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 covered a wide variety of psychiatric issues and industry updates, from important suicide prevention tips to new insights into ketamine response. Here are some highlights from the week.

Study Explores Effects of Experimenter Sex on Ketamine Response

Does a health care provider’s sex impact how well active agents perform? The answer appears to be a “yes,” according to a new study that examined the antidepressant response to ketamine and its bioactive metabolite (

)-hydroxynorketamine when the drug was administered to mice by men compared to women. 

Suicide Prevention Month Tips and Insights

September is National Suicide Prevention Month. In this Mental Health Minute, Susan J. Noonan, MD, MPH, of McLean Hospital and Massachusetts General Hospital shares the risk factors and warning signs of suicide that clinicians must know. 

A traumatic brain injury (TBI) occurs when brain function is altered due to an external blow to the head or body. National surveillance data indicates there are approximately 3 million new cases of TBI each year in the United States, and that the incidence of TBI has been increasing since 1995. Rates of TBI are increasing in all age groups, but particularly for adults over the age of 65, primarily due to falls. According to some estimates, mild traumatic brain injury (mTBI), or concussion, accounts for as many as 75% to 90% of all traumatic brain injuries. 

NDA for Long-Acting Injectable for Schizophrenia and Bipolar I Accepted

The US Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for aripiprazole 2-month, ready-to-use, long-acting injectable, a medication administered for the treatment of schizophrenia in adults and for maintenance monotherapy treatment of bipolar I disorder in adults. It is intended for dosing every 2 months via intramuscular injection in the gluteal muscle. 

. And be sure to stay up-to-date by subscribing to the 

Do you have a comment on any of these or other articles? Have a good idea for an article and want to write? Interested in sharing your perspectives? Write to us at 

From ketamine response to differences between mTBI and concussion, here are highlights from the week in Psychiatric Times.

The Week in Review: September 12-16

A traumatic brain injury (TBI) occurs when brain function is altered due to an external blow to the head or body.

 National surveillance data indicates there are approximately 3 million new cases of TBI each year in the United States, and that the incidence of TBI has been increasing since 1995.

 Rates of TBI are increasing in all age groups, but particularly for adults over the age of 65, primarily due to falls.

 According to some estimates, mild traumatic brain injury (mTBI), or concussion, accounts for as many as 75% to 90% of all 

The American College of Rehabilitation Medicine (ACRM) defines mTBI as:

Any period of loss of consciousness (LOC)

Any loss of memory of events immediately before or after the incident

Any alteration in mental state at the time of the incident (ie, feeling dazed or confused)

Focal neurological deficits that may or may not be transient, but the severity does not exceed:

Initial Glasgow Coma Scale (GCS) score of 13-15

Normal brain imaging results (ie, CT, MRI)

Despite current surveillance data, the actual number of mTBIs occurring each year is difficult to measure because many individuals do not seek medical care immediately following injury. Although the military and most athletic organizations (ie, organized school, college, and professional sports teams) provide education, testing, and strict protocols for identifying and managing concussion, many individuals with noncombat or nonsports-related mTBI/concussion do not seek initial treatment. Some may delay seeking medical care for weeks or months until attempts to self-manage symptoms fail; they are encouraged by family, coworkers, etc, to seek care; or their symptoms become problematic.

mTBI/concussion can result in multiple and complex changes in a number of domains, including physical/somatic, cognitive, emotional, and behavioral.

 Physical or somatic complaints following mTBI include 

, nausea, dizziness/balance disturbance, fatigue, poor sleep, noise or light sensitivity, blurred vision, hearing impairment, and numbness/tingling. Frequently reported cognitive complaints include decreased attention/concentration, poor memory, slow information processing speed, difficulty multitasking, impaired judgment, impulsivity, and subtle language difficulties (such as word-finding problems). Emotional and behavioral problems following mTBI can include anxiety, depression, irritability and agitation, increased emotional lability, apathy, and in some instances, aggression.

Although most symptoms associated with mTBI resolve in a relatively short period of time (ie, 2 to 4 weeks), about 10% to 20% of individuals with mTBI experience symptoms beyond 4 weeks. When symptoms persist beyond 4 weeks, a diagnosis of persistent postconcussive symptoms (PPCS) is offered. Risk factors that predict PPCS include female gender, being older than 40 years of age, history of 

, previous psychiatric diagnoses (ie, anxiety, depression), propensity toward somatization, and pending litigation.

Unfortunately, diagnosis is complicated because usual imaging techniques (ie, CT scans) do not readily detect concussion/mTBI, and there is considerable symptom overlap between mTBI and other psychological conditions. For example, light/sound sensitivity, headache, sleep disturbance, dizziness, fatigue, and cognitive problems such as decreased concentration, impaired attention, and poor memory are present in both mTBI and 

 (PTSD). Likewise, symptoms such as depressed mood, apathy, sleep problems (ie, too much/too little), irritability, decreased attention, and poor memory are present in both mTBI and depression.

Given the symptom overlap between mTBI and other psychological/psychiatric conditions, obtaining a thorough event history is extremely important. During the clinical interview, patients should be queried regarding any recent falls, vehicular or sporting accidents, or any other event that could have caused a blow to the head or body. A thorough neuropsychological evaluation can provide information about a patient’s cognitive and psychological functioning, and personality features necessary for differential diagnosis. It can also begin the rehabilitation process by providing education, reassurance, as well as referral for comprehensive therapies to treat cognitive and emotional consequences of mTBI.

Though not widely available, there are now sophisticated imaging studies and blood biomarkers that can detect concussion/mTBI. Diffusion tensor imaging (DTI) can reliably detect microstructural white matter changes that accompany diffuse axonal injury (DAI) produced by rapid acceleration/deceleration injuries.

 Blood biomarker tests can detect brain-derived proteins that are released into the blood stream within minutes to hours following brain injury. Two such biomarkers—glial fibrillary acidic protein (GFAP) and S 100 calcium-binding protein B (S100B)—have been used in clinical studies to diagnose concussion.

Research indicates that effective management of concussion/mTBI includes early identification and treatment.

After a brief, initial period of rest to lessen symptoms and reduce metabolic demands, patients should be encouraged to begin treatment. For most individuals with concussion/mTBI, treatment should be symptom-focused and include education about the injury, provide optimistic expectations about recovery and outcome, provide information about how to manage symptoms (ie, headache, 

, etc), and caution about returning to activities that involve risk of repeat head injury. Normal physical and cognitive activities can resume slowly while monitoring to ensue symptoms do not worsen. For individuals with PPCS, a multidisciplinary approach may be indicated. The core multidisciplinary team may include physician specialties (physiatry, psychiatry, neurology, etc), occupational therapy (to improve activities of daily living and monitor timing for return to work and driving), physical therapy (to manage pain, balance problems, vestibular issues), speech/language pathology (for treatment of cognitive-linguistic deficits), counseling (for mood disturbance, sleep disorders, etc), and case management to coordinate treatment.

Concussion/mTBI is the most common type of brain injury. It can be difficult to diagnose for a variety of reasons, but primarily because the symptoms of concussion/mTBI are similar to the symptoms of other psychiatric conditions such as anxiety, depression, and PTSD. Although symptoms of concussion/mTBI resolve within 2 to 4 weeks, about 20% of patients with concussion/mTBI will experience persistent or worsening symptoms and may require comprehensive, interdisciplinary treatment. Clinicians should u

nderstand the symptom overlap between concussion/mTBI and other psychiatric conditions in order to provide accurate diagnosis and treatment.

is the regional director of clinical services at the Centre for Neuro Skills, which operates post-acute brain injury rehabilitation programs in California and Texas. He is licensed in Texas as a chemical dependency counselor and psychological associate with independent practice. He also holds a clinical appointment at the University of Texas Medical Branch (UTMB) in Galveston in the Department of Rehabilitation Sciences.

1. Menon DK, Schwab D, Wright DW, et al. 

Position statement: definition of traumatic brain injury.

2. Coronado VC, McGuire LC, Sarmiento K, et al. 

Trends on traumatic brain injury in the United States and the public health response: 1995-2009.

3. Albrecht JS, Hirson JM, McCunn M, et al. 

Increased rates of mild traumatic brain injury occurring in older adults in United States emergency departments.

5. American Congress of Rehabilitation Medicine Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group. 

Definition of mild traumatic brain injury.

Essential Brain Injury Guide, 5th edition. 

Brain Injury Association of America; 2019.

Symptoms of concussion and comorbid disorders.

8. Morgan CD, Zuckerman SL, Lee YM, et al. 

Predictors of postconcussion syndrome after sports-related concussion in young athletes: a matched case-control study.

9. Shenton ME, Hamoda HM, Schneiderman JS, et al. 

A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury.

Systematic review of clinical studies examining biomarkers of brain injury in athletes after sports-related concussion.

11. Silverberg ND, Iaccarino MA, Panenka WJ, et al. 

Management of concussion and mild traumatic brain injury: a synthesis of practice guidelines.

Understanding the symptom overlap between concussion/mild traumatic brain injury and other psychiatric conditions, such as PTSD and depression, can assist clinicians in differential diagnosis and providing effective treatment.

Differentiating mTBI/Concussion

Tales From the Clinic: The Art of Psychiatry

, we delve into a very common neuropsychiatry comorbidity: headaches. This neuropsychiatric condition is a common comorbidity in a variety of psychiatric diagnoses and can be challenging to manage due to a strong overlap with somatization.

“Mr Wright” is a 37-year-old man with no medical comorbidities who has been in the United States for more than 10 years. He presented to primary care with a 4-month history of headaches that were unresponsive to over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs). He is started on amitriptyline 25 mg at bedtime daily and is referred to the psychiatry department for “anxiety” without any further notes on symptoms of 

. The patient is worried he will be labeled “crazy” and is upset that his suffering is not being taken seriously.

He appears to be in good physical health with good grooming, although he is somewhat reluctant during the psychiatric interview. He reports that he has been living with his wife and child, and he works at a restaurant. He has teenaged children who do not live with him, but he reportedly has a good relationship with them.

When describing his headaches, Mr Wright relays that they persist all day long and encompass areas around his bilateral temples and occipital area, although the 

 may migrate between these areas. He has tried lying down to rest, but the relief in pain is temporary. He is unable to focus on driving and has missed several workdays because he did not feel he could pay attention while driving. He stretches his neck in a variety of different angles during our interaction to help relieve the pain, along with some excess eye blinking that he seems unaware of. He denies a premonitory sensation occurring prior to his movements.

After repeated queries into his stressors around the time his headaches started, Mr Wright is able to verbalize an incident that occurred a week before their onset: He was accommodating his sister at his home after an interpersonal conflict with her husband. The brother-in-law had held him at gunpoint outside his home. He ran inside to safety and the brother-in-law eventually left. His sister has since left, and the patient feels that the turmoil of an abusive relationship in his sister’s life is persistent and acceptable to his sister and the rest of the family. He recalls a similar event more than 20 years ago when he was chased by a different family member in his home country. At that time, Mr Wright also felt that his life was in danger and had to run to safety; since then, he has been an anxious person in general. He has never received any mental health treatment (including 

 (PTSD), including nightmares, flashbacks, and avoidance of increased arousal.

A chart review shows that Mr Wright was seen in the emergency department twice since meeting with his primary care provider. On one occasion, he had acute chest pain; negative EKG and cardiac enzymes led to a discharge. On the second occasion, he was evaluated for unprotected sexual contact with an unknown individual. Mr Wright had chosen not to mention either of these instances of his interaction with the medical system, and the psychiatrist chose not to discuss them either.

He was started on amitriptyline 25 mg by his primary care physician 2 weeks ago, and has been using it as needed on nights he is unable to sleep. He finds it useful, but cannot get relief from headaches. He is unable to verbalize any correlation between a life-threatening event and the onset of his headaches.

At the conclusion of the visit, both patient and physician agree that the amitriptyline should be continued, but that the patient should take it more regularly for best therapeutic results.

As per a systematic review of a global burden of disease across the United States, in 2017, the 5 highest incidence rates of neurological diseases included migraines and tension-type headaches.

 Migraines have consistently been among the top 3 neurological diseases in terms of disability-adjusted life years.

 As a testament to how frequently psychiatrists and neurologists see patients with headaches and psychiatric diagnoses, in 2019, the most frequent psychiatric comorbidities in individuals with primary headaches in the United States were anxiety and depression, followed by posttraumatic/stressor and trauma-related stress disorder. These comorbidities are found in 25%, 23%, and 15% of the general population, respectively.

It is inevitable then that one is likely to come across patients with both primary and secondary headaches in psychiatric practice. Recognizing headaches can be a powerful tool in evaluating the quality of life of our patients. Headaches can be triggering and perpetuating factors for psychiatric conditions, in addition to being an important consideration in identifying the best pharmacological options for treatment.

In primary headaches such as migraine and tension headaches, there is no source for nociceptive activity such as a hemorrhage or 

. Many theories have tried to explain the connections between distress and primary headaches. Findings from studies on connections between distress and primary headaches clearly show that the most important triggering events for primary headaches are distress and sleep issues.

 Stress has also been linked with the transformation of episodic migraines to chronic migraines that carry a greater burden of disease.

 Interestingly, repeated exposure to trauma, even without a formal PTSD diagnosis, is prominent in adults with chronic migraine headaches as compared with healthy adults without migraines.

Biopsychosocial factors are believed to be involved in headache perception. Transactional models propose that the mismatch between threat perception and capability to deal with the threat can be applied to the subjective sense of pain in 

 Among personality traits, locus of control being perceived as internal versus external is a predictor of better headache outcomes.

During the COVID-19 pandemic, the role of sudden change in psychosocial environment due to shutdowns among those with preexisting migraines has been investigated. Contrary to the impression that headaches would worsen, results from at least 1 study record improvement. The findings document reduction in migraine intensity and frequency in adolescents during the shutdown in Italy in 2020.

 It is reasonable to speculate that the reduction in academic and social pressures were helpful in this improvement and underscore the role of psychosocial intervention in patients with migraines. Moreover, it would be interesting to see if there is an uptick in migraine presentation to neurologists and psychiatrists due to the chronic stress induced by the pandemic, over and above migraine in individuals caused by the neuropsychiatric effects of COVID-19 infection itself.

Migraine headaches have a bidirectional relationship with a spectrum of psychiatric illnesses, the strongest correlation being with depression, anxiety, and bipolar disorder. There is evidence of shared genetic predisposition, as well as functional and structural alterations in pain-modulating brain areas, including the amygdala, anterior cingulate cortex, and periaqueductal gray in both migraine and affective disorders. Moreover, they share similar abnormalities in the HPA axis as well as common mechanisms of action of treatment modalities.

The concept of central sensitization is often used to explain pain-related conditions, including migraine. Patients with chronic migraines (as compared with episodic migraines) have more somatic complaints. The role of pain sensitization in episodic migraines has also been investigated in episodic migraines. A recent study suggested that slowly repeated evoked pain sensitization could in fact be useful as a clinical predictor for episodic migraines.

Serotonin, norepinephrine, and the GABAergic system have all been implicated in the etiology of psychiatric as well as primary headaches at the neurotransmitters level. As such, the evidence for using serotonin and norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs) that target these receptors for preventive treatment for migraines remains strong.

Managing psychiatric symptoms in patients presenting for treatment with headaches may present a unique advantage in overcoming barriers to talking about optimizing mental health. When establishing goals for treatment, it may be useful to educate the patient about the benefit of SNRIs and TCAs in managing headaches as well as mood and anxiety disorders. This may help patients verbalize their mental health needs in the face of stigma. At times, presenting an SNRI or TCA as a headache medicine only can help with treatment adherence in patients who have difficulty expressing their distress.

One of the many challenges in managing headaches is that initiating SNRIs or TCAs for headache can itself carry a risk for inducing headaches. A careful consideration of the timeline for medication-induced headache may aid in separating the superimposed symptoms. Clinicians may benefit from considering medication withdrawal as a reason for headache exacerbation when treating psychiatric patients with comorbid headaches and a history of 

. Venlafaxine is notable in this regard for its withdrawal syndrome.

Investigators of several studies have been unable to establish the benefit of using selective serotonin reuptake inhibitors (SSRIs) in preventing migraine relapses. Among the most studied SSRIs is fluoxetine, which, to date, has conflicting evidence for its use in primary headaches.

 Other clinical trials of sertraline and citalopram did not show benefit over TCA or placebo. Hence, when a patient with previously established treatment with SSRIs is placed on TCAs for headaches, one has to carefully weigh the risks and benefits of switching to monotherapy with a TCA or continuing with both medications. If the patient is reporting clinical benefit, they could be treated with low doses of both medication categories while monitoring carefully for adverse effects. Patients can be educated regarding early symptoms of serotonin syndrome when treated in the outpatient setting. 

Additionally, many clinicians are concerned about the possibility of inducing serotonin syndrome in patients taking antidepressants who are prescribed triptans for aborting episodes of migraines. Although there was a black box warning for this interaction, results from an electronic health record–based study in 2018 did not show any correlation of serotonin syndrome with co-use of SSRIs and SNRIs and triptans.

In patients with medication-overuse headaches, the prevalence of psychiatric comorbidities is even higher.

 Some point to the similarities between compulsive medication intake for episodes of migraine and obsessive-compulsive disorder. As such, adding behavioral interventions for this subset of patients may be highly effective in improving headache outcomes.

It may be prudent for neurologists to prescribe psychotherapy regularly for treating patients with chronic migraines. Behavioral interventions and forecasting models, including stress variables, seem to be useful in managing migraine. Behavioral treatments with evidence for migraine prevention include stress management, relaxation therapy, 

, biofeedback, mindfulness-based therapies, and acceptance and commitment therapy. Investigators of some studies point out that although headache frequency or intensity improves, there is no change in physiological markers of headaches such as muscle tension. In a landmark study of electromyographic biofeedback training, participants viewed their headaches as having a more internal locus of control and themselves as more self-efficacious (ie, as capable of influencing their headaches) following treatment.

Finally, when addressing this complex patient population, it is essential to avoid labeling and stigmatization. Patients are usually concerned about physical complaints being dismissed and being told “the symptoms are in your head.” Establishing careful therapeutic rapport goes a long way toward open discussions of treatment options and paving the way to productive illness management.

1. GBD 2017 US Neurological Disorders Collaborators; Feigin VL, Vos T, Alahdab F, et al. 

Burden of Neurological Disorders Across the US From 1990-2017: A Global Burden of Disease Study. 

2. GBD 2019 Diseases and Injuries Collaborators. 

Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

3. Caponnetto V, Deodato M, Robotti M, et al; European Headache Federation School of Advanced Studies (EHF-SAS). 

Comorbidities of primary headache disorders: a literature review with meta-analysis.

4. Yokoyama M, Yokoyama T, Funazu K, et al. 

Association between headache and stress, alcohol drinking, exercise, sleep, and comorbid health conditions in a Japanese population.

Predictors of episodic migraine transformation to chronic migraine: a systematic review and meta-analysis of observational cohort studies.

6. Lazarus RS, Folkman S. Stress, Appraisal, and Coping. Springer Publishing Company; 1984.

7. Dallavalle G, Pezzotti E, Provenzi L, et al. 

Migraine symptoms improvement during the COVID-19 lockdown in a cohort of children and adolescents.

8. De la Coba P, Bruehl S, Del Paso GAR. 

Slowly repeated evoked pain (SREP) as a central sensitization marker in episodic migraine patients.

9. Silberstein SD, Holland S, Freitag F, et al; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. 

Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society.

Association of coprescription of triptan antimigraine drugs and selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor antidepressants with serotonin syndrome.

11. Kristoffersen ES, Straand J, Russell MB, Lundqvist C. 

Disability, anxiety and depression in patients with medication-overuse headache in primary care – the BIMOH study.

12. Holroyd KA, Penzien DB, Hursey KG, et al. 

Change mechanisms in EMG biofeedback training: cognitive changes underlying improvements in tension headache.

What's the best way to manage headaches and psychiatric disorders?

Headaches: The Common, Challenging Comorbidity

Global society is faced with interrelated challenges that are complex, systemic, and dynamic from climate change, population displacement, famine, productivity slowdown, and mis- and dis-information to cyber exploitation, mental health crisis epidemics, aging and dementia, COVID-19-related losses, and fraying trust in social and political institutions.

 of neuroscientists, medical doctors, and economists came together to develop new concepts, ideas, and tools to use brain science to tackle some of society’s most pressing problems. A seminal paper outlining their preliminary thinking on brain capital was published in January 2021.

 The agenda has significantly advanced since through deeper, transdisciplinary research and narratives; broader academic, business, and policy networks; and refined measurement to guide all stakeholders and monitor progress. The 

Each of us possesses a complex system—the brain—which is implicated in the emergence, propagation, aggravation, and potential resolution of these challenges. To address these issues, a neuropolitical approach that considers brain capacity as a crucial asset is needed. The insights can be translated into policy, business practices, and civil society advocacy. In response to the urgent needs, a group of researchers and policymakers developed the concept of brain capital.

Brain capital is based on the position that brains are the world’s most important resource and the means by which all problems will be solved, ameliorated, or worsened. The brain capital framework acknowledges the importance of every brain and the corresponding need for brain diversity to achieve equity in solving global issues. Brain capital is a framework incorporating brain health and brain skills in the knowledge economy. In an era that is dependent on intellectual capacity, our brains are our greatest asset. Brain capital provides an approach to define brain issues, quantify them, and track them. Brain preservation and enhancement is critical to advancing brain capital, which can be driven into local, national, and international policies and investments.

Despite the fundamental importance of brain health and brain skills, these factors are often overlooked in policy-making and are not well-reflected in measures of human capital.

 Brain capital differs from human capital in its recognition of the unique role that brain health and brain skills play in human civilization. Unlike human capital measures, which look at broad educational and health metrics, brain capital encompasses and measures brain health as well as society-  and economy-critical variables such as collective confidence, social trust, and shared values and goals. These key social processes in turn depend on critical aspects of individual human functioning such as perceived control, confidence, ability to work collectively, problem-solving capacity, and values-driven goals. It also differs from human capital in its encompassing and measurement of economy-shaping brain health measures such as addiction, depression, anxiety, brain fog, loneliness, and dementia.

There is a range of notable achievements of brain capital in the past 18 months, including new initiatives, expanded partnerships, and more outreach and influence. These are interlocking and mutually reinforcing.

The Organisation of Economic Collaboration and Development (OECD) established the Neuroscience-inspired Policy Initiative in collaboration with the PRODEO Institute.

 Consultations have been held with the United National Development Programme and the World Health Organization (WHO). The OECD NIPI supported the European Brain Initiative in collaboration with EBRAINS, French EU Presidency, the European Commission, the WHO, scientific societies, patient organizations, and health professionals.

 The Meadows Mental Health Policy Institute appointed a senior fellow for brain capital.

 A new chair of excellence in brain capital will be established as part of the recently funded PEPR ProPsy, a project to develop precision psychiatry in France.

 and the Latin American Brain Health Institute (BrainLat)

 both launched brain capital summer courses, respectively.

Brain capital also received notable mentions in 2 US Congressional presentations in front of the Congressional Neuroscience Caucus

 and the US House Select Committee on Economic Disparity and Fairness in Growth.

 There has been engagement with major think tanks including the Center for European Policy Studies

Two working groups were also established. The 

 aims to formalize the field of brain health diplomacy

 and to develop a brain health diplomat toolkit. Working group members include former US State Department official Virginia Bennett and former US Representative Patrick J. Kennedy (D-RI). The 

 aims to quantify and track brain capital and is constituted by economists, neuroscientists, and physicians. This is seen as a critical project and will subserve future policy innovations.

Additional notable achievements for the brain capital agenda are outlined in the 

Most recently, the Brain Capital Alliance, a public-private-people partnership, was launched via a series of events in Europe.

 The alliance aims to advance approaches to measurement, investment, and policy and will further integrate brain capital into policy agendas including productivity, climate change, political stability, gender equality, and neurotechnology. The alliance will raise awareness among public and private leaders for neuroscience-related issues across the life span, from early childhood development to youth resilience and brain reserve, to reduce the risk of cognitive decline in older adults.

The Brain Capital Dashboard will be refined and leveraged in policy discussions. Specific research labs will be developed to experiment at different scales and will be applied to real world problems such as micro-plastic pollution, the youth mental health crisis, caregiver distress, and disinformation. These platforms will improve the statistical bases and analytical foundation to guide decisions and assess progress. Novel financial instruments will also be explored to unlock additional funding for building brain capital such as bonds, venture capital, and exchange traded funds.

The alliance is seeking interested supporters, collaborators, and partners to accelerate this work.

As we look toward the future, it is imperative that brain capital continues to be developed and integrated into policy, business, and society. To sustainably solve the most pressing global challenges, we must place brain capital at the heart of solutions. We must develop ways to use brain science to overcome the most difficult, seemingly intractable global problems.

is the lead of the Brain Capital Alliance, co-lead of the OECD NIPI and Senior Fellow with the Meadows Mental Health Policy Institute. Eyre maintains advisory or adjunct roles with IMPACT at Deakin University, the Heka Fund, Brain Health Nexus at Cohen Veterans Bioscience, GBHI, Baylor College of Medicine, BrainLat, University of Texas Health Sciences Center at Houston, the Davos Alzheimer’s Collaborative, and the Euro-Mediterranean Economists Association (EMEA).

is an associate fellow at the Johns Hopkins School of Advanced International Studies.

is the director of the IMPACT Institute at Deakin University.

is an Atlantic Fellow for Equity in Brain Health at the Global Brain Health Institute, a Thiel Fellow at Stanford University, and a Steering Committee member for the OECD Neuroscience-inspired Policy Initiative. 

is theJoy Chambers-Grundy Professor of Brain Science

director of the Chambers-Grundy Center for Transformative Neuroscience

and co-director of the Pam Quirk Brain Health and Biomarker Laboratory

A brain capital grand strategy: toward economic reimagination

2. Angrist N, Djankov S, Goldberg PK, Patrinos HA. 

Measuring human capital using global learning data

3. Neuroscience-inspired Policy Initiative. Organisation for Economic Co-operation and Development. Accessed August 22, 2022. 

4. Towards a European brain initiative. EBRAINS. Accessed August 22, 2022. 

https://www.ebrains.eu/news/Towards-a-European-Brain-Initiative/

5. Harris Eyre, MBBS, PhD: senior fellow for brain capital. Meadows Mental Health Policy Institute. Accessed August 22, 2022. 

6. Brain Capital Alliance launches to accelerate agenda for change. Newsmatics Inc. News release. July 17, 2022. Accessed August 22, 2022. 

https://www.einnews.com/pr_news/581691203/brain-capital-alliance-launches-to-accelerate-agenda-for-change

7. Brain capital continues to advance. Global Brain Health Institute. September 7, 2022. Accessed September 8, 2022. 

https://www.gbhi.org/news-publications/brain-capital-continues-advance

8. Bär N. Políticas públicas y neurociencia, la deuda con la salud cerebral. 

. September 1, 2022. Accessed September 7, 2022. 

https://www.eldestapeweb.com/sociedad/salud/politicas-publicas-y-neurociencia-la-deuda-con-la-salud-cerebral-2022910526?utm_medium=Social&utm_source=Twitter#Echobox=1662030318

9. Improving brain health and reducing the scale and impact of dementia worldwide. Global Brain Health Institute. Accessed August 22, 2022. 

10. Congressional Neuroscience Caucus Briefing long haul neurological & psychological impacts of COVID19. American Brain Coalition on YouTube. May 18, 2022. Accessed August 22, 2022. 

https://www.youtube.com/watch?v=sdUwKIHccFE

11. Graham C. Addressing America’s crisis of despair and economic recovery: a call for a coordinated effort. Testimony to the House Select Committee on Economic Disparity and Fairness in Growth. September 28, 2021. Accessed August 22, 2022. 

https://www.brookings.edu/wp-content/uploads/2021/10/Carol-Graham-Testimony-Sept-28-2021.pdf

12. Launch event of the Brain Capital Alliance: towards a person-centered approach to brain health. CEPS Think Tank on YouTube. July 4, 2022. Accessed August 22, 2022. 

https://www.youtube.com/watch?v=Mo2dASiMrd4

13. Dawson WD, Graham C, Smith E, et al. Build brains better: a proposal for a White House brain capital council to accelerate post-COVID recovery and resilience. The Brookings Institute. December 22, 2021. Accessed August 22, 2022. 

https://www.brookings.edu/research/build-brains-better-a-proposal-for-a-white-house-brain-capital-council-to-accelerate-post-covid-recovery-and-resilience/

14. Dawson WD, Bobrow K, Ibanez A, et al. 

The necessity of diplomacy in brain health

A transdisciplinary team summarizes key points and reflections after 18 months of activity.

Advancing Brain Capital: Achievements, Lessons, and Next Steps

Serotonin is a ubiquitous neurotransmitter that has earned its reputation as a highly significant molecule in humans that lies at the center of a diverse range of functions. When Vittorio Erspamer first discovered serotonin—which he initially named enteramine—in 1935, he demonstrated that it was produced by enterochromaffin cells, which are endocrine cells adjacent to the lining of the gastrointestinal tract. When released, enteramine increased motility and secretions of the intestines.

At Cleveland Clinic in 1948, 3 researchers discovered a molecule released by platelets in the blood that facilitated vasoconstriction, helping facilitate blood clotting and decrease blood loss. They named this molecule serotonin, which is Latin for 

. Finally, in 1952, it was confirmed that enteramine and serotonin were the same molecule.

Although it is often referred to as serotonin today, its official chemical name is 5-hydroxytryptamine (5-HT). Serotonin is one of several molecules collectively called monoamines, which also include norepinephrine, dopamine, and histamine.

Serotonin is localized in 3 primary systems in the human body, with 90% of it in the enterochromaffin cells in the gastrointestinal tract, 8% in platelets, and the remaining 2% in the central nervous system. Serotonin’s presence in these 3 diverse body systems tells a powerful story about how this single molecule ultimately integrates disparate systems to increase survival of the organism. If you were to eat a toxic substance, the enterochromaffin cells in your gastrointestinal tract would secrete serotonin, which would then agonize the numerous 5HT-4 receptors throughout the gut, which results in increased gastrointestinal motility and secretions. The wisdom of the body wants to get that toxic substance out as quickly as possible.

The increased serotonin diffuses into the vasculature where platelets—which cannot synthesize the vasoconstricting serotonin on their own—use serotonin transport pumps to fill their serotonin vesicles and remove this excess serotonin from the blood at the same time. However, if that toxic substance raises a red alert, the platelets’ serotonin transport pumps get saturated with serotonin, and the blood serotonin levels rise to an abnormal level. As this blood perfuses the brain, the increased serotonin will agonize the 5HT-3 ionotropic receptors in the chemoreceptor trigger zone, which induces vomiting. The serotonin thus facilitates expulsion of the toxin from both ends of the gastrointestinal tract, increasing the likelihood of surviving the ingestion of this toxin.

This example is a microcosm of the massive macrocosms of circuitry that serotonin orchestrates. Serotonin’s activity in the gastrointestinal tract and platelets is straightforward and well established. When we attempt to understand serotonin’s detailed functioning in the brain, the mountains of information that exist give us a few clues here and there. Ultimately, we are not yet smart enough to map out the system, and all the interfaces serotonergic pathways share with the other neuronal circuits and neurotransmitters.

The brain directs its serotonergic pathways starting at the raphe nuclei in the brain stem. Serotonin has been shown to have some involvement in complex processes, including mood, anxiety, sleep, circadian cycles, cognition, thermoregulation, sexual drive, and appetite.

Often in science, as we peel away the layers of the knowledge onion, we simply discover new layers. During the 1930s and ‘40s, the serotonin story began by simply identifying the molecule and discovering a few of its simple properties—increasing intestinal motility/secretions and being released by platelets trying to stop a bleed by helping out with vasoconstriction. The next step was to figure out how serotonin fit into these physiologies, and good basic science discovered the serotonin transport pump on the surface membrane of the platelets and a serotonin receptor in the gastrointestinal tract.

Over the next 4 decades, the receptor part of serotonin’s story exploded, ultimately discovering 7 different families of serotonin receptors, with many families having subfamilies, allowing for heterogeneity of function. The 5HT-7 family was discovered in 1993, and the full sequencing of the human genome in 2003 increased our confidence that we had a basic understanding of the divergent serotonin receptors.

Intensive pharmaceutical research has developed serotonergic receptor-specific drugs with mechanisms of action that fit with what we currently know about this complex system (

Ondansetron, a 5HT-3 receptor antagonist, is an effective antiemetic. Tegaserod, a 5HT-4 agonist, effectively treats constipation (although it has recently been withdrawn from the US market). The many triptans for the treatment of migraine headaches agonize the 5HT-1 B and D receptors, putatively treating the headache through vasoconstriction. The hallucinogens psilocybin, LSD, and mescaline induce a dramatic effect on one’s perception of reality by agonizing the 5HT-2A receptor. The 5HT-2C agonist lorcaserin is associated with weight loss. And the 5HT-2B agonists fenfluramine and pergolide cause cardiac valve fibrosis. Additional discoveries helping us understand the complexity of serotonin’s biography continue to emerge (

"It would be naïve to believe that targeting a single neurotransmitter, receptor, or circuit in the brain will cure any psychiatric or neurological disorder. However, we would be remiss if we did not try."

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