A Campaign for Mental Health Under Way at Janssen Research & Development, a Janssen Pharmaceutical Company of Johnson & Johnson
Kamana Misra PhD, Founding Editor
The economic costs of mental illness will be more than cancer, diabetes, and respiratory ailments put together. – Tom Insel, Director, U.S. National Institute of Mental Health, at the World Economic Forum, January 2015
On New Year’s Day the phone call came. A phone call no parent should ever receive. He thought it was his daughter calling to say hello. Instead a male voice from his daughter’s phone conveyed hesitantly that his daughter had just tried to end her life.
Craig Kramer received this call when his daughter was 24 years old, ten years after she developed an eating disorder at the age of 14. From the outset the family experienced many, many difficulties. Tremendous effort was required in trying to get the appropriate diagnosis and treatments. Interaction with the numerous healthcare professionals required synchronizing treatment schedules from the medical care professionals, mental health services and nutritional therapy to name a few. There was overall lack of coordination between the many healthcare professionals involved. More importantly, health coverage for the wide array of treatments is not covered or very difficult to obtain for many patients.
At the time this crisis hit his family, Kramer was Vice President for Government Affairs & Policy at Johnson & Johnson, based at the World Headquarters in New Brunswick, New Jersey. His job was to shape up and develop policies at both the national and international levels. Kramer’s personal experience showed him firsthand the sorry state of affairs for eating disorder patients in terms of diagnosis, prognosis, inadequate insurance coverage, and beyond. He experienced the tragic effects these disorders have not only on the patients, but also on the families and communities in which they live and work. Once his daughter was in recovery, he decided to utilize his expertise to champion a cause that remains gravely misunderstood and misrepresented.
Kramer was fortunate to work with a company that is committed to making life-changing, long-term differences in human health throughout the world. Through his efforts and the efforts of other Johnson & Johnson leaders, the J&J Global Campaign for Mental Health was initiated as a part of Neuroscience External Affairs at Janssen Research & Development, LLC, one of the Johnson & Johnson Pharmaceutical Companies. Kramer was named Janssen and J&J’s first Mental Health Ambassador and now leads an effort that aims to transform mental healthcare globally by raising awareness, reducing stigma, promoting research, improving access, and ensuring better patient outcomes. The Janssen R&D Neuroscience Therapeutic Area, under the leadership of psychiatrist and neuroscientist Husseini Manji, is leading new research areas to uncover the causes and potential treatments for illnesses like treatment-resistant depression, suicidality, and other mental illnesses.
Key initiatives on the mental health policy front include a global leaders’ coalition to advocate for proven, scalable reforms, and a CEO roundtable to develop “next-in-class” workplace mental health practices. In his words, “It’s an uphill task, but there have been many great pilot programs in recent years around the world. We hope that we can scale those up and advance and replicatemental health solutions.”
From a societal perspective eating disorders are the most misunderstood mental illnesses. These include indications like anorexia nervosa, bulimia nervosa, binge-eating disorder and their variants. They are often perceived with disdain, belittled as a fad or a “phase”, or deemed a lifestyle choice, and therefore overlooked as serious disorders with potentially life-threatening outcomes.
Compounding the mis-information is the lack of scientific understanding about mechanisms underlying disease development and etiology. Fortunately, interest from the scientific community is shedding some light on the bio-psychosocial risk factors associated with eating disorders.
Under normal conditions, food intake and energy expenditure are balanced by a homeostatic system that maintains stability of body fat content over time, a biological process termed energy homeostasis. Pathological disruption of these basic homeostasis and emergency circuits leads to eating disorders like anorexia (1-4). Research efforts over the past 75 years have helped neuroscientists to identify the involvement of the hypothalamus in controlling eating behavior. The arcuate region of the hypothalamus (ARC) along with the CGRP neurons in the parabrachial nucleus (PBN) regions of the brain play important roles in these hunger circuits. A simplified hunger /feeding circuit depends on:
The ARC hunger-satiation seesaw
Two groups of neurons within ARC, occupying less than a millimeter in the mouse brain, drive the hunger circuits by sensing long-term changes in the body’s hormone and nutrient levels. The ARC contains at least two populations of neurons:
- Pro-opiomelanocortin (POMC) Neurons. Activation decreases food intake.
- Agouti-related protein (AgRP) neurons. Activation increases feeding.
- These 2 sets of neurons are functionally organized in a seesaw-like fashion: when AgRP neurons are active, POMC neurons are not, and vice versa.
- It was believed opposing anorexigenic actions of the POMC neurons is critical. It has now been demonstrated that activation of AgRP neurons is necessary and sufficient to promote feeding (and not inhibition of POMC neurons).
- Acute depletion of AgRP neurons in the adult mouse leads to life-threatening anorexia.
- AgRP projections innervate mesolimbic, midbrain, and pontine where they activate feeding and feeding-independent functions such as reward or peripheral nutrient partitioning.
- AgRP neurons also make gamma aminobutyric acid (GABA).
- While the loss of activation functions of AgRP neurons causes transient feeding defects that can be compensated, acute loss of GABA inhibition by AgRP is responsible for anorexic effect.
CGRP neuronal feeding brakes in the Parabrachial nucleus (PBN).
- Hyperactivity of CGRP neurons in in parabrachial nucleus (PBN) is linked to anorexia.
- CGRP neurons relay sensory information to the forebrain. Their axons project to the bed nucleus of the stria terminalis (BNST) and to the lateral capsule region of the central nucleus of the amygdala (lcCeA).
- CGRP neurons are activated by visceral malaise (food poisoning), nausea, satiety etc.
- Activation of these neurons provides a brake on normal feeding activity in mice.
- Activated AgRP neurons are inhibitory to CGRP neurons, a critical function required for normal feeding. Ablation of AgRP neurons in adult mice results in starvation by loss of inhibition on the CGRP neurons.
ALTERED WIRING IN THE ANOREXIC BRAIN.
Although there is some progress in the field of eating disorder research, funding still remains inadequate. To put it into perspective, compare dollars spent per patient supporting research for eating disorders to dollars spent on autism & bipolar disorder 5:
- $0.74 cents for eating disorders
- $34.07 for autism
- $37.78 for bipolar disorder
Kramer’s daughter Katharine’s story on personal struggles and inspiring recovery from anorexia can be found here.
“Mental illnesses occur more frequently, affect more people, require more prolonged treatment, cause more suffering by the families of the afflicted, waste more of our human resources, and constitute more financial drain upon both the public treasury and the personal finances of the individual families than any other single condition.” – John F. Kennedy, February 5, 1963.
- Morton GJ, Meek, TH and Schwartz MW (2014) Neurobiology of food intake in health and disease. Nat Rev Neurosci; 15(6):367–378.
- Wu Q. Clark MS and Palmiter RD (2012). Deciphering a neuronal circuit that mediates loss of appetite. Nature; 483(7391): 594–597.
- Padilla SL, Qiu J, Soden ME, — and Palmiter RD (2016) Agouti-related peptide neural circuits mediate adaptive behaviors in the starved state. Nat Neurosci;19(5):734-41.
- Meng F, Han Y, Srisai D, Belakhov V, Farias M, Xu Y, Palmiter RD, Baasov T, Wu Q (2016). New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism. Proc Natl Acad Sci;113(13):3645