Raised plasma nerve growth factor levels associated with early-stage romantic love

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Summary

Our current knowledge of the neurobiology of romantic love remains scanty. In view of the complexity of a sentiment like love, it would not be surprising that a diversity of biochemical mechanisms could be involved in the mood changes of the initial stage of a romance. In the present study, we have examined whether the early romantic phase of a loving relationship could be associated with alterations in circulating levels of neurotrophins (NTs). Plasma levels of NGF, BDNF, NT-3 and NT-4 were measured in a total of 58 subjects who had recently fallen in love and compared with those of two control groups, consisting of subjects who were either single or were already engaged in a long-lasting relationship. NGF level was significantly higher (p<0.001) in the subjects in love [mean (SEM): 227 (14) pg/ml] than in either the subjects with a long-lasting relationship [123 (10) pg/ml] or the subjects with no relationship [149 (12) pg/ml]. Notably, there was also a significant positive correlation between levels of NGF and the intensity of romantic love as assessed with the passionate love scale (r=0.34; p=0.007). No differences in the concentrations of other NTs were detected. In 39 subjects in love who—after 12–24 months—maintained the same relationship but were no longer in the same mental state to which they had referred during the initial evaluation, plasma NGF levels decreased and became indistinguishable from those of the control groups. Taken together, these findings suggest that some behavioural and/or psychological features associated with falling in love could be related to raised NGF levels in the bloodstream.

Introduction

Intense romantic love, a complex sentiment typically directed toward a single person, is one of the most overwhelming of all affective states and has been the inspiration for some of the greatest achievements of mankind. As it typically involves emotional, cognitive, behavioural and erotic components, the functions of romantic love appear not to be limited to generate offsprings, but also to promote in individuals a stable emotional environment as well as to arise pleasant and safe feelings of happiness and sex arousal (Fisher, 1998, Gonzaga et al., 2001). The process of romantic love in humans begins with falling in love, a subjective experience characterized by intense focused attention on a preferred individual, obsessive thinking about him or her, emotional dependency on and craving for emotional union with this beloved, euphoria and increased energy (Tennov, 1979).

Despite the importance that love assumes, even if transiently, in the lives of most, our current knowledge of the neural substrates and neurochemical systems involved in arousing and sustaining romantic love is still scanty. In any case, preliminary evidence seems to suggest that the neurochemical systems involved in forming romantic bonds may also be powerful stimulators of anxiety (Carter, 1998). To explain this seeming paradox, it has been postulated that human beings are anxious until a social bond is achieved and, once it happens, it is likely, although not necessary, that anxiety will be replaced by positive feelings of integration, stability, and pleasure (Kendrick, 2004). Accordingly, some authors have proposed that falling in love could be regarded as a basic emotion like anxiety or fear, due to activation of the amygdala and related circuits and neurotransmitters (Bartels and Zeki, 2000, LeDoux, 2000). Additionally, the universality, euphoria, and focused attention of early romantic love suggest that reward and motivation systems in the human brain could likely play a role (Aron et al., 2005). It is also feasible that the formation of a romantic bond may induce the synthesis and release of biochemical mediators, which remain to be identified, that may promote positive emotions, pleasant affective states and a reduced perception of anxious feelings (Esch and Stefano, 2005).

To date, the neurochemical bases of love in humans have only been studied in one investigation, which found that the intrusive thoughts of the early romantic phase of a falling in love could be due to a reduced functionality of the serotonin transporter (Marazziti et al., 1999). In any case, in view of the complexity of a sentiment like love, it would not be surprising that a diversity of biological mechanisms could be involved in the mood changes of the initial stage of a romance. It seems therefore reasonable that, apart from conventional monoaminergic systems, many other modulators, including hormones and neurotrophins may be implicated in the altered mental state associated with falling in love. Consistently, a previous report has indicated that to fall in love provokes transient hormonal changes which seem to show a gender-related specificity (Marazziti and Canale, 2004).

At this time, however, no study has examined whether the early romantic phase of a loving relation is associated with alterations in circulating levels of neurotrophins (NTs). The family of NTs in mammals includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins 3 (NT-3) and 4 (NT-4) (Chao, 2004). These molecules, originally described as key regulators of synaptic plasticity and neural survival during development and at adulthood (Pardridge, 2002), have been increasingly recognized as potential mediators of anxiety, emotions and behavioural modifications (Aloe et al., 1994, Alleva and Santucci, 2001, Hadjiconstantinou et al., 2001, Branchi et al., 2004). Given these considerations, it seemed of interest to evaluate the levels of NTs in a cohort of subjects who had recently fallen in love. These subjects were compared with two control groups consisting of individuals who were either single or were already engaged in a long-lasting relationship.

Section snippets

Methods

From August 2002 to December 2003, potential participants required to be ‘truly, deeply and madly in love’ were recruited by word of mouth and with flyers seeking individuals who were recently fallen in love. According to previous methodology (Marazziti and Canale, 2004), only subjects whose relationships have begun within the previous 6 months were considered eligible for study participation. In addition, all individuals were ascertained to spend at least 4 h a day in thinking about the

Results

The three study groups were well matched with regard to gender (χ2=0.149, p=0.92). However, subjects in love were significantly younger than either the subjects with a long-lasting relationship or the singles (p<0.001 and 0.01, respectively).

As expected (Chaudhuri et al., 2005), we found no evidence for age and gender differences in circulating NTs levels (data not shown). Therefore, data were pooled for subsequent analysis.

Table 1 presents the plasma NTs concentrations observed in the three

Discussion

Although the current knowledge of the neurobiological substrates of love in humans remains meagre, studies of pair bonding in sheeps and voles have reported a recurrent association between high levels of activity in the hypothalamic pituitary adrenal (HPA) axis and the subsequent expression of social behaviours and attachments (Carter et al., 1995, DeVries et al., 1995, Aragona and Wang, 2004). On the other hand, the formation of stable pair bonding has been shown to result in a reduced HPA

Acknowledgements

This research was supported in part by a grant (Fondo di Ateneo per la Ricerca) from the University of Pavia, Pavia, Italy.

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