Depression is a condition marked by sadness, emptiness, feelings of worthlessness, and loss of interest for most of the day activities. Other indicators include insomnia or hypersomnia, fatigue/loss of energy, psychomotor agitation or retardation, inability to concentrate, thoughts of death, and suicide ideation [1].
As stated by the Global Burden of Disease Study [2] depression remains, since 1990, one of the major leading cause of disability globally, reflecting a lack of progress in addressing this condition. A study base on the World Health Organization World Mental Health Surveys in 21 countries (four low/lower-middle income, five upper-middle-income, one lower-middle or upper-middle, and 11 high income), showed that one of the most prevalent individual disorders in university students was Major Depression Disorders (MDD), with rates of 4.5 to 7.7% [3]. Research on the prevalence of depressive symptoms among university students in Europe found rates, for female and male students, respectively, from 12.1 to 45.0%, with lower scores in Western countries, Germany 26.7%/ 22.8%, Denmark 24.9%/12.1%, and higher scores in Eastern countries Poland 45.5%/ 27.3%, and Bulgaria 42.9%/33.8% [4]. Similar results were found in a systematic review [5], with prevalence rates ranging from 10 to 85%, mean prevalence of 30.6%, a rate that exceeds the 21,6% found in the general population. Although epidemiological research shows wide variability in the prevalence of depression among countries, the available data is consistent regarding the higher rates of depression in women when compared to men [4, 6]. Depressive symptoms have a negative impact on the quality of life (QOL) [7] and have been associated with school absenteeism and early school dropout [8, 9], poor concentration, general low capacity for work, and poor academic performance [10, 11].
Oxytocin (OT) a neuropeptide synthesized in the hypothalamus and released by the posterior pituitary in systematic circulation, is knowing, for long, as an important hormone involved in parturition and breastfeeding [10,11,12]. In addition to peripheral effects, in humans, oxytocin is released by magnocellular excretory cells and binds to the amygdala, striatum, substantia nigra, hypothalamus [12]. This central action seems to be involved in human behaviours.
Existing evidence suggests that oxytocin serum levels play a role in many aspects of social behavior, improving bonding and attachment [13,14,15] increasing willingness to share emotions [16], positive communication [17] and trust [18, 19] increasing the ability to interpret mental states [20] and modulating the attentional processes [21].
Some of the features inherent to social behavior, such as the openness for relations or stress regulation, are also implicated in other behavioral and psychological processes such as depression, anxiety and post-traumatic stress disorder (PTSD) [22]. Recent research has focused on OT's relevance to developing, maintaining, and treating these disorders.
Research, including clinical trials, have been performed in various conditions, including schizophrenia, anxiety, and depression, and showed an association of this hormone with social individuals' skills, such as bonding, empathy, generosity, and altruism [23].
Mixed findings have been found regarding the correlation between the level of circulating plasma OT and depressive symptomology. Studies with samples of non-human mammals found that higher OT levels either by exogenous administration or by endogenous release, increased positive hedonic states in rats suggesting that OT help alleviate the severity of anhedonia observed in Major Depressive Disorder (MDD) [24]. In humans, low levels of OT have been associated with symptoms that characterize depression, such as loss of interest in maintaining interpersonal relationships [25, 26]. In a population diagnosed with MDD, Scantamburlo et al. [27] found that plasma OT levels were reduced compared to individuals without a mood disorder diagnosis. Similarly, in a study by Gordon et al. with healthy university students, OT was negatively correlated with depressive symptoms, measured by The Beck Depression Inventory (BDI), and psychological distress (i.e. depression and anxiety) proved to be predictors of OT [28]. Reinforcing these results, the study by Ozsoy et al. [29] that compared oxytocin levels between a sample of inpatients with depressive disorder, bipolar affective disorder, depressive episode, and a sample of healthy controls, found that serum oxytocin levels were decreased in patients when compared to controls. These results are consistent with several other studies that showed an inverse association between OT levels and depression [30,31,32]. However, a recent meta-analysis that include 64 studies with several psychiatric disorders, showed no significant differences in peripheral OT between a healthy adult and the MDD groups [33]. Further, Parker et al. [32] reported that Plasma OT concentration was elevated in depressed subjects compared to healthy controls.
It has been proposed that the oxytocin effect is gender-specific, with OT being more biologically relevant to women. Actually, despite some mixed findings, the inverse correlation between OT and stress and mood disorders has been more consistently found in women [29]. For example, Yuen et al. [34] showed that depressed females exhibited lower OT concentrations than depressed males, irrespective of psychotic status, and, unlike males, depressed females exhibited lower OT concentrations than healthy control females.
More recently, Engel et al. [35] carried out a systematic review and meta-analysis that specifically measured basal endogenous oxytocin concentrations in depressive patients and healthy controls. The assessment of nine studies, included in the meta-analytic procedure, showed non-significant differences in basal endogenous oxytocin concentrations between depressive patients and healthy controls. However, significant heterogeneity in effect was detected, and the authors point out that study designs, hormonal assessments, and clinical and demographic factors could explain these results.
Newly studies have begun to focus on other patient characteristics, e.g. temperament and personality traits, that may contribute to the differing results reported by various studies. Rothbart and Derryberry [36] defined temperament as a constitutionally based individual differences in reactivity and self-regulation in emotional, activational, and attentional processes. This approach identified four central constructs of temperament: (1) Extraversion/ Surgency, that consists of sociability and expressions of pleasure in anticipation of rewards or during high intensity/novel activities and motor activity; (2) Negative affect, that encompasses discomfort, anger/frustration, sadness, fear, and low sociability; (3) Effortful Control, that refers to the ability to voluntarily suppress a predominant response to perform a subdominant response according to environmental demands, detecting errors and planning; and (4) Orienting Sensitivity including perceptual, associative and general Sensitivity to stimulus raising from the environment [37]. It has been understood that temperament regards individual differences that (a) have a strong genetic basis; (b) manifest early in life, and (c) are relatively stable over the lifespan [37, 38].
A large body of research showed evidence of a link between temperament and depressive and anxiety disorders. For instance, in a study with a sample of 4773 subjects, members of the population-base, high levels of Harm avoidance and Pessimism were related to both depressive mood (effect sizes; d = 0.84 and d = 1.25, respectively) and depressive disorder (d = 0.68 and d = 0.68, respectively) [39]. More recently, Katz et al. [40], in a meta-analysis that aimed to quantify the relationships between temperament dimension of Sensitivity, depression and anxiety, found that Punishment sensitivity predicted depression (β = 0.37) and anxiety (β = 0.35), and Reward sensitivity predicted depression (β = − 0.07).
Despite this evidence, to the best of our knowledge no research has studied the effects of both oxytocin serum levels and temperament dimensions on depressive symptoms in a healthy sample. The current research is part of an extensive study with university students of the Instituto Politécnico de Lisboa (IPL) to evaluate the prevalence of psychological distress, namely anxiety and depression and their correlates. The present study aimed to: i) assess the relationship between serum oxytocin, depression and temperament traits and ii) analyse the effect of serum oxytocin and temperament in depressive symptomatology, in a sample of 45 young, healthy university female students.