Alcohol and Alcoholism Advance Access originally published online on April 12, 2008
Alcohol and Alcoholism 2008 43(4):423-430; doi:10.1093/alcalc/agn021
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Neuropsychological Function and Platelet Monoamine Oxidase Activity Levels in Type I Alcoholic Patients
1 Alcoholism Unit of the Psychiatric Service of Santa Maria General Hospital, Núcleo de Estudos e Tratamento do Etilo-Risco (NETER), Lisbon, Portugal
2 Genetic Laboratory, Medical School University of Lisbon, Lisbon, Portugal
* Author to whom correspondence should be addressed at: Núcleo de Estudos e Tratamento do Etilo-Risco (NETER), Serviço de Psiquiatria do Hospital de Santa Maria, Avenue Prof. Egas Moniz, 1649-028 Lisboa, Portugal. E-mail: samuelpombo{at}gmail.com
Received 30 July 2007; first review notified 15 November 2007; in revised form 17 December 2007; accepted 29 February 2008
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ABSTRACT |
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Aims: To explore neuropsychological function in two differentiated patterns of platelet monoamine oxidase B (MAO B) activity in alcoholic patients. Methods: Neuropsychological examination and platelet MAO B activity extracted from blood were collected from 42 alcohol-dependent patients recruited in the alcoholism unit (NETER) of the Psychiatric Service of Santa Maria University Hospital. Results: Alcoholics presented significantly low levels of platelet MAO B activity, when compared with control subjects; platelet MAO B activity in alcoholics classified as "under average subgroup" showed significant lower scores in the Raven Progressive Matrix and higher scores in hostility dimension, when compared with platelet MAO B activity in "above average subgroup." Conclusions: Results suggested platelet MAO B as a trait marker also to type I alcohol-dependent patients and the two observed associations between platelet MAO B activity with neurocognitive measures of executive functions (nonverbal reasoning) and psychopathological dimension such as hostility may support the notion about the effect of platelet MAO B activity in the further development of an impulsive cognitive style.
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Introduction |
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TOPABSTRACTIntroductionMethods and SubjectsResultsDiscussionReferences |
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History on research of platelet monoamine oxidase B (MAO B) as a potential trait marker for alcoholism has been contradictory and broadly discussed (for review, see Oreland, 2004
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MAOs (type A and type B) are two insoluble mitochondrial enzymes, which are widely distributed throughout the body. MAOs catalyze the oxidative deamination of exogenous (dietary) and endogenous (neurotransmitters) monoamines, being expressed by most human tissues. MAO B in platelets has been suggested to have the same amino acid sequence as in human brain (Shih et al., 1999). Type A preferentially degrades serotonin and norepinephrine, and type B preferentially degrades phenylethylamine and benzilamine. Dopamine is a substrate for both forms.
In many studies, the level of platelet MAO B activity was significantly different between alcohol-dependent subtypes of alcoholics and healthy controls (Sullivan et al., 1978, 1979; Alexopoulos et al., 1981; Faraj et al., 1987; Pandey et al., 1988). Reports show that low levels of MAO B are associated with personality traits such as impulsiveness and sensation seeking and with "type 2" alcoholism, even in nonhuman primates (von Knorring et al., 1985, 1998; Pandey et al., 1988; Sullivan et al., 1990; Tabakoff et al., 1990; Fahlke et al., 2002). However, Anthenelli et al. (1995) tested the subgrouping methods and found differences only in Gilligan criteria for subtypes I/II. Several other studies failed to find such differences (Tabakoff et al., 1988; Anthenelli et al., 1998; Farren et al., 1998; Farren and Tipton, 1999; Whitfield et al., 2000).
Many other variables have been suggested to contribute to differences in platelet MAO B activity as well as potential confounder factors for the interpretation of platelet MAO B activities in alcoholism. Stability of platelet MAO B enzyme activity might also depend on the time of platelet collection in relation to last alcohol ingestion. For instance, some reports of state-dependent fluctuations show that MAO B activity during early abstinence may transiently increase, suggesting the activity peak has occurred between 1 and 2 weeks after the end of alcohol intake (Wiberg et al., 1977; Alexopoulos et al., 1981; Major et al., 1981; Berggren et al., 2000; Coccini et al., 2002). These findings increased platelet MAO B potential value as an early biological marker of alcohol cessation. Positive family history for alcoholism has also been reported to have lower platelet MAO B activity (Major and Murphy, 1978; Alexopoulos et al., 1983; Rommelspacher et al., 1994), although these findings have been contradictory (Soyka et al., 2000; Whitfield et al., 2000; Berggren et al., 2002). In a number of studies, researchers verified that tobacco use is associated with MAO B activity, raising the question to which extent the inhibitory effect on enzyme activity may be associated with the contribution of cigarette smoking (Norman et al., 1987; Sher et al., 1994; Whitfield et al., 2000) or not (Anthenelli et al., 1995; Berggren et al., 2000, 2002; Coccini et al., 2002). Other factors such as age and gender have all been shown to influence platelet MAO B activity. In adults, platelet MAO activity is characterized by substantial stability over time, although it seems to increase gradually with senescence (Bridge et al., 1985; Parnetti et al., 1992; Mészáros et al., 1998). This increase is hypothesized to be connected to genetic and environmental factors, being potentially attributed to the glial proliferation that accompanies neuronal loss and the decreased levels of many biosynthetic enzymes for catecholamines. Platelet MAO activity has also been reported to be higher in adult females than in males (Veral et al., 1997; Snell et al., 2002).
Strong genetic influence in MAO B activity has been confirmed by twin studies (Pedersen et al., 1993). Several researches showed that different genetic mechanisms might contribute to the regulation of the catalitic capacity of human MAO B, even in alcoholic populations. Garpenstrand et al. (2000) concluded in Caucasian males that MAO B intron 13 genotype might be involved in determining platelet MAO B activity and, based on the assumption that both platelet MAO B activity (MAO B is important for the degradation of dopamine) and alleles for the DRD2 receptor reflect in different ways central dopaminergic neurotransmission, Eriksson et al. (2000), in a preliminary study performed in alcoholics, found a lower platelet MAO B activity in individuals carrying the DRD2 A1 allele polymorphism. On the basis of their structural similarity in their genes, Chen et al. (1993) assumed that MAO B from brain frontal cortex and the one derived from human platelets are identical. Using a positron emission tomography (PET), Bench et al. (1991) showed an association between platelet and brain MAO B activity under "normal" physiological circunstances. Inhibition of platelet MAO B isolated from blood samples taken at the time of scanning correlated strongly with the decrease in whole brain. Although these more recently published studies discussed platelet MAO B activity as a peripheral marker, representing MAO B activity in the brain, other observations do not come in this line (Winblad et al., 1979; Young et al., 1986).
Early reports showed an association between platelet MAO B activity and neuropsychological measures. Computerized tests found that response time, failed inhibition, and maze perceptual check time were related to MAO B activity (af Klinteberg et al., 1990). In contrast to these results, Demir et al. (2002) did not find any relationship between platelet MAO B activity and executive skills in alcoholism subtypes.
This paper explores the aspects of neuropsychological function in two differentiated patterns of platelet MAO B activity in alcoholic patients, taking into account several factors that may influence MAO B enzyme activity.
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Methods and Subjects |
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TOPABSTRACTIntroductionMethods and SubjectsResultsDiscussionReferences |
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A sample of 53 alcohol-dependent patients was recruited from the alcoholism unit (NETER) of the Psychiatric Service of Santa Maria University Hospital. All patients were taken in the therapeutical programme centre for alcohol detoxification.
The exclusion criteria were the presence of history of illicit drugs abuse/dependence; history of benzodiazepines abuse/dependence; history of cerebral trauma or cerebral diseases; history of amnesic disorders; epilepsy; history of seizures with and without alcohol consumption; history of electroconvulsive therapy; marked cognitive deficit (assessed by MMSE); current serious physical disease; and severe psychiatric disorder (schizophrenia and other psychotic disorders, dementia, delirium).
The inclusion criteria were the presence of alcohol-dependence disorder according to DSM-IV-TR and alcohol abstinence for at least 1 month. Nowadays, the identification of alcoholic phenotypes yields a much more accurate picture of alcoholism from basic and clinical research and may be useful in guiding a proper assessment of behavior and neurocognitive features (Dvorak et al., 2006; Babor and Caetano, 2006; Hesselbrock and Hesselbrock, 2006; Pombo et al., 2007a, 2007b). It was decided that only alcohol-dependent patients classified with Cloninger et al.'s (1981) type I would be included, since only eight alcohol-dependent patients were classified as type II. Cloninger et al. (1981) suggested the type I (milieu-limited) versus type II (male-limited) dichotomy. The first one was characterized by a slow progression, beginning after 20 years of age. Type II distinguished a precocious onset of alcohol consumption with a swift progression to dependence associated with a marked impulsiveness. The type I classification was based on the criteria operationalized by von Knorring et al. (1985). Here we provide an overview of the clinical criteria and decision process for subtyping the variation of Cloninger et al.'s approach. Patients’ subtype allocations according to the von Knorring et al. (1985) model are as follows: criteria for type I were the presence of subjective drinking problems starting after age 25, first treatment contact after age 30 and few social complications (legal, work problems). Type II included subjective drinking problems starting before age 25, first treatment contact before age 30 and frequent social complications (legal, work problems). When the specified criterion for each subtype (I or II) was present, subjects received a positive score in each item endorsed (+1), and, when the specified criterion was not in attendance, subjects received a negative score (–1). Afterwards, for patients’ allocation purposes, the algebraic sum of the items was performed and the quantitative scores were transformed into categorical data on the basis of higher total positive scores (or less negative) in each subtype. Type II patients (N = 8) and the cases in which the algebric sums were equal to zero (N = 3) were considered to be undiagnosed and thus were excluded from the statistical procedure. Consequently, the sample included in the study comprised 42 alcohol-dependent patients.
Clinical and sociodemographic information was collected at the patient's hospital admission through the fulfilment of NETER Standardized Interview for alcoholic patients (Barbosa et al., 2004; Cardoso et al., 2006; Pombo et al., 2004, 2007a, 2007b) and the Severity Alcohol Dependence Questionnaire (SADQ) (Stockwell et al., 1983).
Neuropsychological examination was directed to several aspects of executive functioning. Measures of fluency, abstract reasoning, cognitive flexibility, and psychomotor speed normally reflect frontal lobe executive functioning. After a minimum period of 4 weeks of alcohol abstinence, when alcohol detoxification program and withdrawal syndrome had ceased, a neuropsychological battery was administered, comprising the following tests:
- Symptom Check List (SCL-90-R)—drawn and revised by Derogatis (1977). This 90-item inventory evaluates psychopathological symptoms in terms of nine symptomatology dimensions.
- WAIS (Wechsler Adult Intelligence Scale—III)—subtests were chosen based on their established sensitivity as measures of alcoholic cognitive impairment (Groth-Marnat, 2000; O’Mahony, 2004, 2005): information and vocabulary as indicators of premorbid intellectual functioning (Lezak, 1976; Groth-Marnat, 2000), similarities (verbal abstract reasoning and conceptualization abilities), arithmetic (concentration and working memory) and code (visual-motor speed).
- Raven's Progressive Matrices (RPM)-–instrument used to measure a person's capacity to apprehend relationships among meaningless figures and to develop a systematic method of nonverbal reasoning.
- Mini-Mental State Examination (MMSE)—it is the most widely used screening test of cognition in adults. The test attempts to quantify the patients’ capabilities in five fields: orientation, registration, attention and calculation, recall, and language (Folstein et al. 1975).
- Stroop Color-Word Test (SCWT)-–task associated with cognitive flexibility and resistance to interference from outside stimuli. Stroop task performance suggested a putative measure of prefrontal lobe function. The test employed in the study was similar to the Stroop version by Golden (1978).
- Frontal Assessment Battery (FAB)-–neurobehavioral instrument developed by Dubois et al. (2000). It consists of six subtests exploring different frontal-lobe-related executive functions: (1) abstract reasoning; (2) mental flexibility; (3) motor programming; (4) resistance to interference; (5) inhibitory control; and (6) environmental autonomy.
The FAB has shown good psychometric properties in several populations, namely, psychoactive substance abusers (Chayer, 2002; Álamo et al., 2003; Cunha and Novaes, 2004). Cognitive tasks were selected based on the applicability and sensitivity of the alcohol-dependent population (Horner et al., 1999; Munro et al., 2000; Sullivan et al., 2000; Chayer, 2002; Álamo et al., 2003; Davies et al., 2003; Duka et al., 2003; Cunha and Novaes, 2004; Rains, 2004; 2004). Neuropsychological tests (testing) scores were converted into T-scores based on each test normative data (Lezak, 1976; Groth-Marnat, 2000).
Of a sample of 42 alcohol dependents, 78.6% were males (n = 33) and 21.4% were females (n = 9). Age varied between 33 and 62 years, with a mean value of 49.8 years (SD = 7.5). The sample was entirely Caucasian (100%). Regarding marital status, 83.4% were married or lived in a marital union, 14.3% were single, and 2.4% were separated. Education ranged between 3 and 17 years, with a mean value of 7.8 years of school attendance (SD = 4.3). Concerning occupational status, 11.9% integrated as high/average corporate employees; 45.6% were qualified as skilled workers (carpenter, mechanic), and 27.3% had a nonqualified professional activity (agriculture, services). Concerning clinical characterization of alcohol consumption, data show that the average age of onset of drinking was 13.4, age of alcohol abuse onset was 29.3, and age of alcohol dependence onset was 35.5 years, with an average of 20.9 years of pathological alcohol consumption (alcoholism). The subjects reported a daily average of alcohol consumption of 106.4 g, with a 27.4 average of alcohol dependence level (SADQ). Relatively to smoking status, 75% of the sample were regular smokers, with an average of 18.2 (SD = 5.7) cigarettes per day.
The control group selected on the basis of their similarity to the patients included 30 (18 males and 12 females) healthy subjects recruited from the Portuguese National Blood Donor Centre (Instituto Nacional de Sangue), with a mean age of 41.3 (SD = 11.1), ranging from 21 to 58 years. All individuals were ascertained not to be alcohol or drug dependent by interview.
Determination of platelet MAO B activity
Blood (5 ml) was collected in EDTA tubes and centrifuged (100 g for 10 min) to obtain platelet-rich plasma (PRP). The activity of platelet MAO was estimated according to the method of McEwen and Cohen (1963), that consists of a spectrophotometric assay based on the measurement of the conversion of benzylamine into benzaldehyde by the catalytic activity of MAO B. The activity of the enzyme was expressed as nmol/mg of protein per hour. All subjects signed an informed consent.
In an effort to best dichotomize MAO B platelet activity, alcoholic subjects were allocated to two subgroups on the basis that the mean cutoff value of enzyme activity is at 0.22 nmol/mg of protein per hour (SD = 0.16). Patients who had a MAO B platelet activity under the mean value were designated as "under average subgroup" and those who had a score above mean were assigned as "above average subgroup." Three patients were excluded because their score tied with the sample MAO B platelets’ mean score.
Statistical analysis
Considering the normally distributed data from variables (as assessed with a Kolmogorov–Smirnov test), parametric methods were used to calculate numerical relations between data.
To assess potential confounder factors and platelet MAO B activity levels in alcoholics and controls, an analysis of covariance (ANCOVA) was performed. For the elimination of confounds, we entered age as a covariate, since there are some differences between alcoholic subjects (mean = 49.8) and controls (mean = 41.3) age.
The t-test was used to compare neuropsychological tasks and psychopathological continuous variables in the alcoholic sample. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS version 12.0) with a defined significance of P < 0.05.
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Results |
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TOPABSTRACTIntroductionMethods and SubjectsResultsDiscussionReferences |
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There were no statistically significant differences (P
0.05) between alcohol-dependent males and females regarding clinical, sociodemographic, neuropsychological, psychopathological, and platelet MAO B activity measures (data not shown). Platelet MAO B activity levels in the control group did not show any significant relationship with age, gender, and cigarette consumption. ANCOVA showed significant differences between platelet MAO B activity among alcoholics and control subjects, after controlling for the effect of age (F = 107.7; P < 0.01), in which alcoholics presented low levels of platelet MAO B activity (mean = 0.22; SD = 0.18), when compared with control subjects (mean = 2.1; SD = 0.95).
Platelet MAO B activity in alcoholic subjects was stratified in two subgroups: patients who had platelet MAO B activity under the mean value ("under average subgroup"; N = 20) and those who had a score above mean ("above average subgroup"; N = 19). Clinical and sociodemographic measures did not show significant differences(P > 0.05) between the groups. Table 1 shows platelet MAO B activity in alcoholic subgroups with alcoholism clinical measures.
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Regarding neuropsychological tasks, platelet MAO B activity in "under average subgroup" showed significant lower scores in the RPM, when compared with platelet MAO B activity in "above average subgroup". Table 2 shows platelet MAO B activity in alcoholic subgroups and neuropsychological measures.
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In what concerns to psychopathological dimensions measured by SCL-90-R, platelet MAO B activity in "under average subgroup" showed significantly higher scores in hostility dimension, when compared with platelet MAO B activity in "above average subgroup". Table 3 shows platelet MAO B activity in alcoholic subgroups and psychopathological dimensions.
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Discussion |
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TOPABSTRACTIntroductionMethods and SubjectsResultsDiscussionReferences |
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Individual variations in the activity of human platelet MAO B has been observed in alcoholism. Previous studies reported low platelet MAO B activity as a biological marker of "type 2" alcoholism phenotype, which are characterized by an early onset of alcohol problems, associated with personality traits such as impulsiveness and sensation seeking (Cloninger et al., 1981
; von Knorring et al., 1985; Pandey et al., 1988; Sullivan et al., 1990; Tabakoff et al., 1990; von Knorring et al., 1998; Fahlke et al., 2002). In this study, alcoholics showed significantly lower levels of platelet MAO B activity, when compared with controls. These results contradict the hypothesis that lower levels of platelet MAO B activity are only related to "type 2 alcoholism," generalizing this relationship also to Cloninger's type I alcohol-dependent patients. Thus, these current data provide additional support to platelet MAO B activity as a stable endophenotype marker for alcoholism, even for Cloninger's type I (milieu-limited) alcoholic patients who are characterized by a low-severity and -vulnerability subgroup with a later onset of problem drinking, less severe alcohol dependence and alcohol-related problems (Sullivan et al., 1978, 1979; Alexopoulos et al., 1981; Cloninger et al., 1981; Faraj et al., 1987; Pandey et al., 1988; Hesselbrock and Hesselbrock, 2006; Pombo et al., 2007a, 2007b).
Documented features that have been related to platelet MAO B activity, such as alcoholic subtype (only type I were included), last alcohol ingestion, positive family history for alcoholism, cigarette consumption, age, and gender, were equated and failed to find any significative relation (Anthenelli et al., 1995; Berggren et al., 2000, 2002; Soyka et al., 2000; Whitfield et al., 2000; Coccini et al., 2002). These results contrast with other reports that found lower levels of platelet MAO B activity in alcoholic patients with a family history of alcoholism (Major and Murphy, 1978; Alexopoulos et al., 1983; Rommelspacher et al., 1994) or smokers (Norman et al., 1987; Sher et al., 1994; Whitfield et al., 2000).
The relationship between platelet MAO B activity, alcoholism and smoking are difficult to clarify, since alcohol and nicotine dependence are strongly associated with each other and because in many cases abstinent alcoholics persist with their cigarette consumption (Whitfield et al., 2000).
Human platelet enzyme like MAO B may be ideal to offer an insight into the status of central nervous system (CNS). MAO B shares many biochemical properties with the mitochondrial MAO present in brain tissue and some studies preconized that platelet MAO B activity represents MAO B activity in the brain (Bench et al., 1991; Chen et al., 1993). Thus, it has been suggested that MAO B platelet activity might serve as a research model for nerve cell function.
The major aim of the study was to investigate the relationship between platelet MAO B activity and some aspects of alcoholic neuropsychological skills, namely, executive function, since a link has been suggested between platelet MAO B activity and several aspects of cognitive domain (af Klinteberg et al., 1990) and it is assumed that MAO B from brain frontal cortex positive correlates with the one derived from human platelets (Chen et al., 1993).
Data indicate that platelet MAO B activity in "under average subgroup" showed significantly lower scores in nonverbal reasoning (RPM) when compared with platelet MAO B activity in "above average subgroup". In contrast with Demir et al. (2002) who did not find any relationship between platelet MAO B activity and executive function, this result gives additional support to af Klinteberg et al.'s (1990) findings, who verified that cognitive measures such as response time, failed inhibition, and maze perceptual check time were related to MAO B activity in male subjects.
Neuropsychological studies in alcoholics show impairments in domains known as executive functions, cognitive operations linked to frontal cortex, that guide human complex behavior, such as planning, abstraction or reasoning, shifting of attention, mental flexibility, concept generation, and decision making (Beatty et al., 1993; Moselhy et al., 2001; Zinn et al., 2004). Nonverbal reasoning and problem solving depend on the ability to represent and integrate complex relationships among stimuli. Reasoning problems were adapted from the RPM, a neuropsychological measure that is widely associated with abstract or nonverbal reasoning ability, "fluid intelligence," Spearman's general intelligence (g), and frontal lobe lesions (Duncan et al., 1995; Waltz et al., 1999). Neural substrates of human fluid reasoning have established the activation of the dorsolateral prefrontal cortex (Duncan et al., 1995; Prabhakaran et al., 1997; Waltz et al., 1999; Kroger et al., 2002). Fluid reasoning allows people to solve novel problems. However, some other problems can be solved by the direct application of long-term knowledge and routines of crystallized knowledge. This report indicates the relationship between platelet MAO B activity and fluid knowledge assessed by RPM, rather than crystallized knowledge, e.g., assessed with information or vocabulary tasks of WAIS-III.
We also verified higher scores of hostility in platelet MAO B activity in "under average subgroup." This result is some way consistent with other previous reports that demonstrate the implication of low platelet MAO B activity in impulsiveness, sensation seeking, monotony avoidance, aggressiveness, and some degree of violent criminality (von Knorring et al., 1984; Belfrage et al., 1992; Alm et al., 1994; Stalenheim et al., 1997).
Platelet MAO B activity and platelet serotonin content are two human biological markers. Findings suggested a significative correlation involving CSF levels of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) and platelet MAO activity (Oreland et al., 1981, 1999; von Knorring et al., 1986; Fahlke et al., 2002), supporting the hypothesis that the platelet MAO B enzyme activity might be coregulated with CNS serotonin system. In addition, the predisposition for aggressive behavior in alcoholics has also been connected to changes in serotoninergic neurotransmission. Several previous reports have demonstrated that the low levels of brain serotonin concentration and the low-activity short (S) allele of the 5-HTT gene-linked polymorphic-region (5-HTTLPR) polymorphism is associated with aggressive behavior and associated personality traits in alcohol-dependent subjects (Bailly et al., 1990; Soloff et al., 2000; Pivac et al., 2004; Liao et al., 2004; Limosin et al., 2005; Pascual et al., 2007).
Recently, Paaver et al. (2007) have studied the association between impulsiveness and serotonin system capacity measured with platelet MAO B activity and the polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR). The authors observed that subjects with low platelet MAO B activity who carried the "S" allele of 5-HTTLPR had the highest mean scores of self-reported impulsiveness.
The two associations observed between platelet MAO B activity with neurocognitive measures of executive functions (nonverbal reasoning) and psychopathological dimensions such as hostility may support the notion about the effect of platelet MAO B activity in the further development of an impulsive cognitive style. This assumption is in line with af Klinteberg et al.'s (1990) research that reports a strong negative relationship between platelet MAO activity and the number of failed inhibitions in the motor disinhibition task, relating this result with disinhibition syndromes and central serotonergic deficiency. An additional study (af Klinteberg et al., 1992) proposed that only some aspects of the impulsivity concept might be critical for its association with low MAO activity.
In this study, we should consider some important limitations. It should be noted that the majority of platelet MAO B findings in alcoholism are connected to "type 2" alcoholism phenotype and its associated personality traits. However, in this research only type I alcohol-dependent patients were included and personality traits were not assessed. The relationship between serotonin and platelet MAO B may enclose some bias, partially because the main catabolic pathway for the deamination of serotonin is MAO A type.
We should also consider the impact of genetic factors affecting MAO B synthesis and activity in the pathogenesis of alcoholic disease and other psychiatric conditions. For example, Garpenstrand et al. (2000) observed that individuals with the "A allele" in a variable region of MAO B intron 13 displayed significantly lower enzyme activity than those with the "G allele." The authors concluded that the association between platelet MAO B activity and neuropsychiatric disorders is highly unlikely to be related to the direct effects of the platelet MAO B activity on CNS function, and, most probably, there are several genetic mechanisms that rule this catalytic capacity of MAO B. The relation between brain and platelet MAO B activity has not been considered a stabilized sentence in the literature (Winblad et al., 1979; Young et al., 1986), and experimental research is needed to clearly support this notion. Other disturbing effects such as alterations in protein metabolism, hormone-related changes, endogenous inhibitors, and stress should not be excluded. Since the blood to obtain PRP was collected at patient's hospital admission, the stability of platelet MAO B enzyme activity might be related to alcohol ingestion moment in time (Wiberg et al., 1977; Alexopoulos et al., 1981; Major et al., 1981; Berggren et al., 2000; Coccini et al., 2002). At alcoholism unit entry, patients’ psychoactive substance consumption (including alcohol) in urine samples and liver function were not determined. Clinical routine checkup also revealed that alcoholic patients provide limited-reliability reports (particularly during first interviews), given that they tend to underestimate and deny alcohol consumption and related problems. For instance, some of the above-stated circumstances may possibly supply the substantial differences in platelet MAO B activity seen in type I alcoholics and control subjects. Other important issues concern to the reduced sensitivity of some neurocognitive tasks and the small number of selected alcoholic subjects who can increase the risk for type II errors (accept a false hypothesis) which may fail to declare real differences as statistically significant. In a restricted sample-size study, when you want to describe the difference in means between two groups, it is important to look at the effect-size level to see if the difference is practically significant. In fact, statistical significance is not the same as practical significance. For statistical power analyses and effect-size estimations, Cohen's d informs the reader of the practical importance of the research findings. Cohen's d judges the number of standard deviations separating two group means. Regarding the association between platelet MAO B activity and RPM, the results between groups ("under and above average subgroups") concerning RPM mean scores showed higher standard deviation values when compared to the significative difference established between groups (P <.05), resulting in a small effect size. For this particular case, it must be noted that given the fact that RPM overall scores were converted into percentile age-normed T-scores, data were stratified generating a weighted mean that has a less variability than the overall score mean. This could influence the normal distribution of data and increase how much the scores are moving from average. All these limitations may reduce the validity of the findings leading us to interprete them with caution.
In conclusion, platelet MAO B mitochondrial enzyme activity has been extensively investigated in alcoholism with many contrasting results. Our results suggested platelet MAO B as a stable trait marker for alcoholism at least in some alcoholics, not being an artifact related to alcohol ingestion or cigarette consumption. The associations obtained between platelet MAO B activity with executive neurocognitive task and hostility component may support the involvement of platelet MAO B activity in the further development of an impulsive cognitive style.
Additional research, using larger samples of alcoholics and controls, is needed to clarify whether MAO B enzyme activity may serve as a useful marker for the neurobehavioral performance of the alcoholic patients.
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