Rich Murray: Binkley: genetic factors in panic disorder & environmental sensitivity 5.30.1 rmforall

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Rich Murray: Binkley: genetic factors in panic disorder

& environmental sensitivity 5.30.1 rmforall

Rich Murray Room For All rmforall@...

1943 Otowi Road Santa Fe, New Mexico 87505

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http://www.canada.com/cgi-bin/cp.asp?f=/news/cp/stories/20010521/health-837032.h\

tml

20th-century disease genetically linked to panic

disorder, researchers say

by Helen Branswell

TORONTO (CP) - Environmental intolerance, a condition sometimes

known as 20th-century disease, appears to be genetically linked to

panic disorder, University of Toronto researchers have discovered.

That revelation may help medicine unlock the mysteries of the

ailment and aid doctors treating those suffering from the disabling

condition.

" The symptoms are very real and these people are suffering, " lead

author Dr. Binkley said about people with idiopathic - meaning

its origin is spontaneous and unknown - environmental intolerance,

or IEI.

" They need help and we have to be open to anything that can

improve the quality of their lives. "

The article was published in the May issue of the Journal of Allergy

and Clinical Immunology, a peer-reviewed publication of the

American Academy of Allergy, Asthma and Immunology.

People with IEI suffer a wide variety of symptoms when exposed to

an array of products, chemicals and pollutants that are hard to avoid

in modern life. Items commonly blamed for reactions include

perfume, carpets, scented products and household cleaners,

although some sufferers also finger certain foods and

electromagnetic radiation.

Contact with these items can induce reactions such as

breathlessness, chest tightness, lightheadedness, weakness, nausea

or trouble concentrating.

There are no good estimates of how many people suffer from IEI,

though Binkley said it would be incorrect to call the condition rare.

The ailment is often likened to allergies - it is sometimes called

total allergy syndrome - but differs from allergies in one important

way.

Tests have shown that when IEI sufferers are in close contact with

one of their trigger items, but are unaware of its presence because

researchers have managed to mask its scent, they do not

consistently experience symptoms.

People who suffer from pollen allergies or who are allergic to nuts,

for instance, will have an allergic reaction when exposed to their

trigger, regardless of whether they are aware of its presence or not.

" This is a condition clearly distinct from hay fever, clearly distinct

from asthma, clearly distinct from food allergies such as peanuts, "

said Binkley, who added that research " suggests that there may be a

cognitive component to it. "

Because IEI symptoms are so similar to those of panic disorder,

researchers had questioned whether the two were linked.

A discovery made two years ago about panic disorder prompted

Binkley and her colleagues to look for genetic similarities between

people with panic disorder and people with IEI.

Researchers elsewhere reported that patients with panic disorder

had more receptors for a chemical called cholecystokinin than other

people do.

Cholecystokinin is a natural substance made in the human gut and

brain. In the gut, it plays a role in digestion; in the brain, it is

believed to be related to anxiety and fear behaviours.

It is recognized to be a panicogenic agent, meaning it will induce

attacks in patients who suffer from panic disorder. It will not provoke

an attack in those who do not, however.

" It's a kind of a test for panic disorder, " Binkley said.

Given that IEI looked so much like panic disorder in so many ways,

the University of Toronto researchers asked themselves whether the

two shared genetic characteristics was well.

All humans have two types of cholecystokinin receptors, A and B.

Type B comes in 15 different variations, called alleles. Our genetic

code - the interaction of our parents' genes - determines which

alleles we carry.

Allele 7 has been found to be more prevalent in patients with panic

disorder than in the population at large.

So Binkley and her team studied a group of 11 patients with IEI,

comparing them with 11 people who do not have the condition. Of

those with IEI, 41 per cent carried allele 7. Only nine per cent of the

controls had that allele.

Binkley admitted the sample size was small and the results need to

be replicated in a larger study. But she is confident she and her

colleagues are on to something.

" It does fit with all of the studies looking at other aspects of the

problem that suggest that patients with IEI have an underlying

condition very much like panic disorder. "

Will patients with IEI feel relieved at the prospect of proof that

therem is a physiological basis to their condition? Or will the tie to

panic disorder seem like just another attempt to dismiss their

ailment as a form of mental illness?

" I think that the distinction between mind and body is really an

artificial one, " Binkley said. " They function as a whole. You can't

view one without the other. "

While the research continues, Binkley said the findings to date

suggest the multidisciplinary approach used to treat panic disorder -

the combination of relaxation therapy and stress management with

anti-depressants - may prove beneficial for sufferers of

environmental intolerance.

**************************************************

J Allergy Clin Immunol 2001 May;107(5):887-90

Idiopathic environmental intolerance: increased prevalence of panic

disorder-associated cholecystokinin B receptor allele 7.

Binkley K, King N, Poonai N, Seeman P, Ulpian C, Kennedy J.

Gage Occupational and Environmental Health Unit

University of Toronto, Toronto, Ontario, Canada.

http://www.utoronto.ca/occmed/

Send questions or comments about GOEHU to:

stulacj@...

BACKGROUND: A growing body of evidence

suggests that idiopathic environmental

intolerance (IEI) is a psychophysiologic disorder

with prominent features of anxiety/panic and

somatization, although proponents of a toxicogenic

explanation claim, despite a lack of convincing

evidence, that symptoms arise from exposure

to otherwise nonnoxious environmental agents.

Patient behaviour is characterized by

strenuous avoidance of perceived triggers to the point of

severe impairment of normal social and vocational functioning.

IEI proponents claim that previous

studies showing a high prevalence of psychopathology

in patients with IEI and studies showing

panic responses to known panicogenic challenges

merely reflect the anxiety-producing result of

living with IEI. OBJECTIVE: We explored

whether IEI and panic disorder, personality traits, or

both shared an underlying neurogenetic basis

that would predate the anxiety of IEI

symptomatology. The DNA of patients with

IEI was examined for the presence of known panic

disorder-associated cholecystokinin B (CCK-

receptor alleles and for personality

trait-associated dopamine D4 receptor polymorphisms.

METHODS: Eleven patients with typical

IEI symptoms were recruited and were individually

matched to normal control subjects from an

existing bank for age, sex, and ethnic background.

Genomic DNA was extracted from peripheral

blood samples. CCK-B and dopamine D4

receptor polymorphisms were examined by using

standard PCR-based techniques.

RESULTS: There was a significantly higher prevalence of the

panic disorder-associated CCK-B receptor allele 7

in subjects with IEI (9/22 [40.9%])

compared with control subjects (2/22 [9.1%], P =.037).

There was no difference in personality

trait-associated polymorphisms of the gene encoding

dopamine D4 receptor between patients

and control subjects. CONCLUSIONS: These findings

provide preliminary evidence that IEI

and panic disorder share a common neurogenetic basis,

which would predate the

anxiety-producing effects of IEI symptoms.

Further studies with larger samples are warranted,

but these results support previous studies that

suggest that panic disorder may account for much

of the symptomatology in at least some cases of IEI

and provide a basis for rational treatment

strategies. PMID: 11344357

http://www.utoronto.ca/seeman/group.html photo

Binkley, E. MD, FRCPC

St. 's Hospital http://www.stmichaelshospital.com/

Lecturer, University of Toronto, Toronto, Ontario

Division of Clinical Immunology and Allergy

St 's Hospital, University of Toronto, Toront, Canada.

Seaman, Philip MD, PhD Department of Pharmacology,

Medical Science Building, Room 4344, University of Toronto,

Toronto ON M5S 1A8 fax

philip.seeman@...

Ulpian, Carla MSc Department of Pharmacology

fax carla.ulpian@...

King, BSc

Poonai, Naveen MSc

Kennedy, L. MD University of Toronto

New findings in genetics of schizophrenia

Mol Psychiatry 1999 May;4(3):284-5

Investigation of cholecystokinin system genes in panic disorder.

Kennedy JL, Bradwejn J, Koszycki D, King N, Crowe R,

J, Fourie O.

e Division, Centre for Addiction and Mental Health,

University of Toronto, Ontario, Canada.

kennedy@...

There is evidence for the role of the cholecystokinin (CCK)

neurotransmitter system in the

neurobiology of panic disorder (PD).

The CCK receptor agonist, CCK-tetrapeptide (CCK-4)

fulfills criteria for a panicogenic agent and

there is evidence that PD might be associated with an

abnormal function of the CCK system.

For example, PD patients show an enhanced sensitivity to

CCK-4, and exhibit lower CSF and lymphocyte CCK

concentration as compared to healthy

controls (reviewed by Bradwejn et al.).

Also, untreated PD patients display an increased

CCK-4-induced intracellular Ca2+ mobilization

in T cells relative to treated PD, depression and

schizophrenia. The CCK receptors have been

classified into two subtypes: CCK-A and

CCK-B. We report here a study of polymorphisms

in the CCK pre-pro hormone gene (CCK),

CCK-AR, and CCK-BR in DSM-IV

panic patients (n = 99) vs controls matched for gender and

ethnicity. The CCK polymorphism revealed

no association with PD. We identified a new

polymorphism for the CCK-A receptor gene,

and tested it in our sample, with negative results. A

single nucleotide polymorphism has been found

in the coding region of the CCK-B receptor gene

(CCK-BR) and D Collier (personal communication)

identified a highly polymorphic dinucleotide

(CT)n microsatellite in the 5' regulatory region.

For the CCK-B receptor gene polymorphism, PD

patients showed a significant association.

Our genetic dissection of the CCK system thus far

suggests that the CCK-B receptor gene variation

may contribute to the neurobiology of panic

disorder. PMID: 10395221

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