The present paper summarizes the proposed time-dependent sensitization (TDS) and partial
limbic kindling model for illness from low-level chemicals; reviews and critiques prior
studies on CNS aspects of multiple chemical sensitivity (MCS); and outlines possible
experimental approaches to future studies. TDS is the progressive and persistent
amplification of behavioral, neurochemical, endocrine, and/or immunological responses to
repeated intermittent stimuli over time. Partial limbic kindling is a progressive and
persistent lowering of the threshold for eliciting electrical afterdischarges, but not
motor seizures, in certain brain structures such as amygdala and hippocampus; behavioral
consequences include increased avoidant behaviors.
The focus of the paper is the controversial claim of altered sense of smell and illness
from low levels of environmental chemicals (i. e., cacosmia), levels that should not have
any biologically harmful effects by the rules of classical neurotoxicology. A major
perspective of this paper is that the phenomenology of MCS is similar to that of
time-dependent sensitization (reverse tolerance) and tolerance as studied in the substance
abuse literature.
The TDS model for MCS proposes that neurobiological amplification underlies the symptoms
and phenomenology of these patients, including their behavioral features of heightened
affective and somatic distress. It is hypothesized that MCS patients, who are mostly
women, may be individuals who sensitize to substances rapidly and to the extreme, to the
point of aversive symptomatology with less complete capacity for development of tolerance.
Possible parallels between MCS and TDS include: (a) initiation by single or multiple
intermittent
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References
1.
ADAMEC, R.E. (1990).
Does kindling model anything clinically
relevantBiol. Psychiat.27:
249279.
2.
ADAMEC, R.E. (1993).
Partial limbic kindling brain, behavior, and the benzodiazepine
receptor. Physiol. Behav.54:
531545.
3.
ALEXOPOULOS, G.S., MEYERS, B.S.,
YOUNG,
R.C., MATTIS, S., and KAKUMA, T.
(1993). The course of geriatric depression with reversible
dementia: a controlled study. Am. J.
Psychiat.150:
16931699.
4.
ANTELMAN, S.M. (1988).
Time-dependent sensitization as the cornerstone for a new approach to
pharmacotherapy: drugs as foreignstressful stimuli. Drug Devel.
Res.14: 130.
5.
ANTELMAN, S.M. and EICHLER, A.J.
(1979). Persistent effects of stress on dopamine-related
behaviors: clinical implications. In: Catecholamines: Basic and
Clinical Frontiers (E.
Usdin, I.J. Kopin, and J. Barchas, ed.).
Pergamon Press, New
York. pp. 17591761.
6.
ANTELMAN, S.M., EICHLER, A.J.,
BLACK,
C.A., and KOCAN, D. (1980).
Interchangeability of stress and amphetamine in
sensitization. Science207:
329331.
7.
ANTELMAN, S.M., KNOPF, S.,
KOCAN,
D., EDWARDS, D.J., RITCHIE, J.C., and
NEMEROF F,
C.B. (1988). One stressful
event blocks multiple actions of diazepam for up to at least a month.
Brain Res.445:
380385.
8.
ANTELMAN, S.M., CAGGIULA, A.R.,
KOCAN,
D., KNOPF, S., MEYER, D.,
EDWARDS,
D.J., and BARRY, H. (1991).
One experience with lower or higher intensity stressors, respectively,
enhances or diminishes responsiveness to haloperidol weeks later: implications for
understanding drug variability. Brain
Res.566:
276283.
9.
ANTELMAN, S.M., CAGGIULA, A.R.,
KNOPF,
S., KOCAN, D.J., and EDWARDS, D.J.
(1992a). Amphetamine or haloperidol two weeks earlier
antagonized the plasma corticosterone response to amphetamine: evidence for the
stressfulforeign nature of drugs.
Psychopharm.107:
331336.
10.
ANTELMAN, S.M., KOCAN, D.,
KNOPF,
S., EDWARDS, D.J., and CAGGIULA, A.R.
(1992b). One brief exposure to a psychological stressor
induces long-lasting, time-dependent sensitization of both the cataleptic and
neurochemical responses to haloperidol. Life
Sci.51: 261266.
11.
ASHFORD, N.A. and MILLER, C.S.
(1991). Chemical Exposures. Low Levels and High Stakes.
Van Nostrand Reinhold, New
York.
12.
BELL, I.R. (1994).
Somatization disorder: health care costs in the decade of the
brain. Biol. Psychiat.35:
8183.
13.
BELL, I.R. and AMEND, D.
(1994). More cortisol suppression in depressed
cacosmics. Presentation at the 147th Annual meeting of the
American Psychiatric Association. Philadelphia, PA,
2126 May.
14.
BELL, I.R., MILLER, C.S., and
SCHWARTZ,
G.E. (1992a). An
olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationship
to kindling and affective spectrum disorders. Biol.
Psychiat.32:
218242.
15.
BELL, I.R., EDMAN, I.S.,
SELHUB,
I., MORROW, F.D., MARBY, D.W.,
KAYNE,
H.L., and COLE, J.O. (1992b).
Plasma homocysteine in vascular disease and nonvascular dementia of
depressed elderly people. Acta Psychiatrica
Scand.86:
386390.
16.
BELL, I.R., SCHWARTZ, G.E.,
PETERSON,
J.M., and AMEND, D. (1993a).
Self-reported illness from chemical odors in young adults without
clinical syndromes or occupational exposures. Arch. Environ.
Health48: 613.
17.
BELL, I.R., SCHWARTZ, G.E.,
PETERSON,
J.M., and AMEND, D. (1993b).
Symptom and personality prof iles of young adults from a college student
population with self-reported illness from foods and chemicals.
J. Am. Coll. Nutr.12:
693702.
18.
BELL, I.R., SCHWARTZ, G.E.,
PETERSON,
J.M., AMEND, D., and STINI, W.A.
(1993c). Possible time-dependent sensitization to
xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an
older adult population. Arch. Environ.
Health48:
315327.
19.
BELL, I.R., AMEND, D.,
KASZNIAK,
A.W., and SCHWARTZ, G.E. (1993d).
Memory deficits, sensory impairment, and depression in the
elderly. Lancet341:
62.
20.
BELL, I.R., MARKLEY, E.I.,
KING,
D.S., ASHER, S., MARBY, D.,
KAYNE,
H., GREENWALD, M., OGAR, D.A, and
MARGEN,
S. (1993e). Polysymptomatic
syndromes and autonomic reactivity to nonfood stressors in individuals with
self-reported adverse food reactions. J. Am. Coll.
Nutr.12:
227238.
21.
BELL, I.R., MILLER, C.S., SCHWARTZ, G.E., PETERSON,
J.M., and AMEND, D. (1994a). Neurobehavioral and somatic characteristics of young adults
with and without self-reported chemical odor intolerance and chemical sensitivity.
Submitted.
22.
BELL, I.R., SCHWARTZ, G.E.,
AMEND,
D., PETERSON, J.M., and STINI, W.A.
(1994b). Sensitization to early life stress and response to
chemical odors in older adults. Biol.
Psychiat.35:
857863.
23.
BELL, I.R., PETERSON, J.M., and
SCHWARTZ,
G.E. (1994c). Medical histories
and psychological prof iles of middle-aged women with and without self-reported illness
from environmental chemicals. J. Clin. Psychiatry. In
press.
24.
BELL, I.R., SCHWARTZ, G.E.,
AMEND,
D., PETERSON, J.M., KASZNIAK, A.W., and
MILLER,
C.S. (1994d). Psychological
characteristics and subjective intolerance for xenobiotic agents of normal young adults
with trait shyness and defensiveness: a Parkinsonian-like personality
typeJ. Nerv. Ment. Dis.182:
367374.
25.
BLACK, D.W., RATHE, A., and
GOLDSTEIN,
R.B. (1990). Environmental
illness. A controlled study of 26 subjects with 20th Century disease.
J. Am. Med. Assoc.264:
31663170.
26.
BOKINA A.I., EKSLER, N.D.,
SEMENENKO,
A.D., and MERKURYEVA R.V. (1976).
Investigation of the mechanism of action of atmospheric pollutants on the
central nervous system and comparative evaluation of methods of study.
Environ. Health Perspect.13:
3742.
27.
BOLLA-WILSON, K., WILSON, R., and
BLEECKER,
M.L. (1988). Conditioning of
physical symptoms after neurotoxic exposure. J. Occup.
Med.30: 684686.
28.
BOTTIGLIERI, T., HYLAND, K.,
LAUNDY,
M., GODFREY, P., CARNEY, M.W.P.,
TOONE,
B.K., and REYNOLDS, E.H. (1992).
Folate, homocysteine, and monoamine metabolism in
depression. Pteridines3:
151152.
29.
BOWLER, R.M., MERGLER, D.,
RAUCH,
S.S., HARRISON, R., and CONE, J.
(1991). Affective and personality disturbances among female
former microelectronics workers. J. Clin.
Psych.47: 4152.
30.
BRODSKY, C.M. (1983).
Allergic to everything: a medical subculture.
Psychosom.24:
731742.
31.
BURCHFIEL, J.L. and DUFFY, F.H.
(1982). Organophosphate neurotoxicity: chronic effects of
sarin on the electroencephalogram of monkey and man. Neurobehav.
Toxicol. Teratol.4:
767778.
32.
BURCHFIEL, J.L., DUFFY, F.J., and
SIM,
V.M. (1976). Persistent effects
of sarin and dieldrin upon the primate electroencephalogram.
Toxicol. Appl. Pharm.35:
365379.
33.
CABIB, S. and PUGLISI-ALLEGRA, S.
(1991). Genotype-dependent effects of chronic stress on
apomorphine-induced alterations of striatal and mesolimbic dopamine
metabolism. Brain Res.542:
9196.
34.
CAIN, D.P., and CORCORAN, M.E.
(1985). Epileptiform effects of met-enkephalin, B-endorphin,
and morphine: kindling of generalized seizures and potentiation of epileptiform effects
by handling. Brain Res.338:
327336.
35.
CALLENDER, T.J., MORROW, L.,
SUBRAMANIAN,
K., DUHON, D., and RISTOVV, M.
(1993). Three-dimensional brain metabolic imaging in
patients with toxic encephalopathy. Environ.
Res.60: 295319.
36.
CARLSON, J.N., and ROSELLINI, R.A
(1987). Exposure to low doses of the environmental chemical
dieldrin causes behavioral deficits in animals prevented from coping with
stress. Psychopharm.91:
122126.
37.
CHARNEY, D.S., DEUTCH, A.Y.,
KRYSTAL,
J.H., SOUTHWICK, S.M., and DAVIS, M.
(1993). Psychobiologic mechanisms of post-traumatic stress
disorder. Arch. Gen. Psychiat.50:
294305.
38.
CONE, J.E., and SULT, T.A.
(1992). Acquired intolerance to solvents following
pesticidesolvent exposures in a building: a new group of workers at risk for multiple
chemical sensitivity. Toxicol. Ind.
Health8: 2939.
39.
CULLEN, M.R. (1987).
The worker with multiple chemical sensitivities: an
overview. In: Occupational Medicine: State of the Art
Reviews (M.R.
Cullen, ed.). Hanley and
Belfus, Philadelphia. pp.
655662.
40.
DAGER, S.R., HOLLAND, J.P.,
COWLEY,
D.S., and DUNNER, D.L. (1987).
Panic disorder precipitated by exposure to organic solvents in the work
place. Am. J. Psychiat.144:
10561058.
41.
DEMITRACK, M.A., DALE, J.K.,
STRAUS,
S.E., LAUE, L., LISTWAK, S.J.,
KRUESI,
M.J.P., CHROUSOS, G.P., and GOLD, P.W.
(1991). Evidence for impaired activation of the
hypothalamic-pituitary-adrenal axis in patients with chronic fatigue
syndrome. J. Clin. Endocrin. Metab.73:
12241234.
42.
DOTY, R.L., SHAMAN, P.,
KIMMELMAN,
C.P., DANN, M.S. (1984).
University of Pennsylvania smell identification test: a rapid
quantitative olfactory function test for the clinic.
Laryngoscope94:
176178.
43.
DOTY, R.L., DEEMS, D.A,
FRYE,
R.E., PELBERG, R., and SHAPIRO, A.
(1988). Olfactory sensitivity, nasal resistance, and
autonomic function in patients with multiple chemical sensitivities.
Arch. Otolaryngol Head Neck Surg.114:
14221427.
44.
FIEDLER, N., MACCIA, C., and
KIPEN,
H. (1992). Evaluation of
chemically sensitive patients. J. Occup.
Med.34: 529538.
45.
FRIEDMAN, M.J. (1991).
Biological approaches to the diagnosis and treatment of post-traumatic
stress disorder. J. Traum. Stress4:
6791.
46.
GHANTOUS, H., DENCKER, L.,
GABRIELSSON,
J., DANIELSSON, B.R.G., and BERGMAN, K.
(1990). Accumulation and turnover of metabolites of toluene
and xylene in nasal mucosa and olfactory bulb in the mouse.
Pharm. Toxicol.66:
8792.
47.
GILBERT, M.E. (1992).
Neurotoxicants and limbic kindling. In: The
Vulnerable Brain and Environmental Risks. Vol. 1: Malnutrition and Hazard
Assessment. (R.L.
Isaacson and K.F. Jensen, ed.). Plenum
Press, New York. pp.
173192.
48.
GIRGIS, M. (1986).
Biochemical patterns in limbic system circuitry:
biochemical-electrophysiological interactions displayed by chemitrode
techniques. In: The Limbic System: Functional Organization and
Clinical Disorders (B.K.
Doane and K.E. Livingston, ed.).
Raven Press, New York.
pp. 5565.
49.
GRIEP, W.N., BOERSMA, J.W., and
DE KLOET,
E.R. (1993). Altered reactivity
of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia
syndrome. J. Rheum.20:
469474.
50.
HAGGERTY, J.J., STERN, R.A.,
MASON,
G.A., and BECKWITH, T., (1993).
Subclinical hypothyroidism: a modifiable risk factor for
depressionAm. J. Psychiat.150:
508510.
51.
HAUSER, P., ZAMETKIN, A.M., and
MARTINEZ,
P., (1993). Attention
deficit-hyperactivity disorder in people with generalized resistance to thyroid
hormone. N. Engl. J. Med.328:
9971001.
52.
HENKE, P.G. and SULLIVAN, R.M.
(1985). Kindling in the amygdala and susceptibility to
stress ulcers. Brain Res. Bull.14:
58.
53.
HERZOG, A.G. (1986).
Intermittent progesterone therapy and frequency of complex partial
seizures in women with menstrual disorders.
Neurol.36:
16071610.
54.
HERZOG, A.G., SEIBEL, M.M.,
SCHOMER,
D., VAITUKAITIS, J., and GESCHWIND, N.
(1984). Temporal lobe epilepsy: an extrahypolthalamic
pathogenesis for polycystic ovarian
syndromeNeurol.34:
13891393.
55.
HEUSER, G., MENA, I.,
GOLDSTEIN,
J., THOMAS, C., and ALAMOS, F.
(1993). NeuroSPECT findings in patients exposed to
neurotoxic chemicals. Clin. Nucl.
Med.18: 923.
HUDSON, J.L., GOLDENBERG, D.L.,
POPE,
H.G., KECK, P.E., and SCHLESINGER, L.
(1992). Comorbidity offibromyalgia with medical and
psychiatric disorders. Am. J. Med.92:
363367.
58.
HUNT, W.A. and LANDS, W.E.M.
(1992). A role for behavioral sensitization in uncontrolled
ethanol intake. Alcohol9:
327328.
59.
ITO, Y., TEICHER, M.H.,
GLOD,
C.A., HARPER, D., MAGNUS, E., and
GELBARD,
H.A. (1993). Increased
prevalence of electrophysiological abnormalities in children with psychological,
physical, and sexual abuse. J. Neuropsychiat. Clin.
Neurosci.5:
401408.
60.
JESBERGER, J.A. and RICHARDSON, J.S.
(1988). Brain output dysregulation induced by olfactory
bulbectomy: an approximation in the rat of major depressive disorder in
humans. Int. J. Neurosci.38:
241265.
61.
JOY, R.M. (1982).
Mode of action of lindane, dieldrin, and related insecticides in the
central nervous system. Neurobehav. Toxicol.
Teratol.4:
813823.
62.
KAGAN, J., REZNICK, J.S., and
SNIDMAN,
N. (1988). Biological bases of
childhood shyness. Science240:
167171.
63.
KALIVAS, P.W., RICHARDSON-CARLSON,
R., and Van ORDEN, G. (1986).
Cross-sensitization between foot shock stress and enkephalin-induced
motor activity. Biol. Psychiat.21:
939950.
64.
KALIVAS, P.W., SORG, B.A., and
HOOKS,
M.S. (1993). The pharmacology
and neural circuitry of sensitization to psychostimulants.
Behav. Pharm.4:
315334.
65.
KAPLAN, J.G., KESSLER, J.,
ROSENBERG,
N., PACK, D., and SCHAUMBERG, H.H.
(1993). Sensory neuropathy associated with Dursban
(chlorpyrifos) exposure. Neurol.43:
21932196.
66.
KARLER, R., FINNEGAN, K.T., and
CALDER,
L.D. (1993). Blockade of
behavioral sensitization to cocaine and amphetamine by inhibitors of protein
synthesis. Brain Res.603:
1924.
67.
KHANNA, J.M., KALANT, H.,
WEINER,
I., and SHAH, G. (1992).
Rapid tolerance and cross-tolerance as predictors of chronic tolerance
and cross-tolerance. Pharm. Biochem.
Behav.41:
355360.
68.
KJIAERGAARD, S.K, MOLHAVE, L., and
PETERSEN,
O.F. (1991). Human reactions to
a mixture of indoor air volatile organic compounds. Atm.
Environ.25A:
14171426.
69.
KOBAL, G. and HUMMEL, C.
(1988). Cerebral chemosensory evoked potentials elicited by
chemical stimulation of the human olfactory and respiratory nasal
mucosa. EEC Clin. Neurophys.71:
241250.
70.
KOKKA, N. SAPP, D.W., TAYLOR, A.M., and
OLSEN,
R.W. (1993). The kindling model
of alcohol dependence: similar persistent reduction in seizure threshold to
pentylenetetrazol in animals receiving chronic ethanol or chronic
pentylenetetrazol. Alc. Clin. Exp.
Res.17: 525531.
71.
KOLLER, W., VETERE-OVERFIELD,
B., GRAY, C., ALEXANDER, C.,
CHIN,
T., DOLEZAL, J., HASSANEIN, R., and
TANNER,
C. (1990). Environmental risk
factors in Parkinson's disease.
Neurol.40:
12181221.
72.
KREISS, K (1989).
The epidemiology of building-related complaints and
illness. Occup. Med.: State Art Rev.4:
575592.
73.
KURTZ, D., WHITE, T., and
BELKNAP,
E. (1993). Perceived odor
intensity and hedonics in subjects with multiple chemical sensitivity.
Chem. Senses18: 584.
74.
LEVY, C.J. (1988).
Agent Orange exposure and post-traumatic stress disorder.
J. Nerv. Ment. Dis.176:
242245.
75.
LOCATELLI, M., BELLODI, L.,
PERNA,
G., and SCARONE, S. (1993).
EEG power modifications in panic disorder during a temporolimbic
activation task: relationships with temporal lobe clinical
symptomatology. J. Neuropsychiat. Clin.
Neurosci.5:
409414.
76.
LORIG, T.S. (1989).
Human EEG and odor response. Prog.
Neurobiol.3:
387398.
77.
LORIG, T.S. and SCHWARTZ, G.E.
(1988). Brain and odor: I. Alteration of human EEG by odor
administration. Psychobiology16:
281284.
78.
LORIG, T.S., SCHWARTZ, G.E.,
HERMAN,
K.B., and LANE, R.D. (1988).
Brain and odor: II. EEG activity during nose and mouth
breathing. Psychobiol.16:
285287.
79.
LORIG, T.S., HERMAN, K.B.,
SCHWARTZ,
G.E., and CAIN, W.S. (1990).
EEG activity during administration of low-concentration
odors. Bull. Psychonom. Soc.28:
405408.
80.
LORIG, T.S., HUFFMAN, E.,
DeMARTINO,
A., and DeMARCO, J. (1991).
The effects of low-concentration odors on EEG activity and
behavior. J. Psychophysiol.5:
6977.
81.
McCOMB, J.A. and GOLDSTEIN, D.B.
(1979). Additive physical dependence: evidence for a common
mechanism in alcohol dependence. J. Pharm. Exp.
Ther.210: 8790.
82.
MEGGS, W.J. (1993).
Neurogenic inflammation and sensitivity to environmental
chemicals. Environ. Health
Perspect.101:
234238.
83.
MEGGS, W.J. and CLEVELAND, C.H.
(1993). Rhinolaryngocopic examination of patients with the
multiple chemical sensitivity syndrome. Arch. Environ.
Health48: 1418.
84.
MESULAM, M.M. (1985).
Principles of Behavioral Neurology. F.A.
Davis, Philadelphia.
85.
MIDDAUGH, D.A, PINNEY, S.M., and
LINZ,
D.H. (1992). Sick building
syndrome. Medical evaluation of two work forces. J. Occup.
Med.34:
11971203.
86.
MORROW, L.A (1993).
Exposure to organic solvents: cognitive, psychiatric, and
psychophysiological correlates and consequences. Presented at
the 101st Annual Meeting of the American Psychological Association, Symposium on
Neuropsychotoxicology, Toronto, Ontario,
Canada.
87.
MORROW, L.A, RYAN, C.M.,
GOLDSTEIN,
G., and HODGSON, M.J. (1989).
A distinct pattern of personality disturbance following exposure to
mixtures of organic solvents. J. Occup.
Med.31: 743746.
88.
MORROW, L.A, RYAN, C.M.,
HODGSON,
M.J., and ROBIN, N. (1990).
Alterations in cognitive and psychological functioning after organic
solvent exposure. J. Occup. Med.32:
444450.
89.
MORROW, L.A., RYAN, C.M.,
HODGSON,
M.J., and ROBIN, N. (1991a).
Risk factors associated with persistence of neuropsychological deficits
in persons with organic solvent exposure. J. Nerv. Ment.
Dis.179:
540545.
90.
MORROW, L.A, CALLENDER, T.J.,
LOTTENBERG,
S., BUCHSBAUM, M.S., HODGSON, M.J., and
ROBIN,
N. (1991b). PET and
neurobehavioral evidence of tetrabomoethane encephalopathy. J.
Neuropsychiat. Clin. Neurosci.2:
431435.
91.
MORROW, L.A., STEINHAUER, S.R.,
and HODGSON,
M.J. (1992a). Delay in P300
latency in patients with organic solvent exposure. Arch.
Neurol.49:
315320.
92.
MORROW, L.A, ROBIN, N.,
HODGSON,
M.J., and KAMIS, H. (1992b).
Assessment of attention and memory efficiency in persons with solvent
neurotoxicity. Neuropsychologia30:
911922.
93.
MORROW, L.A, KAMIS, H., and
HODGSON,
M.J. (1993). Psychiatric
symptomatology in persons with organic solvent exposure. J.
Consult. Clin. Psych.61:
171174.
94.
MUTTI, A. and FRANCHINI, I.
(1987). Toxicity of metabolites to dopaminergic systems and
the behavioral effects of organic solvents. Br. J. Ind.
Med.44: 721723.
95.
MUTTI, A., VESCOVI, P.P.,
FALZOI,
M., ARFINI, F., VALENTI, G., and
FRANCHINI,
I. (1984). Neuroendocrine
effects of styrene on occupationally exposed workers. Scand. J.
Work Environ. Health10:
225228.
96.
National Research Council
(1992). Multiple Chemical Sensitivities. Addendum to Biologic
Markers in Immunotoxicology. National Academy
Press, Washington, D.C.
97.
NETHERCOTT, J.R., DAVIDOF F, L.L.,
CURBOW,
B., and ABBEY, H. (1993).
Multiple chemical sensitivities syndrome: toward a working case
definition. Arch. Environ. Health48:
1926.
98.
NEWLIN, D.B. and PRETORIUS, M.B.
(1991). Prior exposures to the laboratory enhance the effect
of alcohol. J. Stud. Alc.52:
470473.
99.
NEWLIN, D.B. and THOMSON, J.B.
(1991). Chronic tolerance and sensitization to alcohol in
sons of alcoholics. Alc. Clin. Exp.
Res.15: 399405.
100.
ORENSTEIN, H. (1989).
Briquet's syndrome in association with depression and panic: a
reconceptualization of Briquet's syndrome. Am. J.
Psychiat.146:
334338.
101.
ORENSTEIN, H., RASKIND, M.A,
WYLLIE,
D., RASKIND, W.H., and SOULES, M.R.
(1986). Polysymptomatic complaints and Briquet's syndrome in
polycystic ovary disease. Am. J.
Psychiat.143:
768771.
102.
OVERSTREET, D.H. (1993).
The Flinders sensitive line rats: a genetic animal model of
depression. Neurosci. Biobehav.
Rev.17: 5168.
103.
PAPP, L.A., KLEIN, D.F.,
MARTINEZ,
J., SCHNEIER, F., COLE, R.,
LEIBOWITZ,
M.R., HOLLANDER, E., FYER, A.J.,
JORDAN,
F., and GORMAN, J.M. (1993).
Diagnostic and substance specificity of carbon dioxide-induced
panic. Am. J. Psychiat.150:
250257.
104.
PERIS, J., DeCAMBRE, N.,
COLEMAN-HARDEE,
M.L., and SIMKINS, J.W. (1991).
Estradiol enhances behavioral sensitization to cocaine and
amphetamine-stimulated striatal [3H] dopamine release. Brain
Res.566:
255264.
105.
PEZZOLI, G., RICCIARDI, S.,
MASOTTO,
C., MARIANI, C.B., and CARENZI, A.
(1990). n-Hexane induces Parkinsonism in
rodents. Brain Res.531:
355357.
106.
PITMAN, R.K., ORR, S.P., and
SHALEV,
A.Y. (1993). Once bitten, twice
shy: beyond the conditioning model of PTSD. Biol.
Psychiat.33:
145146.
107.
POEWE, W., GERSTENBRAND, F.,
RANSMAYR,
G., and PLORER, S. (1983).
Premorbid personality of Parkinson patients. J.
Neural Trans.19 (Suppl):
215224.
108.
POST, R.M. (1992).
Transduction of psychosocial stress into the neurobiology of recurrent
affective disorder. Am. J.
Psychiat.149:
9991010.
109.
POST, R.M. and KOPANDA, R.T.
(1976). Cocaine, kindling, and psychosis.
Am. J. Psychiat.133:
627634.
110.
POST, R.M., RUBINOW, D.R., and
BALLENGER,
J.C. (1984). Conditioning,
sensitization, and kindling: implications for the course of affective
illness. In: Neurobiology of Mood Disorders
(R.M.
Post and J.C. Ballenger, ed.).
Williams and Wilkins,
Baltimore, pp.
432466.
111.
RAJPUT, A.H., OF FORD, K.P.,
BEARD,
B., and KURLAND, L.T. (1987).
A case-control study of smoking habits, dementia, and other illnesses in
idiopathic Parkinson's disease.
Neurol.37:
226232.
112.
RANDOLPH, T.G. (1978).
Specific adaptation. Ann.
Allergy40:
333345.
113.
REST, K.M. (1992).
Advancing understanding of multiple chemical sensitivity (MCS): overview
and recommendations from an AOEC workshop. Toxicol. Ind.
Health8: 113.
114.
ROBINSON, T.E. and BECKER, J.B.
(1986). Enduring changes in brain and behavior produced by
chronic amphetamine administration: a review and evaluation of animal models of
amphetamine psychosis. Brain Res.
Rev.11: 157198.
115.
ROBINSON, T.E., BECKER, J.B., and
PRESTY,
S.K (1982). Long-term
facilitation of amphetamine-induced rotational behavior and striatal dopamine release
produced by a single exposure to amphetamine: sex differences.
Brain Res.253:
231241.
116.
ROSENBAUM, J.F., BIEDERMAN, J.,
BOLDUC,
E.A., HIRSHFELD, D.R., FARAONE, S.V., and
KAGAN,
J. (1992). Comorbidity of
parental anxiety disorders as risk for childhood-onset anxiety in inhibited
children. Am J. Psychiat.149:
475481.
117.
ROSENSTOCK, L., KEIFER, M.,
DANIELL,
W.E., McCONNELL, R., and CLAYPOOLE, K.
(1991). Chronic central nervous system effects of acute
organophosphate pesticide intoxication.
Lancet338:
223227.
118.
ROSENTHAL, N.E. and CAMERON, C.L.
(1991). Exaggerated sensitivity to an organophosphate
pesticide. Am. J. Psychiat.148:
270.
119.
ROSS, G.H. (1992).
History and clinical presentation of the chemically sensitive
patient. Toxicol. J. Ind. Health8:
2128.
120.
RYAN, C.M., MORROW, L.A, and
HODGSON,
M. (1988). Cacosmia and
neurobehavioral dysfunction associated with occupational exposure to mixtures of organic
solvents. Am. J. Psychiat.145:
14421445.
121.
SANDMAN, C.A, BARRON, J.L.,
NACKOUL,
K., GOLDSTEIN, J., and FIDLER, F.
(1993). Memory deficits associated with chronic fatigue
immune dysfunction syndrome. Biol.
Psychiat.33:
618623.
122.
SCHOTTENFELD, R.S. and CULLEN, M.R.
(1985). Occupationinduced post-traumatic stress
disorders. Am. J. Psychiat.142:
198202.
123.
SCHURZ, B., SCHON, H.J.,
WENZL,
R., KUBISTA, E., SPONA, J.,
HUBER,
J., and WEINDLMAYRGOETTEL, M. (1991).
Breast cyst fluid concentrations of beta-endorphin, steroids, and
gonadotrophins in premenopausal women with gross cystic disease.
Maturitas13:
123128.
124.
SELHUB, J., JACQUES, P.F.,
WILSON,
P.W.F., RUSH, D., and ROSENBERG, I.H.
(1993). Vitamin status and intake as primary determinants of
homocysteinemia in an elderly population. J. Am. Med.
Assoc.270:
26932698.
125.
SHIPLEY, M.T. (1985).
Transport of molecules from nose to brain: transneuronal anterograde and
retrograde labeling in the rat olfactory system by wheat germ agglutin-horseradish
peroxidase applied to the nasal epithelium. Brain Res.
Bull.15:
129142.
126.
SIMON, G.E., KATON, W.J., and
SPARKS,
P.J. (1990). Allergic to life:
psychological factors in environmental illness. Am. J.
Psychiat.147:
901906.
127.
SIMON, G.E., DANIELL, W.,
STOCKBRIDGE,
H., CLAYPOOLE, K., and ROSENSTOCK, L.
(1993). Immunologic, psychological, and neuropsychological
factors in multiple chemical sensitivity. A controlled study.
Ann. Int. Med.19:
97103.
128.
SIMON, T.R., HICKEY, D.C.,
REA,
W.J., JOHNSON, A.R., and ROSS, G.
(1992). Breast implants and organic solvent exposure can be
associated with abnormal cerebral SPECT studies in clinical impaired
patients.
Radiology185(P):
234.
129.
SMITH, G.R. (1990).
Somatization Disorder in the Medical Setting.U.S. Dept.
of Health and Human ServicesNational Institute of Mental Health,
Rockville, MD.
130.
SMITH, G.R., MONSON, R.A., and
RAY,
D.C. (1986). Patients with
multiple unexplained symptoms. Their characteristics, functional health, and health care
utilization. Arch. Int. Med.146:
6972.
131.
SNYDER-KELLER, A.M. (1991).
Striatal c-fos induction by drugs and stress in neonatally
dopamine-depleted rats given nigral transplants: importance of NMDA activation and
relevance to sensitization phenomena. Exp.
Neurol.113:
155165.
132.
SORG, B.A. and KALIVAS, P.W.
(1991). Effects of cocaine and footshock stress on
extracellular dopamine levels in the ventral striatum. Brain
Res.559: 2936.
133.
STAUDENMAYER, H. and SELNER, J.C.
(1990). Neuropsychophysiology during relaxation in
generalized, universal allergic reactivity to the environment: a comparison
study. J. Psychosom. Res.34:
259270.
134.
STAUDENMAYER, H., SELNER, M.E., and
SELNER,
J.C. (1993). Adult sequelae of
childhood abuse presenting as environmental illness. Ann.
Allergy71:
538546.
135.
TEICHER, M.H., GLOD, C.A.,
SURREY,
J., and SWETT, C. (1993).
Early childhood abuse and limbic system ratings in adult psychiatric
outpatients. J. Neuropsychiat. Clin.
Neurosci.5:
301306.
136.
TERR, A.I. (1989).
Clinical ecology in the workplace. J. Occup.
Med.31: 257261.
137.
THRASHER, J.D., MADISON, R.,
BROUGHTON,
A., and GARD, Z. (1989).
Building-related illness and antibodies to albumin conjugates
offormaldehyde, toluene diisocyanate, and trimellitic anhydride.
Am. J. Ind. Med15:
187195.
138.
Van RIEZEN H. and LEONARD, B.E.
(1990). Effects of psychotropic drugs on the behavior and
neurochemistry of olfactory bulbectomized rats. Pharm.
Ther.47: 2134.
139.
WALLACE, L., NELSON, C.J., KOLLANDER, M., LEADERER,
B., BASCOM, R. and DUNTEMAN, G. (1991). Indoor air quality and work environment study.
Multivariate statistical analysis of health, comfort, and odor perceptions as related to
personal and workplace characteristics. U.S. Environmental Protection Agency vol. 4, EPA
Headquarters Buildings. Atmospheric Research and Exposure Asessment
Laboratory.
140.
WEISS, S.R.B., POST, R.M.,
GOLD,
P.W., CHROUSOS, G., SULLIVAN., T.L.,
WALKER,
D., and PERT, A. (1986).
CRF-induced seizures and behavior: interaction with amygdala
kindling. Brain Res.372:
345351.
141.
WILLIAMS, A (1993).
Hypersusceptibility to chemicals: risk factors for neurological
diseaseJ. Neurol. Neurosurg.
Psychiat.56:
943946.
142.
WILLIAMS, C.L., PETERSON, J.M.,
VILLAR,
R.G., and BURKS, T.F. (1987).
Corticotropin-releasing factor directly mediates colonic responses to
stress. Am. J. Physiol.253:
G582586.
143.
YEHUDA, R. and ANTELMAN, S.M.
(1993). Criteria for rationally evaluating animal models of
post-traumatic stress disorder. Biol.
Psychiat.33:
479486.
144.
YEHUDA, R., SOUTHWICK S.M.,
KRYSTAL,
J.H., BREMNER, D., CHARNEY, D.S., and
MASON,
J.W. (1993). Enhanced
suppression of cortisol following dexamethasone administration in post-traumatic stress
disorder. Am. J. Psychiat.150:
8386.
