IS THERE A NEUROCHEMICAL BASIS FOR FALLING IN LOVE?

Introduction
“Nearly everybody gets twitterpated in the springtime. For example: You’re walking along, minding your own business. You’re looking neither to the left, nor to the right, when all of a sudden you run smack into a pretty face. You begin to get weak in the knees. Your head’s in a whirl. And then you feel light as a feather, and before you know it, you’re walking on air. And then you know what? You’re knocked for a loop, and you completely lose your head!”

In Disney’s Bambi, the wise old owl gives this memorable, and strikingly accurate, description of falling madly in love. The experience of being ‘twitterpated’ is universal, and one with which humankind has long been preoccupied. Of all subjects, it seems ‘twitterpation’ is one of mankind’s most discussed, analysed, dissected, researched and indulged. Love is a central theme in both serious and popular literature, and the dominant focus of music and song throughout the ages. It affects the everyday life of every man. Historically, love is even powerful enough to determine the fate of nations, considering the stories of Antony and Cleopatra, Othello and Desdemona and Napoleon and Josephine. Is there any other subject about which so much is known, but about which so little is truly understood?

Despite the seemingly paramount importance of love to humankind, our current knowledge of its physiological effects, neural substrates and neurochemical systems remains meagre. However, a handful of recent studies have brought to light some interesting findings on the neurochemical basis of romantic love. There is certainly no shortage of chemicals and hormones in the human body with which love can create its overwhelmingly intense myriad of effects. Let’s take a brief look inside “Love’s Laboratory.”

The “Laboratory of Love”

Chemical name: Phenylethylamine
Warnings: Ingest in moderation. May cause false symptoms of love.

Chocolate and lovers have had a long standing… er, love affair. Phenylethylamine, or as we shall affectionately call it, PEA, is an amine structurally related and pharmacologically similar to amphetamine.

PEA is found in chocolate, in the oil of bitter almonds, and in trace amounts in our brains, where it acts as a neurotransmitter, releasing dopamine and producing an antidepressant effect. Due to its admirable ability to induce positive mood changes, PEA was associated with one of the earliest hypotheses on the biology of falling in love (Marazziti and Canale, 2004).

Amphetamines are a class of drugs that affect dopamine release in the brain. Feelings of well-being, alertness and energy, as well as improved capacity for focused attention, rapid heartbeat and loss of appetite characterize an amphetamine high… and when you think about it, also quite accurately describes your roommate, whose new relationship has rendered her incapable of conversing with you on any other topic! However, no empirical data has been found to date that strongly supports the PEA theory of romantic love, and it has subsequently been suggested that different physiological mechanisms are involved in the early stages of falling in love (Marazziti and Canale, 2004).

Chemical Name: Testosterone
Warnings: May occur in excess amounts in males around attractive females. Side effects may be undesirable.

Testosterone, the principal male sex hormone, can be blamed for that crazy, aggressive, and just generally bizarre behaviour that becomes males around the fairer sex. Since falling in love is a little like going crazy, what better chemical to blame it on than testosterone? Testosterone is a steroid hormone from the androgen group, secreted from the male testes and the female ovaries. It is thought to be involved in general health and well-being, playing a key role in libido, energy, immune functions and protection from osteoporosis, among others.

In a unique study in 2004, Marazziti and Canale, noting the lack of data in this field, undertook to determine whether any significant hormonal changes underlie the subjective experience of falling in love. They measured hormone levels in a group of 12 men and 12 women who said they had fallen in love in the past six months (referred to as the Love group). The Control group consisted of 24 people who were either single or in stable long-term relationships. Their findings were intriguing.

Levels of LH, estradiol, progesterone, DHEAS and androstenedione (both androgenic steroid hormones) were consistent across the groups. Interestingly, men from the Love group had lower levels of testosterone than men in the Control group, while women from the Love group had higher testosterone levels than Control-group women. Marazziti and Canale, 2004, suggest that perhaps in the falling-in-love stage of a relationship, these converging hormone levels serve as a mechanism of temporarily eliminating some differences between the sexes. The softening of male features affected by testosterone (aggression, sex drive) and the enhancement of these features in women may aid in facilitating pair bonding, a term often used in animal studies to describe the temporary or permanent association formed between a female and male during courtship and mating (Carter, 1998). Though these possible explanations may be intuitively attractive, further research is needed in this area to gain any conclusive results.

Chemical Name: Cortisol
Warnings: Use sparingly for recovery from stress. Side effects may involve the formation of annoyingly intense attachments.

While investigating love’s effect on hormones, Marazziti and Canale 2004, also noted differing levels of cortisol between the Control and Love groups. Cortisol, the primary hormone product of the adrenal glands, is synthesized from its precursor hormone, progesterone, in the adrenal cortex. The main function of cortisol is to help restore homeostasis after a state of stress, which could definitely include, but is not limited to, stressful states caused by a not-so-understanding significant other!

Heightened arousal and increased stress levels are unsurprisingly associated with creation of new social contacts and specifically, the establishment of new relationships (Marazziti and Canale, 2004). Accordingly, Marazziti and Canale found raised cortisol levels in their Love group as opposed to the Control subjects, with no difference between the sexes. It is noteworthy however, that when hormone levels were measured for Love subjects still in the same relationship 12-28 months later, both cortisol and testosterone had returned to levels identical to the controls. This temporary hypercortisolemia could be viewed as a non-specific response to physiological changes induced by the stress of a new relationship. The apparent change in cortisol levels involved in falling in love suggests the involvement of the hypothalamus in this process, as cortisol synthesis is controlled by hypothalamic corticotropin-releasing hormone (Nelson, 2003). Many neuroendocrine studies reveal a strong association between increased levels of activity in the hypothalamic-pituitary-adrenal (HPA) axis and expression of social behaviour and attachments (Carter, 1998). Interestingly, Marazziti and Canale also noted that males in the Love group had decreased follicle-stimulating hormone (FSH) levels, though these findings are difficult to explain and speak to the need for more research on this topic.

Moderate levels of stress have been previously demonstrated to promote attachments, in both humans and in animals. Research on prairie voles has found that both corticosterone (the animal equivalent to cortisol) and stress facilitate the formation of pair bonds (De Vries et al., 1996). There are also numerous examples of stressful events, ranging from broad global-scale events to personal crises, which bring people together and create strong social bonds. Literature on both human and animal behaviour consistently implicates stressful or threatening situations, as well as interaction of HPA hormones, with the formation of strong social attachments and pair-bonding (Carter, 1998).

Chemical Name: Oxytocin
Warnings: May cause strong emotional attachments. Overuse may result in loss of independence and/or clinical diagnosis of “clingy-ness”.

Affectionately called the ‘cuddle chemical,’ oxytocin is a hormone well known for its roles in birth and lactation in the post-partum period, and the establishment of maternal-infant attachments (Carter, 1998). It is also released during orgasm in both sexes and acts as a neurotransmitter in the brain, facilitating bonding and the formation of trust.

Hormones such as oxytocin can reduce fear or behavioural inhibition, and promote the expression of social behaviours, such as pair bonding, and sexual and maternal behaviours (Carter, 1998). A number of animal studies have looked at the effects of oxytocin on specific behaviours. Female rats with no prior offspring show maternal behaviours within 30 minutes of oxytocin administration, and these behaviours can be completely abolished by treating with oxytocin antagonists (Carter, 1998). Female prairie voles treated with oxytocin show hastened pair bonding, but partner preference is interfered with when oxytocin is blocked, demonstrating the hormone’s role in facilitating pair bonding (DeVries et al., 1996). Oxytocin-treated prairie voles also show increased prosocial behaviour and reduced anxiety. Though there has been very little research in this regard relevant to humans, oxytocin seems to play a major role in reducing neophobia and anxiety, thereby facilitating social contact and establishment of relationships.

Chemical Name: Nerve Growth Factor (NGF)
Warnings: May cause neediness and excessively philanthropic behaviour.

The neurotrophin (NT) family is a group of proteins in mammals, consisting of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophins 3 and 4 (NT-3, NT-4). NGF is secreted by neural targets, and helps to direct growing nerve terminals to make the appropriate connections. What, you may ask, does this have to do with love? Though these molecules were originally only described as playing roles in neural development and synaptic plasticity, they have recently been implicated as mediators in anxiety, emotional responses and changes in behaviour (Emanuele et al., 2005). Research has also demonstrated that NGF can increase concentrations of hormones such as corticosterone in the plasma, thereby activating the HPA axis (Emanuele et al., 2005). Given the postulated involvement of the HPA axis in the physiological changes that occur when an individual is in love, this raises questions about the role of NTs in this process.

Following the precedent set by Marazziti and Canale in 2004, Emanuele et al. carried out a study in 2005 examining the effects of early-stage romantic love on plasma NT levels. The study’s subjects were again separated into a Love group, consisting of individuals who had fallen in love in the past six months, and a Control group including individuals in long-lasting relationships and singles. Their findings were just as intriguing.

Levels of BDNF, NT-3 and NT-4 remained constant between the Love group and both subgroups of the Control group. Curiously, the Love subjects showed greatly elevated levels of NGF when compared to the controls. Individuals who said they were in love had on average 227(n=14) pg/ml NGF, versus 123(n=10) pg/ml for long-lasting relationships, and 149(n=12) pg/ml for singles. However, perhaps most interestingly, Love group subjects who remained in their relationships showed a return to normal levels of NGF when tested 12-24 months later. Study subjects were also required to fill out the passionate love scale (PLS), developed by Hatfield and Sprecher (Emanuele et al., 2005). The PLS is thought to be a reliable means of quantifying the intensity of romantic love. After analysis, a significant positive correlation was found between plasma NGF levels and intensity of the romantic relationship as assessed by the 15-item PLS. The results of this study are both exciting and mystifying, and it is clear that the role of NGF as a mediator of affective states is yet another area that requires further research.

Conclusion
From this concise look at a few of the chemicals in “Love’s Laboratory,” it is clear that an extensive collection of chemicals exists. And changes in any one of these chemicals in our bodies can have a multitude of (literally!) mind-boggling effects. “Experimenting” with these different chemicals likely accounts for the crazy and bewildering behaviour characteristic of people who have fallen in love. Though both Marazziti and Emanuele, and colleagues, take great care to point out the limitations of their studies, their findings do raise some fascinating questions about the biology and chemistry underlying the process of ‘twitterpation’, otherwise known as falling in love. Perhaps the most interesting question brought to light by these studies however, is whether the seemingly all-powerful, all-knowing world of science can, in fact, explain everything. And do we really want to?

Maybe we should all just eat more chocolate.

References
Carter CS. (1998) Neuroendocrine perspectives on social attachment and love. Psychoneuroendocrinology 23(8):779-818

DeVries AC, DeVries MB, Taymans SE, Carter CS. (1996) The effects of stress on social preferences are sexually dimorphic in prairie voles. Proceedings of the National Academy of Science USA 93:11980-11984.

Emanuele E, Politi P, Bianchi M, Minoretti P, Bertona M, Geroldi D (2005) Raised plasma nerve growth factor levels associated with early-stage romantic love. Psychoneuroendocrinology Article In Press:1-7.

Marazziti D, Canale D (2004) Hormonal changes when falling in love. Psychoneuroendocrinology 29:931-936

Nelson RJ (2003) An Introduction to Behavioral Endocrinology, 3rd Edition. Sinauer Associates, Inc. USA.