RESEARCH ARTICLE
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Accttiivviittyy aannd d SSeerroottoonniinn C Coonntteenntt iinn A Allccoohhoolliissm m SSuubbttyyppeess
Gülberk UÇAR*°, Baflaran DEM‹R**, Samiye YABANO⁄LU*, Berna ULU⁄**
Correlation Between Platelet Monoamine Oxidase Activity and Serotonin Content in Alcoholism Subtypes Summary
Since early-onset (Type II) alcoholics who exhibit antisocial be- havior have been suggested to possess serotonergic defects, the present study was undertaken to compare alcoholic subtypes (Type I versus Type II) with regard to their platelet monoamine oxidase (MAO) activities and platelet and blood serotonin (5-HT) contents in order to clarify the possible determinative role of the- se biochemical markers in subtyping of alcoholics. Seventeen Type I and 16 Type II chronic alcoholic patients and 17 healthy volunteers were included in the study. Alcohol intake variables and the severity of drinking problems of the subjects were asses- sed by Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and the Michigan Alcoholism Screening Test (MAST), respectively. When compared to the healthy subjects, platelet MAO activity and platelet 5-HT content were found to be decre- ased whereas plasma 5-HT content was increased in both alco- holic groups. Platelet MAO activity and 5-HT level of the Type II group were significantly lower and plasma 5-HT content signifi- cantly higher than those of Type I patients, suggesting that the al- teration is more predominant in early-onset alcoholism. Since a positive correlation was found between platelet MAO activity and 5-HT content and a negative correlation between platelet MAO activity and plasma 5-HT level, particularly in Type II alcoholics, decreased platelet 5-HT content in Type II alcoholics has been suggested to not result from the increased serotonin metabolism by platelet MAO but rather to be possibly caused by some defects in central 5-HT synthesis or its reuptake mechanisms by platelets.
However, the results suggested that platelet 5-HT content and MAO activity still appear to be useful biochemical measures for the subtyping of alcoholics.
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Keeyy WWoorrddss :: Alcoholism subtypes, platelet, monoamine oxida- se, serotonin (5-HT).
Received : 17.06.2005 Revised : 19.08.2005 Accepted : 22.08.2005
Alkolizm Alt Tiplerinde Platelet Monoamin Oksidaz Aktivitesi ve Serotonin ‹çeri¤i Aras›ndaki ‹liflki Özet
Alkole erken yaflta bafllayan ve antisosyal davran›fllar sergile- yen (Tip II) alkol ba¤›ml›lar›nda serotonerjik sistemle ilgili bo- zukluklar daha s›k gözlenmektedir. Bu araflt›rma alkol ba¤›m- l›l›¤› alt gruplar›n› (Tip I ve Tip II) platelet monoamin oksidaz (MAO) ile kan ve platelet serotonin (5-HT) düzeyleri aç›s›ndan karfl›laflt›rmak üzere planland›. Çal›flmaya 17 Tip I ve 16 Tip II alkolik hasta ve 17 gönüllü sa¤l›kl› kifli kat›ld›. Ba¤›ml›lar›n alkol al›m› ile iliflkili de¤iflkenleri ve alkole ba¤l› problemlerinin derecesi s›ras›yla SCAN (Schedules for Clinical Assessment in Neuropsychiatry) ve Michigan Alkolizm Tarama Testi (MAST) ile de¤erlendirildi. Her iki ba¤›ml›l›k alt grubunda da hastalar›n platelet MAO aktivitesi ve 5-HT içerikleri kontrollerine oranla düflük; plazma 5-HT içeri¤i ise yüksek bulundu. Tip II grubun- da platelet MAO aktivitesi ve 5-HT içeri¤i Tip I’e oranla daha düflük, plazma 5-HT içeri¤i ise yüksek bulundu¤undan alkole erken bafllayan alkoliklerde sözkonusu de¤iflikliklerin daha bas- k›n oldu¤u düflünüldü. Özellikle Tip II grubunda platelet MAO aktivitesi ile 5-HT içeri¤i aras›nda pozitif; platelet MAO aktivi- tesi ile plazma 5-HT içeri¤i aras›nda negatif bir iliflki bulun- mas›, bu grupta gözlenen platelet 5-HT düzeyindeki azalman›n platelet MAO aktivitesi ile indüklenen bir serotonin metaboliz- ma h›z› art›fl›ndan kaynaklanmay›p santral 5-HT sentezinin defektinden ya da 5-HT’nin plateletlerce geri al›n›m›ndaki bir bozukluktan kaynaklanabilece¤ini düflündürdü. Bununla bir- likte elde edilen bulgular, platelet 5-HT içeri¤i ve MAO akti- vitesinin alkol ba¤›ml›lar›n›n alt tiplendirilmesinde kullan›labi- lecek yararl› biyokimyasal ölçümler olabilece¤i fikrini verdi.
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Annaahhttaarr KKeelliimmeelleerr :: Alkolizm alt tipleri, platelet, monoamin oksidaz, serotonin (5-HT)
IINNTTRROODDUUCCTTIIOONN
Alcoholism appears as a complex syndrome charac-
terized by a high morbidity, comorbidity, treatment resistance, chronic course and a high suicidal rate, which is suggested to be related to alterations in ne-
* Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, 06100 Ankara, TURKEY
** Hacettepe University, Faculty of Pharmacy, Department of Psychiatry, 06100 Ankara, TURKEY
° Corresponding author e-mail: gulberk@hacettepe.edu.tr
holics, which might result from the lowered 5-HT synthesis, decreased platelet reuptake, increased platelet release or increased metabolism by mono- amine oxidase (MAO)16.
The main metabolic pathway of 5-HT is oxidative de- amination by MAO, a flavoenzyme which plays an essential role in the metabolism of biogenic amines17. MAO is found in two different forms designated as MAO-A and MAO-B18. MAO-A was reported to ca- talyze the breakdown of 5-HT and play an important role in the regulation of intracellular 5-HT levels in the central nervous system, whereas MAO-B was re- ported to be the only isoform in human platelets which is thought to be responsible for the deaminati- on of 5-HT19. Since platelets share similar biochemical processes with neurons and platelet MAO activity was found to be related to central monoamine turno- ver, platelet MAO has been suggested as a possible marker for alcoholism20. There have been multiple re- ports that platelet MAO activity is decreased in alco- hol-dependent subjects and in relatives of alcoholics compared to controls11,13,21,22. Lower platelet MAO activity is claimed to be a characteristic of the early- onset (Type II) group, which is associated with a po- sitive family history of alcoholism and personality traits, such as suicidal and criminal behaviors, impul- siveness and sensation-seeking personality21,23. Since we previously have reported that platelet MAO activity, a marker of serotonin turnover, was decreased in Type II alcoholics in the same research sample21 and since the platelet 5-HT content was shown to be diminished in alcoholics by some other authors12,14,15, the present study focused more di- rectly on the association of platelet serotonin level and MAO activity in alcoholic subtypes. With this aim, we have examined a possible differentiated pattern of platelet MAO activity and platelet and plasma serotonin content in patients with Types I and II alcoholism classified on the basis of the age of onset of alcoholism.
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The patient group consisted of 33 voluntary male al- urobiological systems1,2. Two subtypes of alcoho-
lism were defined by Cloninger et al.3, based on the implication that age-of-onset for symptoms of alco- holism might be a discriminative marker. According to these authors, Type I alcoholics have a later onset of alcohol abuse, weak heredity, less psychiatric dis- turbance, a more benign alcohol- related problem profile and a better prognosis. Type II alcoholics ma- nifest alcohol problems at an early age, are socially disruptive when drinking, having more psychiatric disturbance, greater symptom severity, history of hyperactivity, antisocial personality traits, a poor prognosis and a strong urge to consume alcohol in response to an intravenous infusion of serotonin re- ceptor agonists4. Each of the two types of alcoho- lism is proposed to have a different neurobiologic background, with anxiety-mediated Type I alcoho- lism based primarily on a central nervous system noradrenaline excess, and impulse-mediated, male- limited Type II alcoholism based primarily on a central nervous system serotonin deficit3.
Serotonin (5-HT) is a biogenic monoamine, synthesi- zed in the central nervous system, where it modula- tes a variety of behavioral functions, including the regulation of sleep, appetite, nociception, mood, stress and sexual behavior4-6. Serotonergic dysfunc- tion is implicated in various types of psychopatholo- gical conditions, such as antisocial personality disor- der, alcoholism, depression with suicidality, antiso- cial behavior with aggression, obsessive-convulsive syndromes, psychosis, eating disorders, substance abuse and schizophrenia7-11. It has been suggested that male alcoholics who start drinking early and ex- hibit antisocial behavior have a serotonergic de- fect12,13. Decreased serotonergic function is thought to be related to impulse control disorders, with an inverse relationship between platelet 5-HT content and antisocial behavior and aggression14. Since di- rect measurement of brain 5-HT is not possible, and uptake, storage and release of platelet 5-HT resemb- le the corresponding processes in the central seroto- nergic neurons, the platelet is proposed as a perip- heral model for the central nervous system ne- uron15. Previous studies indicated that platelet 5-HT content was found to be decreased in drinking alco-
coholic patients who satisfied the diagnostic criteria of the International Criteria of Diseases (ICD-10) for alcohol dependence24(WHO, 1992). All the patients were receiving treatment for their withdrawal symptoms at an in-patient treatment center during the time of the investigation. Alcohol and Drug Mo- dules of Schedules for Clinical Assessment in Ne- uropsychiatry (SCAN)25were administered to each patient in order to gather data on alcohol intake va- riables and drinking related behavior. The lifetime severity of drinking problems was assessed by the Michigan Alcoholism Screening Test (MAST)26.
Seventeen Type I and 16 Type II male chronic alco- holic patients were included in the study. The pati- ents whose subjective alcohol problems had started before reaching 21 years of age (≤ 20) were categori- zed as Type II. For inclusion in the Type II group, the reporting of at least two instances of social complications related to alcoholism before reaching 21 was required (i.e. job loss, alcohol-related absen- ce from school or work, arrest for intoxicated beha- vior, or violence while intoxicated). Those who did not meet these criteria were categorized as Type I dependent. The time when alcoholic patients satisfi- ed the rule for the social complications of alcoholism was considered the beginning of their alcohol misu- se. In the Type II group, ages ranged from 27 to 62 years with an average of 41.6 ± 9.6. In the Type I group, ages ranged from 34 to 56 years with an ave- rage of 45.1 ± 6.3. Blood samples were obtained on the fifteenth abstinent day of the alcoholic patients.
Seventeen healthy males selected on the basis of the- ir similarity to the patients in terms of age, years of education and smoking status were taken as control group. Exclusion criteria included neurological, psychiatric and major medical illnesses, a history of alcohol/drug dependence and family history of al- cohol or drug abuse or dependence. Their ages ran- ged from 29 to 56 years (mean ± SD: 40.3 ± 8.4). They were all alcohol-free for at least 24 h.
All subjects provided written informed consent for participation in the study, which was approved by the local ethics committee (99-7).
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All chemicals were obtained from Sigma Chemical Co. (Germany). Spectrophotometric measurements were performed using Shimadzu 1601 PC spectrop- hotometer and high performance liquid chromatog- raphy (HPLC) measurements were performed using the HPLC system of Dionex, USA.
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Deetteerrmmiinnaattiioonn ooff ppllaassmmaa aanndd ppllaatteelleett 55--HHTT lleevveellss
Blood samples were drawn by venipuncture after an overnight fast into tubes containing EDTA as antico- agulant. 10 ml of blood was divided into two porti- ons. One portion was centrifuged for 5 min. at 1,000 x g and the supernatant was kept as plasma. The next portion was centrifuged for 5 min. at 10,000 x g and 4°C, to obtain platelet rich plasma (PRP). Plate- let counts were determined on aliquots of pooled PRP diluted in Isoton II and counted twice on a thrombocounter (Coulter Electronics, STKS). After the platelet count, 2 ml PRP was centrifuged for 10 min. at 2,000 x g. The supernatant was discarded and the pellet was suspended in 1 ml of a mixture containing 4% perchloric acid and 0.15% EDTA. The mixture was centrifuged for 10 min. at 2,000 x g and 4°C. The resulting supernatant was filtered through 0.45 µm Millipore filters by centrifugation for 5 min.
at 2,000 x g (Sigma, microcentrifuge filter ultrafree- CL, Durapore PVDF membrane) and 4°C12. The elu- ate was divided into two portions: one portion was used for the determination of platelet MAO activity while the rest was used for the determination of platelet 5-HT level. The samples were kept frozen at -80°C until used.
The portions kept for 5-HT determination in plasma and PRP were thawed and centrifuged for 3 min. at 2,000 x g. Plasma and platelet 5-HT contents were determined according to a previous method12. Ali- quots of the supernatants were applied to the HPLC system equipped with a 5 µm C18 column. The elu- tion buffer consisted of 50 mM potassium phospha- te (KP), pH 5.0 and 12% methanol, with flow rate of 1 ml.min-1 under isocratic conditions. The fluores- cence detector (Dionex, RF 2000) was set at 230 nm
excitation and 338 nm emission. Plasma and platelet 5-HT contents were expressed as nmol/L and nmol/109platelets, respectively.
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Deetteerrmmiinnaattiioonn ooff ppllaatteelleett MMAAOO aaccttiivviittyy
Platelet MAO-B activity was measured in PRP samples by the method of Holt27. A chromogenic so- lution, consisting of 1 mM vanillic acid, 500 µM 4- aminoantipyrine, 4 U.ml-1 peroxidase in 0.2 M KP buffer, pH 7.6, was prepared daily. Assay mixture contained 167 µl chromogenic solution, 667 µl 500 µM benzylamine, and 133 µl KP buffer, pH 7.6. The mixture was preincubated at 37°C for 10 min. before the addition of enzyme. Reaction was initiated by the addition of the PRP (100 µl ) and absorbance inc- rease was monitored at 498 nm at 37°C for 60 min.
Molar absorption coefficient of 4654 M-1. cm-1 was used to calculate the initial velocity of the reaction.
Results were expressed as nmol/109platelets.
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Clliinniiccaall cchheemmiissttrryy
Biochemical parameters were measured in the plas- ma samples of the subjects in autoanalyzer (Roche Modular System) and the hematological parameters were determined using an electronic cell counter (Coulter STKS).
SSttaattiissttiiccaall aannaallyyssiiss
The results were expressed as the mean ± SD. Krus- kall-Wallis analysis and Mann-Whitney U test of va- riance were used for comparison of the groups of the variables. Chi-square test was used for comparison of some demographic characteristics of the groups. Pos- sible relationships between biochemical measures and some clinical variables, such as the lifetime seve- rity of alcohol consumption, were assessed by the Pe- arson product-moment correlation analysis. A value of p< 0.05 was considered as statistically significant.
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REESSUULLTTSS
No statistically significant difference was found bet- ween the study groups in age and years of educati-
on (Table 1). The average age of the onset of alcohol abuse symptoms was 30.4 ± 5.5 in the Type I and 19.4 ± 0.5 in the Type II groups, respectively (p<
0.01). Duration of alcohol abuse/dependence was found as 14.1 ± 9 years in Type I and 22.3 ± 9.7 years in Type II alcoholics, respectively (p<0.01). The life- time severity of alcohol abuse symptoms, as measu- red by MAST, was not statistically different between the alcoholic groups (33.0 ± 7.3 and 36.3 ± 6.9, for Type I and II alcoholic groups, respectively).
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Taabbllee 11.. Demographic and clinical features of the study group
Both alcoholic groups had lower platelet 5-HT and higher plasma 5-HT levels than control subjects (p<
0.001, Table 2). Among alcoholics, platelet 5-HT con- tent was significantly lower in Type II alcoholics compared to Type I alcoholics while plasma 5-HT content was significantly higher in Type II alcoholics compared to Type I alcoholics (p< 0.01, Table 2). Pla- telet 5-HT contents were found to be decreased by 53.5% and 37.25% in Type II alcoholics when compa- red to age- and sex-matched control subjects and Type I alcoholics, respectively. Plasma 5-HT con- centrations were increased by 47.09% and 24.89% in Type II alcoholics when compared to control sub- jects and Type I alcoholics, respectively. There was a strong negative correlation between the platelet and plasma 5-HT levels in all study groups (r= -0.55, - 0.70, -0.79, in control, Type I and Type II alcoholic groups, respectively) (p<0.001) (Figure 1). There was no difference between the platelet counts of alcoho- lics and controls (Table 3).
FFiigguurree 11.. Relationship between the plasma and platelet serotonin (5-HT) levels in the study subjects. Plasma and platelet 5-HT contents were expressed as nmol/L and nmol/109platelets, respectively.
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Taabbllee 22.. Platelet and plasma 5-HT levels and platelet MAO activities of the study groups
Mean platelet MAO activity of alcoholics (25.53 ± 2.80 nmol/109 platelets) was found to be signifi- cantly lower than that of the healthy controls (36.28
± 4.90 nmol/109platelets) (p< 0.01) (Table 2). Addi- tionally, Type II alcoholics had lower platelet MAO activity than that of Type I alcoholics (p< 0.01) and controls (p< 0.001). A significant positive correlati- on was detected between the platelet MAO activity and 5-HT content (p< 0.001) (Figure 2), whereas a strong negative correlation was found between the platelet MAO activity and the plasma 5-HT content (p< 0.001) (Figure 3) in all study groups.
FFiigguurree 22.. Relationship between the platelet serotonin (5-HT) con- tent and monoamine oxidase (MAO) activity in the study subjects. Platelet 5-HT content and MAO activity were expressed as nmol/109platelets.
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Taabbllee 33.. Some biochemical parameters in blood of the study subjects
FFiigguurree 33.. Relationship between the plasma serotonin (5-HT) con- tent and platelet monoamine oxidase (MAO) activity in the study subjects. Platelet 5-HT content and MAO activity were both expressed as nmol/109platelets.
Table 3 represents the biochemical parameters me- asured in the blood of the study subjects. Transami- nase and α-glutamyltransferase (GGT) activities, to- tal lipid, cholesterol, and low density lipoprotein (LDL-C) contents were found to be increased, while high density lipoprotein (HDL-C), total protein, al- bumin and hemoglobin contents, packed cell volu- me (PCV), mean corpuscular volume (MCV) and red blood cell (RBC) count were found to be decre- ased in alcoholics when compared to control sub- jects (p<0.01). Alanine aminotransferase (ALT), as- partate aminotransferase (AST) and GGT activities, total lipid, total cholesterol and LDL-C levels were negatively correlated with platelet 5-HT content in Type I and II alcoholics (r= -52, r= -0.50, r= -54, r= - 53, r= -51 and r= -55 in Type I; r= -60, r= -61, r= -59, r= -60, r= -62 and r=-63 in Type II alcoholics, respec- tively) (p< 0.01). These parameters were positively correlated with plasma 5-HT content both in Type I and II alcoholics (r= 49, r= 0.50, r= 49, r= 51, r= 52 and r= 50 in Type I; r= 55, r= 57, r= 61, r= 60, r=63 and r=59 in Type II alcoholics, respectively) (p<
0.05). HDL-C level, hemoglobin content, RBC count and PCV were positively correlated with platelet 5- HT content and negatively correlated with plasma 5-HT content only in Type II alcoholics (r= 50, 49, 58, 51; -54, -50, -57, -55, respectively) (p< 0.05).
ALT, AST and GGT activities, total lipid, total cho- lesterol and LDL-C levels were also found to be ne-
gatively correlated with platelet MAO activity in Type I and II alcoholics (r= -57, r= -0.56, r= -58, r= - 53, r=-55 and r= -54 in Type I; r= -61, r= -61, r= -66, r= -65, r= -68 and r=-66 in Type II alcoholics, respec- tively) (p< 0.01), while HDL-C level, hemoglobin content, RBC count and PCV were positively corre- lated with platelet MAO activity only in Type II al- coholics (r= 53, r= 55, r= 58, and r= 56, respectively) (p< 0.05).
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DIISSCCUUSSSSIIOONN
In the present study, no statistically significant diffe- rence was found between the study groups in age and years of education. The average age of onset of alcohol abuse symptoms was significantly lower in Type II alcoholics (p<0.01). Duration of alcohol de- pendence was found to be significantly higher in al- cohol or drug abuse Type II alcoholics (p<0.05). The lifetime severity of alcohol abuse symptoms, as me- asured by MAST, however, was not statistically dif- ferent between the alcoholic groups.
In our study, platelet 5-HT concentration was mar- kedly decreased in alcoholic subjects when compa- red to healthy controls, with significantly lower pla- telet 5-HT content in Type II versus Type I alcoho- lics. Since it is generally accepted that low platelet 5- HT levels might be the result of decreased 5-HT synthesis, decreased platelet uptake, increased pla- telet release or increased 5-HT deamination by MAO, decreased platelet 5-HT levels are mostly att- ributed to the lower neuronal 5-HT levels in the central nervous system (CNS). In alcoholics, it was reported that plasma tryptophan availability was decreased28 and the affinity of 5-HT for its carriers or receptors was increased, providing other eviden- ces of a diminished availability of 5-HT in the synapse29 and confirming the hypothesis of 5-HT deficiency in alcoholism.
The alcohol withdrawal syndrome has been consi- dered to be a manifestation of neuroadaptive res- ponses to chronic alcohol use and a central feature of alcohol dependence. This period, which overlaps with early abstinence, has been linked to increased
metabolism, and reduced function of platelet 5-HT30 and selective serotonin reuptake inhibitors (SSRI) have been reported to reduce craving for alcohol31. Our finding demonstrating a significant reduction in platelet 5-HT levels in the alcoholic subjects is in good agreement with a previous report32suggesting a decrease in the 5-HT levels of alcoholics during withdrawal. Although it is not clear whether plate- let or plasma 5-HT levels reflect corresponding sero- tonergic changes in the human brain, it seems pos- sible that central serotonergic function may be dec- reased in alcoholics since it was previously sugges- ted that alcohol consumption has been known to sti- mulate serotonin turnover, and the withdrawal pro- cess may decrease 5-HT release from serotonergic neurons16. It has been previously postulated that the effect of alcohol on 5-HT neurotransmission and me- tabolism may be modified by the presence of tole- rance or dependence and comorbidities11. However, we excluded these variables by measuring the blood 5-HT levels only in alcoholics who are alcohol de- pendent, but sober, during withdrawal.
Our data showing that Type I and II alcoholics diffe- red regarding platelet and plasma 5-HT levels sup- ported the previous investigations reporting that Type I and II alcoholics may differ in 5-HT measu- res13, and there is a significant difference between these two subtypes in platelet tritiated imipramine binding32. In this regard, platelet 5-HT content ap- pears to be a useful biochemical measure for the subtyping of alcoholics.
The platelet and plasma 5-HT concentrations were found to be negatively correlated in all study gro- ups, supporting the idea that there is neither a rele- vant 5-HT synthesis nor a marked 5-HT turnover in platelets and that platelets may have a role as a sca- venger for free extracellular 5-HT uptake. Since the correlation between the platelet and plasma 5-HT concentrations in Type II alcoholics was found to be much stronger than that of the controls, it was sug- gested that 5-HT reuptake by platelets may be disor- dered in early-onset alcoholics.
The present study also confirmed the previous in-
vestigations indicating that alcoholics had lower platelet MAO activity when compared to the he- althy controls22,33,34. The platelet MAO activity of Type II alcoholics was found to be significantly lo- wer than that of Type I alcoholics, in accordance with the earlier reports23,35. In order to explain the association of lower platelet MAO activity and alco- holism, particularly the early-onset type, it was sug- gested that platelet MAO is a genetic marker for the size or functional capacity of the central monoamine systems, and the serotonergic system in particular23. The significant positive correlation found between platelet MAO activity and 5-HT content and the strong negative correlation found between platelet MAO activity and plasma 5-HT content in alcoholics are not in accordance with some early reports sug- gesting that increased platelet MAO activity in alco- holics may lead to an increase in 5-HT catabolism and cause a decrease in platelet serotonin levels5,11. However, our finding was supported by a report suggesting that a low level of platelet MAO seems to be constitutional rather than an effect of alcohol con- sumption and that platelet MAO acts as a genetic marker for the central serotonin system23.
Transaminase and GGT activities, total lipid, choles- terol and LDL-C contents were found to be incre- ased, while HDL-C, total protein, albumin and he- moglobin contents, PCV, MCV and RBC counts we- re found to be decreased in alcoholics when compa- red to control subjects, indicating the disordered li- ver functions and anemia in alcoholics, in accordan- ce with the previous reports36. ALT, AST and GGT activities, total lipid, total cholesterol and LDL-C le- vels were found to be negatively correlated with platelet 5-HT and MAO content and positively cor- related with plasma 5-HT content, whereas HDL-C level, hemoglobin content, RBC count and PCV we- re positively correlated with platelet 5-HT and MAO content and negatively correlated with plasma 5-HT content in Type II alcoholics. Collectively these data suggest that even though its nature is still unclear, there are important correlations between some pla- telet monoaminergic parameters and hematological and biochemical variables.
In summary, the present study confirmed the notion that platelet 5-HT content and MAO activity are al- tered in alcoholic subgroups and that these measu- res can be regarded as useful discriminative markers for subtyping of alcoholism.
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Acckknnoowwlleeddggeemmeenntt
The present study was supported by a grant from the Scientific Research Unit of Hacettepe University (HÜBAB 03-G014-2003).
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