This article reviews the current state of knowledge of the role of massage therapy in the treatment of common psychiatric disorders and symptoms. It briefly discusses the prevalence of psychiatric disorders and the popularity of complementary and integrative treatments in the general population. The authors touch on the growing literature describing the biology and neurobiology of massage therapy. The impact of massage as both a therapy for major psychiatric disorders and a treatment for psychiatric symptoms is reviewed, and how massage therapists conceptualize and treat their patients with psychiatric complaints is discussed. If psychiatrists are going to partner with massage therapists, they need to understand how massage therapists’ perspectives differ from those of traditional practitioners of allopathic medicine. A model of how psychiatrists and other mental health professionals can work with massage therapists to care for patients is proposed, followed by a summary of the article’s key points.
Of the top 25 disorders associated with years lost because of disability, seven are major psychiatric disorders (1). Major depression is the second leading cause of years living with disability in the world, anxiety disorders are the ninth leading cause, and schizophrenia is the 11th leading cause. Thus, major psychiatric syndromes are clearly associated with a major cost to society. Major psychiatric syndromes are also remarkably prevalent. One in four individuals will have a major psychiatric syndrome at some point in their lifetime (2). This means that everyone knows someone with a major psychiatric disorder, and every family is touched by the presence of these diseases. Despite significant advances toward both understanding the neuroscience of and developing new psychotherapies and pharmacotherapies to treat these disorders, a great unmet treatment need still exists. Using major depressive disorder as an example, we know from the National Institute of Mental Health–funded Sequenced Treatment Alternatives to Relieve Depression study that only one-third of individuals go into remission with initial treatment for depression (3). Furthermore, although close to two-thirds may enter remission with multiple successive treatments, the majority of these individuals will relapse within one year of reaching remission status (3). Thus, there is clearly a need for additional options to treat people with depression. It is reasonable to extrapolate from depression to other psychiatric disorders for which there are even fewer available treatment options. We contend that approaches to identifying potential treatment interventions for patients need to be broadened.
Systematic investigation into the popularity of complementary and alternative medicine (CAM) for treatment in the United States began in 1990 with the survey spearheaded by Eisenberg and colleagues (4). In this initial report in the New England Journal of Medicine, they documented that 33.8% of the adults surveyed had used some type of alternative or complementary medical service in the past 12 months. These findings were a revelation to most individuals in traditional Western or allopathic medical communities. Eisenberg and colleagues followed this report with a paper that compared and contrasted their 1990 data with those from a survey conducted in 1997 (5). This later publication documented an increase in the use of alternative therapies from 33.8% to 42.0%, with herbal medicine, massage, megavitamins, self-help groups, folk remedies, homeopathy, and energy healing increasing the most. They reported that some of the most frequent reasons for using complementary and alternative therapies included back pain, anxiety, depression, and headaches. In the 1997 paper, they estimated that the cost for services provided was $21.2 billion, with at least $12.2 billion being paid out of pocket. These initial findings by Eisenberg and colleagues were updated in the 2002 and 2007 Centers for Disease Control and Prevention–sponsored CAM surveys. In both of these surveys (6, 7), approximately 40% of adults reported having used some type of complementary and alternative therapy in the past 12 months. Also, both of these surveys indicated that approximately 5% of the U.S. adult population had used massage therapy. Purohit and colleagues (8) performed a reanalysis of the 2007 National Health Interview data of 23,393 adults that focused on the presence of neuropsychiatric symptoms and their impact on CAM usage. The prevalence of the use of CAM therapies was 43.78% for individuals with self-reported symptoms of depression, insomnia, headaches, memory deficits, attention deficits, and sleep problems versus 29.7% for individuals who did not report any of these symptoms. Of those individuals with at least one neuropsychiatric symptom who used CAM therapies, 20% used CAM therapy because they felt that standard treatments were either too expensive or ineffective, and 25% used CAM therapies because they were recommended by their traditional medical provider.
In conclusion, there is an interface between psychiatric disorders and complementary and alternative therapies such as massage. Accordingly, validated alternative therapies are now being integrated within the medical mainstream under the rubric “complementary and integrative medicine” (CIM). Consistent with this, and reflecting an emphasis on well-being and treatment of disease, the National Institutes of Health have renamed the center addressing CAM therapies the National Center for Complementary and Integrative Health. Psychiatric disorders are common and disabling, and current treatment methods, although helpful for many, are not the treatment of choice for many patients and are insufficient to alleviate disability and suffering for many others. This suggests that allopathic practitioners should think about two questions: What is the body of evidence supporting CIM interventions, and what is the best way for a psychiatrist or other mental health service provider and a CIM practitioner to interact with each other in the care of a patient? We address these two important issues.
Biology of Massage
Rigorous study of the biology of therapeutic massage is still in a relatively nascent phase. Although studies have attempted to understand the impact of various forms of massage on the body since the early 1990s, the research has been fraught with problems, in particular a lack of consistent funding for investigation of the biological effects of massage. Another challenge faced by the field is that there are many different types of massage and great variation in research study designs. As a result, current knowledge of the biology of massage rests mainly on a number of small studies investigating very different interventions that have been done for different lengths of time and at different frequencies. Despite these limitations, certain biological patterns seem to have emerged from recent studies.
Human Studies of the Neurobiology of Massage
A few EEG and imaging studies have investigated the impact of massage on brain circuitry or brain regions. One of the first studies was performed by the Touch Institute. In this study, 26 adults were given chair massage for 15 minutes twice weekly for five weeks, and 24 adults were asked to sit quietly in the massage chair twice weekly for five weeks (9). Field and colleagues found that twice-weekly massage was associated with an increase in frontal delta power in the EEG and a decrease in frontal alpha and beta power. This pattern is consistent with increased relaxation yet enhanced alertness, which was supported by the massage group’s having increased speed and accuracy on mathematical computations and decreased levels of anxiety. Salivary cortisol levels were also lower in the massage condition but not in the control condition. In a study of an aromatherapy massage intervention versus no treatment, Wu and colleagues (10) were able to replicate an increase in alpha wave activity in their aromatherapy massage sample, but they found a reduction in delta wave activity. However, they reported decreases in state anxiety and depression and an increase in psychological well-being as well as a reduction in salivary cortisol levels and an increase in plasma brain-derived neurotrophic factor in the aromatherapy group.
Neuroimaging studies investigating the impact of massage on the brain have been limited. In a small positron emission tomography study in 2006, Ouchi and colleagues (11) reported that being placed in the scanner in a prone position versus a supine position caused increased activation in the precuneus. This activation was further enhanced by both four minutes and 20 minutes of palm pressure massage applied to participants’ backs. The 20 minutes of massage also caused a greater increase in parasympathetic tone as well as activation of the parieto-occipital region. Ouchi and colleagues also reported activation in the cerebellum associated with massage. The authors concluded that this pattern of activation of the precuneus with back massage might reflect augmentation of arousal in consciousness functions associated with positive affect and that their findings of increased activity in the forebrain-amygdala system might be responsible for an increase in parasympathetic tone in the brain. The latter would also be consistent with a cerebellar increase in blood flow, which again would help regulate parasympathetic tone. These findings were partially replicated and extended by Sliz and colleagues (12), who looked at the neurocorrelates of a single session of massage versus those of a resting control condition, reflexology and massage with an object. They found that Swedish massage of the right foot while the participant performed a cognitive task in the scanner was associated with increased activation of the subgenual anterior and retrosplenial-posterior cingulate cortices. This increased activation of the retrosplenial-posterior cingulate cortex was sustained even without activation by the task.
If one integrates these findings investigating the impact of massage with those of a series of elegant studies that have been performed to attempt to understand the basic neurobiology of touch, one can come up with unifying theory of the impact of massage on the brain. An MRI study by Golaszewski and colleagues (13) demonstrated that vibrating tactile stimulation of the plantar surface of the foot increased activity in the inferior and posterior cingulate gyri along with the somatosensory cortex, insula, thalamus, caudate, and cerebellum. These brain regions integrate tactile and sensory information from mechanoreceptors, the myelinated A-beta and A-alpha afferents, and the unmyelinated sensory nerve fibers called c-tactile afferents that are thought to be associated with positive affect. The c-tactile afferents are stimulated by gentle stroking of hairy skin surfaces. They project to the limbic cortex, including the orbital frontal cortex and posterior insulate bilaterally.
In summary, although the data on the impact of massage on EEG and neuroimaging changes in the brain are limited, when these data are combined with the emerging data on somatic sensory pleasure circuitry, it is reasonable to postulate that massage’s beneficial effects on affiliation and feelings of well-being may be due to stimulation of specific brain circuits involved in pleasure and reward (14).
Impact of Massage on the Hypothalamic-Pituitary-Adrenal Axis and Neurohormones
A myriad of small studies of massage have measured either salivary or plasma cortisol levels. Many of these studies investigated only single time-point measures of cortisol before and after a series of massage interventions. The consensus of existing meta-analyses as well as of this review is that massage tends to decrease measures of plasma and salivary cortisol versus either a wait-list or a no-treatment condition (15). However, in general these studies have not looked at the sustained impact of massage after cessation of treatment. Rapaport and colleagues (16) have compared and contrasted the impact of a single 45-minute session of manualized Swedish massage with that of a manualized light-touch control condition in adults with no psychiatric disorder. They sampled cortisol, oxytocin, vasopressin, and adrenocorticotropic hormone after a 30-minute accommodation period at two points before initiation of massage or touch and then at several time points during the hour after the intervention. These authors found that a single session of either massage or touch was associated with a small effect-size decrease in cortisol levels in healthy young participants as well as a large effect-size increase in oxytocin in both groups. However, compared with changes found in cortisol and oxytocin, the massage group showed a profound significant decrease in vasopressin compared with the touch control group.
In a subsequent study, Rapaport and colleagues investigated the impact of weekly massage versus weekly touch for five weeks, as well as the impact of twice-weekly massage or twice-weekly touch for five weeks (17). Weekly massage versus weekly touch was associated with a pattern of results similar to that observed with a single session of massage. However, twice-weekly massage caused a significantly greater cumulative increase in oxytocin and decrease in vasopressin than twice-weekly touch. Although these data are of interest and consistent with previous studies reporting a decrease in cortisol levels and an increase in sense of affiliation associated with massage, these small studies require replication with larger cohorts of participants.
In summary, data suggest that massage may be associated with a decrease in hypothalamic-pituitary-adrenal activation and possibly with an increase in oxytocin levels. However, larger rigorous studies are needed.
Impact of Massage on the Immune System
A great deal of the pioneering work investigating the relationship between massage and the immune system occurred at the University of Miami. This group investigated the impact of massage on immune function in a variety of different patient populations including depressed individuals, HIV-positive young women, and HIV-positive adolescents (18–20). In general, this group reported an increase in natural killer (NK) cells and an increase in NK cell activity associated with massage compared with control conditions such as muscle relaxation. Rapaport and colleagues reported that a single session of Swedish massage versus a touch control condition caused a leukocytosis with a moderate effect-size increase in CD56+ NK cells and an increase in activated T cells (16). They have also reported that massage was associated with a significant decrease in Type 2 T helper (TH2) mitogen-stimulated cytokines compared with both baseline levels and the touch control condition (16). Massage was also associated with a decrease in mitogen-stimulated proinflammatory cytokine production when contrasted with the touch control condition. In 2012, Rapaport and colleagues reported that these effects were sustained for at least one week and that they were specific to individuals who received one massage per week in contrast to the groups receiving two massages per week (17). These findings are consistent with a report by Donoyama and Ohkoshi (21), who reported that two healthy female participants had an increase in gene expressions associated with immune response in the immune system compared with a 40-minute resting control condition. These findings are also consistent with work that has been done to investigate the local impact of massage on muscles that have been injured during exercise (22). Consistent with reports of both a single session of massage and repeated massage on TH2 cytokine production is a paper by Loft and colleagues that reports that massage decreased antibody responses after hepatitis B vaccination (23). In summary, although these findings require replication, they suggest that massage may affect the immune system in a way that enhances immune surveillance and NK cell activity while decreasing inflammation and TH2-type responses.
Summary of the Biology of Massage
In summary, although much more extensive investigation of the neurobiology of massage is needed, the data suggest that there is a parsimonious way of conceptualizing the mechanisms underlying its beneficial effects. The brain circuitry stimulated by c fibers is associated with feelings of positive affect and well-being. Massage also stimulates brain circuits involved in the control of sympathetic and parasympathetic activity, with an enhancement of parasympathetic tone. These effects could in turn lead to a decrease in stress response as well as modulation of certain aspects of immune function, such as a decrease in inflammatory response. Thus, it is possible to synthesize the existing data regarding the biology of massage into a cogent working hypothesis about its benefits for certain psychiatric disorders.Go to:
Massage, Depression, and Depressive Symptoms
As previously discussed, the use of CAM to treat depressive symptoms and major depression is common (5, 24). A reanalysis of a national survey by Kronenberg and colleagues (25, 26) that focused on 220 women with depression who were part of a national telephone survey of 3,060 women indicated that 54% of the depressed women reported using CAM in the past year and that half of those respondents indicated that they used some form of manual therapy. Despite the clear data suggesting that many patients with major depression or depressive symptoms are interested in CIM therapies and, in particular, manual therapies, the data have significant limitations. A meta-analysis by Coelho and colleagues (27) reviewed 595 articles and excluded all but four from their meta-analysis of massage therapy for treatment of major depression or depressive symptoms. A more recent meta-analysis of massage therapy for depressed people by Hou and colleagues (28) used less stringent criteria and identified 17 studies with 786 participants from among 246 references. This meta-analysis included many studies whose participants were recruited because of a primary disorder other than depression, including insomnia, breast cancer, fibromyalgia, HIV infection, and low back pain. They concluded that these clinical trials were of moderate quality and that the pooled standardized mean differences from fixed and random effects models were .76 and .73, respectively. However, they cautioned that these 17 studies had considerable heterogeneity and that standardized protocols for massage therapy are needed, using validated depression scales with larger and more homogeneous participant populations.
In a comprehensive review of the use of CAM for perinatal depression, Deligiannidis and Freeman (29) suggested that a growing body of literature supports the use of antenatal massage therapy either in combination with psychotherapy or as a monotherapy to treat pregnant women with mild depressive symptomatology. Poland and colleagues (30) published results of a randomized, parallel-group, open-label controlled trial of massage versus light touch and wait-list control for the treatment of major depressive disorder in individuals infected with HIV. They reported that twice-weekly massage therapy was effective in decreasing depressive symptoms as measured by both the Hamilton Depression Rating Scale and the Beck Depression Inventory, beginning at week 4 and continuing throughout the eight-week trial period.
When the data presented here are synthesized with those of previous meta-analyses investigating the biology and efficacy of massage therapy across multiple disorders, they suggest that massage may be beneficial, at least as an adjuvant treatment, for depressed patients interested in a manual alternative therapy (15, 31, 32).Go to:
Massage and Anxiety Symptoms and Disorders
Not surprisingly, similar to the findings about the use of complementary and alternative therapies for the treatment of depressive symptoms, massage and other complementary and alternative therapies are frequently used to treat symptoms of anxiety by the general population as well as by individuals with a host of different medical conditions (4–7). In fact, 43% of people who were treated in the National Institutes of Health–funded Coordinated Anxiety and Learning Management study reported using some type of complementary and alternative treatment for their anxiety disorder (33). These individuals met the DSM-IV criteria for generalized anxiety disorder, panic disorder, social anxiety disorder, or posttraumatic stress disorder. However, despite the high rate of use of complementary and alternative treatments for anxiety disorders as well as for symptoms of anxiety, very little systematic research has investigated massage therapy as a treatment for the anxiety disorders. Four published studies have investigated the use of massage for patients with generalized anxiety disorder. Billhult and Määttä (34) reported that eight women with generalized anxiety disorder who were treated twice weekly with one-hour massages had decreased feelings of anxiety and increased feelings of self-confidence associated with this open-label pilot treatment.
In contrast, Sherman and colleagues (35) compared and contrasted therapeutic massage with thermal therapy and relaxing room therapy for 10 sessions over a 12-week period. They reported that all three treatments were equally as effective in decreasing symptoms of anxiety. The patients in this study were allowed to be medicated and the treatment protocols were flexible in terms of the 10 intervention sessions. McPherson and McGraw (36) reported results of a multimodule intervention with 25 individuals with generalized anxiety disorder and comorbid disorders. In this multimodule therapy that included partner-assisted massage, they found significant reductions on the GAD-7, decreased anxiolytic medication use, and decreased pain scale ratings. In a randomized, single blind comparison of massage and light touch for patients with generalized anxiety disorder, Rapaport and colleagues found that the group randomized to twice-weekly Swedish massage therapy had significant improvements in both clinician and self-report ratings of anxiety (37). They further observed significant improvement in both clinician and self-report ratings of depression. There currently are no published studies evaluating massage as a treatment for posttraumatic stress disorder, social anxiety disorder, or panic disorder.
In conclusion, a growing body of evidence has suggested that massage may be a beneficial intervention either as an adjuvant or as a monotherapy for decreasing anxiety symptoms. The data demonstrating the efficacy of massage in specific psychiatric disorders are quite limited, and more rigorous studies are needed.Go to:
Evidence Supporting the Use of Massage for Other Psychiatric Symptom Clusters
A growing number of studies have suggested that a variety of massage interventions may facilitate greater sleep quality and sleep length for patients with primary and postpartum insomnia, insomnia and fatigue secondary to renal failure and hemodialysis, post–coronary bypass graft surgery sleep disturbance, and insomnia secondary to perimenopausal and postmenopausal symptoms (38–42). Massage therapy has also been linked to both improvement in sleep and improvement in behavior for patients with dementia (43, 44). Other studies have also suggested that massage interventions may decrease anxiety and enhance mood in nursing home residents with cognitive impairment (45, 46). The data on the use of massage therapy to decrease symptoms of autism are relatively limited (47), but one recently published trial of Qigong massage delivered by the parents of preschool children with autism reported improvement on measures of autism as well as in sensory and self-regulation responses (48). Although a comprehensive review of the complex literature investigating the relationship of decreasing pain and massage is beyond the scope of this review, data suggesting that massage may be useful in decreasing a variety of forms of musculoskeletal pain are increasing (49–51).
In summary, the extant, albeit limited, data on the relationships between the treatment of sleep, agitation, climacteric symptoms associated with menopause, and pain have suggested that massage may be helpful for at least some patients. Clearly, more rigorous study is needed before definitive conclusions can be reached about the value of massage therapy, especially in light of the marked variety of massage interventions and the cultural and societal factors influencing their use.Go to:
How Massage Therapists Conceptualize and Treat Clients With Psychiatric Complaints
Therapeutic massage is an intentionally holistic treatment approach that can complement the traditional practice of medicine. Massage therapy is not a substitute for traditional medical care, and the massage therapist cannot diagnose. The community practice of therapeutic massage has three basic themes: It is client centered, its practice has a formal structure, and factors influence practice (52). Establishing trust is the basis for a therapeutic relationship forged between practitioner and client. The emphasis on shared decision making in CIM empowers clients to take an active role in their health (53). A typical outline of activities involved in the practice of massage therapy includes ongoing assessment and evaluation, development of a treatment plan, treatment, health messages, documentation, and closure (52). Assessment starts when a client enters the treatment space; basic massage therapy education includes postural analysis and instruction in observing other cues such as breathing patterns. Massage therapists are trained to conceptualize health as a natural relaxed and aware state and any disease as an imbalance in that state. Accordingly, therapeutic massage assessment and treatment focuses on promoting interoceptive awareness (of both individuals in the therapeutic dyad), allowing the individual to feel more relaxed and comfortable in his or her body. The massage therapist may use special orthopedic assessment tests before continuing with a tactile assessment (often using broad holistic strokes to palpate the underlying tissues). An individualized treatment plan—including type of massage, session frequency, and session length—is developed on the basis of a combination of the client’s health history and current health status, balancing client goals with reality, referencing the best available evidence (research and resources such as pharmacology textbooks) and the massage therapist’s clinical expertise (52, 54). Assessment of the client through conversation and nonverbal clues is continuous both during the session and after the session is completed.
The literature has no consensus regarding the optimal type of massage therapy, frequency of treatment, or length of the sessions. All modalities of massage therapy are performed with intention and presence, providing an opportunity for the client to interact with another human being (the massage therapist) in a safe environment. Initial contact with the patient during treatment allows the massage therapist to gauge surface tension or ease before systematically progressing deeper or working a larger area. Most massage therapists are trained in a variety of modalities, allowing them to choose the tools best suited to the client’s current needs. In a treatment session, the client is in control of his or her experience (54).
Few studies have reported attempts to identify clinically relevant massage therapy frequency and dose (17, 55, 56). In practice, considerations of budget, schedule, accessibility, and acuity of symptoms are considered in determining the individualized treatment plan. Massage therapists on our team who have a community practice generally recommend that sessions occur every 10–14 days. In follow-up interviews for a recent study on massage for cancer-related fatigue, several participants indicated that the positive effects of the sessions lasted for days beyond completion of treatment. This is consistent with Rapaport and colleagues’ findings that the biological effects of massage were sustained for at least a week after the last session (17), as well as with those of the study by Perlman and colleagues (55), who reported that the positive effects of a massage intervention were sustained throughout the follow-up period for their study of osteoarthritis of the knee.
Along with the aforementioned factors, session length depends on techniques used and could vary in length from 15 to 90 minutes. Relaxing and revitalizing techniques are used at the end of a treatment session and establish closure. Finally, an exit interview is conducted, which may include home care suggestions relevant to the massage experience. All sessions should be formally documented, typically using SOAP (subjective, objective, assessment, and plan) note format.
Two factors influence the practice of massage therapy in the community: scope of practice and professional standards and ethics (52). Massage therapy is often thought of as a treatment for soft tissue dysfunction (i.e., muscle aches, tightness, and pain). However, an individual massage therapist’s scope of practice depends on his or her training, education, and location of practice. Basic educational requirements for massage therapy vary from state to state, as do regulatory laws (which can also vary by municipality). A massage therapist may choose to specialize in a certain type of treatment or work with a particular population. The practice of therapeutic massage is not static but continues to evolve as parameters change (57). Participation in continuing education classes, professional meetings, and experience continually shapes and refines a massage therapist’s practice and potentially expands the scope of practice.
Professional massage therapy organizations maintain and refine a repository of professional standards and ethics statements to guide the practice of massage therapy (https://www.amtamassage.org/articles/3/MTJ/detail/2493). In the case of a client currently in the care of a psychiatrist, collaboration between the psychiatrist and the massage therapist may be beneficial in establishing boundaries to preserve safety of the client and the massage therapist.Go to:
How Psychiatrists and Massage Therapists Can Work Together
Many individuals with psychiatric disorders are already using CIM. A mail survey of adults with serious mental illness found that 31% of respondents reported using massage therapy (58). A starting point may be to begin by asking which of your existing clients uses massage therapy, which massage therapist they frequent, and what the massage therapist’s intake process entails. This query may lead the psychiatrist to seek out massage therapy to better understand available treatment options, but it may also prove helpful in identifying characteristics of individuals who may benefit most from referrals to therapeutic massage.
Communication is key to facilitating collaboration and ensuring that the patient is given consistent messages. Collaboration between psychiatrists and massage therapists can yield an integrated approach that capitalizes on the benefits of both forms of treatment while incorporating patient preferences and priorities. In addition, collaboration can expand treatment options, potentially allowing patients to have a more active role in their health care. Therapeutic massage invites a patient to actively engage in optimizing his or her mind-body awareness. The massage therapist serves as a witness to changes the patient undergoes through treatment, both conventional and complementary or integrative. Massage therapy is best viewed as an adjunct therapy rather than as an alternative to conventional treatment.
Identification of a well-suited massage therapist to add to your professional network can be accomplished through word of mouth or professional associations. For a successful partnership, the massage therapist will have a treatment philosophy that aligns with the physician’s treatment philosophy and a basic understanding of psychiatric disorders. Professional massage therapy organizations offer massage therapist locator services, and these services only list members in good standing (https://www.amtamassage.org/findamassage/index.html)Go to:
In closing, patients accept and commonly use complementary and integrative therapies. They frequently seek out massage therapy to treat symptoms of depression and anxiety. Although data have suggested that massage may help decrease problems with depressed mood or acute anxiety, less information is available regarding the use of massage as a therapy for depression or anxiety disorders. Current data do suggest that massage may have some benefit as at least an adjuvant to conventional therapies. Although the data are limited, some findings have suggested that massage may acutely decrease hypothalamic-pituitary-adrenal activity, have a positive effect on immune function, enhance parasympathetic tone, and modulate brain circuitry. The approach and philosophy of well-trained massage therapists is complementary to conventional psychiatric training and can thus be an important additional resource in treating patients. A respectful and collaborative approach to care may truly help patients.Go to:
Dr. Schettler reports being a statistical analysis consultant to LivaNova. Dr. Nettles reports participation in the Novartis Employees Retirement Fund, being a consultant to Wolf Greenfield—Boston Drug Discovery IP, and serving as an expert witness. Dr. Rapaport, Ms. Larson, Mr. Carroll, Ms. Sharenko, and Dr. Kinkead report no financial relationships with commercial interests.