New Syndrome Links Anxiety and Physical Disorders

Liam Davenport

July 22, 2015

Patients with anxiety disorder may suffer from a range of comorbid physical conditions that constitute a novel syndrome, say US researchers, who claim that the syndrome has been overlooked by physicians who have previously dismissed the connections as simply somatic disorders.

ALPIM (anxiety, laxity, pain, immune, mood) is an acronym for anxiety and the domains of its most commonly occurring comorbidities: joint laxity, pain disorders, immune disorders, and mood disorders.

Testing the prevalence of the comorbid domains in patients with anxiety disorder, it was found that their prevalences were far higher than those seen in the general population. Furthermore, there were a number of significant associations between disorders within the domains.

"Our results provide further evidence to support a possible common pathophysiologic pathway toward the development of a related set of psychiatric and physical conditions, which were previously considered and, in certain instances, were unrelated," the investigators write.

Noting that several disorders that were previously labeled as purely somatic symptoms in psychiatry are now recognized as bona fide disorders in other medical fields, the researchers note: "Patients are entitled to receive a medical diagnosis that has a biological basis and facilitates effective and, in certain instances, Food and Drug Administration–approved treatments."

"Viewing patients as sharing a psychological propensity toward somatizing behavior essentially denies patients access to care for the diagnosable medical conditions with which they present," they add.

The research was published in the Journal of Neuropsychiatry and Clinical Neurosciences.

The team had previously observed through clinical experience and the literature that there are a number of relationships between anxiety disorders and physical illnesses.

From this, they formulated a domain-defined clinical syndrome, termed ALPIM, in which comorbidites exist along a spectrum; patients may experience anything from one disorder under one domain to multiple disorders under multiple domains.

The anxiety domain, for example, includes panic disorder, generalized anxiety disorder, and social anxiety disorder; the laxity domain includes joint laxity, mitral valve prolapse, scoliosis, double jointedness, and easy bruising.

The pain domain comprises fibromyalgia, chronic daily headaches, interstitial cystitis, and prostatitis. Asthma, hypothyroidism, chronic fatigue syndrome, and allergic rhinitis make up the immune domain. Finally, the mood domain contains bipolar I, bipolar II, and bipolar III disorders, major depressive episodes, and antidepressant medication tachyphylaxis.

The researchers then developed the ALPIM Inventory Questionnaire, which was designed to identify the conditions that fall within the ALPIM spectrum. Performing a cross-sectional, naturalistic study, they administered the questionnaire to 72 patients with anxiety disorder (average age, 43.19 years; 76% women).

Compared with studies carried out in the general population, the prevalence of the comorbid conditions was consistently higher in the study group. For example, the prevalence of joint laxity and mitral valve prolapse was 59.3% and 32.9%, respectively, vs 10% - 15% and 2.4%, respectively, in the general population.

The prevalence of fibromyalgia and irritable bowel syndrome in the study population was 80.3% and 76.3%, respectively, compared with 2.1% - 5.7% and 17%, respectively, in the general population.

Similar differences were seen for immune conditions such as allergic rhinitis and chronic fatigue syndrome. Furthermore, the prevalence of major depressive disorder in the study population was 92.2% vs 16.6% in the general population. The respective figures for bipolar II and III disorders were 71.1% vs 3.9% and 67.1% vs 0.56%; and for tachyphylaxis, 92.1% vs 9% - 57%.

Logistic regression analysis indicated that more than 80% of patients had a lifetime history of panic disorder, fibromyalgia, major depressive episode, and tachyphylaxis; these were therefore considered as a core phenotype of ALPIM syndrome.

Further analysis indicated that there were significant associations between joint laxity and bipolar III disorder (odds ratio [OR], 4.3; P = .005). There was a near-significant relationship between mitral valve prolapse and bipolar III disorder (OR, 0.4; P = .05).

Among other associations that the team identified, headache was significantly comorbid with bipolar II disorder, asthma, and rhinitis (OR, 6.8, 7.1, and 6.8, respectively; P = .001, P = .004, and P = .001, respectively).

Despite the significance of the findings, lead author Jeremy D. Coplan, MD, professor of psychiatry at SUNY Downstate Medical Center, New York City, is not hopeful that the syndrome will gain acceptance in the medical community.

"I know that the citations are going to be low on this kind of article, even though there's been a lot of lay interest," Dr Coplan told Medscape Medical News.

"Clinicians don't really give a hoot. You know, medicine's in a very arrogant state of mind right now. They really think everything evidence-based, and we've got to test for everything," he added.

"They're not really speaking to patients anymore because, what's the point? They've got the test. But the test doesn't work for diagnosing ALPIM syndrome."

Dr Coplan believes that until ALPIM syndrome is recognized and accepted, patients will end up being treated solely for one of their physical comorbidities, rather than the underlying anxiety disorder.

"When we treat anxiety and mood disorder, it helps us sleep, it helps with stress, it stops the cytokine cascade...and so it will become a lot easier to manage."

He added: "With the doctors, we've got a long, long way to go to get them to change their thinking, which can be very rigid and very minimally out of the box."

Dr Coplan concluded: "The point I'd like to make is that, with these disorders where we have tests, we have to keep our minds open."

"There's a lot about medicine that we don't know and we don't have the technology to find out, but we can be physicians, and while being physicians, we can see that the patient has a certain array of disorders that occur too commonly together to be there by chance."

The research was supported in part by a National Institute of Mental Health Grant and NIMH Research Scientist Development Award to Dr Coplan. All relevant financial relationships are listed in the original article.

J Neuropsychiatry Clin Neurosci. 2015;27:93-103. Abstract

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