An antisaccade is a rapid eye movement (saccade) made away from a visual stimulus. The task is a good measure of the conflict between an unwanted reflexive response (which must be inhibited) and a volitional response (which must instead be generated). Deficits on the antisaccade task constitute a promising schizophrenia endophenotype. In this talk I will review studies that have demonstrated antisaccade deficits in sibling and twin pairs discordant for schizophrenia. I will then data from present recent investigations of association between antisaccade performance and candidate polymorphisms for schizophrenia and cognition. Finally, I will discuss results from an investigation of the relationship between brain function during eye movements and a single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene, a candidate gene for schizophrenia and brain function. The COMT val158met SNP (rs4680) was genotyped and the brain response during antisaccades was measured using fMRI in 36 healthy humans. Val158 carriers (N=24) showed reduced BOLD response in ventromedial and dorsomedial frontal areas during antisaccades compared val158 non-carriers (N=12). These findings suggest that COMT val158met genotype may affect the brain response during antisaccades; the results may be compatible with a hypothesis on the role of COMT val158met genotype in tonic and phasic dopamine levels in cortex and measures of cognitive plasticity (e.g. antisaccades).

Neuropsychological assessment of prefrontal cortex activity included several tests: The Stroop Color Word Interference Test is a method for the assessment of verbal abilities, attention, verbal working memory and executive functions, whereas Trail Making Test measures psychomotor speed, the ability to shift strategy, executive functions and visuospatial working memory. The N-back Test measures visual working memory and visuomotor abilities. Normalization of these tests for Polish population has not been done so far. The goal of the study was exploratory analysis of possible associations between performance of the Stroop Color-Word Interference Test, Trail Making Test and N-back Test in healthy subjects and basic demographic features. The study included 200 healthy volunteers (100 male, 100 female), aged 18-60 (mean 32±10,6) years.

Increasing epidemiological evidence suggests that environmental stressors such as trauma and life events are associated with the development of psychosis. The underlying mechanism however remains unclear. Previous studies of our group have demonstrated that increased sensitivity to daily life stress is part of the underlying vulnerability for psychosis. It is therefore attractive to hypothesize that early trauma increases the risk for psychosis through sensitizing people for the small stresses of daily life. This hypothesis has been investigated in three different data sets (both general-population and clinical samples) using the Experience Sampling Method (ESM; a structured diary technique) to assess stress-reactivity in daily life defined as emotional and psychotic reactivity to stress. The results suggest that a history of childhood trauma sensitizes people to the stresses of normal life resulting in stronger emotional and psychotic reactions to stress. However, this sensitization process is most pronounced in subjects with an increased vulnerability for psychosis.

Since substance use, misuse, harmful use and dependence are associated with considerable mortality and physical and psychological morbidity, the multiple and complex interactions of substance misuse with health will be explored.

Gender differences in substance use accrued from prevalence studies will be outlined and will be presented in the context of predisposing or complicating psychological symptoms or psychiatric syndromes. Observations that women are more likely to report a comorbid psychiatric condition than males, especially depression or borderline personality disorder but also impulsivity, aggression and disinhibition, anxiety, psychotic illness, post-traumatic stress disorder (as a result of early life stress and physical abuse) and eating disorders, will be examined in relation to the course and outcome of illness. Evidence for the high risk behaviours and chaotic life style that may be associated with comorbidity, such that self-harm may result, with eventual suicide, will be described.

In view of the fact that patients with comorbid conditions have poorer prognosis and place a heavy burden on services because of disengagement, high rates of relapse and re-hospitalisation, serious infections, and homelessness, unemployment, poverty, prostitution, violence, arrest and even imprisonment, it is important to have a grasp of the nature and extent of the problems so that patients can be sensitively managed. The likely impact of these conditions on women and their social roles as mother and carer will be analysed as part of the need to develop effective services, which detect problems early and deliver appropriate interventions which are sensitively managed.

Epidemiological data show pronounced gender differences in the prevalence of substance use disorders (alcohol, sedatives, opioids, nicotine, psychostimulants, cannabinoids). Social, psychological and biological including genetic factors contribute to the gender differences. Several studies show in men a higher participation of genetic factors in the development of an addiction disease than in women, in which besides genetic factors other factors seem to be more prominent. The occurrence of psychic dependence with drug seeking behaviour is the outcome of a number of variables including sex hormonal, neuronal (dopamine and interactive transmitters f.e glutamate, GABA, serotonine, opioid peptides), genetic, developmental, age, neurodegenerative and environmental elements that interact to produce profound individual (gender) differences in both initial and longterm responsiveness to addictive drugs. Sex steroids, especially estrogens, are responsible for the synthesis and secretion of neuropeptides (eg opioids peptides), but also of the neurotransmitters dopamine, serotonine etc and may exert by these mechanisms and environmental interaction gender effects in addiction diseases. The diverse factors also have a significant impact on the accessibility to and effectiveness of pharmacological and psychotherapeutic treatment of different substance disorders in women and men.

Single representive results from animal and clinical studies especially on individual (genetic, sex hormonal, gender identification) differences will be presented which focus on key issues which may improve treatment effectiveness and models of service provision.

Women and men differ in the development of drug and alcohol dependence. In alcoholism, a phenomenon called "telescoping" has been described, i.e. women usually start later with excessive alcohol intake but develop neurotoxic effects (e.g. brain atrophy) earlier than men. On the other hand, estrogens may show neuroprotective effects, which has been postulated to explain relatively preserved serotonin transporter availability in female compared with male alcoholics. Once alcohol dependence is manifest, the relapse risk seems to be higher in women compared with men. Female patients usually report more emotional distress and reduced quality of life. They also show increased comorbidity with respect to anxiety and depression, while men more often display so-called "antisocial" personality traits. Borderline personality disorder also seems to be more frequent in women and may demand specific treatment options.

The majority of women in drug treatment facilities are of childbearing age. According to a SAMHSA Report, four percent of women aged between 15 and 44, are pregnant while entering treatment systems. These women represent a challenging patient population, that is in need of a comprehensive model of care, consisting of psychiatrists, psychologists, social workers, nurses and OBGYNs. Exposure to illegal substances during pregnancy may have consequences on the course of pregnancy and neonatal outcome. The fact that almost all patients showing up are also nicotine-dependent, should be taken into account, as neonatal withdrawal symptoms can be worsened. Furthermore, substance dependent women often find themselves in a situation of psychosocial instability. Prevalence of co-morbid somatic (e.g. hepatitis C, malnutrition) and psychiatric disorders (PTSD, depression)is high. As these pregnancies are rated as “high-risk”, prenatal checks should be undergone frequently. Recommended treatment for opioid-dependent, pregnant women is maintenance therapy with opioids. Post-delivery, 55 – 94% of infants exposed to substances in utero, may develop a neonatal abstinence syndrome (NAS). Incidence, time of onset and severity of NAS are associated with type of substances used. A standardized procedure of assessment and monitoring of NAS, as well as pharmacological and non-pharmacological treatment of these neonates is highly needed. By the means of a multi-professional treatment approach, the length of hospital stay may be shortened dramatically. In regard to a better future outcome, special aftercare (medical care plus psychosocial support) for mothers and infants should be provided, as well as further research.

The clinical phenomenology of psychiatric disorders includes both subjective psychological experiences and objective behavioral changes. Nevertheless, the diagnostic process in psychiatry is based almost exclusively on the evaluation of the psychological symptoms as voiced by the patient with virtually no use of direct observation of behavior. The weakness of such an approach to behavioral assessment has several negative consequences for clinical practice. It is difficult to estimate to what extent the findings of biological studies are confounded or invalidated by the fact that they are generally based on correlations between accurate physiological measurements and crude behavioral ratings, sometimes of the type “better/worse” or “much/less.” Another negative consequence of psychiatry's neglect for direct observation of behavior is the difficulty of integrating animal and human data about the effects of drugs on behavior. If the clinical phenomenology of mental illnesses could be reformulated in ethological terms, the same, or similar, definitions could then be applied to the development of animal models, and analogs for specific behaviors might then become more feasible. Finally, the weakness of behavioral assessment in psychiatry has negative implications for clinical practice as well. Several studies have shown that the objective and quantitative recording of patients’ behavior may sometimes yield different results from those obtained using rating scales or structured interviews. These findings cast doubt on the validity of routine psychiatric assessments and suggest caution in basing important clinical decisions (e.g., when to discharge a patient or whether to increase drug dosage) exclusively on patients’ reports of their symptoms.

Psychopathology is a science of methods in psychiatry for evaluation of abnormal mental states and mental disorders based on psychic alterations. Different methodological approaches have been used to enlight the phenomenology, pathogenesis, significance and nosological position of psychiatric disorders resulting in an enormous amount of knowledge concerning explanation and understanding of mental disorders. But the more the monstrous contemporary classification systems, e.g. ICD-10 and DSM-IV gained importance in the last decades, the smaller the interest in accurate phenomenological and psychopathological analyses and knowledge became. The main requirement for diagnostics and classification systems is its clinical relevance with respect to treatment and prognosis. Various empirical studies showed that classical categorical classification systems of mental disorders were of minor value concerning pathogenesis-oriented treatment approaches. A possible alternative to the classical categorical approach may be a dimensional approach. Such diagnostics focus on the constellation of conditions of single psychopathological phenomena and/or symptoms and its meaning for the patient suffering from them. According to the results of recent phenomenological and psychopathological studies the pathogenesis of a mental disorder has to be considered as a multidimensional process in which various mental, physical and social factors and their meanings for the sufferer act as predisposing, triggering, and disorder-prolonging factors. Effective treatment strategies have to be based on an accurate differential diagnosis concerning the complex constellation of conditions underlying and establishing the dynamic process of a disorder and its meaning

Qualitative analyses is a phenomenological-oriented framework for psychopatological research useful in hypothesis formulation and exploratory studies, as well as in assessement of real world, first-personal experiences of laboratory findings or sub-personal impairments. Its aim is a wide range understanding of the patient's morbid subjectivity, not constrained in a priori fixed schemata.

We describe the basic principles of this method applied to psychopathological research. The qualitative approach to anomalous experience is concerned with bringing forth the typical feature(s) of actual personal experiences. A three-step procedure is described entailing assessement of subjective experiences, positing of subjective experiences within personal narratives and finally the construction of trans-personal prototypes. Qualitative research method is based on systematic but flexible interrogation of initially unstructured phenomena; it requires maximum elasticity in generating new categories from phenomena and enhances dense conceptual development and dialectical process between phenomena and the clinician's conceptualizations. It promotes also clinical setting as a source of relevant data of research; it also allows knowledge of single patients deeper than the experimental setting and may promote s a more circunstantiated comprehension of them.

According to a stress-vulnerability model, genetic set-up, as well as environmental exposure to psychological stress, contributes to a person's predisposition for suicidality, as well as to Major Depression (MD). The main neurochemical findings on suicidality have suggested alterations in neurosytems which are usually implicated in MD; a lowered serotonergic (5HT) activity, depletion of the noradrenergic (NA) system and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Whereas the genes of e.g. the 5HT system and of the key NA-biosynthesis enzyme, tyrosine hydroxylase, have been studied extensively in this context the genes in the HPA axis have only begun to be investigated recently.

Our group was the first to study the genetic variation in the CRHR1 gene in connection to depression and stress among suicidal individuals. We reported also findings that genetic variation in a transcription factor of the POMC gene, TBX 19, which is regulated by CRH, showed association and linkage to the anger/hostility personality trait and suicidality. Those results suggest that genetic variation in the CRH-mediated regulation of the HPA axis is a factor of importance in suicidality and, as other have shown as well, for major depression.

During symposiums the results obtained from the replication analyses of single nucleotide polymorphisms (SNPs) in candidate genes, in 1000 family trios with suicide attempter offspring, by using the transmission disequilibrium test both in a two-stages screening/replication sample design and in detailed reanalysis in the entire sample, will be discussed.

Suicidal behaviour is a serious problem world-wide. However, the number of risk factors and the complex nature of their interactions do not allow sufficiently accurate prediction of whether a given individual is likely to try to commit suicide. Several lines of evidence suggest that suicidal behaviour has a genetic component.

In recent years, a growing number of molecular genetic studies have focused on the serotonin system, suggesting that this system may be involved in the pathogenesis of suicidal behaviour, aggression, and impulsivity. Post-mortem studies have reported fewer serotonin transporter (5-HTT) binding sites and greater expression of serotonin 2A (5-HT2A) receptors in the brains of suicide victims compared to control subjects, partly due to functional polymorphisms that affect the expression of these genes.

In this the presentation we discuss data suggesting an association between the A-1438G (rs6311) polymorphism of the 5-HT2A receptor gene and the impulsivity of the suicidal behaviour. However, we found an excess of the -1438A allele in non-impulsive suicide attempts as compared with impulsive suicide attempts and with a healthy control group. These findings agree prior report by Giegling et al (2006) and suggest that this functional polymorphism may modify the phenotype of suicidal behaviour and could be related to the impulsivity of the attempt.

Suicidal individuals are constantly submitted to the influence of psychosocial life events that may act as triggers as well as vulnerability factors to the suicidal behaviour. On the other hand, suicidal persons nearly always suffer from psychiatric disorders, and growing evidence suggest that they carry vulnerability traits related to psychological traits and genetic factors. In recent studies we shown that decision makingwas involved in the vulnerability to suicidal behaviour independently from the psychiatric disorders of the patients. We reported that decision making was influenced by several serotonergic genotypes associated with the vulnerability to suicidal behaviour.

First, we will examine the nature of the interactions between candidate genes and environmental factors in the susceptibility to suicide attempts. Some data suggest that the genes coding for 5HTT and BDNF influence role of childhood maltreatment on suicidal risk. Moreover, we investigated the existence of such interactions on the risk of severity of the suicidal behaviour. We created an index of suicidal severity by assessing various characteristics of the suicidal act. We investigated whether this suicidality index was influenced by 5HTT genotypes, history of childhood maltreatment and their combination.

Second, by assessing several cognitive functions including decision making, in suicide attempters, we reported the influence of cognitive functioning on the risk of occurrence of some specific stressful life events and a correlation with childhood early maltreatment.

In conclusion, the data presented here suggest that the relationship between environmental factors, genes and cognitive functioning in suicide attempters are of both interactive and correlative natures.