Jarmila Hallman

Autoantibodies against α-MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients

The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing α-melanocyte-stimulating hormone (α-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN and/or BN patients studied had in their plasma Abs that bind to melanotropes and/or corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to α-MSH-positive neurons and their hypothalamic and extrahypothalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with α-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with α-MSH or adrenocorticotropic hormone. Additionally, 3 AN/BN sera bound to luteinizing hormone-releasing hormone (LHRH)-positive terminals in the rat median eminence, but only 2 of them were adsorbed with LHRH. In the control subjects, 2 of 13 sera (16%) displayed similar to AN/BN staining. These data provide evidence that a significant subpopulation of AN/BN patients have autoantibodies that bind to α-MSH or adrenocorticotropic hormone, a finding pointing also to involvement of the stress axis. It remains to be established whether these Abs interfere with normal signal transduction in the brain melanocortin circuitry/LHRH system and/or in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to and/or could be involved in the pathophysiology or clinical presentation of AN/BN, and to what extent increased stress is an important factor for production of these autoantibodies.

Thrombocyte monoamine oxidase activity and personality traits in women with severe premenstrual syndrome

ABSTRACT: Women with premenstrual syndrome (PMS) of such severity that they actively had sought medical attention for their symptoms were compared with healthy female students with regard to platelet MAO activity and temperamental correlates by means of the Karolinska Scales of Personality (KSP), scales from the Eysenck Personality Questionnaire (EPQ) and Eysencks IVE inventory. The women with PMS were divided into two groups; irritability and depression as predominating symptom. No variation in platelet MAO was found during the menstrual cycle, either in patients or in controls. Both PMS groups had significantly lower platelet MAO activity than the controls. There was no difference between the two groups with PMS. Also with regard to personality traits there were considerable differences between the females with PMS and the controls. There were few differences between the two groups of PMS patients. Thus, the patients scored significantly higher as regards somatic anxiety, muscular tension, indirect aggression, verbal aggresion and neuroticism and lower as regards socialization than the controls.

Chapter 8 The correlation between platelet MAO activity and personality: short review of findings and a discussion on possible mechanisms

Publisher Summary This chapter discusses the researches based on the correlation between platelet monoamine oxidase (MAO) activity and personality. The associations between platelet MAO activity and personality most probably provide the basis for the associations between platelet MAO activity and various psychiatric disorders. In some cases, such as drug abuse and psychopathy, basic personality could be expected to play a vital role in the development of the disorder, while in other cases, such as schizophrenia, depression, or panic disorder, platelet MAO reflecting premorbid personality might correlate to the symptoms or subclasses of the disorder. Low platelet MAO activity has been demonstrated in alcoholics. The sub classification of alcoholism into types 1 and 2, based on heritable and environmental factors in a series of adopted children, has provided valuable information on the relation between platelet MAO activity and alcoholism. Another area in relation to platelet MAO activity is psychopathy, criminality, and aggressive behavior. Yu and colleagues contributed to this, although the results were not entirely conclusive. Their indications of a connection between criminality and low platelet MAO activity could be verified by the findings of considerably lower platelet MAO activity in consecutive patients undergoing forensic psychiatric examination in comparison with construction builders.

Aggressive Behavior Linked to Corticotropin-Reactive Autoantibodies

BACKGROUND Altered stress response is characteristic for subjects with abnormal aggressive and antisocial behavior, but the underlying biological mechanisms are unclear. We hypothesized that autoantibodies (autoAbs) directed against several stress-related neurohormones may exist in aggressive subjects. METHODS Using enzyme-linked immunosorbent assay, we studied whether autoAbs directed against corticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), oxytocin, and vasopressin are present in serum of male subjects with conduct disorder and prisoners with history of violence. Healthy blood donors served as control subjects. RESULTS Both conduct disorder and prisoners groups displayed strongly increased levels of ACTH-reactive immunoglobulin G (IgG) and immunoglobulin M (IgM) autoAbs compared with control subjects. Levels of oxytocin-reactive IgM autoAbs were slightly increased in both groups of aggressive subjects, whereas levels of vasopressin-reactive IgG and IgM autoAbs were lower only in conduct disorder. No differences in the levels of alpha-MSH-reactive autoAbs were found between aggressive and control subjects. CONCLUSIONS High levels of ACTH-reactive autoAbs as well as altered levels of oxytocin- and vasopressin-reactive autoAbs found in aggressive subjects may interfere with the neuroendocrine mechanisms of stress and motivated behavior. Our data suggest a new biological mechanism of human aggressive behavior that involves autoAbs directed against several stress-related neurohormones.

Monoamine oxidases : activities, genotypes and the shaping of behaviour

SummaryThe importance of an interaction between environment and biological factors for the expression for a particular behaviour is illustrated by results from a series of adolescents in which effects of platelet MAO activity and psychosocial environment on criminality was investigated. In a favourable environment platelet MAO-B activity was not associated with criminality, while a very strong association was found in adolescents from a bad psychosocial environment. Essentially similar findings were obtained when a MAO-A promoter polymorphism was analysed instead of platelet MAO-B activity. In boys, presence of the low functioning allele seemed to be protective against criminal activity in combination with a good environment, while it predisposed for criminality in a bad psycho-social environment. In girls, instead, homozygosity for the high activity MAO-A allele interacted with environment to predict criminality. Possible mechanisms underlying the role of monoamine oxidases for behaviour are discussed.

Exploring the connections between platelet monoamine oxidase activity and behavior: relationships with performance in neuropsychological tasks.

Platelet MAO activity has been found to have behavioral (psychiatric and personality) correlates. The purpose of the present study was to explore the nature of the connections between platelet MAO activity and behavior by analyzing performance in neuropsychological tasks in relation to platelet MAO activity, measured in 37 male subjects. The following neuropsychological tests were given: a finger tapping and alternation test, a reaction time test, a perceptual maze test, a perspective fluctuation task (the Necker cube), and a lexical decision task. The reaction time tasks comprised a motor disinhibition task, in which auditory stimuli given simultaneously with light stimuli were signals for response inhibition. Significant relationships were obtained between low MAO activity and short response times and small variations in response times to left-sided visual stimuli, suggesting a readiness for higher right hemisphere activation in low MAO subjects, and between low platelet MAO activity and many perspective reversals, in line with expectations. Furthermore, high MAO subjects had equal tapping speed for both hands, which has been found in schizophrenic patients. Of special interest in the present results is the strong negative relationship obtained between platelet MAO activity and number of failed inhibitions in the motor disinhibition task, which in a multiple regression analysis highly significantly contributed to the prediction of platelet MAO activity. This finding is in line with the poor passive avoidance performance associated with serotonergic deficiency and syndromes of disinhibition, and thus supports the assumption that platelet MAO activity may be considered as a genetic marker for some properties of the central serotonergic system.

Personality traits on the basis of the Temperament and Character Inventory in female fibromyalgia syndrome patients

The study was designed to investigate personality traits in fibromyalgia syndrome (FMS) patients by means of the Temperament and Character Inventory (TCI) and, furthermore, to relate the personality traits to the presence of psychiatric disorders. Thirty-eight female FMS patients and sex- and age-matched healthy control subjects (HCS) completed the 238-item self-rating personality inventory TCI. The Structured Clinical Interview for DSM-III-R (SCID) I was used to determine psychiatric disorders. To expand the diagnostic procedure for depression, the self-rating Beck Depression Inventory (BDI) was also used. The results of the TCI rating showed that 82% of the FMS patients had a temperament type with high Harm Avoidance. The FMS patients scored significantly higher than the HCS in this variable (P=0.0001), regardless of concomitant psychiatric disorder. High Harm Avoidance is suggested to be strongly correlated to anxiety and depression. Thirty-seven per cent of the FMS patients fulfilled the SCID I criter...

Personality Traits and Platelet Monoamine Oxidase Activity in a Swedish Male Criminal Population

Background: A Swedish male criminal population was grouped into personality disorder subgroups and investigated with regard to personality traits and platelet monoamine oxidase (MAO) activity. The main aim of the study was to examine the possibility of a risk factor combination by having low platelet MAO activity as well as belonging to a certain diagnostic DSM-IV axis I (drug abuse in the present series) and/or II subgroup. Methods: Personality disorders were grouped into clusters according to the cluster system used in DSM-IV axis II. The prisoners were grouped into five subgroups and each subject completed the Karolinska Scales of Personality self-report questionnaire. The comparison group for the personality data comprised 51 non-criminal males from a longitudinal Swedish project. Platelet MAO activity was assessed for the criminals as well as for a control group including 60 non-criminal healthy male Caucasians. For testing the existence of syndromes, a configuration frequency analysis (CFA) was used. Results: The results showed low scores on the socialisation and high scores on the sensation seeking-related traits impulsiveness and monotony avoidance, and the somatic anxiety-related muscular tension in the criminals with any DSM-IV mental disorder, however most markedly in cluster AB and cluster B subjects. In addition, cluster AB subjects had significantly lower platelet MAO activity than controls. Two significant ‘types’ were found among the criminals: one was characterised by low platelet MAO activity, cluster B personality diagnosis as well as drug abuse disorder diagnosis; and the other by a pattern of normal platelet MAO activity, no cluster B personality disorder and no drug abuse disorder diagnosis. Conclusion: The aggregation of certain risk factors in the same individual has been shown to contribute to the development of criminal behaviour.

Smoking only explains part of the associations between platelet monoamine oxidase activity and personality

Summary. Platelet monoamine oxidase (MAO) activity has been shown to be inversely associated with personality traits such as sensation seeking, impulsiveness and extraversion. Those personality traits have also been linked to vulnerability for substance abuse, e.g. tobacco smoking and early onset or “type 2” alcoholism. Compounds in cigarette smoke have been shown to be inhibitors of MAO, which has led several authors to claim that there is no association between alcoholism, which is the most studied psychiatric condition, and platelet MAO if the effect of smoking is removed. With regard to the association between personality and platelet MAO, authors have in general been cautious. In the present paper we describe a number of results which show that there is such an association, both in clinical series if the effect of smoking is removed and in series where smoking have never taken place. A cornerstone in this regard is the significant association between platelet MAO activity and both behaviour/personality, voluntary alcohol intake and biochemical measures of CNS serotonergic activity in non-human primates. Strong evidence that the regulation of platelet MAO activity takes place on a transcriptional level with an involvement of transcription factors, likely to also regulate central monoaminergic activity, are presented.

Genetic Variation of the Ghrelin Signaling System in Females With Severe Alcohol Dependence

INTRODUCTION Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co-morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro-ghrelin gene (GHRL) and the ghrelin receptor gene (GHSR) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence (n = 113) and in a selected control sample of female low-consumers of alcohol from a large cohort study in southwest Sweden (n = 212). METHODS Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals. RESULTS We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol-dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early-onset, more heredity-driven, type 2 form of alcohol dependence in the patient group. CONCLUSION Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward- and energy-related factors such as smoking and BMI.