Psychiatry Research 121 (2003) 145–158
0165-1781/03/$ - see front matter ᮊ 2003 Publishedby Elsevier IrelandLtd.
Long-term immune-endocrine effects of bereavement: relationships
with anxiety levels andmood
Gilberto Gerra *, Daniela Monti , Alberto E. Panerai , Paola Sacerdote ,
Roberta Anderlini , Paola Avanzini , Amir Zaimovic , Francesca Brambilla ,
ba a c
Centro Studi Farmaco-Tossico Dipendenze, AUSL, Via Spalato 2, Parma 43100, Italy
Department of Biomedical. Sciences, Section of General Pathology, University of Modena, Modena, Italy
Department of Pharmacology and Centro di Psiconeuroendocrinologia, University of Milan, Milan, Italy
Received18 March 2002; receivedin revisedform 7 August 2002; accepted15 November 2002
Psychological, endocrine and immune parameters were measured over a 6-month period in 14 healthy subjects
who underwent an unpredictable acute emotional stress (e.g. sudden death of a loved one) comparedwith 14 controls
who did not. Probands were profoundly stressed as assessed 10 days after bereavement by their scores on the
Hamilton Rating Scales of Anxiety andDepression, adrenocorticotropin andcortisol plasma concentrations, andnon-
suppression in response to dexamethasone. Functional alterations of immune parameters, such as responsiveness of
peripheral bloodlymphocytes to mitogens, were found40 days after bereavement. Despite a normal number of
circulating lymphocyte subsets, the functional activity of natural killer (NK) cells was markedly reduced at day 40.
Changes in the intracellular concentration of b-endorphin in peripheral blood mononuclear cells correlated with
anxiety and depression scores. Controls showed no changes in psychometric, endocrine and immune measures during
the 6-month study. Cluster analysis revealedtwo groups of bereavedsubjects with different patterns of immune and
endocrine changes: (1) Five subjects, characterized by harm-avoidant temperament and long-lasting dysphoric mood,
showedreducedresponsiveness of peripheral bloodlymphocytes to mitogens, decreasedNK cell activity andnon-
suppression in response to dexamethasone that persisted for 6 months. (2) Nine subjects showedsignificant changes
only during the early phase after bereavement. Our data suggest that the immunological consequences of stress do
not simply overlap with psychological andendocrine alterations, andare particularly severe andlong-lasting in a
subgroup of subjects, indicating the importance of individual variability in the capacity to cope with stress.
ᮊ 2003 Publishedby Elsevier IrelandLtd.
Keywords: Bereavement; Psychological stress; b-endorphin; Anxiety; Depression; Natural killer cells; Neuro-immunomodulation;
Corticotropin; Hydrocortisone; Dexamethasone
*Corresponding author. Present address: Dipartimento Nazionale Politiche Antidroga Via Quintino Sella, 69 00187 Roma, Italy.
Tel.: q39-0521-393125; fax: q39-0521-393150.
E-mail address: firstname.lastname@example.org (G. Gerra).