Leptin is a 16-kDa protein secreted from white adipocytes; it acts by binding to specific hypothalamic receptors to alter the expression of several neuropeptides regulating neuroendocrine function, food intake and the whole body energy balance. Actually leptin is considered a modulator of withdrawal-induced craving in alcoholic subjects. We studied the hypothesis that leptin might modulate cocaine craving in detoxified cocaine abusers, evaluating any possible correlation with metabolic, hormonal and psychometric parameters.

A sample of 50 cocaine dependent subjects, according to DSM-IV-TR, has been evaluated as follows: Body Mass Index, blood pressure, heart rate, substance and drug consumption, triglicerides, cholesterol, plasma leptin value, cortisol, insulin, ACTH, FT3, FT4, TSH and: SHAPS (Snaith Hamilton Pleasure Scale), VASc/f/s (Visual-Analogue-Scale for cocaine/food/sex), CCQ (Cocaine-Craving-Questionnaire), Barratt Impulsiveness Scale, HAM-D, HAM-A at baseline and after 15 days of abstinence.

Leptin levels, corrected for the BMI, resulted positively correlated with CCQ (p<.05). CCQ was positively correlated with VASc (p<.001). SHAPS was positively correlated with VASc (p<.05), CCQ (p<.05), HAM-A (p<.05) and HAM-D (p<.05). Finally HAM-A was negatively correlated with VASs (p<.05). These data are confirmed even after 15 days from baseline.

In our sample leptin correlates with cocaine craving measured by CCQ, independently from the hypothalamic-pituitary-adrenal axis. At baseline VASc (mean) was less than VAS f and s mean score, confirming the shifting craving phenomenon. Although our data confirm the correlation between leptin and cocaine craving, further studies are required.

Serotonin and dopamine neurotransmitters have been extensively studied in association with temperamental and character traits.

In the present study we considered the association between 1A, 2A and 2C serotonin receptor and COMT SNPs and personality traits, as measured by the Temperament and Character Inventory (TCI), in a sample of suicide patients and controls. The SNPs considered were for 1A receptor rs1423691, rs878567 and rs6295, for 2A receptor rs643627, rs594242, rs6311 and rs6313, for 2C receptor rs547536, rs2192372, rs6318, rs2428707, rs4272555 and rs1801412, and for COMT rs737865, rs4680 and rs165599.

The sample was composed of three groups: two German samples, consisting of a healthy control group of 289 subjects (42.6% males, mean age: 45.2±14.9) and a psychiatric patient group of 111 suicide attempters (38.7% males, mean age: 39.2±13.6), and an Italian sub-sample, composed of 70 mood disorder patients (44.3% males, mean age: 42.9±14.4).

Controlling for sex, age and educational level, single markers and haplotypes were not or only marginally associated with personality dimensions.

Our study does not support 1A, 2A, 2C and COMT role on personality traits.

There has been extensive research concerning the role of the serotonin transporter gene (SLC64A) in depression. The STin2 VNTR polymorphism in the second intron has been found to influence the transcriptional activity of the gene, however, its relationship to major depressive disorder (MDD) has so far been less widely investigated.

71 MDD patients and 99 healthy controls participated in a case-control study. In case of the two populations STin2 allele frequencies were compared. The subjects also completed several tests to establish neurocognitive endophenotypes related to MDD.

A significantly higher frequency of the STin2 10/10 homozygous genotype in the MDD patients’ group was found compared to controls (X2=6,01, df=2, P<0.05). The results of neurocognitive tests indicated cognitive dysfunctions in case of MDD patients compared to controls. The clinical subgroup with at least one copy of the 10-repeat allele showed a decreased interference threshold in attention and cognitive interference as compared to patients without the 10-repeat allele. Average performance of the clinical subgroup without the 12-repat allele proved to be significantly weaker in the verbal learning memory and recall tasks compared to patients having at least one copy of the 12-repeat allele.

After further confirmation our results suggest that the presence of STin2.10 and absence of STin2.12 allele may be considered a possible genetic endophenotype for cognitive dysfunctions detected in MDD.

Anorexia nervosa is a serious eating disorder with highest mortality among psychatric disorders. DSM-IV classification differentiates two type of Anorexia Nervosa (AN): the restricting type (AN-R) and the binge-eating/purging type (AN-BP). Orexigenic and anorexigenic peptides and cytokines are involved in mechanism of food intake and energy balance. Four young women suffered from Anorexia Nervosa (two with AN-BP and two with AN-R) took part in the study. Three girls were our reference group. The aim of our study was to estimate of differentiates genes between two types of Anorexia Nervosa: AN-R and AN-BP.

The total RNA was extracted from peripheral blood mononuclears. The oligonucleotide microarray method (HG-U133A, Affymetrix) was used to determine the expression profile of 161 transcripts for genes connected with AN. The oligonucleotide microarray method analyzes genes expression by using the phenomenon of hybridization of single-thread RNA fragments with complementary DNA probes. The results were normalized using RMAExpress. The Bland Altman method was used to examine transcripts of genes which differentiate two types of AN.

Among 161 transcripts (cytokines, orexigenic and anorexigenic peptides) only cytokines have differentiated two type of AN. IL6R, IL6ST, IL1B, IL2RB and TGFB1 differentiate two type of AN: the restrictive type of AN and binge-eating type of AN. IL1B differentiates the restrictive type of AN and the reference group and TGFB1, IL6ST and IL1B differentiate the binge-eating type of AN and the reference group.

Orexigenic and anorexigenic peptides are responsible for eating behavior but not for food intake.

In psychiatry there exist, parallel trends of splitting and clumping of disorders. Former represents dichotomous Kraepelinian trend and latter stands for integrated approach of unitary psychosis .Advancement of biochemical studies and genetics have provided some evidences in favor of unitary psychosis.

Authors made an internet search at various databases websites including pub med, and Blackwell synergy using, early psychosis, prodrom, neuroprotection, apoptosis as key words. It was followed by manual and internet study of authentic psychiatric journals.

Anatomical, functional and neurochemical studies of brain reveal structural changes in early psychosis.

In schizophrenia, pathological process is progressive. Brain volume loss continues even after onset of overt symptoms.

Study of subjects in prodromal phase shows 15-point drop in GAD. Significant proportion also met criterion of anxiety 86% depression 76% low energy 62% and, social with drawl 71%.

Unitary psychosis symbolizes concept of unity in diversity. Neurodevelopmental apoptotic process has its own direction that manifests in form of affective symptoms, anxiety symptoms, obsessive symptoms cognitive deficits, positive psychotic symptoms and ends with negative symptoms. It is assumed that neurodevelopmental process move from lower to higher centers of brain. Neuroprotection during emerging phase of psychotic disorder can delay the onset. Neurochemical studies shows that SSRIs atypical antipsychotic, anticonvulsants, and lithium has antiapototic properties which modulate the progression This suggests that apoptotic process is the thread that connects apparently different disorder is unitary psychosis.

Neurobiological model can account for unitary psychosis.

The Mirror System (MS) may facilitate emotional processing, including the experience of empathy. We explored MS involvement in emotional processing using a novel affective startle paradigm and examined whether results were associated with empathy levels in a group of healthy participants.

Participants (n=69) viewed pictures that were divided into emotionally positive, neutral and negative categories. Pictures were preceded by emotionally congruent primes: half the primes consisted of a videoclip showing hand-object interaction designed to recruit the MS and half consisted of a control sequence showing static images of the interaction. Acoustic startle probes were presented during picture viewing and startle eyeblink responses were recorded. Participants were divided into high and low empathy groups based on their responses for the empathy subscale of the I7 questionnaire.

Startle amplitude was inhibited during positive picture viewing and potentiated during negative picture viewing when pictures were primed with moving videoclips compared to static controls. The biggest difference between amplitude associated with moving and static primes was found in the positive condition (p=0.009). The high empathy group exhibited a greater difference in startle amplitude between the moving and static conditions than the low empathy group for positive pictures (p=0.04).

Our results suggest that the MS modulates emotional processing, as reflected by enhanced startle reactivity when pictures were primed with moving videoclips designed to recruit the MS. This effect was more marked in the high empathy group, suggesting that high empathisers may be more sensitive to MS involvement in emotional processing.

We have recently found an association between smoking and mental distress in a three year follow up study among Norwegian adolescents. Earlier studies have demonstrated that the serotonin transporter gene interact on the association between negative life events and depression.

The aim of this study is, in stratified analyses by sex, to investigate whether there is a similar interaction of the serotonin transporter genotype on the relationship between smoking and mental distress.

All 10th graders in Oslo in 2000 and 2001 (n=7343, 88%) filled in questionnaires during school classes. The 2001 cohort (n = 3811) constituted the baseline. Of the participants in the baseline study 2489 (65%) participated in the follow-up. The response rate was 58% in boys and 74% in girls. The Hopkin's Symptom Cecklist-10 was used to measure mental distress. At follow up almost all participants provided genetic material using a cyto-brush on the buccal mucosa. The tag SNPs were analysed with Taqman MGB.

There was a significant interaction effect between the different genotype alleles and smoking among girls (F=4.0, p=0.019), but not among boys (F=0.8, p=0.44). Girls that are smoking daily with the long gene allele variant had lower mental distress scores than those with the short allele variant. Those with the heterozygote variant had scores that were between those with the short and long variant.

There is an interaction effect for the serotonin transporter genotype among adolescent girls, but not in boys in the relationship between smoking and mental distress.

One of the most often reasons of anomalies development of patrimonial activity is absence of the generated patrimonial dominant.

The study has been carried out on the basis of a maternity hospital of Chelyabinsk city. Group of 38 pregnant females sorts on term (38-40 weeks). It was lead monopolar electroencephalography on 11 channels with epselateral ear referent electrodes. Record EEG was carried out on standard procedure. The correlation analysis was carried out with the help of statistical package SPSS version 11.0.

Еру interrelation between anomalies of patrimonial activity and average frequency of a beta-rhythm is established at opening eyes (r = 0,450 at p=0,005), an index of a teta-rhythm (r =-0,419 at p=0,009) at closing eyes in left frontal assignment F1.

The revealed direct interrelation of increase of average frequency of a beta-rhythm in the left frontal assignment and increases in probability of occurrence of anomalies of patrimonial activity allows to specify a hypothesis about connection of expressiveness of high-frequency activity in frontal zones of a brain with formation of a patrimonial dominant.

This study explores the interplay of maternal depressive symptoms and use of antidepressant medication during gestation on the intranatal development of the infant limbic-hypothalamic-pituitary axis (LHPA). Infant neurologic markers at two weeks of age are also examined. Patterns of infant sleep within these groups are also explored.

In the study, pregnant women were screened for depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS), and their symptom severity was assessed longitudinally with the Beck Depression Inventory. Women were divided into 6 risk groups: low/stable, intermediate, and high/increasing depression based upon longitudinal symptom severity and medication use. The infant neuroendocrine system was examined using cord blood ACTH and cortisol. These infants were examined at 2 weeks of age using Neonatal Intensive Care Unit Neurobehavioral Scale (NNNS).

Infants born to women of the high/increasing depression group had significant elevations in cord blood ACTH at birth. On NNNS examination at two weeks, these infants were more hypotonic and less attentive. They habituated to stimuli more quickly and had fewer visual signs and higher skin reactivity. Infants born to women using antidepressants had further elevations in cord blood ACTH, and were found to be more tremulous and excitable during NNNS examination. Infants born to women with higher depression severity demonstrating aberrations in their early sleep patterns and sleep entrainment.

Maternal depression risk and antidepressant use may construe a different developmental pathway for development of the infant neuroendocrine axis which may impact early neonatal neurologic development.

Mild hypercortisolemia is a biological marker found in a subset of patients with major depression. The cause is supposed to be a malfunction in the corticosteroid receptor. Long standing cortisol excess is toxic to nerve cells and especially the hippocampus seem vulnerable to hypercortisolemia. The well known memory and concentration difficulties found in stress and depressive illnesses are supposed to be partly caused by deterioration of the function of the hippocampus.

The cortisol awakening response(CAR)were measured in saliva by repeated saliva specimens (awakening, 20 min and 60 minutes after awakening) in patient participating in a double blind study using a fixed dosage of sertraline and randomised to either dim or bright light treatment. Cortisol measurements were made before medication and light treatment started. The hypothesis, stated in the protocol, was that saliva cortisol would have a predictive validity of the short term depression outcome.

A statistically significant increase in cortisol levels were found during the first hour after awakening. The area under the curve (AUC) from the CAR results was calculated and was found to have a statistically significant predictive validity for depression scores and remission at endpoint. Thus a statistically significant higher proportion of patient with low CAR values were in remission compared to patient with high CAR values. This effect was predominantly seen in the bright light treated group.

Patients with a high CAR were less likely to attain remission at endpoint. The high CAR seemed to block the effect of light treatment.

The 5HTTLPR polymorphism of the serotonin transporter gene has been found to be significantly associated with suicide and it has also been described that suicidality is associated with increased impulsiveness, aggression and hopelessness. The aim of our study was to investigate the possible association of affective temperaments, hopelessness, aggression, impulsiveness and the 5HTTLPR s allele in a psychiatrically healthy population who have never attempted suicide.

135 psychiatrically healthy women participated in the study. All participants completed the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS-11), the Beck Hopelessness Scale and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego questionnaire (TEMPS-A). 5HTTLPR genotypes were determined by PCR. Results were analysed using Analysis of Covariance and forward stepwise regression.

We found a strong association between the presence of the s allele and the studied characteristics. ANCOVA indicated that there is a strong relationship between Hopelessness and aggressiveness, impulsiveness and affective temperaments. Forward stepwise regression indicated a significant role for depressive temperament, anxious temperament, irritable temperament, hostility and motor impulsiveness in predicting hopelessness. Adjusted whole model R2 was 37.61%.

Our study indicates a strong association between the s allele and factors related to increased risk of suicide. Our results show that depressive, anxious and irritable affective temperaments, hostility and motor impulsiveness influence Hopelessness, which has an important predictive role in the emergence of suicidal behaviours. Our results have implication for the recognition and prevention of possible emergence of suicidal behaviours within the healthy, non-depressed population.

Study biological markers of families with neurotic, stress-related and somatoform disorders for definition of probability of occurrence of mental disorders.

131 families of patients with neurotic, stress-related and somatoform disorders. The clinical and genealogical analysis, immunofermantal analysis for definition of concentration of steroid and thyreoid hormones, estimate of processes of apoptosis at receptor and cell-like levels for patients and relatives of the first degree of relationship were carried out.

Spreading of mental pathology among relatives was about 6,85 %. There was the accumulation of repeated cases of similar disorders in these families and basic share of pathology was marked among the first degrees of relationships. Among relatives of patients the group of the raised risk of occurrence of mental disorders is revealed: 1,35 siblings; 1,04 children; 0,3 grandsons; 0,85 spouses corresponds to 1 patient. The statistically significant increased levels of cortizol, triiodthyronin and thyroxine (p<0,05) and the lowered maintenance of dehydroepiandrosteronum (p<0,05) is characteristic for patients in comparison with control. We have observed statistically significant increase of expression of a receptor CD95 in patients in comparison with control (p<0,05). For patients is characteristic the statistically significant increase of levels of spontaneous apoptosis of neutrophils (p<0,05) and lymphocytes. For their relatives is characteristic the tendency to an amplification of this process.

Neurotic disorders are accompanied by features of biological processes, the knowledge of these features will allow rendering assistance with great efficiency.

The investigation supported by project of RHSF №06-06-00691а.

Depressive symptoms very often could be the only manifestation of the subclinical thyroid dysfunction (STD). Patients with the STD have the lifetime prevalence of depression approximately double that in the general population and display a lower response rate to antidepressant treatment and greater likelihood of responding to liothyronine augmentation.

To assess the stimulate-thyroid hormone (TSH) levels in the first depressive episode (FDE) sample and to evaluate the correlation between severity of depressive symptoms and the TSH levels.

The study included 27 patients with FDE (ICD X, F 32) treated in Psychiatric Hospital, University Hospital Zvezdara (Belgrade, Serbia). The exclusion criteria were presence of detected thyroid dysfunction, other psychiatric disorder, chronic somatic disease and/or using drugs. The TSH blood levels were measured. The 21-item Hamilton Rating Scale for Depression (HDRS, scored >17) was used in order to evaluate the severity of depression.

Mean age in our sample was 48.6 years, with female predominance (55.6 %). We found TSH levels elevated (>5.5 mEg/L) in 11.1 % (all were females) and decreased (<0.4 mEg/L) in 11.1 % (p<.05). We found positive correlation between the HDRS scores and the TSH measures (r=.445, p<.05).

The STD is a risk factor for developing the FDE. The greater TSH levels imply the greater severity of the FDE. Each clinician should be aware of possible underlying the STD with its implications on diagnosis, treatment and prognosis of the FDE.

Fuzzy genetic and environmental associations, variable phenotypes, and difficult to measure symptoms argue for comprehensive pathway studies on neuropsychiatric disease. Here, dopamine metabolism was dissected in the frontal cortex of ill individuals using a combination of measurement.

The activity of MB-COMT was assessed in 115 post-mortem frontal lobe samples as a function of genotype (VAL158MET), promoter methylation status, and mRNA level using conventional methods. Also analyzed were the promoter methylation status and mRNA expression levels of DRD1, DRD2, DRD4 and RELN.

MB-COMT promoter methylation was lower, and mRNA expression level higher in patients versus the control subjects (p=0.02). Further, hyper expression of MB-COMT was associated with hypo expression and hyper promoter methylation of DRD1, DRD2 and RELN. An enrichment of the overactive Val allele with MB-COMT hypomethylation in patients vs controls. For example, 87% vs 13%, ill vs well, respectively, were homozygous for Val/Val genotype and had an unmethylated MB-COMT promoter. In contrast, 18% of the samples with Met/Met genotype and a methylated MB-COMT promoter were among the SCZ/BD patients versus 82% in the controls (p=0.001). Preliminary studies on patients suggests, COMT antagonist are useful as adjunct therapeutics.

MB-COMT over-activity from the presence of an hyperactive allele (VAL), or promoter hypo-methylation may increases dopamine degradation in the frontal lobe, fine-tuning of down-stream gene expression, and provide a molecular basis for the shared symptoms of SCZ and BD. Hence, down regulation of COMT activity is a useful target for therapeutic intervention.

A paradox of genetic and environmental factors are linked to schizophrenia. For example, cases may be familial or spontaneous. Extensive studies have failed to identify a single gene or small group of genes that accounts for the majority of cases. The complex inheritance pattern suggests a strong environmental component even for those who are predisposed to disease. Environmental factors linked to disease occur early in development. Our goal is to identify common biochemical pathways affected by factors linked to schizophrenia.

Our studies included DNA comparisons between monozygotic twins discordant for schizophrenia, computational evaluations of genomic positions of candidate genes using Genbank resources, and molecular genetic/epigenetic studies on dopamine metabolism in the synaptic cleft.

Twins studies linked schizophrenia to somatic DNA instability (p = <0.01). Genomic studies linked schizophrenia to interspersed fragile site regions (p = 0.001) of the genome that are hot spots for mutation and epigenetics changes. The molecular studies on dopamine metabolism linked schizophrenia to aberrant genetic and epigenetic changes.

These, and other results, point to the confluence of DNA stability (i.e. DNA replication/repair) and epigenetic modification. DNA replication/repair and epigenetic modification are linked at both the macromolecular and biochemical level, require folate, methionine, and cobalamine, and compete for intermediates important for the cellular response to oxidative stress. Mutations in these pathways are linked to schizophrenia, as have deficits in the essential nutrients. The consequences of genetic and/or environmental perturbations to these pathways are complex because many essential pathways and processes are affected.

This study investigated the duration of emotional responses to emotionally valenced stimuli and explored the relationship between objective [as assessed by skin conductance activity (SC)] and subjective measurements of emotional reactivity.

A sample of 100 healthy volunteers, stratified for age and gender, viewed 54 images from the International Affective Picture System equally split in positive, negative and neutral categories. Subjects pressed a button to view the next image when they judged that their response had subsided (time to emotional resolution, TTR) and then rated the intensity of their response on a scale from 1 to 9 (highest). The number of skin conductance responses (SCRs) and the maximum amplitude (μS) were also acquired and averaged for each condition (mean ± SD).

Picture valence had a significant effect on all measures(p<0.001). TTR (sec) was 11.01±6.57, 14.74±7.82 and 5.27±3.57 while arousal ratings were 5.65±1.80, 7.46±1.78 and 1.77± 0.87 for positive, negative and neutral images, respectively. Maximum amplitude was 0.19±0.14, 0.22±0.17 and 0.16±0.12 while SCRs were 23.76±14.06, 29.67±19.04 and 18.52±10.81 for positive, negative and neutral images, respectively. A correlation matrix of all measures showed significant association between TTR and SCRs (p<0.001) only.

TTR correlated with SCRs indicating that participants viewed the next image when their level of arousal subsided. However, the poor correlation between SC and arousal ratings suggests that when appraising the intensity of their responses, participants were accessing other aspects of emotional processing than arousal alone.