Sensory and Immune Systems in Mental Disorders

Tatyana Nevidimova
Mental Health Research Institute, Tomsk, Russia

Introduction and Design

Sensory perception is an important part of mental health. Sensory and immunological abnormalities are frequently observed in patients with depression and addiction. Pica is one of the examples of sensory vulnerability. Pica is an eating disorder relating to the consumption of non-nutritive substances and changes of olfactory and taste preferences. Olfaction, nociception and immunity in mental disorders are the next steps of our research.

Purpose and Methods

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Purpose: to study interactions between sensory vulnerability and immunological abnormalities in addictive and affective disorders. Object: about 800 patients with addictive and affective disorders and controls were studied. Methods: Questionnaires, Zuckermans Sensation Seeking Scale, Bems Gender Test, Hamilton rating scale. 40-item University of Pennsylvania Smell Identification Test (UPSIT), Alcohol Sniff Test (AST), androstenone test, taste test, pressure-pain thresholds test, visual analogous scale. Parameters of immunity and iron metabolism were studied by ELISA and flow cytometry. Statistics: Mann-Whitney, chi-square and logistic regression.

Results
Pathological gustatory and olfactory sensations are registered in childhood and adolescence more then in a half of the cases. Craving for taste of chalk, for smell of petrol and other chemicals is observed in patients.

Pica and addiction

Pica occurs in patients with iron deficiency. The biology of the syndrome is unknown. Could pica and changes of sensory perception thresholds form a stereotype of addictive behavior?

Blue sectors indicate frequency of teenagers having addiction features

Features of addiction Adolescents having are found often in 1,5 sensory disorders which (p<0,05) times beside is pica teens have higher risk having sensory of having addiction disorders.

Pica and addiction

Early pica was detected in heroin addicts more often than in the controls (43% and 22%, p<0,05).

Addicts

Control

Dark sectors indicate pica Early pica No pica

Sensory vulnerable persons with anamnestic pica have higher level of ferritin and lower level of CD71 lymphocytes which correlates with the level of interleukin-6.

Controls, no pica Controls, pica Addicts, no pica Addicts, pica

CD71

ferritin

IL-6

Our hypothesis was proven. What's next?

During the study of the pica we faced very interesting phenomena. It is related to perception of some special odors and pain sensitivity. SMELLS: Smell of isopropyl alcohol is more attractive for addicts and occasionally drug users. Smell of androstenone is more aversive for adolescent drug users.

Perception of isopropyl alcohol smell and drug craving

Addicts and drug users are much less likely to be aversed by isopropyl alcohol smell (its attractive)

Y axe aversion in analogous visual scale scores 1 controls, 2 occasional drug users, 3 - addicts

Smell attractive and aversive effects in addicts (dark bars) and controls
50

45 40 - , 35 22 1,5 23,45 24,64 14,77 30 28,5 17,5 15,81 16,77 15,06 25 47 39 15 0 47 20 2 42 19,1 18,2 16,8
15 10 5 0 isopropanol aversion androstenone aversion testosterone

Androstenone aversion correlates with low level of testosterone in male addicts.

Is it way of non-invasive testosteron level estimating using smell test ?

Perception of the odor of androstenone (aversive effect)

90 80 70 60 50 40 30 20 10 0

controls

addicts

sexual disorders

We found similar statistic in adolescents with sexual disorders. Its one of the biologic reasons of gender deviations in young addicts

Interleukine-6 and nociception in male addicts

100% 80% 60% 40% 20% 0%

IL 6, pg/ml

Pain threshold, score

Pain tolerancy, score

Low masculinity

Normal masculinity

So we focus on the variation in gender. Masculinity was estimated by Bems test. Low masculinity was related with high production of interleukin-6 and higher pain sensitivity in addicts.

Nociception and anti-norepinephrine antibodies in occasionally drug users

100% 80% 60% 40% 20% 0%

Pain delta*

Antibodies to norepinephrine control risk

*Pain delta = (Pain tolerance score Pain threshold score)

Our recent studies shows that risk of occasional drug usage is higher for adolescents with changed pain sensitivity and lower level of antibodies to norepinephrine Possibly it is related to decreased production of norepinephrine and reward system deficiency

Conclusion
Pica is a risk factor that increases risk of addiction in adolescents; Other risk factors are: decreased sensitivity to bitter and salty taste stimuli, absence of aversion to olfactory stimuli and the unusual pain sensitivity; The following factors increase the risk of developing of craving for psychoactive substances: male sex, need for sensory stimulation, the presence of clinical signs of immune deficiency, a high level of anxiety.

Recent results
Low masculinity was related with high production of interleukin-6 and pain sensitivity deviations in addicts. Antibodies to norepinephrine are related to nociception and risk of drug craving. Taste test values, alcohol sniff test values and pain thresholds are related to the effects of antidepressants.

Acknowledgement and Cooperation

RAMS Mental Health Research Institute (Tomsk): Addictive disorders Department Affective disorders Department Institute of Pathology and Pathophysiology (Moscow) RAS Institute of Atmospheric Optics (Tomsk) Institute of Chemical Biology and Fundamental Medicine (Novosibirsk) Healthcare Narcology centers (Tomsk, Kemerovo) Medical University (Tomsk)

Thank you for your attention