011) on the efficacy of treatments to
reduce loneliness identified a need for well-controlled randomized clinical trials focusing on the
rehabilitation of maladaptive social cognition. We review assessments of loneliness and build on
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this meta-analysis to discuss the efficacy of various treatments for loneliness. With the advances
made over the past 5 years in the identification of the psychobiological and pharmaceutical
mechanisms associated with loneliness and maladaptive social cognition, there is increasing
evidence for the potential efficacy of integrated interventions that combine (social) cognitive
behavioral therapy with short-term adjunctive pharmacological treatments.

Life in America in the 21st century is unlike any period in human history. People are living
longer than ever before, and the rise in the Internet has transformed how Americans work,
play, search, shop, study, communicate, and relate to one another. People are increasingly
connected digitally, but the prevalence of loneliness (perceived social isolation) also appears
to be rising. From a prevalence estimated to be 11–17% in the 1970s (Peplau, Russell, &
Heim, 1979), loneliness has increased to over 40% in middle aged and older adults1
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(Edmondson, 2010; Perissinotto, Cenzer, & Covinsky, 2012). Over the past 40 years,
loneliness has also become more widespread overseas (e.g., Victor, Scambler, Bowling, &
Bond, 2005; Randall, 2012; Victor & Yang, 2012; Stickley et al., 2013). For instance, a
2010 survey from Statistics New Zealand shows that 33% of individuals aged 15 and above
experienced loneliness in the four weeks preceding the survey. In the U.K., prevalence of

Address correspondence to the first author at the Department of Psychiatry and Behavioral Neuroscience, University of Chicago
Medical Center, Chicago, IL 60637, or to [email protected].
1Although significant overlaps exist between loneliness in adults and loneliness in children and adolescents (Qualter et al., in the
present issue), we focus in the present article on reports involving adults.
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loneliness is estimated between 5%–6% (for individuals reporting feeling “often” lonely),
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21%–31% (for individuals reporting feeling “sometimes” lonely; Victor et al., 2005; Victor
& Yang, 2012), and prevalence rates as high as 45% have been reported throughout the U.K.
according to an online survey that took place in March 2010 (Griffin, 2010). As the
prevalence of loneliness rises, evidence accrues that loneliness is a major risk factor for poor
physical and mental health outcomes.

Definition of Loneliness
Psychiatrist Fromm-Reichmann (1959) raised awareness of loneliness and noted the need for
a rigorous, scientific definition of loneliness. In the decades that followed, loneliness as a
psychological condition was characterized, and measures for quantifying individual
differences were introduced (e.g., Lynch & Convey, 1979; Peplau, Russell, & Heim, 1979;
Russell, Peplau, & Cutrona, 1980; Weiss, 1973). Loneliness corresponds to a discrepancy
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between an individual’s preferred and actual social relations (Peplau & Perlman, 1982). This
discrepancy then leads to the negative experience of feeling alone and/or the distress and
dysphoria of feeling socially isolated even when among family or friends (Weiss, 1973).
This definition underscores the fact that feeling alone or lonely does not necessarily mean
being alone nor does being alone necessarily mean feeling alone (see J. T. Cacioppo et al.,
this issue). One can feel lonely in the crowd or in a marriage. Reciprocally, one may enjoy
being alone (a pleasant state defined as solitude; Tillich, 1959) at times in order to reach
personal growth experiences (such as those achieved through solitary meditation or
mindfulness exercises) or to simply take a temporary break from dealing with the demands
of modern life.

Loneliness emphasizes the fact that social species require not simply the presence of others
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but also the presence of significant others whom they can trust, who give them a goal in life,
with whom they can plan, interact, and work together to survive and prosper (J. T. Cacioppo
& Patrick, 2008). Moreover, the physical presence of significant others in one’s social
environment is not a sufficient condition. One needs to feel connected to significant others
to not feel lonely. Accordingly, one can be temporarily alone and not feel lonely as they feel
highly connected with their spouse, family, and/or friends – even at a distance. Subjectivity
and perception of the friendly or hostile nature of one’s social environment is, thus, a
characteristic of loneliness. As comedian Robin Williams said: “I used to think the worst
thing in life was to end up all alone. It’s not. The worst thing in life is to end up with people
who make you feel all alone” (2009). Although this crucial component of loneliness helps
better differentiate subjective social isolation (loneliness) from objective social isolation, it
has led occasionally to a conflation of loneliness and other dysphoric states (e.g., social
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anxiety, depression) in which a person’s subjective experiencing of their social environment

plays also a crucial role.

A main challenge for physicians and mental health clinicians has been, therefore, to become
sufficiently informed about the scientific definition of loneliness so that other mental
disorders were not mistakenly diagnosed and treated when loneliness was either the primary
presenting problem or the cause of the depression for which treatment was sought (Booth,
2000). For instance, because loneliness and depression share some characteristics and a

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correlation ranging from .38 to .71 (cf., Booth, 2000; J. T. Cacioppo et al., 2006), many
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clinicians believed, for decades, that loneliness was simply an aspect of depression with no
distinct concept worthy of study (cf. Young, 1982). There is now considerable evidence
showing that loneliness and depression are separable and that loneliness increases the risk
for depression (J. T. Cacioppo et al., 2006; Heinrich & Gullone, 2006). In 1980, for instance,
Weeks et al. administered loneliness and depression scales to undergraduate college
students. Using data from 333 subjects, they concluded that loneliness and depression,
though correlated with each other, were “clearly different constructs.” These results have
been replicated and extended in recent longitudinal research (J. T. Cacioppo et al., 2010;
VanderWeele et al., 2011), and reinforced Ostrov and Offer’s (1978) clinical observation
that a potential difference between loneliness and depression was that while both are filled
with helplessness and pain, loneliness is characterized by the hope that all would be perfect
if only the lonely person could be united with another longed for person.
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Who Can Feel Lonely?

Loneliness does not discriminate. Although loneliness is more likely in populations who are
at risk for social alienation, isolation, and separation (such as older individuals who live
alone and are isolated from friends and families; patients with psychiatric disorders; patients
with long-term health conditions that limit their communicative capacities or mobility;
and/or stigmatized groups; for reviews see Andersson, 1998, J. T. Cacioppo in this special
issue), anyone can feel lonely at any time. For instance, the same objective social
relationship can be perceived as caring and protective or as exploitive and isolating based on
a host of factors including an individual’s prior experiences, current attributions, and overall
preference for social contact (J. T. Cacioppo, Cacioppo, Capitanio, & Cole, 2015).
Accordingly, loneliness is not limited to older adults who are infirmed and live alone but is
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evident across the lifespan and is even evident in people surrounded by large numbers of
other young adults or with numerous contacts/followers/friends on social media (e.g.,
Qualter et al., this issue).

Dimensions of Loneliness
Loneliness is a complex construct that includes three related facets or dimensions: 1)
Intimate loneliness; 2) Relational loneliness; and 3) Collective loneliness (Hawkley et al.,
2005; Hawkley, Gu, Luo, & Cacioppo, 2012). These three dimensions match the three
dimensions surrounding one’s attentional space (Hall, 1963, 1966; Figure 1): intimate space
(the closest space surrounding a person), social space (the space in which people feel
comfortable interacting with family and acquaintances), and the public space (a more
anonymous space). These three dimensions of loneliness also appear to share some
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correspondence with the structure of human personal social networks identified by Weiss
(1973) and Dunbar (2014; Figure 1). The translation of these three dimensions into a
structured attentional personal space (Ortigue, Megevand, Perren, Landis, & Blanke, 2006;
Ortigue et al., 2003; Rizzolatti et al., 1983, 1987) are interesting in light of analyses of the
mental organization for people’s loneliness/social connection (Figure 1). In loneliness, these
three dimensions have been found in various populations, such as college students (Hawkley
et al., 2005; McWhirter, 1990b) and older adults in the U.S. (Hawkley et al., 2005; Peplau &

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Perlman, 1982), and in young and older adults in China. (Hawkley et al., 2012)2. Each
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dimension also corresponds to different types of loneliness.

Intimate Loneliness
Intimate loneliness, or what Weiss (1973) termed emotional loneliness, refers to the
perceived absence of a significant someone (e.g., a spouse), that is, a person one can rely on
for emotional support during crises, who provides mutual assistance, and who affirms one’s
value as a person. This form of intimate connection often has considerable self-other overlap
(such as that observed between close friends e.g., husband-wife, best-friends; Hall, 1966;
Ortigue et al., 2003, 2006). This dimension corresponds to what Dunbar described as the
inner core, which can include up to 5 people (the “support clique”) and comprises the
people we rely on for emotional support during crises (Dunbar, 2014).

A population-based study of middle-age and older adults showed that the best (negative)
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predictor of intimate loneliness was marital status, indicating that intimate partners tend to
be a primary source of attachment, emotional connection, and emotional support for adults
(Hawkley et al., 2005). These results are consistent with several studies indicating that
having a significant partner/spouse is associated with lower levels of intimate loneliness and,
reciprocally that losing a partner (through divorce or widowhood) is linked to greater
intimate loneliness (e.g., J. T. Cacioppo & Patrick, 2008; Hughes et al., 2004; Lopata,
Heinemann, & Baum, 1982; Russell, 1982; Waite & Gallagher, 2001; Weiss, 1973).

Relational Loneliness
The second dimension is relational loneliness, or what Weiss (1973) termed social
loneliness. It refers to the perceived presence/absence of quality friendships or family
connections, that is, connections from the “sympathy group” (Buys & Larson, 1979;
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Dunbar, 2014) within one’s relational space. According to Dunbar the “sympathy group”
can include among 15 and 50 people and comprises core social partners whom we see
regularly and from whom we can obtain high-cost instrumental support (e.g. loans, help with
projects, child care; Dunbar, 2014).

The relational space is delimitated by the multi-modal (visual, auditory, and tactile) space
that permits face-to-face communications and interactions. Like intimate loneliness, social
loneliness is found in women as well as men, although there is some evidence that this
dimension may tend to play a slightly greater role in influencing loneliness in women than in
men (Hawkley et al., 2005). The best (negative) predictor of relational loneliness in middle-
aged and older adults is the frequency of contact with significant friends and family, even
after statistically controlling for the other two dimensions of loneliness (Hawkley et al.,
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2005). Nevertheless, it is not the quantity of friends, but the quality of significant friends/
confidants that counts (Hawkley et al., 2008). This point is crucial when diagnosing
loneliness.

2To evaluate the three dimensions of loneliness, one typically uses the R-UCLA Loneliness scale (either the 20-item, 9-item or 3-item
version; Russell et al., 1980; Hughes et al., 2004; Hawkley, Browne, & Cacioppo, 2005; Masi et al., 2011).

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Collective Loneliness
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The third dimension is collective loneliness, an aspect that Weiss (1973) did not identify in
his qualitative studies. Collective loneliness refers to a person’s valued social identities or
“active network” (e.g., group, school, team, or national identity) wherein an individual can
connect to similar others at a distance in the collective space. As such, this dimension may
correspond to what Dunbar (2014) described as the outermost social layer, which can
include among 150 and 1500 people (the “active network”) who can provide with
information through weak ties (Granovetter, 1973), as well as low-cost support (Dunbar,
2014). The best (negative) predictor of collective loneliness found in middle-age and older
adults was the number of voluntary groups to which individuals belonged: the more
voluntary associations to which individuals belonged, the lower their collective loneliness,
again even after statistically controlling for the two other dimensions. This dimension of
loneliness is found in women as well as men but tends to be slightly more heavily weighted
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in men than in women (Hawkley et al., 2005). The emergence of a collective dimension of
loneliness suggests that we may have evolved the capacity for and motivation to form
relationships not only with other individuals but also with groups (e.g., villages or armies),
with the consequence being the promotion of social identification and cooperation in
adverse conditions (e.g., competition, hunting, or warfare; Brewer, 2004). The identification
with and investments in the group, in turn, may increase the likelihood of the continuity of
the group, its members, and their individual genetic legacy (J. T. Cacioppo, Cacioppo, &
Boomsma, 2014).

Consequences of Loneliness
Loneliness can contribute to a constellation of physical and psychiatric dysfunctions and/or
psychosocial risk factors, including depressive symptomatology (J. T. Cacioppo et al., 2006;
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J. T. Cacioppo, Hawkley, & Thisted, 2010; VanderWeele, Hawkley, Thisted, & Cacioppo,
2011), alcoholism (Akerlind & Hornquist, 1992), suicidal thoughts (Rudatsikira, Muula,
Siziya, & Twa-Twa, 2007), aggressive behaviors, social anxiety, and impulsivity (e.g., S.
Cacioppo, Capitanio, & Cacioppo, 2014; Ernst & Cacioppo, 1999; Kearns et al., 2014). In
addition, loneliness is a risk factor for cognitive decline and the progression of Alzheimer’s
Disease (Wilson et al., 2007), recurrent stroke (for review see S. Cacioppo, Capitanio, &
Cacioppo, 2014), obesity (Lauder, Mummery, Jones, & Caperchione, 2006), increased
vascular resistance (J. T. Cacioppo, Hawkley, Crawford et al., 2002), elevated blood
pressure (J. T. Cacioppo, Hawkley, Crawford et al., 2002; Hawkley et al., 2006), increased
hypothalamic pituitary adrenocortical activity (Adam, Hawkley, Kudielka, & Cacioppo,
2006; Steptoe, Owen, Kunz-Ebrecht, & Brydon, 2004), decreased sleep salubrity (J. T.
Cacioppo, Hawkley, Berntson et al., 2002; Pressman et al., 2005), diminished immunity
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(Kiecolt-Glaser et al., 1984a b; Pressman et al., 2005), an under-expression of genes bearing

anti-inflammatory glucocorticoid response elements and an upregulation of pro-
inflammatory gene transcripts (Cole et al., 2007, 2011), abnormal ratios of circulating white
blood cells (e.g., neutrophils, lymphocytes, and monocytes; Cole, 2008), and premature
mortality (e.g., Luo et al., 2012).

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Interventions to Reduce Loneliness

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Increased recognition of loneliness as a risk factor for adverse psychological and physical
health outcomes has elevated interest in interventions to reduce chronic loneliness. For
instance, the British government is developing several initiatives aiming to improve the life
quality and satisfaction of people suffering from the (real or perceived) absence of social
relationships (Victor, Scambler, Bowling, & Bond, 2005). Campaigns designed to raise
awareness about the growing problem of loneliness and isolation have also been launched in
the United Kingdom by five partner organizations (http://
www.campaigntoendloneliness.org/about-the-campaign/), in Denmark by the Crown
Princess and her Mary Foundation (http://www.maryfonden.dk/en/loneliness) and the
DaneAge Association (Ældre Sagen; http://www.aeldresagen.dk/presse/nyheder/Sider/
Folkebevaegelse-skal-bryde-tabu-om-ensomhed.aspx), in Canada by the Canadian Seniors
Council (http://www.seniorscouncil.gc.ca/eng/home.shtml), and in the United States by
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Oprah Winfrey, Sanjay Gupta, and Gayle King and supported by Skype (http://
www.oprah.com/health/Just-Say-Hello-Fight-Loneliness), the AARP Foundation Initiative
on Social Isolation (http://www.aarp.org/aarp-foundation/our-work/isolation/), and the Do-It
Campaign to end isolation (http://women.oshkoshareacf.org/endisolation). These campaigns
are essential to raise awareness about and to reduce the stigma surrounding loneliness, but
these represent only a first step. Effective treatments are also needed.

Different types of treatments

To date, there have been a number of attempts to mitigate loneliness. Such interventions
include one-on-one interventions (e.g., befriending, Mead et al., 2010; or mentoring,
Dickens et al., 2011), group therapy (e.g., groups of lonely people), and wider community
interventions (e.g., community events reaching out to a lonely person/s; Cattan et al., 2005;
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Findlay, 2003; Masi et al., 2011 for reviews). Most of them have been based on the intuitive
understanding of loneliness. For instance, a first model has been to provide social support to
lonely individuals. That said, as described above, loneliness is not only about getting
support, it is also about giving support back and mutual aid.

A second model has been to increase opportunities for social interaction. But, as noted
above, a large number of contacts is not equivalent to high quality relationships (Masi et al.,
2011). Effects of our own mentation (what we think, what we perceive) involves both
conscious and nonconscious mechanisms. Even if lonely individuals want to connect, their
non-conscious hypervigilance for social threat can lead them to be negative with or
withdraw from others.
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A third model to reduce loneliness is based on teaching lonely people to master social skills.
For unfortunate individuals who lack of social skills, this may be effective but people are
lonely for many reasons other than poor social skills. Experimental research in which
loneliness was manipulated shows that most adults have at least minimal social skills, but
these adults are more likely to call upon these social skills when they feel low rather than
high in loneliness (Cacioppo et al., 2006).

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Which type of behavioral intervention is most effective to reduce loneliness?

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—We addressed this question in a quantitative meta-analysis on the efficacy of the various
treatments tested to reduce loneliness between 1970 and 2009 (Masi et al., 2011), and we
investigated various moderator variables, such as the experimental design (single group
pretest-posttest; nonrandomized comparison group; randomized comparison group) and
intervention format (individual or group). Results showed that the mean effect size was
much lower when appropriate experimental and statistical controls were implemented, with
the effect size for nonrandomized group comparison studies being −.459, and single-group
pretest-posttest designs being −.367, whereas the effect size for randomized controlled
studies being −.198. This finding implies that if a program or intervention to reduce
loneliness is to be evaluated for efficacy – including large-scale programs such as those
being introduced in the United States, Canada, Denmark, and the United Kingdom – it is
important to control for potential confounding variables (time, expectancy effects,
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Hawthorne effects, confounding individual differences) to avoid biases that are likely to lead
to an overestimate of treatment efficacy.

Contrary to the conclusion of previous narrative reviews carried out since the 1980s, Masi et
al.’s (2011) quantitative literature review revealed little evidence for better efficacy of one-
to-one individual therapies compared to group therapies. Type of intervention program was
a significant moderator, however. Twenty studies met the criteria for randomized group
comparison design, and all four primary types of interventions known to reduce loneliness
were present in this group. These four primary types of intervention programs were (a) those
that increased opportunities for social contact (e.g., social recreation intervention), (b) those
that enhanced social support (e.g., through mentoring programs, Buddy-care program,
conference calls), (c) those that focused on social skills (e.g., speaking on the phone, giving
and receiving compliments, enhancing nonverbal communication skills), and (d) those that
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addressed maladaptive social cognition (e.g., cognitive behavioral therapy). Among these
four types, interventions designed to address maladaptive social cognition were associated
with the largest effect size (mean effect size = −.598).

These studies ranged from one with elderly adults from a nursing home in Tapei who
participated in eight weekly sessions designed to increase awareness and expression of their
feelings, to identify positive relationships from their past, and to apply these prior
experiences to their current relationships (Chiang et al., 2009) to one with high-risk Naval
recruits at basic training who met for 45 minutes per week for 9 weeks to learn, discuss, and
practice strategies for increasing one’s sense of belonging, decreasing thought distortion,
and improving one’s coping and stress management (Williams et al., 2004). Interventions
designed to enhance social support produced a significant but small reduction in loneliness
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(mean effect size = −.162), while interventions to increase opportunities for social
interaction (mean effect size = −.062, n.s.) and interventions to improve social skills (mean
effect size = −.017, n.s.) were not found to be effective in lowering loneliness. These
findings reinforce the notion that interpersonal contact or communication per se is not
sufficient to address chronic loneliness in the general population.

One key to (social) cognitive behavioral therapy (CBT) in the framework of reducing
loneliness is to educate individuals to identify the automatic negative thoughts that they have

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about others and about social interactions more generally, and to regard these negative
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thoughts as possibly faulty hypotheses that need to be verified rather than as facts on which
to act (Anderson, Horowitz, & French, 1983; McWhirter, 1990a; Young, 1982). By aiming
to change maladaptive social perception and cognition (e.g., dysfunctional and irrational
beliefs, false attributions, and self-defeating thoughts and interpersonal interactions; Young,
1982; for reviews: Cacioppo & Patrick, 2008; Masi et al., 2011; McWhirter, 1990a), CBT
approach implies that loneliness can be decreased (Masi et al., 2011, McWhirter, 1990a, for
reviews).

Research on social cognition as a function of loneliness has resulted in the model depicted in
Figure 2. According to this model, lonely individuals typically do not voluntarily become
lonely; rather, they “find themselves” on one edge of the continuum of social connections
(S. Cacioppo & Cacioppo, 2012) and feeling desperately isolated (Booth, 2000). The
perception that one is socially on the edge and isolated from others increases the motive for
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self-preservation. This, then, increases the motivation to connect with others but also
increases an implicit hyper-vigilance for social threats, which then can introduce attentional,
confirmatory, and memory biases. Given the effects of attention and expectation on
anticipated social interactions, behavioral confirmation processes then can incline an
individual who feels isolated to have or to place more import on negative social interactions,
which if unchecked can reinforce withdrawal, negativity, and feelings of loneliness (e.g., see
J. T. Cacioppo & Cacioppo, 2014; J. T. Cacioppo & Hawkley, 2009). This model points to a
number of sources of dysfunctional and irrational beliefs, false expectations and attributions,
and self-defeating thoughts and interpersonal interactions on which interventions might be
designed to operate. For instance, the attentional, confirmatory, and memory biases could be
targeted by training in perspective taking, empathy, and identifying automatic negative
thoughts about others and about social interactions and in regarding these negative thoughts
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as possibly faulty hypotheses that need to be verified, whereas faulty behavioral

confirmation processes could be targeted by training in mindfulness (Baer, 2003; Creswell et
al., 2012) and capitalization (sharing good times; Gable & Reis, 2010; Woods et al., 2014).

In sum, a primary criterion for empirically supported therapies is that they demonstrate
efficacy in randomized controlled studies. Although more research is needed, the meta-
analysis suggests that interventions designed to modify maladaptive social cognition may be
especially worth pursuing. Such interventions can be expensive and time-consuming, and
the client’s lack of openness to changing their thoughts about and interactions with others
can be an obstacle to effective treatment. It is possible that these interventions may be more
effective (or effective for a greater proportion of individuals) if augmented initially by an
appropriate pharmacologic treatment.
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Potential Adjunctive Pharmacological Treatments

To date, there is no adjunctive pharmacological treatment for loneliness, but animal research
sheds promising light on this issue. For instance, research in which a social animal (e.g.,
prairie voles, titi monkeys) is chronically housed either with a preferred partner or alone has
shown that isolation has deleterious neurological (see review by S. Cacioppo, Capitanio, &
Cacioppo, 2014) and neuroendocrinological effects (see review by J. T. Cacioppo,

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Cacioppo, Capitanio, & Cole, 2015). Interestingly, animal research showed that the
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behavioral effects of social isolation could be improved with pharmacological help. For
instance, pharmacological help includes administration of: 1) antidepressants of the selective
serotonin reuptake inhibitors (SSRIs) class that have a broad range of effects including (but
not restricted to) improving anxiety-like behavior and fear responses (fluoxetine; Pinna,
2010); 2) neurosteroids (such as allopregnanolone, ALLO) that activate the hypothalamic
pituitary adrenocortical (HPA) axis, thereby facilitate the recovery of physiological
homeostasis following stressful stimuli (e.g., Evans, Sun, McGregor, & Connor, 2012; cf. S.
Cacioppo, Capitanio, & Cacioppo, 2014); or 3) oxytocin, a neuropeptide.

For instance, fluoxetine, an antidepressant of the selective serotonin reuptake inhibitors

(SSRIs) class, has a broad range of effects including (but not restricted to) improving the
behavioral effects of social isolation, anxiety-like behavior and fear responses (Pinna, 2010;
Mayo-Wilson et al., 2014). For patients who decline psychological interventions (such as
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CBT), SSRIs show consistent evidence of improvement. Interestingly, this improvement

does not occur through the inhibition of selective serotonin reuptake (as in depression), but
rather through elevated cortico-limbic levels of allopregnanolone (ALLO) and BDNF
mRNA expression (Pinna, 2010).

Research supporting the hypothesis of a crucial role of ALLO in social isolation

demonstrates that: i) the exaggerated contextual fear response expressed by socially-isolated
mice can be normalized with a single injection of ALLO (Pibiri, Nelson, Guidotti, Costa, &
Pinna, 2008); ii) HPA dysfunction and impairment of hippocampal neurogenesis
respectively can be normalized or prevented with the administration of exogenous ALLO
either during or following a period of chronic stress; iii) the establishment of depressive/
anxiety-like behaviors in rats can be precluded also with administration of exogenous ALLO
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(Evans et al., 2012; S. Cacioppo, Capitanio, & Cacioppo, 2014; Nelson & Pinna, 2011;
Pinna, 2010); and iv) contextual fear conditioning and aggression can be regulated with
ALLO (Nelson & Pinna, 2011). Although further investigations of the effects of ALLO on
social isolation are needed in humans, ALLO may provide an adjunctive therapeutic target
early in cognitive behavioral interventions to alleviate chronic loneliness.

A third potential adjunctive pharmacological treatment for loneliness is oxytocin, a

hypothalamic neuropeptide known to have a high sensitivity to social affiliation (Carter et
al., 2008; Goossens et al., in this issue; Grippo, 2009; Young et al., 2014). Recent work with
prairie voles raises the possibility that oxytocin may help buffer the deleterious neural,
behavioral, immune and autonomic effects of social isolation from a pair-bonded partner
(Grippo et al., 2009). The prairie vole is a monogamous rodent whose social structure has
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similarities to that of humans. In prairie voles, long-term social isolation from a mate or
partner produces several negative behavioral and physiological alterations, including
depressive and anxiety-relevant behaviors, and autonomic and cardiac dysfunction (Grippo
et al., 2007a–c, 2008, 2011, 2012; McNeal et al., 2014). The exogenous peripheral
administration of oxytocin eliminates the adverse behavioral and autonomic changes
associated with social isolation in the prairie vole (Grippo et al., 2009, 2012).

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Oxytocin administration in humans has been shown to promote pro-social behaviors,

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affiliation, and trust (Kosfeld et al., 2005), cooperation with others (Declerck, Boone, &
Kiyonari, 2014), social synchrony (Arueti et al., 2013), autonomic cardiac control (Norman,
Cacioppo et al., 2011a), and to decrease the emotional arousal in response to threatening
human stimuli (Norman, Cacioppo et al., 2011b), but negative and inconsistent social effects
have also been observed (see Bethlehem et al., 2014, and Bali & Jaggi, 2014, for reviews).
For instance, some research studies suggest that oxytocin may make neurologically healthy
individuals evaluate participants as more trusting and more pro-social in relaxed social
situations and more aggressive in tense social situations (for review see: Bartz, Zaki, Bolger,
& Ochsner, 2011), whereas others indicate that oxytocin administration increases outgroup
aggression (e.g., De Dreu et al., 2010; Taylor et al., 2006). The fact that oxytocin has some
prosocial effects, at least for some individuals or situations, is intriguing but how precisely
oxytocin might prove helpful in the treatment of chronic loneliness requires additional
Author Manuscript

research.

Conclusion
The etiology of loneliness and its consequences are complex. When the 1978 Task Panel
report to the US President’s Commission on Mental Health emphasized the importance of
improving health care and easing the pain of those suffering from loneliness, few would
have thought that their recommendation would be even more relevant and important today.
With increasing evidence that loneliness is a risk factor for mental and physical health
problems, attention has begun to turn to interventions for addressing chronic loneliness.

As a first step, there is a need for increased public awareness – and awareness among
healthcare providers – that loneliness is a condition that, like chronic pain, can become an
Author Manuscript

affliction for almost anyone. Even popular and high status individuals can find themselves
feeling lonely, and the stigma of loneliness further complicates assessment and treatment.
Despite the fact that loneliness is a common emotional distress syndrome with a high risk
factor for early mortality and a broad variety of physical health and psychiatric issues, it still
gets little attention in medical training or in healthcare more generally.

In Masi et al.’s meta-analysis (2011), we identified a need for well-controlled randomized

studies focusing on the rehabilitation of the underlying maladaptive social cognition. With
the advances made over the past 5 years in the identification of the psychobiological and
pharmaceutical mechanisms associated with loneliness and maladaptive social cognition, it
may soon be possible to combine (social) cognitive behavioral interventions with short-term
adjunctive pharmacological treatments in order to reduce the prevalence of loneliness and its
harmful consequences.
Author Manuscript

Acknowledgments
Preparation of this article was supported by the Department of the Army, Defense Medical Research and
Development Program Grant No. W81XWH-11-2-0114.

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 Cacioppo et al. Page 11

References
Author Manuscript

Adam EK, Hawkley LC, Kudielka BM, Cacioppo JT. Day-to-day dynamics of experience--cortisol
associations in a population-based sample of older adults. Proceedings of the National Academy of
Sciences. 2006; 103:17058–63.10.1073/pnas.0605053103
Akerlind I, Hörnquist JO. Loneliness and alcohol abuse: a review of evidences of an interplay. Social
Science & Medicine. 1992; 34:405–414.10.1016/0277-9536(92)90300-F [PubMed: 1566121]
Anderson CA, Horowitz LM, French R. Attributional style of lonely and depressed people. Journal of
Personality and Social Psychology. 1983; 45:127–136.10.1037//0022-3514.45.1.127 [PubMed:
6886964]
Andersson L. Loneliness research and interventions: A review of the literature. Aging & Mental
Health. 1998; 2(4):264–274.10.1080/13607869856506
Arueti M, Perach-Barzilay N, Tsoory MM, Berger B, Getter N, Shamay-Tsoory SG. When two
become one: The role of oxytocin in interpersonal coordination and cooperation. Journal of
Cognitive Neuroscience. 2013; 25:1418–1427.10.1162/jocn_a_00400 [PubMed: 23574582]
Baer RA. Mindfulness training as a clinical intervention: A conceptual and empirical review. Clinical
Author Manuscript

Psychology: Science and Practice. 2003; 10:125–143.10.1093/clipsy.bpg015

Bali A, Jaggi AS. Multifunctional aspects of allopregnanolone in stress and related disorders. Progress
in Neuro-Psychopharmacology & Biological Psychiatry. 2014; 48:64–78.10.1016/j.pnpbp.
2013.09.005 [PubMed: 24044974]
Bartz JA, Zaki J, Bolger N, Ochsner KN. Social effects of oxytocin in humans: Context and person
matter. Trends in Cognitive Sciences. 2011; 15:301–309.10.1016/j.tics.2011.05.002 [PubMed:
21696997]
Bethlehem RA, Baron-Cohen S, van Honk J, Auyeung B, Bos PA. The oxytocin paradox. Frontiers in
Behavioral Neuroscience. 2014; 8:48.10.3389/fnbeh.2014.00048 [PubMed: 24596548]
Booth R. Loneliness as a component of psychiatric disorders. Medscape General Medicine. 2000; 2:1–
7.
Brewer MB. Taking the social origins of human nature seriously: Toward a more imperialist social
psychology. Personality & Social Psychology Review. 2004; 8:107–113.10.1207/
s15327957pspr0802_3 [PubMed: 15223509]
Author Manuscript

Buys CJ, Larson KL. Human sympathy groups. Psychology Reports. 1979; 45:547–553.10.2466/
pr0.1979.45.2.547
Cacioppo JT, Cacioppo S. Social relationships and health: The toxic effects of perceived social
isolation. Social and Personality Psychology Compass. 2014; 8:58–72. [PubMed: 24839458]
Cacioppo JT, Cacioppo S, Boomsma DI. Evolutionary mechanisms for loneliness. Cognition and
Emotion. 2014; 28:3–21.10.1080/02699931.2013.837379 [PubMed: 24067110]
Cacioppo JT, Cacioppo S, Capitanio JP, Cole SW. The neuroendocrinology of social isolation. Annual
Review of Psychology. 2015; 6610.1146/annurev-psych-010814-015240
Cacioppo JT, Cacioppo S, Cole SW, Capitanio JP, Goossens L, Boomsma DI. Loneliness across
phylogeny and a call for animal models. Perspectives on Psychological Science. in press.
Cacioppo JT, Ernst JM, Burleson MH, McClintock MK, Malarkey WB, Berntson GG. Lonely traits
and concomitant physiological processes: The MacArthur Social Neuroscience Studies.
International Journal of Psychophysiology. 2000; 35:143–154.10.1016/S0167-8760(99)00049-5
[PubMed: 10677643]
Cacioppo JT, Fowler JH, Christakis NA. Alone in the crowd: The structure and spread of loneliness in
Author Manuscript

a large social network. Journal of Personality and Social Psychology. 2009; 97:977–991.
[PubMed: 19968414]
Cacioppo JT, Hawkley LC. Perceived social isolation and cognition. Trends in Cognitive Sciences.
2009; 13:447–454.10.1016/j.tics.2009.06.005 [PubMed: 19726219]
Cacioppo JT, Hawkley LC, Berntson GG, Ernst JM, Gibbs AC, Stickgold R, Hobson JA. Do lonely
days invade the nights? Potential social modulation of sleep efficiency. Psychological Science.
2002; 13:384–387.10.1111/1467-9280.00469 [PubMed: 12137144]

Perspect Psychol Sci. Author manuscript; available in PMC 2016 March 01.
 Cacioppo et al. Page 12

Cacioppo JT, Hawkley LC, Crawford LE, Ernst JM, Burleson MH, Kowalewski RB, Berntson GG.
Loneliness and health: potential mechanisms. Psychosomatic Medicine. 2002; 64:407–
Author Manuscript

417.10.1097/00006842-200205000-00005 [PubMed: 12021415]

Cacioppo JT, Hawkley LC, Thisted RA. Perceived social isolation makes me sad: Five year cross-
lagged analyses of loneliness and depressive symptomatology in the Chicago Health, Aging, and
Social Relations Study. Psychology and Aging. 2010; 25:453–463. [PubMed: 20545429]
Cacioppo JT, Hughes ME, Waite LJ, Hawkley LC, Thisted RA. Loneliness as a specific risk factor for
depressive symptoms: Cross sectional and longitudinal analyses. Psychology and Aging. 2006;
21:140–151. [PubMed: 16594799]
Cacioppo, JT.; Patrick, W. Loneliness: Human nature and the need for social connection. New York:
Norton; 2008.
Cacioppo S, Cacioppo JT. Decoding the invisible forces of social connections. Frontiers in Integrative
Neuroscience. 2012; 51:1–7.10.3389/fnint.2012.00051
Cacioppo S, Cacioppo JT. Do you feel lonely? You are not alone: Lessons from social neuroscience.
Frontiers in Neuroscience for Young Minds. 2013 Nov 9.
Cacioppo S, Capitanio JP, Cacioppo JT. Toward a neurology of loneliness. Psychological Bulletin.
Author Manuscript

201410.1037/a0037618
Carter CS, Grippo AJ, Pournajafi-Nazarloo H, Ruscio MG, Porges SW. Oxytocin, vasopressin and
sociality. Progress in Brain Research. 2008; 170:331–336.10.1016/S0079-6123(08)00427-5
[PubMed: 18655893]
Cattan M, White M, Bond J, Learmouth A. Preventing social isolation and loneliness among older
people: A systematic review of health promotion interventions. Ageing and Society. 2005; 25:41–
67.10.1017/S0144686X04
Chiang KJ, Chu H, Chang HJ, Chung MH, Chen CH, Chiou HY, Chou KR. The effects of
reminiscence therapy on psychological well-being, depression, and loneliness among the
institutionalized aged. International Journal of Geriatric Psychiatry. 2009; 25:380–388.10.1002/
gps.2350 [PubMed: 19697299]
Cole SW. Social regulation of leukocyte homeostasis: the role of glucocorticoid sensitivity. Brain
Behav Immun. 2008; 22:1049–1055.10.1016/j.bbi.2008.02.006 [PubMed: 18394861]
Cole SW, Hawkley LC, Arevalo JM, Sung CY, Rose RM, Cacioppo JT. Social regulation of gene
Author Manuscript

expression in human leukocytes. Genome biology. 2007; 8:R189.10.1186/gb-2007-8-9-r189

[PubMed: 17854483]
Declerck CH, Boone C, Kiyonari T. The effect of oxytocin on cooperation in a prisoner’s dilemma
depends on the social context and a person’s social value orientation. Social Cognitive and
Affective Neuroscience. 2014; 9:802–809.10.1093/scan/nst040 [PubMed: 23588271]
De Dreu CK, Greer LL, Handgraaf MJ, Shalvi S, Van Kleef GA, Feith SWW. The neuropeptide
oxytocin regulates parochial altruism in intergroup conflict among humans. Science. 2010;
328:1408–1411.10.1126/science.1189047 [PubMed: 20538951]
Dickens AP, Richards SH, Hawton A, Taylor RS, Greaves CJ, Campbell JL. An evaluation of the
effectiveness of a community mentoring service for socially isolated older people: A controlled
trial. BMC Public Health. 2011; 11:218.10.1186/1471-2458-11-218 [PubMed: 21477273]
Dunbar RIM. The social brain: Psychological underpinnings and implications for the structure of
organizations. Current Directions in Psychological Science. 2014; 23:109–
114.10.1177/0963721413517118
Edmondson B. All the lonely people. AARP: The Magazine. 2010 Nov-Dec;(83)
Author Manuscript

Ernst JM, Cacioppo JT. Lonely hearts: Psychological perspectives on loneliness. Applied and
Preventive Psychology. 1999; 8:1–22.
Evans J, Sun Y, McGregor A, Connor B. Allopregnanolone regulates neurogenesis and depressive/
anxiety-like behavior in a social isolation rodent model of chronic stress. Neuropharmacology.
2012; 63:1315–1326. [PubMed: 22939998]
Findlay RA. Interventions to reduce social isolation amongst older people: Where is the evidence?
Ageing and Society. 2003; 23:647–658.

Perspect Psychol Sci. Author manuscript; available in PMC 2016 March 01.
 Cacioppo et al. Page 13

Gable, SL.; Reis, HT. Good news! Capitalizing on positive events in an interpersonal context. In:
Zanna, MP., editor. Advances in Experimental Social Psychology. Vol. 42. San Diego, CA:
Author Manuscript

Elsevier Academic Press; 2010. p. 195-257.

Goossens L, Verhagen M, van Roekel E, Cacioppo JT, Cacioppo S, Boomsma DI. The genetics of
loneliness: The quest for underlying mechanisms and developmental processes. Perspectives on
Psychological Science. in press.
Granovetter M. The strength of weak ties. American Journal of Sociology. 1973; 78:1360–
1380.10.1086/225469
Griffin, J. The lonely society?. London: The Mental Health Foundation; 2010.
Grippo AJ. Mechanisms underlying altered mood and cardiovascular dysfunction: The value of
neurobiological and behavioral research with animal models. Neuroscience and Biobehavioral
Reviews. 2009; 33:171–180. [PubMed: 18703084]
Grippo AJ, Carter CS, McNeal N, Chandler DL, LaRocca MA, Bates SL, Porges SW. 24-Hour
autonomic dysfunction and depressive behaviors in an animal model of social isolation:
Implications for the study of depression and cardiovascular disease. Psychosomatic Medicine.
2011; 73:59–66. [PubMed: 21097661]
Author Manuscript

Grippo AJ, Lamb DG, Carter CS, Porges SW. Social isolation disrupts autonomic regulation of the
heart and influences negative affective behaviors. Biological Psychiatry. 2007a; 62:1162–
1170.10.1016/j.biopsych.2007.04.011 [PubMed: 17658486]
Grippo AJ, Cushing BS, Carter CS. Depression-like behavior and stressor-induced neuroendocrine
activation in female prairie voles exposed to chronic social isolation. Psychosomatic Medicine.
2007b; 69:149–157.10.1097/PSY.0b013e31802f054b [PubMed: 17289829]
Grippo AJ, Gerena D, Huang J, Kumar N, Shah M, Ughreja R, Carter CS. Social isolation induces
behavioral and neuroendocrine disturbances relevant to depression in female and male prairie
voles. Psychoneuroendocrinology. 2007c; 32:966–980.10.1016/j.psyneuen.2007.07.004 [PubMed:
17825994]
Grippo AJ, Wu KD, Hassan I, Carter CS. Social isolation in prairie voles induces behaviors relevant to
negative affect: Toward the development of a rodent model focused on co-occurring depression
and anxiety. Depression & Anxiety. 2008; 25:E17–E26. [PubMed: 17935206]
Grippo AJ, Trahanas DM, Zimmerman IIRR, Porges SW, Carter CS. Oxytocin protects against
negative behavioral and autonomic consequences of long-term social isolation.
Author Manuscript

Psychoneuroendocrinology. 2009; 34:1542–1553.10.1016/j.psyneuen.2009.05.017 [PubMed:

19553027]
Grippo AJ, Pournajafi-Nazarloo H, Sanzenbacher L, Trahanas DM, McNeal N, Carter SC. Peripheral
oxytocin administration buffers autonomic but not behavioral responses to environmental stressors
in isolated prairie voles. Stress. 2012; 15:149–161. [PubMed: 21854168]
Grippo A, Ihm E, Wardwell J, McNeal N, Scotti M, Preihs K. The effects of environmental enrichment
on depressive and anxiety-relevant behaviors in socially isolated prairie voles. Psychosomatic
Medicine. 2014; 76:277–284.10.1097/PSY.0000000000000052 [PubMed: 24804886]
Hall ET. A System for the Notation of Proxemic Behavior. American Anthropologist. 1963; 65:1003–
1026.
Hall, ET. The Hidden Dimension. Garden City, N.Y: Doubleday; 1966.
Hawley LC, Browne MW, Cacioppo JT. How can I connect with thee? Let me count the ways.
Psychological Science. 2005; 16:798–804.10.1111/j.1467-9280.2005.01617.x [PubMed:
16181443]
Author Manuscript

Hawkley LC, Gu Y, Luo YJ, Cacioppo JT. The mental representation of social connections:
Generalizability extended to Beijing adults. PLoS ONE. 2012; 7(9):e44065.10.1371/journal.pone.
0044065 [PubMed: 23028486]
Hawkley LC, Hughes ME, Waite LJ, Masi CM, Thisted RA, Cacioppo JT. From social structure
factors to perceptions of relationship quality and loneliness: The Chicago Health, Aging, and
Social Relations Study. Journal of Gerontology: Social Sciences. 2008; 63B:S375–S384.
Hawkley LC, Masi CM, Berry JD, Cacioppo JT. Loneliness is a unique predictor of age-related
differences in systolic blood pressure. Psychology and Aging. 2006; 21:152–
164.10.1037/0882-7974.21.1.152 [PubMed: 16594800]

Perspect Psychol Sci. Author manuscript; available in PMC 2016 March 01.
 Cacioppo et al. Page 14

Heinrich LM, Gullone E. The clinical significance of loneliness: a literature review. Clinical
Psychology Review. 2006; 26:695–718.10.1016/j.cpr.2006.04.002 [PubMed: 16952717]
Author Manuscript

Holt-Lunstad J, Smith TB. Loneliness and Social Isolation as Risk Factors for Mortality: A Meta-
Analytic Review. Perspectives on Psychological Science/. in press.
Hughes ME, Waite LJ, Hawkley LC, Cacioppo JT. A short scale for measuring loneliness in large
surveys: Results from two population-based studies. Research on Aging. 2004; 26:655–
672.10.1177/0164027504268574 [PubMed: 18504506]
Kearns A, Whitley E, Tannahill C, Ellaway A. Loneliness, social relations and health and well-being
in deprived communities. Psychology, Health, & Medicine. 2014:1–
13.10.1080/13548506.2014.940354
Kiecolt-Glaser JK, Garner W, Speicher CE, Penn GM, Holliday JE, Glaser R. Psychosocial modifiers
of immunocompetence in medical students. Psychosomatic Medicine. 1984a; 46:7–
14.10.1097/00006842-198401000-00003 [PubMed: 6701256]
Kiecolt-Glaser JK, Ricker D, George J, Messick G, Speicher CE, Garner W, Glaser R. Urinary cortisol
levels, cellular immunocompetency, and loneliness in psychiatric inpatients. Psychosomatic
Medicine. 1984b; 46:15–23.10.1097/00006842-198401000-00004 [PubMed: 6701251]
Author Manuscript

Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature.
2005; 435:673–676.10.1038/nature03701 [PubMed: 15931222]
Lauder W, Mummery K, Jones M, Caperchione C. A comparison of health behaviours in lonely and
non-lonely populations. Psychol Health Med. 2006; 11:233–245.10.1080/13548500500266607
[PubMed: 17129911]
Lopata, HZ.; Heinemann, GD.; Baum, J. Loneliness: Antecedents and coping strategies in the lives of
widows. In: Peplau, LA.; Perlman, D., editors. Loneliness: A sourcebook of current theory,
research and therapy. New York: Wiley-Interscience; 1982. p. 310-326.
Luo Y, Hawkley LC, Waite LJ, Cacioppo JT. Loneliness, health, and mortality in old age: A national
longitudinal study. Social Science & Medicine. 2012; 74:907–914.10.1016/j.socscimed.
2011.11.028 [PubMed: 22326307]
Lynch JJ, Convey WH. Loneliness, disease, and death: Alternative approaches. Psychosomatics. 1979;
20:702–708. [PubMed: 504545]
Masi CM, Chen HY, Hawkley LC, Cacioppo JT. A meta-analysis of interventions to reduce loneliness.
Author Manuscript

Personality and Social Psychology Review. 2011; 15:219–266.10.1177/1088868310377394

[PubMed: 20716644]
Mayo-Wilson E, Dias S, Mavranesouli I, Kew K, Clark DM, Ades AE, Pilling S. Psychological and
pharmacological interventions for social anxiety disorder in adults: A systematic review and
network meta-analysis. The Lancet Psychiatry. 2014; 1:368–376.10.1016/S2215-0366(14)70329-3
Mead N, et al. Effects of befriending on depressive symptoms and distress: Systematic review and
meta-analysis. British Journal of Psychiatry. 2010; 196:96–100.10.1192/bjp.bp.109.064089
[PubMed: 20118451]
McNeal N, Scotti MA, Wardwell J, Chandler DL, Bates SL, Grippo AJ. Disruption of social bonds
induces behavioral and physiological dysregulation in male and female prairie voles. Autonomic
Neuroscience: Basic and Clinical. 2014; 180:9–16.10.1016/j.autneu.2013.10.001 [PubMed:
24161576]
McWhirter BT. Loneliness: A review of current literature, with implications for counseling and
research. Journal of Counseling & Development. 1990a; 68:417–422.10.1002/j.
1556-6676.1990.tb02521.x
Author Manuscript

McWhirter BT. Factor analysis of the revised UCLA Loneliness Scale. Current Psychology: Research
and Reviews. 1990b; 9:56–68.10.1007/BF02686768
Nelson M, Pinna G. S-norfluoxetine infused into the basolateral amygdala increases allopregnanolone
levels and reduces aggression in socially isolated mice. Neuropharmacology. 2011; 60:1154–1159.
[PubMed: 20971127]
Norman GJ, Cacioppo JT, Morris JS, Malarkey WB, Berntson GG, De Vries CA. Oxytocin increases
autonomic cardiac control: Moderation by loneliness. Biological Psychology. 2011a; 86:174–
180.10.1016/j.biopsycho.2010.11.006 [PubMed: 21126557]

Perspect Psychol Sci. Author manuscript; available in PMC 2016 March 01.
 Cacioppo et al. Page 15

Norman GJ, Cacioppo JT, Morris JS, Karelina K, Malarkey WB, DeVries AC, Bernston GG. Selective
influences of oxytocin on the evaluative processing of social stimuli. Psychopharmacology. 2011b;
Author Manuscript

25:1313–1319.10.1177/0269881110367452
Ortigue S, Megevand P, Perren F, Landis T, Blanke O. Double dissociation between representational
personal and extrapersonal neglect. Neurology. 2006; 66:1414–1417.10.1212/01.wnl.
0000210440.49932.e7 [PubMed: 16682676]
Ortigue S, Viaud-Delmon I, Michel CM, Blanke O, Annoni JM, Landis T. Pure imagery hemi-neglect
of far space. Neurology. 2003; 60:2000–2002.10.1212/01.WNL.0000068028.63291.B6 [PubMed:
12821753]
Ostrov, E.; Offer, D. Adolescent youth and society. Chicago: University of Chicago Press; 1978.
Peplau, LA.; Perlman, D. Perspectives on loneliness. In: Peplau, LA.; Perlman, D., editors. Loneliness:
A sourcebook of current theory, research and therapy. New York: Wiley; 1982. p. 1-8.
Peplau, LA.; Russell, D.; Heim, M. The experience of loneliness. In: Frieze, IH.; Bar-Tal, D.; Carroll,
JS., editors. New approaches to social problems: Applications of attribution theory. San Francisco,
CA: Jossey-Bass; 1979. p. 53-78.
Perissinotto CM, Cenzer IS, Covinsky KE. Loneliness in older persons: A predictor of functional
Author Manuscript

decline and death. Archives of Internal Medicine. 2012; 172:1078–1083.10.1001/archinternmed.

2012.1993 [PubMed: 22710744]
Pibiri F, Nelson M, Guidotti A, Costa E, Pinna G. Decreased corticolimbic allopregnanolone
expression during social isolation enhances contextual fear: A model relevant for posttraumatic
stress disorder. Proceedings of the National Academy of Sciences. 2008; 105:5567–5572.
Pinna G. In a mouse model relevant for post-traumatic stress disorder, selective brain steoidogenic
stimulants (SBSS) improve behavioral deficits by normalizing allopregnanolone biosynthesis.
Behavioral Pharmacology. 2010; 21:438–450.
Pressman SD, Cohen S, Miller GE, Barkin A, Rabin BS, Treanor JJ. Loneliness, social network size,
and immune response to influenza vaccination in college freshmen. Health Psychology. 2005;
24:297–306.10.1037/0278-6133.24.3.297 [PubMed: 15898866]
Qualter P, Vanhalst J, Harris R, Van Roekel E, Lodder G, Bangee M, Maes M, Verhagen M.
Loneliness across ontogeny. Perspectives on Psychological Science. in press.
Randall C. Measuring national well-being – Our relationships, 2012. Office of National Statistics.
Author Manuscript

2012
Rizzolatti G, Matelli M, Pavesi G. Deficits in attention and movement following the removal of
postarcuate (area 6) and prearcuate (area 8) cortex in macaque monkeys. Brain. 1983; 106:655–
673.10.1093/brain/106.3.655 [PubMed: 6640275]
Rizzolatti G, Riggio L, Dascola I, Umiltà C. Reorienting attention across the horizontal and vertical
meridians: evidence in favor of a premotor theory of attention. Neuropsychologia. 1987; 25:31–
40.10.1016/0028-3932(87)90041-8 [PubMed: 3574648]
Rudatsikira E, Muula AS, Siziya S, Twa-Twa J. Suicidal ideation and associated factors among
school-going adolescents in rural Uganda. BMC Psychiatry. 2007; 7:67. [PubMed: 18034906]
Russell, D. The measurement of loneliness. In: Peplau, LA.; Perlman, D., editors. Loneliness: A
sourcebook of current theory, research and therapy. New York: Wiley; 1982. p. 81-104.
Russell D, Peplau LA, Cutrona CE. The revised UCLA loneliness scale: Concurrent and discriminant
validity evidence. Journal of Personality and Social Psychology. 1980; 39:472–
480.10.1037//0022-3514.39.3.472 [PubMed: 7431205]
Steptoe A, Owen N, Kunz-Ebrecht SR, Brydon L. Loneliness and neuroendocrine, cardiovascular, and
Author Manuscript

inflammatory stress responses in middle-aged men and women. Psychoneuroendocrinology. 2004;

29:593–611.10.1016/S0306-4530(03)00086-6 [PubMed: 15041083]
Stickley A, Koyanagi A, Roberts B, Richardson E, Abbott P, Tumanov S, Mckee M. Loneliness: Its
correlates and association with health behaviors and outcomes in nine countries of the former
soviet union. Plos One. 2013; 8:e67978.10.1371/journal.pone.0067978 [PubMed: 23861843]
Taylor SE. Tend and befriend: Biobehavioral bases of affiliation under stress. Current Directions in
Psychological Science. 2006; 15:273–277.10.1111/j.1467-8721.2006.00451.x
Tillich, P. The external now. In: Feifel, H., editor. The meaning of death. New York: McGraw-Hill;
1959. p. 30-38.

Perspect Psychol Sci. Author manuscript; available in PMC 2016 March 01.
 Cacioppo et al. Page 16

U.S. President’s Commission on Mental Health. Report to the President from the President’s
Commission on Mental Health. Vol. 4. Washington, D.C: U.S. Government Printing Office;
Author Manuscript

1978.
VanderWeele TJ, Hawkley LC, Thisted RA, Cacioppo JT. A marginal structural model analysis for
loneliness: Implications for intervention trials and clinical practice. Journal of Clinical and
Consulting Psychology. 2011; 79:225–235.10.1037/a0022610
Victor CR, Scambler SJ, Bowling A, Bond J. The prevalence of, and risk factors for, loneliness in later
life: a survey of older people in Great Britain. Aging and Society. 2005; 25:357–375.10.1017/
S0144686X04003332
Victor CR, Yang K. The prevalence of loneliness among adults: A case study of the United Kingdom.
Journal of Psychology. 2012; 146:85–104.10.1080/00223980.2011.613875 [PubMed: 22303614]
Waite, LJ.; Gallagher, M. Case for marriage: Why married people are happier, healthier, and better off
financially. New York: Doubleday; 2001.
Weeks DG, Michela JL, Peplau LA, Bragg ME. The relation between loneliness and depression: A
structural equation analysis. Journal of Personality and Social Psychology. 1980; 39:1238–
1244.10.1037/h0077709 [PubMed: 7205551]
Author Manuscript

Weiss, RS., editor. Loneliness: The experience of emotional and social isolation. Cambridge, MA:
MIT Press; 1973.
Williams RA, Hagerty BM, Yousha SM, Horrocks J, Hoyle KS, Liu D. Psychosocial effects of the
boot strap intervention in Navy recruits. Military Medicine. 2004; 169:814–820. [PubMed:
15532347]
Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Bennett DA. Loneliness and risk of
Alzheimer disease. Archives of General Psychiatry. 2007; 64:234–240.10.1001/archpsyc.
64.2.234 [PubMed: 17283291]
Woods S, Lambert N, Brown P, Fincham F, May R. “I’m so excited for you!” How an enthusiastic
responding intervention enhances close relationships. Journal of Social and Personal
Relationships. 2014; 4:1–17.10.1177/0265407514523545
Young, JE. Loneliness, depression and cognitive therapy: Theory and application. In: Peplau, LA.;
Perlman, D., editors. Loneliness: A sourcebook of current theory, research and therapy. New
York: Wiley; 1982. p. 379-406.
Author Manuscript

Young KA, Liu Y, Gobrogge KL, Wang H, Wang Z. Oxytocin reverses amphetamine-induced deficits
in social bonding: Evidence for an interaction with nucleus accumbens dopamine. The Journal of
Neuroscience. 2014; 34:8499–8506.10.1523/JNEUROSCI.4275-13.2014 [PubMed: 24948805]
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Figure 1.
The three dimensions of loneliness and different compartments of space.
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 Cacioppo et al. Page 18
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Figure 2.
The effects of loneliness on social cognition. Modified from J. T. Cacioppo and Hawkley
(2009).
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Perspect Psychol Sci. Author manuscript; available in PMC 2016 March 01.