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LEK-8829 [9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8- aminomethylergoline bimaleinate] is an antagonist of dopamine D2 receptors and serotonin (5-HT)2 and 5-HT1A receptors in intact animals and a D1 receptor agonist in dopamine-depleted animals. In the present study, we used rats with unilateral striatal lesions with ibotenic acid (IA) to investigate the dopamine receptor activities of LEK-8829 in a model with innervated dopamine receptors. The IA-lesioned rats circled ipsilaterally when challenged with apomorphine, the mixed agonist on D1/D2 receptors. LEK-8829 induced a dose-dependent contralateral turning that was blocked by D1 receptor antagonist SCH-23390. The treatment with D1 receptor agonist SKF-82958 induced ipsilateral turning, whereas the treatment with D2 receptor antagonist haloperidol induced contralateral posture. The combined treatment with SKF-82958 and haloperidol resulted in a weak contralateral turning, indicating the possible receptor mechanism of contralateral turning induced by LEK-8829. Bromocriptine induced a weak ipsilateral turning that was blocked by haloperidol. The ipsilateral turning induced by bromocriptine was significantly potentiated by the coadministration of a low dose but not by a high dose of LEK-8829. The potentiation of turning was blocked either by SCH-23390 or by haloperidol. The potentiation of ipsilateral turning suggests the costimulation of D2 and D1 receptors by bromocriptine and LEK-8829, respectively, whereas the lack of potentiation by the highest dose of LEK-8829 may be explained by the opposing activity of LEK-8829 and bromocriptine at D2 receptors. We propose that the D2 and 5HT2 receptor-blocking and D1 receptor-stimulating profile of LEK-8829 is promising for the treatment of negative symptoms of schizophrenia.

IntroductionAdolescence is a time of developmental shifts that may leave young people especially vulnerable to suicidal behaviour. Suicidal rates in different European countries differ, which may be due to many factors, including cross-cultural differences.AimsWe aimed to explore differences in risk factors for suicidal behaviour (poor subjective health and low life satisfaction, health-related behaviours, including alcohol drinking habits, family and peer factors) between European countries with different suicidal rates.MethodsThe data were collected through questionnaires in the survey ‘Health Behaviour in School-aged Children’, 2005/2006, using nationally representative samples of 15 year old students (N = 11,093) from 7 countries (Lithuania, Finland, Ireland, Slovenia, Norway, Italy, Greece).ResultsPrincipal component analyses were used to characterize how selected risk factors for suicide cluster together into factors. Differences for these factors were compared between 3 groups of countries: countries with low, average and high magnitude of suicidal rates (SDR; suicide death rate per 100 000, 15–29 years). Between group differences on first two factors, loaded by items measuring health-related behaviours, were significant and medium-sized and indicated cultural differences in alcohol use. Youth from Northern European countries - with high SDR, reported greater number of drunkenness occasions, whereas frequency of alcohol intake was greater for youth from Southern European countries - with low SDR.ConclusionsResults indicated a possible association of suicidal behaviour and different drinking cultures, arising from different geographical locations and socio-cultural environments. Therefore research and preventive measures should consider specific socio-cultural context.

IntroductionQuality of life (QoL) is reported to be markedly impaired even in interepisode bipolar disorder. Recent depressive episode correlates with poorer QoL than recent manic episode in remitted patients.AimsWe compared QoL between bipolar patients with regard to the polarity of most recent episodes and control group in order to assess relationships between clinical factors and quality of life in bipolar outpatients.Methods33 remitted bipolar outpatients (19 depressive and 14 manic according to the polarity of recent episode), and 22 healthy individuals completed the World Health Organization Quality of Life Instrument-Short Version (WHOQOL-BREF).ResultsOutpatients with recent depressive episode reported the lowest overall QoL and health satisfaction and had the lowest scores on psychological domain among all groups. Polarity of most recent episode didn’t correlate significantly with QoL. In outpatient group as a whole, several clinical factors including previous depressive episodes were significantly correlated with WHOQOL-BREF scores.ConclusionsQoL is impaired in remitted bipolar outpatients. Despite the insignificant association between polarity of most recent episode and QoL, our data confirm that depressive symptoms are among the most significant contributors to reduced QoL in bipolar disorder. The importance of gaining full remission is associated with improved QoL.

ObjectivesAlthough previous studies have suggested that bipolar disorder symptoms could result from increased impulsivity and vulnerability of the Behavioural Activation System (BAS), the association of the Behavioural Inhibition System (BIS) with the disorder remains unclear.AimsGiven that motivational systems, especially BAS, and impulsivity are closely intertwined, we aimed to assess the associations between BIS and BAS and impulsivity among healthy volunteers and remitted bipolar outpatients.Methods70 euthymic bipolar outpatients and 70 healthy controls were self assessed with the BIS/BAS Scale and the Barratt Impulsivity Scale.ResultsOur data revealed elevated BIS and BAS sensitivity (Figure 1a) as well as impulsivity (Figure 1b) in the group of bipolar outpatients. Both motivational systems seem to be unrelated to the trait impulsivity.ConclusionsOur results indicate that BIS/BAS sensitivity and impulsivity represent a distinct trait. Furthermore, elevated BIS and BAS sensitivity and impulsivity in the euthymic phase of the disorder could represent an indicator of relatively stable personal traits which persist throughout all phases of the illness, thus signifying a vulnerability factor that could be relevant in the early diagnostic picture of affective disorders.

IntroductionSeveral cognitive and behavioural disturbances persist in interepisodic bipolar disorder (BD). Affective temperaments may influence impairments as they contribute to the predisposition to BD and may share a common neurobiological basis with elevated trait impulsivity.AimsWe aimed to assess a relationship between temperamental traits and impulsivity as a trait and state dependent behaviour among euthymic bipolar outpatients and healthy volunteers.Methods38 euthymic bipolar outpatients and 24 healthy volunteers completed TEMPS-A and BIS-11. Computerised picture- based affective go/no-go task was applied to examine emotional response inhibition as an indicator of state dependent impulsivity.ResultsClinical group scored significantly higher than healthy volunteers on trait impulsivity and affective temperaments scales, and displayed poorer control of emotional response inhibition (Table 1). Correlation patterns were similar in both groups, with strong associations between the majority of affective temperaments and trait impulsivity components, while correlations between state dependent impulsivity measures appeared weak.ConclusionsDuring euthymia, distinctive temperament profile, elevated trait impulsivity and impaired emotional inhibition, prevailed among bipolar outpatients. This is consistent with data suggesting persistent abnormalities within specific areas of the prefrontal cortex and limbic structures which may underlie the emotional, cognitive and behavioural disturbances observed in all phases of BD.

ObjectivesThe aim of the present study was to assess the preventive and promotion activities in the mental health area in 12 Slovenian regions. In addition, some of sociodemographic and health indicators related to increased probability of mental health problems were analysed in order to estimate the amount of preventive/promotion programmes in the regions with highest threats to mental health.Methods301 mental health services have been assessed according to their promotion and preventive activities in the mental health area. Services were surveyed according to their implemented activities, prevention types, funding sources, target groups, addressed risk and preventive factors and available staff at services.Results98% of assessed services were involved in one or more preventive and/or promotion activity. The selective primary prevention approach prevailed, whereas services mainly focused on major mood disorders and addiction. The most common types of activities were: individual / group counselling, lecture, workshop and media appearance, where the plan of support, interpersonal conflicts and organised lifestyle as addressed risk and protective factors predominated. In the preventive/promotion programmes were the most represented social workers, psychologists and volunteers. In the contrast with the scarcity of activities in Zasavska and Savinjska region, the most abundant choice of programmes was found in Osrednjeslovenska and Obalno-kraška region.ConclusionsOur study indicated that considerable differences appeared between Slovenian regions in the view of diversity and extent of preventive / promotion activities since availability and variety of this activities were particularly scarce in the regions with highest threats to mental health.

ObjectivesAlthough numerous studies agree that bipolar patients demonstrate extensive cognitive deficits, it is still unclear to which extent these impairments persist across different mood states, including euthymia. Given that the emotional and cognitive processes are closely intertwined, we aimed to examine selective attention, cognitive inhibition, and social cognition within different emotional context in the group of remitted bipolar outpatients.Methods80 euthymic bipolar outpatients and 66 healthy volunteers matched for sex, age and education participated in the study. Internal State Scale and Barratt Impulsiveness Scale were used to assess self-reported affective states and trait impulsivity. Computerised versions of Colour-Word Stroop, Emotional Stroop, Affective Go/NoGo and Ekman Recognition of Facial Expression task were administered to assess selective attention, inhibition of cognitive control and social cognition.ResultsSeveral cognitive deficits in selective attention, inhibition of cognitive control and social cognition tasks have been identified in the group of euthymic bipolar outpatients. They revealed worse recognition of negative, positive and neutral affect than controls. Besides cognitive disruptions which were reflected in longer reaction times and more erroneous performance to different emotional stimuli and in different emotional contexts, also trait impulsivity was considerably elevated in the group of bipolar euthymic outpatients.ConclusionsBipolar outpatients in our study demonstrated relatively marked impairments in cognitive functioning within different emotional contexts also during the euthymia. Applied neuropsychological inventory proved as useful tool for assessing specific cognitive impairments in bipolar mood disorder, and could contribute to more effective diagnosing and treatment of patients.

ObjectivesSeveral neurocognitive deficits present in the euthymic state of bipolar disorder suggest that some of them could be seen as vulnerability trait markers of the illness. Psychoeducation proved as effective therapeutic approach which decreases the risk of relapse and prolongs remission. In our study we aimed to examine the psychoeducational effects on cognitive functioning in the sample of euthymic bipolar outpatients.MethodsA neuropsychological tests battery for assessing selective attention (Emotional and Colour-Word Stroop), cognitive control (Emotional Go/NoGo task) and social cognition (Face recognition task and Recognition of emotional expression task) was administered to 29 bipolar euthymic outpatients before and after attendance at six weeks psychoeducation program. The same procedure was applied on 10 bipolar euthymic outpatients without participating in psychoeducation.ResultsDespite statistically insignificant differences between groups in cognitive performance, some considerable within group differences in domains of selective attention and cognitive control of emotional stimuli emerged. In the Emotional Stroop there was faster processing speed of emotional stimuli after psychoeducation compared to baseline in the intervention group which was not found in the control group. Similarly, coping with emotional stimuli in different emotional contexts markedly improved in the intervention group compared to the control group. Changes in social cognition, in particular better recognition of negative affect were found in the bipolar group with psychoeducation but not in the control group.ConclusionsThough preliminary, our results support psychoeducation as clinically feasible way of cognitive rehabilitation in terms of improved cognitive control of emotional stimuli in bipolar patients.