A New York psychiatrist, Jeremy Coplan has been attempting to bridge the gap between mood and biological disorders for decades. Most studies to date have examined the overlap between mood disorders. A large 2013 study, for instance, found that alterations in calcium channel genes increase the risk of coming down with a wide variety of psychological disorders.

Coplan’s experience, however, suggests that that kind of analysis is too limiting. He believes that many psychological disorders transcend the boundaries that have been imposed by researchers and vice versa. They are better viewed on a spectrum that includes both psychological and physiological components.


Coplan suggests diseases may not be what they seem

His research bears this out. Panic, for instance, can be caused by physiological factors that are not often associated with it. In 2009 Coplan found that increased brain lactate – found in both chronic fatigue syndrome and fibromyalgia – is associated with panic-like symptoms in rats.  (Coplan co-authored two of the ME/CFS brain lactate papers and the latest fibromyalgia study.) In 2005 he found that reduced blood flows to the frontal cortical regions of the brain induced anxiety in laboratory animals. In 2007 he noted that over or under activity of the prefrontal cortex could induce panic-like symptoms.

In his most recent paper Coplan proposed that a vast spectrum of illness exists that encompasses a wide variety of both physical and mental illnesses. To test his hypothesis he gathered together a set of people with an anxiety disorder who also had a physical condition, and assessed the incidence of a wide variety of pain, muscoskeletal, immune and psychiatric conditions present.

He hoped to expand the view we have of what a panic or anxiety disorder consists of.  I would say he succeeded.


The results were astonishing. Joint laxity (loose joints) were found in almost 60% of the anxiety patients compared to 10% of the population. Mitral valve prolapse, scoliosis and double-jointedness were approximately ten, three and seven times as common in the anxiety patients as in the general population.

Occurring in about 80% of the anxiety-plus patients, fibromyalgia was 30-40 times more commonly found in the anxiety plus group.  Irritable bowel syndrome (IBS) and headache were five and three times as commonly found.

On the immune side allergic rhinitis (71%), hypothyroidism, chronic fatigue syndrome and asthma were three, eighteen, nine and four times more commonly found in the anxiety plus patients.

Major depression and bipolar depression were five and seventeen times more commonly found in the people with anxiety.

By the end of the paper it seemed crazy to refer to these as simply anxiety patients. They had a wide range of other conditions that most researchers rarely connect with mood disorders. Joint problems are common. Autoimmune processes may be present. Coplan proposed that these patients had a spectrum disorder in which five symptom/condition domains dominated.

  • A = Anxiety disorder (mostly panic disorder);
  • L = Ligamentous laxity (joint hypermobility syndrome, scoliosis, double-jointedness, mitral valve prolapse, easy bruising);
  • P = Pain (fibromyalgia, migraine and chronic daily headache, irritable bowel syndrome, prostatitis/cystitis);
  • I = Immune disorders (hypothyroidism, asthma, nasal allergies, chronic fatigue syndrome); and
  • M = Mood disorders (major depression, Bipolar II and Bipolar III disorder, tachyphylaxis. Two thirds of patients in the study with mood disorder had diagnosable bipolar disorder and most of those patients had lost response to antidepressants).

The title  of the study indicated Coplan’s findings were preliminary. Because it included a select group of people with documented anxiety disorder and another physical disorder it probably reflected a special subset of anxiety patients. The study also did not contain a healthy control group and it was not very large.


Work on Ehlers Danlos Syndrome (joint hypermobility) appears have driven much of Coplan’s thinking. EDS and other genetically determined connective tissue disorders such as Marfan’s disease have been associated with a high risk of psychiatric disorders (anxiety disorders, depression, schizophrenia, autism, attention deficit/hyperactivity disorder, eating disorders, personality disorders and substance use/misuse.) Clearly some common genetic underpinning is present.


Do similar pathophysiological problems underlie these disorders?

In fact many of the conditions listed have a spectrum-like appearance; i.e. they often appear together and transcend disease boundaries. A recent study, for instance, found that inflammatory disorders, “functional somatic syndromes” (i.e. ME/CFS, FM, IBS, etc.) and psychiatric disorders are also commonly found in migraine. The symptom spread in migraine, like ME/CFS and FM (and apparently anxiety, EDS, etc.) is enormous.

The authors concluded that migraine was a central sensitization disorder.  A central sensitization disorder involving the immune system (the microglia) that impacts different parts of the sensory apparatus, could be present in many of these disorders.

Chronic Fatigue Syndrome and Fibromyalgia and FM

“Our argument is that delineations in medicine can be arbitrary and that some disorders that are viewed as multiple disparate and independent conditions may best be viewed as a single spectrum disorder with a common genetic etiology,” Dr. Coplan

My interest in this subject lies in the edginess, the inability to settle down, the increased sensitivities, the touchy nervous system etc. that have been a constant part of my chronic fatigue syndrome. These symptoms have never been enough for me to meet the criteria for anxiety or panic disorder but they are enough for me to wonder which connections might be present.

A similar study of ME/CFS and FM patients would likely have similar and different findings. Joint laxity, headache, migraine, irritable bowel syndrome, hypothyroidism and depression appear to be fairly common in ME/CFS and perhaps FM. Bipolar disorder, tachyphylaxis and anxiety disorder don’t appear to be nearly as common.

Boundaries Falling

Smashing boundaries between diseases is getting to be pretty common. Inflammation is now judged to play a major role not just in diseases like heart disease and diabetes but in about a third of people with depression.  Fibromyalgia is found in a significant subset of people with arthritis and other conditions. Antidepressants don’t just help with depression but reduce pain in people without depression, improve sleep in people without depression, and reduce inflammation. Now we see that elements of anxiety pervade many disorders and many disorders pervade anxiety.

Whether studies like this are helpful or hurtful to diseases like ME/CFS and FM that are struggling for legitimacy is another question.. Does involving ME/CFS in a spectrum of diseases that includes some mood disorders – as well as connective tissue, immune and endocrine disorders help or hurt a disease that has struggled to gain legitimacy?




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