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Biomedical subjects

J Hallman

Publications and source records attributed to J Hallman.

At least 19 recordsLinked to original sources
PubMed2004

Platelet MAO and personality--function and dysfunction.

Research on the association between platelet monoamine oxidase (MAO) activity and personality traits, such as sensation seeking and impulsiveness, is reviewed with an emphasis on early history and current situation. The effects of MAO-inhibiting compounds in cigarette smoke for the interpretation of this association are discussed and recent results confirming a true association between platelet MAO activity and personality and vulnerability, for e.g. type 2 alcoholism are presented. From a clinical point of view, the link between platelet MAO activity, which is highly genetically regulated and is stable in the individual, and personality traits, has had its greatest impact on the understanding of the nature of constitutional factors making individuals vulnerable, for e.g. substance abuse and other forms of sociopathic behaviour. The molecular mechanisms underlying the association between platelet MAO and behaviour are discussed and evidence that common transcriptional factors, e.g. within the AP-2 family, regulating both the expression of platelet MAO and components of the central monoaminergic systems, such as synthesising enzymes, receptors and transporters, are presented. A hypothesis is put forward, that such common transcription factors may not directly regulate platelet MAO expression, but rather mitochondrial density, or outer mitochondrial membrane surface.

Animals↗
PubMed2002

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

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.

Blood Platelets↗
PubMed2001

Expression of microtubule-associated protein 2 in benign and malignant melanocytes: implications for differentiation and progression of cutaneous melanoma.

Cutaneous melanocytic neoplasms are known to acquire variable characteristics of neural crest differentiation. Melanocytic nevus cells in the dermis and desmoplastic melanomas often display characteristics of nerve sheath differentiation. The extent and nature of neuronal differentiation characteristics displayed by primary and metastatic melanoma cells are not well understood. Here, we describe induction of a juvenile isoform of microtubule-associated protein 2 (MAP-2c) in cultured metastatic melanoma cells by the differentiation inducer hexamethylene bisacetamide. Up-regulation of this MAP-2 isoform, a marker for immature neurons, is accompanied by extended dendritic morphology and down-regulation of tyrosinase-related protein 1 (TYRP1/gp75), a melanocyte differentiation marker. In a panel of cell lines that represent melanoma tumor progression, MAP-2c mRNA and the corresponding approximately 70-kd protein could be detected predominantly in primary melanomas. Immunohistochemical analysis of 61 benign and malignant melanocytic lesions showed abundant expression of MAP-2 protein in melanocytic nevi and in the in situ and invasive components of primary melanoma, but only focal heterogeneous expression in a few metastatic melanomas. In contrast, MAP-2-positive dermal nevus cells and the invasive cells of primary melanomas were TYRP1-negative. This reciprocal staining pattern in vivo is similar to the in vitro observation that induction of the neuronal marker MAP-2 in metastatic melanoma cells is accompanied by selective extinction of the melanocytic marker TYRP1. Our data show that neoplastic melanocytes, particularly at early stages, retain the plasticity to express the neuron-specific marker MAP-2. These observations are consistent with the premise that both benign and malignant melanocytes in the dermis can express markers of neuronal differentiation.

Acetamides↗
PubMed2001

Genetic mechanisms of behavior--don't forget about the transcription factors.

Major changes in psychiatric phenotypes due to genetic factors are seldom the result of single gene polymorphisms, but more often the result of several genetic mechanisms. In this millennium article we discuss the notion that the expression of numerous candidate genes could be regulated by the same transcription factors, and that polymorphisms in transcription factor genes might explain some phenotypes. We describe recent results of studies on the biological marker thrombocyte monoamine oxidase (trbc MAO) and the transcription factor AP-2beta. Low levels of trbc MAO is associated with temperamental characteristics such as sensation seeking and impulsiveness, and the enzyme is genetically regulated by specific transcriptional mechanisms. Transcription factor AP-2beta is important for the development of midbrain structures and AP-2beta has several binding sites in the regulatory regions of genes encoding key proteins in the monoamine transmitter systems. We have recently shown AP-2beta to be linked to personality, binge-eating disorder, treatment with antidepressant drugs, and also to trbc MAO. Regardless of whether transcriptions factors, such as AP-2beta, regulate the expression of eg, the number of monoamine neurons or a variety of candidate genes within the monoamine systems, or both, we would like to emphasize the role of transcription factors, besides polymorphisms in monoaminergic candidate genes, when explaining inter-individual differences in temperament and psychiatric vulnerability.

Animals↗
PubMed2000

The genotype of human transcription factor AP-2beta is associated with platelet monoamine oxidase B activity.

Platelet monoamine oxidase B (MAO; EC 1.4.3.4.) activity is stable in the individual and is mainly genetically regulated. Levels of MAO-B in platelets have repeatedly been shown to be associated with personality traits. We have recently also demonstrated an association between the genotype of AP-2beta to a variety of personality traits as well as binge-eating disorder. In the present study we have analysed blood samples from 158 males and 64 females with regard to platelet MAO activity and genotype of transcription factor AP-2beta. In both sexes homozygotes for the long allele [CAAA](5) were significantly associated with low platelet MAO activity P<0.0001 (males) and P=0.0158 (females). This study represents a novel approach to increase the understanding about the molecular mechanisms for how the MAOB gene is regulated in blood cells and how this regulation is linked to personality traits.

Alleles↗
PubMed1998

Erythrocyte and brain methionine adenosyltransferase activities in patients with schizophrenia.

The activity of methionine adenosyltransferase (MAT) was investigated in erythrocytes and postmortem brain specimens (cortex gyrus frontalis, hippocampus and thalamus) of patients with schizophrenia treated with neuroleptics. In comparison with the control group, abnormally low values of MAT Vmax and an increased MAT affinity towards methionine (lower Km values) were found in erythrocytes. In the brain, a regionally selective decrease of MAT Km was found in cortex gyrus frontalis but the Vmax values were however, unchanged. In the regions of cortex gyrus frontalis and hippocampus, but not in thalamus, the values of Vmax and Km were inversely correlated with the duration of schizophrenia. In rats treated for 28 days with the typical neuroleptic haloperidol and the atypical clozapine, a significant increase of MAT activity was found in the corpus striatum. There is the possibility that the changes observed in MAT activity in patients with schizophrenia are attributed to the neuroleptic medication.

Adult↗
PubMed1997

Platelet monoamine oxidase activity in relation to alleles of dopamine D4 receptor and tyrosine hydroxylase genes.

Human personality characteristics and vulnerability to psychopathology are to a large extent dependent upon genetic factors which have yet to be fully defined. The allele distribution of the dopamine D4 receptor (D4DR) and thrombocyte monoamine oxidase (trbc MAO) activity have both been associated with personality traits which are supposedly related, namely 'sensation seeking' according to Zuckerman and 'novelty seeking' according to Cloninger, respectively. In this report, the D4DR allele distribution and trbc MAO activity were studied in 31 psychiatric patients and 21 control subjects. Trbc MAO activity is a biochemical marker of personality that has been shown to be under strong genetic influence. However, no association between the D4DR alleles and trbc MAO could be observed in this material. To our knowledge, this is the first report comparing these two markers, and based upon the results obtained, we speculate that they may be connected with different types of overlapping personality characteristics. The allele distribution of the tyrosine hydroxylase (TH) gene was also determined. TH is the rate-limiting enzyme in the biosynthesis of catecholamines, and it is believed to be involved in different kinds of psychopathology. No covariation between TH gene alleles and trbc MAO activity or D4DR alleles was observed in this material.

Alleles↗
PubMed1997

Is severity of premenstrual symptoms related to illness in the climacteric.

The purpose of this study was to investigate whether women in the climacteric who have previously had severe premenstrual problems have a different pattern of reporting sick than other women. The material in the study comprised women with different degrees of severity of premenstrual symptoms who participated in an epidemiological study in 1982 on patterns of reporting sick and those women who at this time were of premenopausal or menopausal age were included. Women who previously had had such serious premenstrual problems that they had to be put on the sick-list were compared with women who had had moderate or no premenstrual problems. Information about to which extent these women have reported themselves sick has been obtained from the Regional Social Insurance Office in Uppsala County. The results show that women who have previously had severe premenstrual problems and who are now of menopausal age have a significantly greater number of diagnoses and occasions and have more long-term absences from work than women in the two control groups. They also have a greater number of sick days per year compared with statistics from the National Social Insurance Board on all women in the country.

Adult↗
PubMed1996

Personality disorders according to DSM-III-R and thrombocyte monoamine oxidase activity in type 1 and type 2 alcoholics.

OBJECTIVE: Several criteria used to distinguish type 2 alcoholics from Type 1 alcoholics, as well as the incidence of lower platelet monoamine oxidase (MAO) activity in the former group, would indicate that personality disorders might be more common in Type 2 alcoholics. The purpose of the present study was to investigate the relation between personality disorders, according to DSM-III-R, platelet MAO activity and Type 1/Type 2 alcoholism. METHOD: The occurrence of personality disorders, according to DSM-III-R, was studied in a series of 34 male inpatients with alcohol dependence, subclassified into Type 1 (n = 18) and Type 2 (n = 16). Platelet MAO activity was studied in the same series of patients. RESULTS: Patients with Type 2 alcoholism had significantly higher frequencies of self-defeating, schizotypal, antisocial and borderline personality disorders than Type 1 alcoholics. Patients with Type 2 alcoholism had significantly lower mean activity of platelet MAO than Type 1 alcoholics. No correlation was found between platelet MAO activity and personality disorders according to DSM-III-R. CONCLUSIONS: Disorders of the antisocial personality and borderline personality types as well as low platelet MAO can all predict the occurrence of Type 2 alcoholism with rather high specificity but with a comparatively low degree of sensitivity.

Adult↗
PubMed1992

Low platelet gamma-aminobutyrate aminotransferase and monoamine oxidase activities in chronic alcoholic patients.

The activities of gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) were estimated in blood platelets from 25 male chronic alcoholics and from 27 healthy male volunteers without histories of alcohol abuse. Based on clinical criteria, the alcoholics were classified into type 1 or type 2 alcoholism. The activity of GABA-T was found to be lower both in type 1 and type 2 alcoholics than in healthy volunteers. With regard to MAO, the platelet activity was found to be significantly lower only in type 2 alcoholics in concordance with previous reports. No significant correlation was found between the activities of GABA-T and MAO in the blood platelets of healthy volunteers. The inhibitory effect of 400 mM ethanol on the platelet MAO activity increased with decreasing concentrations of the substrate phenylethylamine. The degree of inhibition of ethanol on the platelet MAO activity, however, did not differ significantly between alcoholics and controls.

4-Aminobutyrate Transaminase↗
PubMed1992

Exploring the connections between platelet monoamine oxidase activity and behavior. II. Impulsive personality without neuropsychological signs of disinhibition in air force pilot recruits.

Platelet monoamine oxidase (MAO) activity and serum levels of the adrenal androgen metabolite dehydroepiandrosterone sulfate (DHAS) were measured in 18 male air force pilot recruits and 19 randomly selected male conscripts. Personality scales from three inventories were given, and computerized neuropsychological tests were performed: finger tapping and alternation, reaction time, perceptual maze, perspective fluctuation and lexical decision. The pilot recruits had higher scores in sensation-seeking-related scales suggesting disinhibited behavior in the social sphere, interest in sports and activities involving some danger, and a need for change. They also had higher scores on an impulsivity scale which comprises sensation-seeking content. In the neuropsychological tasks, the pilot recruits were faster in finger-tapping alternation and performed more efficiently in the perceptual-maze test than the conscripts. In a linear discriminant analysis, neuropsychological-task performance discriminated significantly between the pilot and conscript groups. In the biochemical measures, the pilot recruits had higher DHAS levels but similar MAO activity levels compared to the conscripts, which is in contrast to what has been found in other sensation-seeking groups in comparison to controls. This result is in accordance with the normal scores in one of the impulsivity scales in the pilot recruits, and with the absence of signs of disinhibition in neuropsychological tasks. It is proposed that only some aspects of the impulsivity concept might be critical for the association with low MAO activity.

Adolescent↗
PubMed1991

Personality traits and platelet monoamine oxidase activity in alcoholic women.

Twenty-nine women, sent to an inpatient treatment facility for rehabilitation and social training after treatment for heavy alcohol abuse, were compared with 29 female students of pharmacy or medicine with regard to platelet monoamine oxidase (MAO) activity and extraversion-impulsivity and anxiety-proneness personality traits. The alcoholic females were found to have slightly lower platelet MAO activity than the controls, the difference being considerably smaller than that previously found between male alcoholics and male controls. The personality pattern of the female alcoholics is in line with that previously found in alcoholic males. Thus, the female alcoholics were characterized by high anxiety proneness, impulsive acting-out behaviour, sensation seeking, social withdrawal, and a hostile attitude.

Alcoholism↗
PubMed1991

Platelet monoamine oxidase activity in type 1 and type 2 alcoholism.

Earlier studies have identified at least two distinct subtypes of alcoholism. Type 2 is characterised by high heritability, early onset, frequent social complications and mixed misuse. With regard to temperament, the type 2 alcoholics score high in impulsiveness and sensation-seeking behaviour. Type 1 alcoholics have a later onset, lower degree of heritability and rarely there is misuse of illegal drugs. In the present study, 37 type 1 and 62 type 2 male alcoholics were compared with 36 male controls with regard to platelet monoamine oxidase (MAO) activity, which is a stable biological marker, inversely correlated to personality traits such as impulsiveness and sensation seeking. The platelet MAO activity was found to be lower in type 2 alcoholics when compared both with healthy controls and with type 1 alcoholics. Also, the type 1 alcoholics had lower platelet MAO activity than the controls. The result confirms a previous study and validates the subclassification of alcoholism according to the type 1 and 2 concept. This should be of value for future studies concerning etiology, epidemiology, treatment and prevention of alcoholism.

Alcoholism↗
PubMed1990

Clinical characteristics of female alcoholics with low platelet monoamine oxidase activity.

The aim of the present study was to see if female alcoholics had low platelet MAO activity and whether there was a correlation between low MAO activity in female alcoholics and specific clinical characteristics often observed in type II male alcoholics. In earlier studies, male alcoholics have been subdivided into type I and type II alcoholics. Type II alcoholics were characterized by early onset, a high frequency of depression and alcoholism in first degree relatives, a high frequency of drug abuse and social complications, sensation seeking behavior, extraversion, impulsive sensation seeking psychopathy, and low platelet MAO activity. In the present series it was demonstrated that the female alcoholics had significantly lower platelet MAO activities than the female healthy volunteers. The subgroup of female alcoholics with low platelet MAO activity, however, did not differ from female alcoholics with normal platelet MAO activity in the same way as male alcoholics with low platelet MAO activity have been shown to differ from male alcoholics with normal platelet activity. They did not have early onset, higher frequency of depression or alcoholism in their first degree relatives, nor more social complications than the female alcoholics with normal platelet MAO activity. Furthermore, they did not differ from the female alcoholics with normal platelet MAO activity in any personality trait covered by the Karolinska Scales of Personality (KSP).

Adult↗