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Alcohol dependence is a chronic relapsing mental disorder with heterogeneous and complex underlying biology. It is frequently associated with nicotine dependence, severity of alcohol dependence symptoms, and diverse alcohol-related phenotypes, including the presence of delirium tremens and withdrawal symptoms, early or late onset of alcohol abuse, aggression, suicidal behavior, and anxiety. While searching for peripheral biomarkers of altered serotonergic (5-HT) function in alcohol dependence and alcohol-related behaviors, we determined a peripheral biomarker, i.e., platelet 5-HT concentration in a large group of Caucasian subjects with alcohol dependence subdivided according to the presence of specific alcohol-related phenotypes and smoking status. Individuals with alcohol dependence (n = 661) of both sexes were evaluated using Structural Clinical Interview based on DSM-IV criteria, while platelet 5-HT concentration was determined using the spectrophotofluorimetric method. Smoking is significantly associated, while sex and age are not, with platelet 5-HT concentration. Severe alcohol dependence and lack of withdrawal symptoms were associated with significantly decreased platelet 5-HT concentration in alcohol-dependent non-smokers. In smokers, significantly lower platelet 5-HT concentration was found in patients with the late onset of alcohol abuse. These results suggested that platelet 5-HT concentration might be used as a peripheral marker of different alcohol-related phenotypes, after controlling for the effects of smoking and sex.

Post-traumatic stress disorder (PTSD) is a trauma and stress related disorder frequently associated with cognitive decline. War veterans with PTSD have a higher risk of developing dementia than healthy subjects. Brain derived neurotrophic factor (BDNF) is an important protein that modulates plasticity, memory consolidation and cognitive processes. Lower circulating BDNF levels were related to memory impairment and cognitive deterioration. The aim of this study was to evaluate cognitive deterioration and plasma BDNF concentration in 120 veterans with combat related PTSD, 120 healthy controls, 47 subjects with mild cognitive impairment (MCI) and 76 patients with Alzheimer's disease (AD), and to assess if plasma BDNF concentration might be used as biomarker of cognitive deterioration. Veterans with PTSD had significantly decreased plasma BDNF concentration and worse cognitive performances (assessed using the Mini Mental State Examination, Clock Drawing test and Montreal Cognitive Assessment scores/categories) than healthy subjects, and similarly reduced plasma BDNF and cognitive decline as MCI subjects. Reduced plasma BDNF was found in cognitively impaired subjects. These results suggest that veterans with PTSD should be closely monitored in order to early detect and predict cognitive worsening and promote interventions that might help restore blood BDNF levels and cognitive functions.

Nowadays depression is considered as a systemic illness with different biological mechanisms involved in its etiology, including inflammatory response, hypothalamic-pituitary- adrenal (HPA) axis dysregulation and neurotransmitter and neurotrophic systems imbalance. Novel "omics" approaches, such as metabolomics and glycomics provide information about altered metabolic pathways and metabolites, as well as disturbances in glycosylation processes affected by or causing the development of depression. The clinical diagnosis of depression continues to be established based on the presence of the specific symptoms, but due to its heterogeneous underlying biological background, that differs according to the disease stage, there is an unmet need for treatment response biomarkers which would facilitate the process of appropriate treatment selection. This paper provides an overview of the role of major stress response system, the HPA axis, and its dysregulation in depression, possible involvement of neurotrophins, especially brain- derived neurotrophic factor, glial cell line- derived neurotrophic factor and insulin-like growth factor-1, in the development of depression. Article discusses how activated inflammation processes and increased cytokine levels, as well as disturbed neurotransmitter systems can contribute to different stages of depression and could specific metabolomic and glycomic species be considered as potential biomarkers of depression. The second part of the paper includes the most recent findings about available medical treatment of depression. The described biological factors impose an optimistic conclusion that they could represent easy obtainable biomarkers potentially predicting more personalized treatment and diagnostic options.

Subjects with schizophrenia or conduct disorder display a lifelong pattern of antisocial, aggressive and violent behavior and agitation. Monoamine oxidase (MAO) is an enzyme involved in the degradation of various monoamine neurotransmitters and neuromodulators and therefore has a role in various psychiatric and neurodegenerative disorders and pathological behaviors. Platelet MAO-B activity has been associated with psychopathy- and aggression- related personality traits, while variants of the MAOA and MAOB genes have been associated with diverse clinical phenotypes, including aggressiveness, antisocial problems and violent delinquency. The aim of the study was to evaluate the association of platelet MAO-B activity, MAOB rs1799836 polymorphism and MAOA uVNTR polymorphism with severe agitation in 363 subjects with schizophrenia and conduct disorder. The results demonstrated significant association of severe agitation and smoking, but not diagnosis or age, with platelet MAO-B activity. Higher platelet MAO-B activity was found in subjects with severe agitation compared to non-agitated subjects. Platelet MAO-B activity was not associated with MAOB rs1799836 polymorphism. These results suggested the association between increased platelet MAO- B activity and severe agitation. No significant association was found between severe agitation and MAOA uVNTR or MAOB rs1799836 polymorphism, revealing that these individual polymorphisms in MAO genes are not related to severe agitation in subjects with schizophrenia and conduct disorder. As our study included 363 homogenous Caucasian male subjects, our data showing this negative genetic association will be a useful addition to future meta-analyses.

The aim of this study was to investigate the differences in the prevalence of somatic diseases among combat veterans and their contemporaries who were not exposed to the traumatic experience at the battlefield, and to determine whether socio-demographic factors, exposure to war-time trauma and/or injury might predict individual somatic diseases. The study included 1,558 subjects living in south Croatia: 501 male combat veterans with Posttraumatic Stress Disorder (PTSD) and the corresponding control group of 825 men who were not exposed to combat experience. Veterans with PTSD, regardless of the length of time spent in war, suffered more often from cardiovascular, dermatological, musculoskeletal, pulmonary and metabolic diseases than corresponding control subjects who were not exposed to combat experience. The predictors of cardiovascular, musculoskeletal and malignant diseases in veterans were age, length of time spent in combat, having been wounded. A longer period in the combat zone was associated with arrhythmias in veterans with PTSD complicated with other psychiatric comorbidities. PTSD as a result of exposure to war trauma increases the possibility of developing somatic diseases.El propósito de este estudio ha sido comparar la frecuencia de trastornos somáticos en veteranos de guerra y personas no expuestas a la experiencia traumática del campo de batalla, así como determinar si la exposición a factores socio-demográficos en tiempo de guerra pueden predisponer a traumas, alteraciones o trastornos somáticos. El estudio incluye 1,558 sujetos del sur de Croacia: 501 varones veteranos de guerra con síndrome de estrés postraumático (TEPT) y un grupo de control de 825 varones no expuestos a la experiencia de combate. Los veteranos con TEPT, independientemente del tiempo pasado en la guerra, desarrollan más a menudo alteraciones gastrointestinales, cardiovasculares, dermatológicas, locomotoras, pulmonares y metabólicas que los sujetos del grupo control. Los indicadores de alteraciones cardiológicas, locomotoras, entre otros, en veteranos han sido la edad, el tiempo pasado en combate y el daño allí sufrido. Un largo período en la zona de combate ha sido asociado con arritmias y otras complicaciones de tipo psiquiátrico. El TEPT, como resultado de la exposición a experiencias traumáticas del campo de batalla, incrementa la posibilidad de desarrollo de trastornos somáticos.

Introduction. A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression. Methods. The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α-14C-methyl-L-tryptophan as a tracer. Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hour before the injection of the tracer (30 µCi). Results. There were no significant effect on plasma free tryptophan. After Benjamini-Hochberg False Discovery Rate correction, a significant decrease in the 5-HT synthesis rate in the fluvoxamine treated rats, was found in the raphe magnus (-32 %), but not in the median (-14 %) and dorsal (-3 %) raphe nuclei. In the regions with serotonergic axon terminals, significant increases in synthesis rates were observed in the dorsal (+41 % ; ) and ventral (+43 %) hippocampus, visual (+38 %), auditory (+65 %) and parietal (+37 %) cortex, and the substantia nigra pars compacta (+56 %). There were no significant changes in the 5-HT synthesis rates in the median (+11%) and lateral (+24 %) part of the caudate-putamen, nucleus accumbens (+5 %), VTA (+16 %) or frontal cortex (+ 6 %). Conclusions. The data show that the acute administration of fluvoxamine affects 5-HT synthesis rates in a regionally specific pattern, with a general elevation of the synthesis in the terminal regions and a reduction in some cell body structures. The reasons for the regional specific effect of fluvoxamine on 5-HT synthesis are unclear, but may be mediated by the presynaptic serotonergic autoreceptors.

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.

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.

Lumped constant (LC) is a constant used to convert brain trapping constant of α-methyl-l-tryptophan (using α-(14)C-methyl-l-tryptophan) into the constant for conversion of tryptophan into serotonin (5-hydroxytryptamine, 5-HT), which can be then used with certain assumptions in the calculation of the brain regional 5-HT synthesis rate. The aim of the present study was to investigate the acute effects of two drugs on the regional stability of the LC and possible effect on its value. Drugs used were a selective 5-HT reuptake inhibitor, fluoxetine, and a drug that releases 5-HT and inhibits 5-HT uptake, d,l-fenfluramine. The values of the LC from those experiments were compared with the value of LC obtained in the saline treated rats. KT is the constant for tryptophan conversion into 5-HT, which was measured by an autoradiographic method in more than twenty brain regions, using labelled tryptophan ((14)C-Trp) as tracer, after the fraction incorporated into proteins was removed. The trapping constant K(α) for α-methyl-l-tryptophan was also measured autoradiographically in a separate group of rats. All measurements were done in drug and saline (control) treated rats. The regional LC constants were calculated as the ratios between KT and K(α). Statistical evaluation showed that the regional values in each of these three sets were normally distributed, and that the three sets of LC values calculated as the mean of logarithmic differences (saline 0.450 ± 0.055; fluoxetine 0.429 ± 0.091; d,l-fenfluramine 0.48 ± 0.09) did not differ significantly. The overall weighted mean value of the LC from all three sets of measurements was 0.452 ± 0.041, and this value was not significantly different from the LC value of 0.42 ± 0.07, i.e. value obtained in our previous studies. These results showed the unaltered LC value in discrete rat brain regions after treatment with fluoxetine or d,l-fenfluramine, and confirmed that the numerical value of the LC used in our previous studies was not altered by treatment with drugs affecting 5-HT transmission and 5-HT synthesis rate.

Alzheimer's disease (AD) is the most common form of dementia and the most common neurodegenerative disease, with a complex genetic background. Genome wide association studies (GWAS) have yielded important new insights into genetic mechanisms of AD pathology. Current results unequivocally confirm apolipoprotein E (APOE) as a major genetic risk factor for development of late onset AD. Additional associations of more than twenty genes have also been identified and replicated in subsequent genetic studies. Despite the exciting new GWAS data which have emerged in the last few years, it has become clear that common variants within the genome cannot fully explain the underlying genetic risk for AD. Novel approaches such as genome-wide analysis of copy number variations (CNV) or low-frequency rare functional gene variants may provide additional insight into genetic basis of AD. In this review we summarize the findings of eighteen GWAS studies in AD performed to date, with an emphasis on potential future developments in the quest for genetic risk factors of AD.

The role of the serum lipids (total cholesterol, high-density lipoprotein cholesterol /HDL-C/, low-density lipoprotein cholesterol /LDL-C/, triglycerides /TG/) in the pathophysiology of the mood disorders is not clear. The aim of this study was to determine lipid profile in patients with affective disorders. The study included medication free female subjects: 41 patients with bipolar disorder (22 in a manic and 19 in a depressive phase), 34 patients with major depression and 50 healthy controls. Serum lipids levels were determined using standard laboratory tests. All patients had significantly lower HDL-C values than control subjects. Increased TG levels were found in patients with bipolar disorder compared to healthy subjects. The changes in lipids profiles persisted when data were adjusted for age, smoking and menopause. The results revealed no differences in the cholestrol and LDL-C levels and body mass index, but significant differences in the ratios of cholesterol/HDL-C and LDL-C/HDL-C values (atherogenic index) among groups. Our results suggest that low HDL-C levels and high atherogenic index might be a hallmark of affective disorders. Since low HDL-C levels could be a risk factor for the development of coronary heart disease, further investigation of the lipids metabolism in affective disorders is warranted.

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

Posttraumatic stress disorder (PTSD) is a serious and global problem, a psychiatric disorder that frequently occurs with different comorbidities, and is associated with a high suicide rate. Pathophysiologically, both PTSD and suicidal behavior are related to disturbances in the central serotonergic system. Serotonin (5-hydroxytryptamine, 5-HT) controls emotional behavior, anxiety, impulsivity and aggression, and nearly all known antidepressants and antianxiety drugs affect 5-HT transmission. Platelet 5-HT can be used as a limited peripheral marker of the central serotonergic synaptosomes, since it is related to particular basic psychopathological characteristics of several psychiatric disorders. Platelet 5-HT concentration has been reported to be similar in PTSD subjects and healthy controls, but suicidal patients across different psychiatric diagnoses have reduced platelet 5-HT concentration. This study examined platelet 5-HT concentration by the spectrofluorimetric method in male subjects: 73 suicidal and 47 non-suicidal veterans with current and chronic combat related PTSD, 45 suicidal and 30 non-suicidal comparative non-PTSD subjects and 147 healthy men. The presence of suicidal behavior (score=0, non-suicidal; scores > or =1, suicidal) was assessed with the Hamilton Depression Rating Scale-17 (HDRS). Platelet 5-HT concentration was significantly lower in suicidal PTSD and non-PTSD patients compared to non-suicidal patients or healthy controls. Since the majority of patients scored very low on item 3 of HDRS, no significant correlation between suicidal scores and platelet 5-HT concentration was found. These results show that reduced platelet 5-HT concentration is related to suicidal behavior in PTSD, and suggest that platelet 5-HT concentration might be used as a peripheral marker to predict suicidal behavior across psychiatric diagnoses.

The neurobiology of posttraumatic stress disorder (PTSD) involves alterations in multiple neuroendocrine and neurotransmitter systems. Platelet monoamine oxidase (MAO-B) has been associated with susceptibility to various psychiatric disorders, personality traits and behaviours. Platelet MAO-B activity and MAO-B intron 13 polymorphism (a G/A substitution) were determined in male war veterans (n=106) with DSM-IV diagnosed current and chronic PTSD, divided into subgroups of PTSD patients with (n=28) or without (n=78) psychotic features, combat exposed veterans (n=41) who did not develop PTSD, and healthy control men (n=242). Two-way ANOVAs revealed a significant effect of diagnosis and smoking, a significant effect of smoking, no significant effect of genotype, and no significant interaction between genotype, smoking or diagnosis, on platelet MAO-B activity. One-way ANOVAs showed significantly lower platelet MAO-B activity in smokers than in nonsmokers. After controlling for smoking, veterans with psychotic PTSD had significantly higher platelet MAO-B activity than veterans with or without PTSD, or healthy subjects. The results were obtained on peripheral biochemical marker, i.e. platelet MAO activity. The MAO-B intron 13 polymorphism was not functional, and did not affect platelet MAO-B activity. The aallele frequencies of the MAO-B genotype were similarly distributed among healthy controls and veterans with or without PTSD and/or psychotic symptoms. The results suggest that platelet MAO-B activity, controlled for smoking status, might be used as a peripheral marker of the psychotic symptoms in PTSD.

This special issue, “Monoamine oxidase (MAO) and aggression”, considers the evidence linking the monoaminergic neurotransmitters as regulated by the breakdown enzymes MAO-A and MAO-B, and aggressive behavior. This issue of Progress in Neuro-Psychopharmacology and Biological Psychiatry presents five reviews and one original research article from the experts in the field. All articles offer comprehensive analyses and novel findings on the role of MAO in aggression. The common link for all articles is that they incorporate basic and clinical research and connect data from psychiatry, neurology, psychology, neuropharmacology and medicinal chemistry. These articles explore the association between MAO abnormalities and aggressive behavior, possible mechanisms underlying vulnerability to environmental adversity in the pathogenesis of aggression, as well as therapeutic strategies focusing on MAO targets. Encoded by separate genes on the X chromosome, MAO-A and B both catalyze the breakdown of amines but have different catalytic properties, distinctly different distribution across the brain and diverse effects on various personality traits and behaviors.

Various studies have implicated the involvement of noradrenaline (NA) and/or serotonin (5-hydroxytryptamine (5-HT)) in the pathogenesis and treatment of depression. The aim of the present study was to investigate the effects of acute and 7 days of administration of desipramine, a NA re-uptake inhibitor, on the rate of 5-HT synthesis in the rat brain. The study was done by an autoradiographic method using α-[ 14 C ]-methyl- l -tryptophan as a tracer. The acute (10 mg/kg, i.p., 2 h before i.v. infusion of the tracer) or 7 days of desipramine (10 mg/kg per day, i.p.) did not affect plasma tryptophan (Trp) concentrations, as compared to control (saline treated) rats. Acute treatment with desipramine decreased the rate of 5-HT synthesis in the brain regions that contain 5-HT cell bodies between 19 and 28%, and increased the rate of 5-HT synthesis in the majority of areas containing 5-HT terminals between 21 and 65%. In contrast to the acute treatment, a 7-day administration increased 5-HT synthesis rates in the dorsal raphe (24%), but decreased it in raphe magnus (35%), superior olive (45%), caudate (31%), superior (38%) and inferior (53%) colliculus, and in the auditory cortex (35%). This suggests that the effect of desipramine on 5-HT synthesis rate is time-dependent and differs in the cell bodies and structures containing 5-HT nerve terminals.

Serotonergic system is implicated in the pathogenesis of depression. Peripheral biochemical markers, platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity, were determined spectrofluorimetrically at baseline and after 4 and 24 weeks of sertraline (a selective serotonin reuptake inhibitor) treatment in 15 female nonsuicidal, nonpsychotic patients with major depression, and compared with 15 drug free healthy women. The aim of the study was to determine the effects of 4 and 24 weeks of sertraline treatment on platelet 5-HT concentration and platelet MAO activity in depressed patients subdivided according to the treatment response into remitters, responders and nonresponders after 4 and 24 weeks of sertraline treatment, based on the 70%, 50-69% and less than 49% reductions in baseline Montgomery-Asperg Depression Rating Scale (MADRS) scores, respectively. Platelet 5-HT concentration was significantly lower in all depressed patients at baseline than in healthy subjects. Among patients platelet 5-HT concentration or platelet MAO activity did not differ before treatment. There was no significant correlation between MADRS scores and peripheral biochemical markers. The limitation of the study was in a small number of patients, but its advantage was in a long-term (24 weeks) follow-up of both patients and healthy controls. Our results show that long-term sertraline treatment induced remission and response in 87% patients, decreased platelet 5-HT concentration after 4 and 24 weeks of treatment and decreased platelet MAO activity after 24 weeks, and suggest that pretreatment values of platelet 5-HT and platelet MAO might not predict therapeutic outcome to sertraline treatment in female depressed patients.

Background : The serotonergic system is implicated in the pathophysiology of posttraumatic stress disorder (PTSD) and depression. The present study focused on platelet serotonin (5-HT) concentration and symptoms of comorbid depression in war veterans with or without PTSD. Methods : PTSD and depression were evaluated using Clinician Administered PTSD Scale, Davidson Trauma Scale, Montgomery–Asberg Depression Rating Scale and Hamilton Anxiety Scale. Sixty-five male drug-free war veterans (48 with PTSD and 17 without PTSD) and 65 age- and sex-matched healthy controls were studied. Results : Comorbid depression occurred in 54 and 31% of war veterans with PTSD and without PTSD, respectively. Platelet 5-HT concentration was similar in the groups of depressed and nondepressed war veterans with or without PTSD and healthy controls. Platelet 5-HT concentration was found to differ between war veterans with various degrees of appetite loss. A positive correlation was observed between platelet 5-HT concentration and severity of appetite loss in veterans with PTSD. There was no relationship between platelet 5-HT concentration and severity of other symptoms of PTSD or depression. Limitations : War veterans included in the study were outpatients. Conclusions : War veterans with PTSD had a high incidence of comorbid depression, that was not related to platelet 5-HT concentration. The marked relationship between platelet 5-HT concentration and severity of appetite loss, suggested that 5-HT system is involved in the regulation of appetite, at least in depressed war veterans with PTSD.

The influence of seasons on platelet serotonin (5-HT) concentration was determined in 88 unipolar depressed and 117 schizophrenic male inpatients, and 90 normal male controls. Platelet 5-HT concentrations showed moderate, but insignificant intragroup seasonal variations in healthy controls and in the groups of depressed (psychotic and nonpsychotic) and schizophrenic (positive and negative) patients. In spring, platelet 5-HT concentrations were higher in schizophrenic patients than in normal controls or in depressed patients, while in other seasons platelet 5-HT concentrations were not significantly different between the groups. Higher platelet 5-HT concentrations were detected in psychotic when compared to nonpsychotic depressed patients in summer, fall, and winter. Increased platelet 5-HT concentrations observed in schizophrenic patients with positive symptomes clearly separated these patients from patients with negative schizophrenia, especially in spring, summer, and fall. Our results indicate the necessity to match patients with regard to the season of the sampling, and to divide depressed and schizophrenic patients into subtypes.

High rates of suicide among adolescents are a growing concern worldwide, while 8% of adolescents show high suicidal risk in Croatia. There are different psychiatric, psychological, environmental, biological and genetic factors for suicidal behavior that can lead to completed suicide. Aggression and agitation present risk factors for suicide. Gene for the enzyme catechol-o-methyl-transferase (COMT), that degrades dopamine, is frequently studied candidate gene for suicide risk. A functional polymorphism COMT Val108/158Met, consists of G to A transition, i.e. substitution of valine (Val) with methionine (Met). The Val/Val genotype has a 3-4 times higher COMT activity than the Met/Met genotype. This polymorphism was associated with suicidal behavior in adults. The hypothesis of this study was that COMT Val108/158Met polymorphism will be significantly associated with suicidal behavior and/or aggression in adolescents. The study included 187 female and 141 male adolescents (15.2 ± 2.4 years, range 7-19). The psychiatric diagnoses, suicidal behavior and aggression were established according to the SCID and DSM- IV criteria, and the Overt Aggression Symptom Checklist. DNA was isolated from the blood samples taken during regular laboratory check- ups. Genotyping was carried out on the ABI Prism 7000 Sequencing Detection System apparatus (ABI, Foster City, USA) with Taqman- based allele-specific PCR, according to the procedure described by Applied Biosystems (ABI, Foster City, USA). Statistical evaluation of the data was done using the Chi-square test, with p

Literature data suggest that alterations in serotonergic system and cholesterol homeostasis could be implicated in the pathophysiology of mood disorders like mania. Blood platelets have an important place in the investigations of the ethiology and treatment of mental disorders as a peripheral model for central serotonergic synaptosomes. The purpose of our study was to investigate the relationship between platelet 5-HT concentration, platelet monoamine oxydase (MAO) activity and serum lipids (cholesterol, triglycerides, HDL and LDL) levels and psychotic and nonpsychotic symptoms in patients with mania. Study included 50 male patients (age 42.2  14.1 years) with bipolar affective disorder, current episode mania (DSM-IV criteria), and 38 healthy persons (age 36.8  10.3 years). Patients with mania were subdivided according to the presence of psychotic features into two groups consisted of 28 nonpsychotic and 22 psychotic patients. Platelet 5-HT concentration and platelet MAO activity were determined using spectrofluorimetric methods, while plasma lipid levels were measured by the standard clinical laboratory procedures. There was a significant difference in platelet 5-HT concentration, serum cholesterol and LDL values between healthy persons and patients with mania subdivided according to the presence of psychotic and nonpsychotic symptoms. Patients with psychotic features had significantly higher values of platelet 5-HT, and significantly lower values of serum cholesterol and LDL than nonpsychotic patients and control subjects. There was no difference in platelet MAO activity and serum values of TG and HDL among groups. Our results suggest that high levels of platelet 5-HT and low levels of serum total cholesterol and LDL could be used as peripheral biological markers for mania with psychotic features.