Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes.

Alcoholism is a chronic psychiatric disorder affecting neural pathways that regulate motivation, stress, reward and arousal. Brain-derived neurotrophic factor (BDNF) regulates mood, response to stress and interacts with neurotransmitters and stress systems involved in reward pathways and addiction. Aim of the study was to evaluate the association between a single nucleotide polymorphism (BDNF Val66Met or rs6265) and alcohol related phenotypes in Caucasian patients. In ethnically homogenous Caucasian subjects of the Croatian origin, the BDNF Val66Met genotype distribution was determined in 549 male and 126 female patients with alcohol dependence and in 655 male and 259 female healthy non-alcoholic control subjects. Based on the structured clinical interview, additional detailed clinical interview, the Brown-Goodwin Scale, the Hamilton Rating Scale for Depression and the Clinical Global Impression scores, alcoholic patients were subdivided into those with or without comorbid depression, aggression, delirium tremens, withdrawal syndrome, early/late onset of alcohol abuse, prior suicidal attempt during lifetime, current suicidal behavior, and severity of alcohol dependence. The results showed no significant association between BDNF Val66Met variants and alcohol dependence and/or any of the alcohol related phenotypes in either Caucasian women, or men, with alcohol dependence. There are few limitations of the study. The overall study sample size was large (N=1589) but not well-powered to detect differences in BDNF Val66Met genotype distribution between studied groups. Healthy control women were older than female alcoholic patients. Only one BDNF polymorphism (rs6265) was studied. In conclusion, these data do not support the view that BDNF Val66Met polymorphism correlates with the specific alcohol related phenotypes in ethnically homogenous medication-free Caucasian subjects with alcohol dependence.

Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking.

Nicotine addiction, related to cigarette smoking, develops as a product of the complex interactions between social, environmental and genetic factors. Genes encoding the components of the dopaminergic system are thought to be associated with smoking. Literature data showed not only an association, but also a lack of association between variable number of tandem repeats (VNTR) polymorphism located in the third exon of dopamine D4 receptor (DRD4) gene and smoking. Repetitive sequence of DRD4 VNTR is 48 bp long and maximum 11 tandem copies were reported in humans. Presence of alleles with 6 and more repeats (i.e. long alleles) was associated with greater tendency to novelty seeking and addictive behaviors than the presence of 5 and less alleles (short alleles). The aim of this study was to determine the association between VNTR in DRD4 gene and present smoking status in ethnically homogenous Caucasian population from the Eastern European (Croatian) origin. Genotyping was done in 565 healthy subjects, 511 men and 54 women, respectively, who were subdivided into 176 smokers and 389 nonsmokers. Logistic regression analyses, adjusted for age and sex, revealed the lack of significant (p>0.05) effect of the 4/4, 4/7 and 7/7 genotypes, or carriers of the long and short allele, or all genotypes of the DRD4 VNTR on smoking status. The results of this study failed to confirm the hypothesis that long allele of the DRD4 VNTR is associated with smoking status in Caucasian subjects.

The association between brain-derived neurotrophic factor Val66Met variants and psychotic symptoms in posttraumatic stress disorder.

OBJECTIVES: Psychotic symptoms frequently occur in veterans with combat-related posttraumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) plays a major role in neurodevelopment, neuro-regeneration, neurotransmission, learning, regulation of mood and stress responses. The Met allele of the functional polymorphism, BDNF Val66Met, is associated with psychotic disorders. This study intended to assess whether the Met allele is overrepresented in unrelated Caucasian male veterans with psychotic PTSD compared to veteran controls. METHODS: The BDNF Val66Met variants were genotyped in 576 veterans: 206 veterans without PTSD and 370 veterans with PTSD subdivided into groups with or without psychotic features. RESULTS: Veterans with psychotic PTSD were more frequently carriers of one or two Met alleles of the BDNF Val66Met polymorphism than veterans with PTSD without psychotic features and veterans without PTSD. CONCLUSIONS: The study shows that veterans with psychotic PTSD carried more Met alleles of the BDNF Val66Met than non-psychotic veterans with PTSD or veterans without PTSD. The results might add further support to the hypothesis that psychotic PTSD is a more severe subtype of PTSD.

Insomnia, platelet serotonin and platelet monoamine oxidase in chronic alcoholism.

Insomnia is a common sleep disorder frequently occurring in chronic alcoholic patients. Neurobiological basis of insomnia, as well as of alcoholism, is associated with disrupted functions of the main neurotransmitter systems, including the serotonin (5-hydroxytryptamine, 5-HT) system. Blood platelets are considered a limited peripheral model for the central 5-HT neurons, since both platelets and central 5-HT synaptosomes have similar dynamics of 5-HT. Platelet 5-HT concentration and platelet monoamine oxidase type B (MAO-B) are assumed to represent biomarkers for particular symptoms and behaviors in psychiatric disorders. The hypothesis of this study was that platelet 5-HT concentration and platelet MAO-B activity will be altered in chronic alcoholic patients with insomnia compared to comparable values in patients without insomnia. The study included 498 subjects: 395 male and 103 female medication-free patients with alcohol dependence and 502 healthy control subjects: 325 men and 177 women. The effects of early, middle and late insomnia (evaluated using the Hamilton Depression Rating Scale), as well as sex, age and smoking on platelet 5-HT concentration and platelet MAO-B activity were evaluated using one-way ANOVA and multiple regression analysis by the stepwise method. Platelet 5-HT concentration, but not platelet MAO-B activity, was significantly reduced in alcoholic patients with insomnia compared to patients without insomnia. Multiple regression analysis revealed that platelet 5-HT concentration was affected by middle insomnia, smoking and sex, while platelet MAO activity was affected only by sex and age. The present and previous data suggest that platelet 5-HT concentration might be used, after controlling for sex and smoking, as a biomarker for insomnia in alcoholism, PTSD and in rotating shift workers.

Association study of a functional catechol-o-methyltransferase polymorphism and cognitive function in patients with dementia.

A functional catechol-o-methyltransferase (COMT Val158/108Met) polymorphism, a valine (Val) to methionine (Met) substitution, has been associated with cognitive processing in the normal brain, older age, mild cognitive impairment and in various dementias. COMT is involved in the breakdown of dopamine and other catecholamines, especially in the frontal cortex; hence the carriers of Met allele, with the lower enzymatic activity, are expected to perform better on particular neuro-cognitive tests. The study included 46 patients with dementia and 65 healthy older subjects. The neurological status was assessed, using the Mini Mental Status Examination (MMSE), and the batery of different neurological tests. In DNA samples COMT polymorphism was genotyped. Patients with dementia exhibited significant genotype-induced differences in scores for MMSE, Visual Association Test (VAT) duration of numbers test, VAT time of response to numbers test, VAT average response to numbers test and WPLCR/PPLR unanswered. Carriers of Met/Met genotype had significantly lower scores of MMSE, significantly longer time to respond to VAT duration of numbers test, VAT time of response to numbers test and VAT average response to numbers test, and significantly greater number of unanswered questions to WPLCR/PPLR when compared to Met/Val or Val/Val genotypes. Our preliminary data showed significantly impaired performance in several neuro-cognitive tests in carriers of Met/Met genotype in patients with dementia compared to either Met/Val or Val/Val genotype carriers. Although Met/Met genotype with more dopamine available in the frontal cortex should be associated with better neuro-cognitive test results than Met/Val or Val/Val genotype, our data on patients with dementia did not confirm this hypothesis. Further study on larger sample of patients is needed to clarify the role of COMT polymorphism in cognitive functions.

Suicide attempt, smoking, comorbid depression, and platelet serotonin in alcohol dependence.

The risk of suicide in patients with alcoholism increases if alcoholism is related to comorbid depression. Both alcoholism and suicidal behavior are associated with reduced serotonin (5-hydroxytryptamine [5-HT]) function. Because suicide is enormous public health problem worldwide, to prevent suicide attempts, it is important to find peripheral marker of suicidal behavior. The aim of this study was to assess whether platelet 5-HT concentration is altered in alcoholic patients with or without suicide attempt. Platelet 5-HT concentration was evaluated in 397 male and 108 female ethnically homogenous medication-free patients with alcoholism, subdivided according to smoking status, comorbid depression, and a history of suicide attempt and in 450 male and 139 female healthy control (nonsuicidal) subjects. Suicide attempt was assessed by two measures: according to the score 4 on the item 3 from the Hamilton Rating Scale for Depression and according to the Structured Clinical Interview regarding suicidal attempt during lifetime. Both male and female patients with alcoholism who were nonsmokers had significantly lower platelet 5-HT concentration than the corresponding healthy subjects. Multifactor analyses of variance revealed the significant effects of alcoholism and smoking, but the lack of significant effects of suicide attempt, sex, or comorbid depression, and no interactions between variables, on platelet 5-HT concentration. Platelet 5-HT concentration did not differ significantly between suicidal patients compared with nonsuicidal patients with alcoholism. Because the results from the present study showed similar platelet 5-HT values between patients with or without a history of suicide attempt, our data did not support the hypothesis that platelet 5-HT concentration might be used as a peripheral marker of the pronounced suicidal behavior in alcoholism.

Brain derived neurotrophic factor Val66Met polymorphism and psychotic symptoms in Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder with a high prevalence. Since behavioral disturbances, such as psychotic symptoms, represent a key feature of AD, genes related to dopamine, serotonin and brain derived neurotrophic factor (BDNF), are considered as candidate genes for AD. BDNF is a neurotrophin that regulates neurodevelopment, neuroplasticity, and neuronal functions. BDNF is involved in the etiopathogenesis of psychiatric and neurodegenerative disorders. A single base pair polymorphism (BDNF Val66Met) was reported to be associated with AD and/or schizophrenia, as well as other psychoses, although some studies failed to replicate these findings. The aim of the study was to evaluate the association between BDNF Val66Met variants and AD, as well as onset of AD or presence of psychotic symptoms in AD. METHOD: BDNF Val66Met was analyzed in 211 patients with AD and in 402 aged healthy control subjects. All subjects were ethnically homogenous Caucasians from Croatia, and were subdivided according to the gender, onset of AD, and presence of psychotic symptoms. A χ(2) test, with Bonferroni correction and standardized residuals were used to evaluate the data. RESULTS: Distribution of the BDNF Val66Met genotypes differed significantly between male and female AD patients with or without psychotic symptoms. This difference was due to the significant contribution of the Met/Val genotype and the combined Met/Met and Met/Val genotypes between psychotic and non-psychotic symptoms in male, but not in female patients with AD. The frequency of the gene variants of the BDNF Val66Met did not differ significantly among male and female patients with AD and control subjects, or between male and female patients with early or late onset AD. There were significant sex related differences in age, duration of illness and scores of dementia between patients with AD. CONCLUSION: Our male patients were younger, had shorter duration of illness, and had less severe dementia and higher cognitive performance than female AD patients. The gene variants of the BDNF Val66Met polymorphism were significantly associated with the presence of psychotic symptoms in male, but not in female patients with AD. The results had adequate statistical power to suggest that BDNF Val66Met was not related to susceptibility to AD or the onset of AD, but that presence of one or two Met alleles of BDNF Val66Met polymorphism might present a risk factor for psychosis in AD.

The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) mediates neural plasticity, mood, different behaviours, and stress response. A functional BDNF polymorphism (BDNF Val66Met) was reported to influence the effects of stressful life events or childhood adversity on depression and suicidal behaviour in various psychopathologies. The study evaluated the association between BDNF Val66Met variants and suicide, committed with violent or non-violent methods, in victims with or without stressful childhood experience. METHODS: BDNF Val66Met polymorphism was genotyped on 560DNA samples from 359 suicide victims and 201 control subjects collected on autopsy from unrelated Caucasian subjects and subdivided according to gender, method of suicide, and influence of childhood adversity. RESULTS: A similar frequency of BDNF Val66Met variants was found between all included suicide victims and the control groups, and also between the male groups. The frequency of the combined Met/Met and Met/Val genotypes and the homozygous Val/Val genotype was significantly different between the female suicide victims and female controls, between the female suicide victims who used violent suicide methods and female controls, and between all included suicide victims with or without stressful life events. The combined Met/Met and Met/Val genotypes contributed to this significance. LIMITATION: A small group of suicide victims with available data on childhood adversity was studied. CONCLUSIONS: The combined Met/Met and Met/Val genotypes of the BDNF Val66Met variant could be the risk factor for violent suicide in female subjects and for suicide in victims exposed to childhood trauma. These results confirm a major role of BDNF in increased vulnerability to suicide.

Association study of a functional catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and suicide attempts in patients with alcohol dependence.

Alcohol dependence is frequently associated with aggressive and suicidal behaviour. Genetic factors contribute to both behaviours. Candidate genes, related to suicide and aggression, include genes involved in serotonin, norepinephrine and dopamine pathways. The enzyme catechol-O-methyl transferase (COMT) degrades dopamine, epinephrine and norepinephrine. The functional polymorphism (COMT Val108/158Met) affects COMT activity, with the valine (Val) variant associated with higher and the methionine (Met) variant with lower COMT activity. This polymorphism is associated with aggressive and suicidal behaviour, but the literature data on this relationship is contradictory and inconsistent. The hypothesis of this study was that Met allele carriers with alcohol dependence will have a higher frequency of suicide attempts compared to other genotypes. Participants were 312 male and 81 female medication-free patients with alcohol dependence and 487 male and 122 female unrelated, non-suicidal medication-free Caucasian healthy subjects. Our results showed significant (χ2 test with standardized residuals) differences in the frequencies of COMT variants in all alcoholics, alcoholics with different comorbid diagnoses, and in male but not in female alcoholics, with or without suicide attempts. Male alcoholic suicide attempters, compared to male non-attempters, had the higher frequency of Met/Met genotype or Met allele, and significantly (Kruskal-Wallis ANOVA on ranks and Mann-Whitney test) higher aggression and depression scores. These results confirmed the associations between Met allele and aggressive behaviour or violent suicide attempts in various psychiatric diagnoses, and suggested that Met allele of the COMT Val108/158 Met might be used as an independent biomarker of suicidal behaviour across different psychopathologies.

Human plasma glycome in attention-deficit hyperactivity disorder and autism spectrum disorders.

Over a half of all proteins are glycosylated, and their proper glycosylation is essential for normal function. Unfortunately, because of structural complexity of nonlinear branched glycans and the absence of genetic template for their synthesis, the knowledge about glycans is lagging significantly behind the knowledge about proteins or DNA. Using a recently developed quantitative high throughput glycan analysis method we quantified components of the plasma N-glycome in 99 children with attention-deficit hyperactivity disorder (ADHD), 81 child and 5 adults with autism spectrum disorder, and a total of 340 matching healthy controls. No changes in plasma glycome were found to associate with autism spectrum disorder, but several highly significant associations were observed with ADHD. Further structural analysis of plasma glycans revealed that ADHD is associated with increased antennary fucosylation of biantennary glycans and decreased levels of some complex glycans with three or four antennas. The design of this study prevented any functional conclusions about the observed associations, but specific differences in glycosylation appears to be strongly associated with ADHD and warrants further studies in this direction.

Association study of a functional catechol-O-methyltransferase polymorphism and smoking in healthy Caucasian subjects.

Tobacco smoking is a global health problem. The association of a functional common polymorphism in the catechol-o-methyltransferase gene (COMT Val158Met) with smoking behavior has been extensively studied, but with divergent findings. In the present study the frequency of COMT genotypes and alleles was evaluated in 578 male and a smaller group of 79 female unrelated, medication-free Caucasian healthy subjects of Croatian origin. Smokers were classified as subjects smoking

Platelet monoamine oxidase activity in children with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable developmental disorder characterized by symptoms of impulsivity, hyperactivity and/or inattention, and associated with structural and biochemical abnormalities in cortical and limbic structures innervated by dopamine, noradrenalin and serotonin. The enzyme monoamine oxidase, type B (MAO-B), is expressed in platelets, and metabolizes endogenous amines. Its activity has been proposed to represent a peripheral marker of various traits and forms of psychopathology. This study evaluated platelet MAO activity with a spectrofluorimetric method in 72 boys and 12 girls with predominantly hyperactive, predominantly inattentive, and combined subtype of ADHD (DSM-IV criteria), and in 64 control children. The results showed significantly lower platelet MAO activity in children with hyperactive, inattentive, and combined subtype of ADHD than in control children. There was no significant association between platelet MAO activity and gender or age. The limitation of the study was in the small sample of girls with ADHD (N=12), and in the determination of only one peripheral marker. In line with hypotheses of lower platelet MAO activity in different types of psychopathology, children with different subtypes of ADHD had significantly lower platelet MAO-B activity than control children.

The lack of genotype-phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy subjects.

A polymorphism in the serotonin transporter gene (5-HTTLPR) is frequently studied for association with antidepressant treatment response, different personality traits, and psychiatric disorders. Baseline platelet serotonin (5-HT) concentration has been proposed to indicate a good or a poor treatment response to antidepressant drugs and to be associated with particular symptoms in psychiatric disorders. The aim of the study was to elucidate the genotype-phenotype relationship between platelet 5-HT concentration and 5-HTTLPR in healthy subjects. The frequency of 5-HTTLPR genotypes and alleles, as well as platelet 5-HT concentration was evaluated in 434 male and 86 female unrelated healthy medication-free Caucasian subjects of Croatian origin. A two-way ANOVA revealed no significant difference in platelet 5-HT concentration subdivided according to the particular 5-HTTLPR genotype, no significant effect of sex, no significant effect of genotype, and no significant interaction between sex and genotype on platelet 5-HT concentration. In addition, one-way ANOVA did not detect significant effects of homozygous S/S genotype, or homozygous L/L genotype on platelet 5-HT concentration. Our results showed a lack of significant association between platelet 5-HT concentration and 5-HTTLPR variants, suggesting that there is no functional relationship between 5-HTTLPR alleles and platelet 5-HT concentration in the large groups of healthy male and female medication-free Caucasian subjects, free of neuro-psychiatric disorders.

Platelet serotonin concentration and monoamine oxidase type B activity in female patients in early, middle and late phase of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder with unclear aetiology. Cognitive impairment in AD might be associated with altered serotonergic system. The aim of the study was to determine platelet serotonin (5-HT) concentrations and platelet monoamine oxidase type B (MAO-B) activity in patients with different severity of AD. Platelet 5-HT concentrations and MAO-B activity were determined spectrofluorimetrically in 74 female patients with AD (NINCDS-ADRDA, DSM-IV-TR criteria), subdivided according to the Mini Mental State Examination (MMSE) scores in three groups with a) 23 patients in early (MMSE scores 19-24), b) 23 patients in middle (MMSE 10-18), and c) 28 patients in late (MMSE 0-9) phase of AD, and in 49 age-matched healthy women. Platelet 5-HT concentrations and MAO-B activity were similar between all patients with AD and healthy subjects, but were significantly lower in patients in the late phase of AD than in other phases of AD, and in healthy controls. The significant correlations were found between MMSE scores and platelet 5-HT concentrations, MAO-B activity and age. Lower platelet 5-HT concentration and MAO-B activity in the late phase of AD suggested that these markers might indicate severity and/or clinical progress of AD.

Ethnic differences in brain-derived neurotrophic factor Val66Met polymorphism in Croatian and Korean healthy participants.

AIM: To compare the frequency of alleles and genotypes in brain-derived neurotrophic factor (BDNF) val66met polymorphism in ethnically homogenous Caucasian (from Croatia) and ethnically homogenous Asian (from South Korea) healthy participants, as inter-population differences in BDNF val66met may be responsible for the divergent findings in genetic and association studies. METHODS: BDNF val66met was genotyped in 800 (556 Croatian and 244 Korean) healthy participants. Frequencies of alleles and genotypes were evaluated using a chi(2) test. RESULTS: The frequencies for genotypes (chi(2)2=114.69; P<0.001) and alleles (chi(2)1=120.07; P<0.001) between Korean and Croatian individuals differed significantly, due to significantly lower (46.3% and 19.5%, P<0.001) frequency of "Met" allele and significantly higher (53.7% and 80.5%, P<0.001) frequency of "Val" allele in Croatian than in Korean participants. CONCLUSION: The study found significant ethnic differences in BDNF val66met polymorphism. The most frequent genotype among Korean participants was "Met/Val" and they had similar distribution of "Met" and "Val" alleles. In contrast, the most frequent genotype among Caucasian participants was "Val/Val" and they had different distribution of "Met" and "Val" alleles. These ethnic differences require matching participants for ethnicity in pharmacogenetic studies and in the studies investigating genetic variations in neuropsychiatric disorders.

Platelet serotonin concentration in children with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder highly prevalent in children. The neurobiology of ADHD is still not clear, but is assumed to be related to disturbances in catecholaminergic and serotonergic (5-hydroxytryptamine, 5-HT) systems. Peripheral indices of central 5-HT function were shown in recent studies to be lower, unaltered, or increased in ADHD. METHODS: The study determined platelet 5-HT concentration in 84 medication-free 9-year-old (range 4-14 years) boys and girls with DSM-IV diagnosis of ADHD, subdivided according to the different symptoms (inattention, hyperactivity, and impulsivity) and clinical ADHD subtypes (predominantly hyperactive, predominantly inattentive, and combined subtype), and in 30 age- and sex-matched healthy controls. RESULTS: Children with ADHD had similar platelet 5-HT concentrations to control children. Platelet 5-HT concentration did not differ between boys and girls, or between children with a hyperactive, inattentive, or combined subtype of ADHD. In children with ADHD there was a significant positive correlation between platelet 5-HT concentration and impulsive symptoms, but not with symptoms of inattention or hyperactivity.Platelet 5-HT concentration wassignificantly higher in impulsive compared to non-impulsive children with ADHD. CONCLUSION: The data provide preliminary evidence that increased platelet 5-HT concentration might be a trait marker predictive of impulsivity in ADHD.

Ethnic differences in the serotonin transporter polymorphism (5-HTTLPR) in several European populations.

The serotonin transporter (5-HTT) is a protein that has a major role in divergent psychiatric disorders, personality traits and behaviors, by regulating serotonergic synaptic function. Transcriptional activity of the 5-HTT gene (5-HTT or SLC6A4) is modulated by a polymorphic repetitive element (5-HTT gene-linked polymorphic region, 5-HTTLPR), which consists of a 44-base pairs insertion-deletion in the promoter region, creating a short (S) allele and a long (L) allele. Ethnic differences in the allele frequencies of the 5-HTTLPR exist between Caucasian and Asian populations. This study investigated ethnic differences in 5-HTTLPR in 1804 healthy Caucasian subjects from several European populations living in Croatia and the Russian Federation. The genotype and allele frequency of the 5-HTTLPR differed significantly (P<0.001) between male and female Croats, Russians, Tatars and Bashkirs, due to the lower frequency of the S allele (38% and 37%) and S/S genotype (14% and 15%) in Croat men and women compared to other studied groups. When male and female data were collapsed, Russians had marginally different allele and genotype distribution compared to Bashkirs and Tatars. Bashkirs and Tatars had similar allele and genotype frequency. The higher frequency of the S/S genotype was found in Tatars and Bashkirs compared to Croats and Russians. Gender related differences occurred only in the allele distribution within Bashkir population. These ethnic differences might be responsible for the inconsistent findings in the studies of the association between various psychiatric disorders, personality traits, behaviors and 5-HTTLPR across different ethnicities, and should be controlled to enable the generalization of results across various population groups.

The effect of lamotrigine on platelet monoamine oxidase type B activity in patients with bipolar depression.

Lamotrigine is an anticonvulsant drug effective in the treatment of epilepsy and bipolar depression. Preclinical data showed that lamotrigine inhibited monoamine oxidase (MAO) activity in vitro. The aim of the study was to determine the effects of 6-weeks lamotrigine treatment on platelet MAO type B (MAO-B) activity in patient with bipolar depression. The study included 26 female patients with bipolar I disorder in depressive episode (DSM-IV criteria, Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale). Platelet MAO-B activity was determined spectrofluorimetrically before and after 6 weeks of the treatment with a relatively low dose of lamotrigine (100 mg/day). Six weeks of treatment with lamotrigine significantly decreased platelet MAO-B activity in bipolar depressed patients. This inhibitory effect was not related to smoking status and was independent of the treatment combinations (lamotrigine alone or in combination with either lithium or antipsychotics). Lamotrigine treatment induced a decrease in total HAMD scores in bipolar depressed patients, which was not significantly correlated with reduction of platelet MAO-B activity. These findings provide in vivo insight of lamotrigine effect on platelet MAO-B activity in patients with bipolar depression. Its in vivo MAO-B inhibiting effect might have contributed in part to its antidepressant activity.