European Neuropsychopharmacology 60 (2022) 22–24

www.elsevier.com/locate/euroneuro

Social Stress in Bipolar Disorder

Bipolar and Depressive Disorders Unit, Department of Psychiatry and Psychology, Hospital Clínic
Barcelona, Institute of Neurosciences, University of Barcelona, Biomedical Research Networking Centre
for Mental Health Network (CIBERSAM), August Pi I Sunyer Biomedical Research Institute (IDIBAPS),
Barcelona, Catalonia, Spain

Received 18 March 2022; received in revised form 1 April 2022; accepted 4 April 2022

KEYWORDS
Childhood Trauma;
Stress;
Interpersonal
Relations;
Loneliness;
Mood Instability;
Intervention;
Affective Disorder

Social stress is an unavoidable part of human lives. The nored, rejected or discriminated. Thus, social stress arises
most common form of stress stems from one’s social envi- when evaluating a situation as relevant, but not having re-
ronment and is perceived as more intense than other types sources to cope or handle that specific situation.
of stressors (Wood and Bhatnagar, 2014). Anything that dis- People with bipolar disorder (BD) maybe disproportion-
rupts or threatens relationships with others, self-steem or ately affected by the effects of social stress, especially
sense of belonging within a dyad, group or larger social con- in family, romantic and peer relationships (Johnson et al.,
text can result in social stress: an unhappy marriage, caring 2016). BD represents a chronic and recurrent mental disor-
for a relative with a chronic illness, the threat of or actual der characterized by mood instability (Carvalho et al., 2020)
death of a loved one, and social isolation are all sources of that relates to severe social and neurocognitive functional
social stress. Navigating social stress effectively is essential disruptions associated with poor well-being and quality of
to thriving in this challenging world. life. Feelings of disconnection and isolation from others due
Specifically, social stress can emerge in situations and to lack of social contact can further aggravate decreases in
interactions where others could be judgmental or critical mood in individuals with BD, particularly loneliness, which
and represent perceptions of lower role or standing within in turn, are among the most robust known risk factors for
a group or community in contexts which someone feels ig- poor health and accelerated mortality, including depression
and anxiety (Wang et al., 2018). Yet, mitigating these so-
cial risk factors may call into question the effectiveness of
Abbreviations: CT:, Childhood Trauma; BD:, Bipolar Disorder. available interventions for both, reducing loneliness and in-
∗ Corresponding author. creasing social contact in these patients.
E-mail address: [email protected] (N.E. Fares-Otero).

https://doi.org/10.1016/j.euroneuro.2022.04.002
0924-977X/© 2022 Elsevier B.V. and ECNP. All rights reserved.
 European Neuropsychopharmacology 60 (2022) 22–24

Fig. 1 Conceptual model of cumulative social stress exposure, clinical and psychosocial outcomes in individuals with bipolar
disorder and childhood trauma.

Even with pharmacological and psychological treatments, renders people with BD especially susceptible to deleterious
individuals with BD often fail to obtain complete remis- effects of social stress.
sion and continue to report residual symptoms within sev- Moreover, CT may inhibit the ability to socialize effec-
eral years. A recent meta-analysis (Wrobel et al., 2022) tively and form good quality and meaningful long-term re-
implicates childhood trauma (CT) in differential treatment lationships in patients with BD. CT introduces victims to the
outcomes, maybe associated with greater improvement in isolation, insecurity and stigma a mental health diagnosis
global functioning, among individuals with BD. (as BD) can bring, leading to avoidance and fear in meet-
CT is a major risk factor (reported by more than half of ing other people and reluctance to seek support. The low
patients) in the worsening clinical course and expression of self-steem and pervasive feelings of shame and guilty can
BD, primarily an earlier age at onset, increased risk of sui- lead victims to isolation driven by the belief that any at-
cide attempt, substance misuse and persistent comorbidi- tempts to be social will be futile; viewing themselves as not
ties, with studies showing a dose-response relationship be- mattering to others, unlikable and unworthy of affection,
tween cumulative CT experiences and mood instability risk they expect to be rejected. Further alterations in interper-
(Grillault Laroche et al., 2022) and rapid cycling – which sonal distance regulation, social touch and trust processing
all might be related to diminished social involvement in pa- (Neil et al., 2022) may disrupt social bonds and contribute
tients with BD. to a reduction in the extent and quality of social relation-
CT is further associated with disrupted brain function- ships, leaving those patients affected by CT more vulnera-
ing and connectivity among (limbic threat-related) struc- ble to environmental stressors, increasing the risk of mental
tures (involving the hypothalamic pituitary axis) which are health difficulties.
responsible for stress response and regulation, increas- It is therefore particularly important to strengthen the
ing stress sensitivity and vulnerability to subsequent so- interpersonal well-being of individuals with BD and CT given
cial stressors (Starr et al., 2021). In line with these al- that: 1. Developing social relationships may prevent from
terations, also associated with BD progression, CT relates adverse stress-related consequences, and 2. Building and
to impaired emotion regulation, impulse control, inter- maintaining positive relations can foster resilience to pro-
personal relations, occupational and cognitive functioning tect against mental and physical health problems.
(Jiménez et al., 2017) that might decrease the ability to Despite the well-documented long-lasting and negative
cope with social life stress. It is thus possible that prior CT impact of CT on BD, evidence on treatment alternatives

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 N.E. Fares-Otero and A. Martinez-Aran

(to standard pharmacotherapy and psychological interven- Grillault Laroche, D., Godin, O., Belzeaux, R., M’Bailara, K., Lof-
tions) remains scant. To date, only one published study pro- tus, J., Courtet, P., Dubertret, C., Haffen, E., Llorca, P.M.,
tocol has reported a clinical trial for trauma victims with BD Olie, E., Passerieux, C., Polosan, M., Schwan, R., B, T.F.,
(involving functional intervention targets), but mainly for Leboyer, M., Bellivier, F., Marie-Claire, C., Etain, BCollaborators,
those with Posttraumatic Stress Disorder (PTSD) (Moreno- 2022. Association between childhood maltreatment and the
clinical course of bipolar disorders: a survival analysis of mood
Alcázar et al., 2017). Based on the above considerations
recurrences. Acta Psychiatr. Scand. doi:10.1111/acps.13401,
(see also Figure 1) we highlight that there is a high-risk n/a(n/a).
group of patients with CT (without PTSD) for social stress- Jiménez, E., Solé, B., Arias, B., Mitjans, M., Varo, C., Reinares, M.,
related vulnerability who need a particular approach. Bonnín, C.D.M., Ruíz, V., Saiz, P.A., García-Portilla, M.P.,
Hence, our recommendations are: 1. Both, detecting and Burón, P., Bobes, J., Amann, B.L., Martínez-Arán, A., Tor-
recording CT in clinical settings are crucial for patients with rent, C., Vieta, E., Benabarre, A., 2017. Impact of childhood
BD; 2. Given the importance of CT in the prognosis and trauma on cognitive profile in bipolar disorder. Bipolar Disord.
course of BD, researchers should provide evidence-based 19 (5), 363–374. doi:10.1111/bdi.12514.
trauma interventions to overcome cumulative social stress- Johnson, S.L., Cuellar, A., Gershon, A., 2016. The influence of
trauma, life events, and social relationships on bipolar depres-
related consequences in patients; and 3. A targeted in-
sion. Psychiatr. Clin. North Am. 39 (1), 87–94. doi:10.1016/j.psc.
tervention on establishing positive social relationships and
2015.09.003.
functioning should be considered for patients with CT to de- Martinez-Aran, A., Vieta, E., 2022. Precision psychotherapy. Eur.
termine resilience and improve their mental and physical Neuropsychopharmacol. 55, 20–21. doi:10.1016/j.euroneuro.
health. 2021.10.771.
Of note, as of this time, a significant proportion of Moreno-Alcázar, A., Radua, J., Landín-Romero, R., Blanco, L.,
worldwide population is at risk of social stress (e.g., so- Madre, M., Reinares, M., Comes, M., Jiménez, E., Crespo, J.M.,
cial isolation) as a result of the ongoing COVID-19 pan- Vieta, E., Pérez, V., Novo, P., Doñate, M., Cortizo, R., Valiente-
demic (Verdolini et al., 2021). Even if society could achieve Gómez, A., Lupo, W., McKenna, P.J., Pomarol-Clotet, E.,
lower numbers of hospitalizations and deaths, stressful un- Amann, B.L., 2017. Eye movement desensitization and repro-
certainty of life and traumatic impacts of this crisis are cessing therapy versus supportive therapy in affective relapse
prevention in bipolar patients with a history of trauma: study
likely to be enduring. Particularly, measures employed to
protocol for a randomized controlled trial. Trials 18 (1), 160.
control the pandemic may have led to maladaptive coping doi:10.1186/s13063- 017- 1910- y.
with social distancing and loneliness in a substantial subset Neil, L., Viding, E., Armbruster-Genc, D., Lisi, M., Mareschal, I.,
of individuals with BD and CT. This leads to the suggestion Rankin, G., Sharp, M., Phillips, H., Rapley, J., Martin, P., Mc-
that clinicians should assess CT for every patient with BD – Crory, E., 2022. Trust and childhood maltreatment: evidence of
at least for those with severe, unstable or relapsing course. bias in appraisal of unfamiliar faces. Journal of Child Psychology
Finally, the identification of risk indicators of negative and Psychiatry doi:10.1111/jcpp.13503, n/a(n/a).
outcomes could facilitate early detection of patients with Starr, L.R., Stroud, C.B., Shaw, Z.A., Vrshek-Schallhorn, S., 2021.
greatest clinical needs and risk of poor social functioning. Stress sensitization to depression following childhood adver-
sity: moderation by HPA axis and serotonergic multilocus pro-
Understanding and improving the care pathway for individ-
file scores. Dev. Psychopathol. 33 (4), 1264–1278. doi:10.1017/
uals with BD and CT could contribute to the design and
S0954579420000474.
provision of more personalized treatment plans (Martinez- Verdolini, N., Amoretti, S., Montejo, L., García-Rizo, C., Hogg, B.,
Aran and Vieta, 2022) for patients highly vulnerable to social Mezquida, G., Rabelo-da-Ponte, F.D., Vallespir, C., Radua, J.,
stress exposure during the pandemic and beyond. Martinez-Aran, A., Pacchiarotti, I., Rosa, A.R., Bernardo, M., Vi-
eta, E., Torrent, C., Solé, B., 2021. Resilience and mental health
during the COVID-19 pandemic. J. Affect. Disord. 283, 156–164.
Funding doi:10.1016/j.jad.2021.01.055.
Wang, J., Mann, F., Lloyd-Evans, B., Ma, R., Johnson, S., 2018. As-
sociations between loneliness and perceived social support and
This work was supported by the Spanish grant FIS PI17/00941
outcomes of mental health problems: a systematic review. BMC
from Instituto de Salud Carlos III (ISCIII).
Psychiatry 18 (156). doi:10.1186/s12888- 018- 1736- 5.
Wood, S.K., Bhatnagar, S., 2014. Resilience to the effects of social
stress: evidence from clinical and preclinical studies on the role
Declaration of Competing Interest of coping strategies. Neurobiol Stress 1, 164–173. doi:10.1016/
j.ynstr.2014.11.002.
None. Wrobel, A.L., Jayasinghe, A., Russell, S.E., Marx, W., Alameda, L.,
Dean, O.M., Cotton, S.M., Berk, M., Turner, A., 2022. The in-
fluence of childhood trauma on the treatment outcomes of
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