A recent Institute of Medicine report acknowledges the efficacy of a broad range of psychosocial interventions.1 It challenges us to “identify key elements that drive an intervention’s effect.” The report describes key clinical tasks such as the therapist’s ability to engage with a patient, understand the patient’s worldview, and help the patient manage his or her emotional responses. The psychiatric community should also look into the neurobiological changes that accompany and may be responsible for an intervention’s effect. Although early psychoanalysts made little effort to connect functions of the mind to definable portions of the brain, from the beginning there was a belief that such a relationship may exist. Freud confidently predicted that one day there would be a neurological understanding of the work he initiated.
The deficiencies in our description would probably vanish if we were already in a position to replace psychological terms by physiological or chemical ones. Biology is truly a land of unlimited possibilities. We may expect it to give us the most surprising information and we cannot guess what answers it will return in a few dozen years to the questions we have put to it.2
Almost 100 years have passed since Freud wrote those words, and many of his questions remain unanswered. Steady progress, however, has been made in the development of a neurobiological understanding of what happens in the brain when the mind is engaged in psychotherapy. Advances in cognitive neuroscience and neuroimaging have facilitated a greater appreciation of the neuroanatomy and neurophysiology of the CNS. The technology to study the real-time functioning of the brain through measurement of blood flow or glucose uptake, for example, has been widely used for a quarter of a century. Numerous challenges endure, such as subtle individual variations of neural circuitry, uncertainty as to the proper area to study, and the possibility that differing forms of therapy affect the brain differently. Within the boundaries created by these limitations, however, there is an emerging understanding of the neurobiological correlates of some common psychotherapy elements.
Although different approaches utilize various terms and concepts, there are some components that are found in most forms of efficacious psychotherapy. There must be some emotional engagement (attachment) between the patient and therapist. The therapist will struggle to understand and express the patient’s experience (empathy). By learning about themselves and their environment, patients will decide to make changes. As therapy continues, they will develop new abilities to regulate their emotions. Many patients will be forced to face and overcome feared relationships or situations (fear extinction). There is a neurobiological literature developing on each of these common components of psychotherapy.
Forming nurturing attachments with others remains a challenge throughout life especially for those with early trauma. The neurochemistry of attachment involves the neuropeptides oxytocin and arginine vasopressin. Both of these messengers are released from the hypothalamus by sexual stimulation and stress. In combination with estrogen, oxytocin helps induce maternal behavior, while the absence of oxytocin makes it more difficult for animals to adapt to social settings and leads to abnormal displays of aggression. Infusing or blocking oxytocin also causes dramatic changes in mating behaviors. Arginine vasopressin has myriad effects on normal mammals including altering displays of aggression and the animal’s tendency to affiliate with or protect others.
In humans, oxytocin is associated with a number of factors that affect attachment including trust, empathy, eye contact, and generosity. Oxytocin infusions in healthy individuals tend to decrease anxiety and the stress associated with social situations while shifting attention from negative to positive information. The reduction in distress appears related to a reduction in activity in the amygdala. In a study of women with borderline personality disorder, oxytocin infusion decreased their amygdala activation when exposed to angry faces.3 Although the effect is mediated by past experiences, intra-nasal infusion of oxytocin may increase an individual’s ability to infer the mental state and intention of others based on their facial expression. Oxytocin specifically aids in parent-child bonding. Administering oxytocin to parents increases the social engagement of the parent and child and leads to an increase in oxytocin in the child.
The mu-opioid receptor also appears to be involved in attachment. Activation of the mu-opioid receptor leads to a general sense of pleasure as well as analgesia. In animal models, removing the mother from the child leads to distress that is at least partially mediated through mu-opioid activity. Animals with an increased activation of the opioid system had more attachment behaviors and louder and more prolonged protests when separated. Their separation distress could be partially reversed by non-sedating opioid agonists.4 Patients with borderline personality disorder have differences in baseline mu-opioid receptor concentrations and in the endogenous opioid system response to negative emotional challenges. These differences might be related to their difficulty with emotion regulation.
Attachment therefore correlates with neurochemical changes within the brain. This might be most evidenced in parent-child interactions but may play a significant role in psychotherapy as well. A study of mothers with postpartum depression undergoing psychodynamic psychotherapy found that daily infusions of oxytocin over 12 weeks were associated with a decrease in narcissistic traits but not in depressive personality traits or depressive symptoms.5 Depressed men who received oxytocin infusions while in psychotherapy performed better on tests of inferring the mental state of others but were more likely to experience anxiety during the session.6 These findings hint of a complex interaction between oxytocin and the therapist-patient relationship (Table 1).
Empathy entails the ability to consider the world from another’s point of view and in some way to share his or her emotional experiences. Neurobiological correlates of empathy were first described in the early 1990s with the discovery of mirror neurons. Researchers who were studying the neuronal activity involved in organizing and monitoring movements noted that some of the same premotor cortex neurons were activated while observing others make corresponding movements.7,8 Neurons that were activated when a monkey grabbed food were activated when the researcher grabbed food but not when the researcher pushed or struck the food. These neurons were referred to as mirror neurons.
Dr Welton is Associate Professor of Psychiatry and Director of Residency Training and Dr Kay is Emeritus Professor of Psychiatry, Boonshoft School of Medicine, Wright State University, Dayton, OH. The authors report no conflicts of interest concerning the subject matter of this article.
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