Suicide and Suicide Attempt Descriptors by Multimethod Approach.

BACKGROUND: Suicide is a complex action of suicidal methods and peripheral factors with seemingly threatening components representing actual cause for the suicidal actions. It is especially those, apparently unimportant factors that represent a crucial milestone in the network of all the other, personal, cultural, genetic and biochemical factors, forming the method of action consequently deciding between life and death. SUBJECTS AND METHODS: Based on the Register of Suicides in the Republic of Slovenia kept by the University Psychiatric Clinic Ljubljana, we used a combination of attributes varying within a variable and between variables. Due to limited application of standard statistical methods and analyses in such cases, we used the Machine learning method, Multimethod hybrid approach, which allows combining of different approaches to machine learning (decision trees, genetic algorithms and supplementary vectors). The research included 56712 persons attempting suicide and 21913 persons committing suicide. We chose a form of a suicide action with both possible results: attempted suicide and suicide. RESULTS: Based on the analysis of machine learning, we defined attributes of the action regarding their lethal effect: attempted suicide and suicide commitment. The suicide register kept for the last 40 years shows hanging as the most commonly used suicidal method, used by men with the purpose of causing suicidal death rather than a suicidal attempt. On the other hand, use of medicaments is linked to the suicidal attempt and mostly used by females. CONCLUSIONS: All methods of suicidal actions cannot predict suicidal death, thus we examined different methods of suicide to most accurately predict the link between the method and its effect in terms of suicide attempt or suicide. The Machine learning method confirmed the attributes of suicide methods in connection with their different outcomes. This analytical method is useful in processing large databases since it enables one variable's intensity to affect other variables in terms of result and meaning. The identification of the most decisive risk factors for suicidal behaviour can serve as basis for planning an effective prevention strategies, timely identification and adequate proffessional help to the high risk persons.

The Role of Microbiota in Depression - a brief review.

The microbiota-gut-brain axis is a bidirectional homeostatic route of communication between both of the organs direct via receptors of the CNS or via epigenetic mechanisms of divers metabolites e.g. SCFA, GABA, ß-hydroxybutyrate. Thus, a modulation of gut microbiota via nutrition, lifestyle etc. might be effective for emotional status and depressive disorders. The dietary composition has an influence on gut microbiota composition, microbial metabolite profile and the according consequences on emotional status and depression within a system biologic approach. There are changes in gut microbiota composition and gut microbial profile (butyrate, GABA, ß-hydroxybutyrate) effecting epigenetic regulation (histone acetylation, DNA methylation) and gene expression of receptors and mediators (SLC6A4, BDNF, GABA, GPRs) involved in depressive disorders.

Clinical exome sequencing in dementias: a preliminary study.

BACKGROUND: Dementias are clinically and genetically heterogeneous group of neurodegenerative disorders. Often, dementias with genetic etiology are clinically indistinguishable from non-genetic ones. The aim of this retrospective study was to evaluate the yield of clinical exome sequencing in dementias, potentially associated with monogenic genetic predisposition. SUBJECTS AND METHODS: For this purpose 20 consecutive patients younger than 65 years were studied in the period from January 2014 to December 2017; 14 with the diagnosis of Frontotemporal dementia (FTD), 3 with early-onset Alzheimer disease (EOAD) and 3 with unspecified dementia. In addition to clinical exome sequencing including 57 genes associated with dementia, C9orf72 hexanucleotide expansion as tested in all patients. RESULTS: We found genetic etiology in 6 patients: 2 mutations in the PSEN1 gene (p.Pro264Ser and p.Phe105Cys) in the EOAD patients, C9orf72 expansion and MAPT (c.1920+16C>T), mutation in the FTD group of patients as well as MAPT (c.1920+16C>T) mutation and likely pathogenic mutation in the TYROBP mutation (p.Asp32Asn) in patients with unspecified diagnosis. CONCLUSIONS: Our preliminary results imply significant diagnostic yield in identifying rare genetic causes of dementia, combining comprehensive clinical exome sequencing and targeted C9orf72 expansion testing.

The relationship between baseline EEG spectra power and memory performance in older African Americans endorsing cognitive concerns in a community setting.

The finding that some older individuals report declines in aspects of cognitive functioning is becoming a frequently used criteria to identify elderly at risk for mild cognitive impairment (MCI) and dementia. Once concerns are identified in a community setting, however, effective means are necessary to pinpoint those individuals who should go on to more complex and costly diagnostic evaluations (e.g., functional imaging). We tested 44 African American volunteers endorsing cognitive concerns (37 females, 7 males) age≥65years with CogState battery subtests and recorded resting-state EEG, with eyes closed. After current source density (CSD) transformations of EEG recordings we obtained spectral power for delta, theta, alpha, and beta frequency bands. We characterized CogState One Card Back Learning (OCL, memory) with diffusion model parameters drift rate, boundary and non-decision time (NDT). Forward regression models showed that lower OCL drift rate, slower accumulation of information needed for decision making was linked to increased absolute and relative delta at occipital region. Lower drift rate was also linked to decrease in OCL theta power at parietal region, with no findings for ONB. Results show that cortical resting, eyes closed EEG rhythms are related to memory in African American seniors endorsing cognitive concerns. This study further supports the use of EEG as an easily accessible, cost-effective, culture-fair, and noninvasive clinical measurement that could provide potentially reliable diagnostic (and perhaps prognostic) information to differentiate at-risk from stable African American seniors.

Male anorexia and bulimia nervosa: Disorder symptoms and impulsive behaviour during hospital treatment and one year follow-up period.

BACKGROUND: The study aimed to evaluate treatment efficacy in male patients with anorexia (AN) and bulimia nervosa (BN) treated at the Eating Disorder Unit, University Psychiatric Clinic Ljubljana, Slovenia (EDU UPCL), using longitudinal assessments of eating disorder (ED) symptoms and selected impulsive behaviours highly correlated with these entities from hospital admission till twelve months after. SUBJECTS AND METHODS: 35 male AN and 35 male BN patients were included. Participants were aged 17 or more and somatically stable with the BMI>12 kg/m(2). Patients with psychiatric comorbidity, mental disorder due to a general medical condition, or serious somatic or neurological disease were excluded. Intensity of ED symptoms and presence of selected impulsive behaviours were evaluated at hospital admission and discharge, and three, six and twelve months after, using an internal Eating Disorder Unit Questionnaire. For statistical analysis multivariate analysis of variance was used. RESULTS: Throughout the research period the appropriate changes in BMI were observed in both patient groups. In both, AN and BN patient groups, the evaluation of longitudinal differences regarding the intensity of all ED symptoms and the presence of studied impulsive behaviours showed a significant decline at discharge and all subsequent assessments compared to the results obtained upon admission to the hospital. The re-hospitalization rates of patients with AN and BN in the first year after discharge from the hospital were 3.84% vs. 3.7% respectively. CONCLUSIONS: In male patients with AN and BN treated at the EDU UPCL, ED symptoms, BMI, and studied impulsive behaviours show a substantial improvement during hospital treatment. These changes seem to be long lasting, still being effective through one-year post-hospitalization follow-up.

Cortical configuration by stimulus onset visual evoked potentials (SO-VEPs) predicts performance on a motion direction discrimination task.

The slowing of information processing, a hallmark of cognitive aging, has several origins. Previously we reported that in a motion direction discrimination task, older as compared to younger participants showed prolonged non-decision time, an index of an early perceptual stage, while in motion onset visual evoked potentials (MO-VEPs) the P1 component was enhanced and N2 was diminished. We did not find any significant correlations between behavioral and MO-VEP measures. Here, we investigated the role of age in encoding and perceptual processing of stimulus onset visually evoked potentials (SO-VEPs). Twelve healthy adults (age<55years) and 19 elderly (age>55years) performed a motion direction discrimination task during EEG recording. Prior to motion, the stimulus consisted of a static cloud of white dots on a black background. As expected, SO-VEPs evoked well defined P1, N1, and P2 components. Elderly participants as compared to young participants showed increased P1 amplitude while their P2 amplitude was reduced. In addition elderly participants showed increased latencies for P1 and N1 components. Contrary to the findings with MO-VEPs, SO-VEP parameters were significant predictors of average response times and diffusion model parameters. Our electrophysiological results support the notion that slowing of information processing in older adults starts at the very beginning of encoding in visual cortical processing, most likely in striate and extrastriate visual cortices. More importantly, the earliest SO-VEP components, possibly reflecting configuration of visual cortices and encoding processes, predict subsequent prolonging and tardiness of perceptual and higher-level cognitive processes.

Aging effects on visual evoked potentials (VEPs) for motion direction discrimination.

Age-related declines in motion perception have been well documented. We investigated the impact of age on electrophysiological correlates of motion perception, namely the P1 and N2 components of motion onset visual evoked potentials (MO-VEPs). Additionally, we used a model of response times based on the diffusion model to pinpoint the cognitive processes affected by aging. Twelve healthy adults (age <55 years) and 19 elderly (age >55 years) performed a motion direction discrimination task during EEG recording. Behaviorally, younger and older participants had similar, high accuracy rates--98% correct, but older adults exhibited 85 ms longer response times. Fitting behavioral results with a diffusion model revealed differences between young adults and elderly in non-decision time, which we argue reflects an early perceptual stage. Electrophysiologically, aging effects were present at MO-VEPs P1 and N2 components at the posterior sites. For the P1 component, older as compared to younger adults showed greater topographical voltage distribution. For the N2 component of elderly as compared to young adults we found delayed onsets and diminished amplitudes. We did not find any significant correlations between behavioral and MO-VEP measures. However, regression analysis showed that N2 amplitude and latency were significant age predictors. Overall, our results indicate that in motion perception, age-related changes occur in early stages of visual processing, most likely in striate and extrastriate visual cortices.

Differences in mood between elderly persons living in different residential environments in Slovenia.

BACKGROUND: Mood disorders are an important health risk factor in the elderly population. Studies on the relationship between residential environment and elder's psychological wellbeing show the worst psychological status results in institutionalized subjects. To elucidate this relationship in Slovenia, we compared cognitive functioning and the levels of anxiety and depression of Slovenian elders among different residential arrangements. SUBJECTS AND METHODS: The subjects were recruited from elderly clubs (EC; living at home; n=32), elderly day care centers (EDC; living at home; n=22), and elderly homes (EH; institutionalized; n=49). All were female, 65-80 years of age and matched for their duration of education. We compared the cognitive status (Mini Mental State Examination) and the levels of depression and anxiety (Zung self-rating depression scale inventory, Zung self-rating anxiety scale inventory) among the three groups. For statistics ANOVA, MANOVA, and ANCOVA were used. RESULTS: The EDC group showed the highest levels of anxiety, depression and cognitive decline compared to the EC and EH groups, with no statistically significant differences between the EC and EH groups did not differ significantly in these respects. Controlling for the cognitive status revealed that general cognitive functioning and residential environment did not exert their influence directly on the depression level, but rather through their interaction. Regarding anxiety levels, after controlling for the cognitive status no significant differences were found between the study groups. CONCLUSIONS: In terms of anxiety and depression among Slovenian elders without or with moderate cognitive decline, home environment may be favored versus institutionalization. Visitors of EDC should probably receive more attention to their psychological wellbeing, including possible earlier transfer to EH.

The overlap of cognitive impairment in depression and schizophrenia: a comparative study.

BACKGROUND: Schizophrenia (SCH) is primarily a cognitive dysfunction. Its specific cognitive impairment profile was identified and suggestions have been made to include it in present diagnostic instruments as a special differential diagnostic criterion. However, studies indicate a substantial overlap of cognitive deficits between SCH patients and those with depression (DEP). In order to elucidate the structure of cognitive functioning in both entities, principal cognitive domains of SCH and DEP patients were assessed in the acute phase of disease. SUBJECTS AND METHODS: 44 SCH and 30 DEP patients, matched according to age, gender, education, IQ score, and duration of hospitalization were included. Neurocognitive assessments were performed in the first week of hospitalization using Digit Span test (working memory, attention), Trail Making Test (psychomotor speed, sustained attention, shifting), Rey's Complex Figure Test and Verbal Learning Test (perceptual organization, visual and verbal learning and memory). Results were evaluated according to demographically matched test norms. For statistics Student's t tests were used. RESULTS: In both study groups deficits in maintenance and shifting of attention during psychomotor tasks were found, while automatic processes (working memory, sustained attention) were preserved. In both groups memory and learning processes were impaired, in DEP however, deficits in attention shifting during cognitive tasks and delayed recall of visual material were more intense. CONCLUSIONS: In the acute phase of schizophrenia and depression similar cognitive impairment profiles can be found. Further studies are needed to assess longitudinal dynamics and possible later development of specific patterns of cognitive functioning in these patients.

Aggression and impulsivity with impulsive behaviours in patients with purgative anorexia and bulimia nervosa.

BACKGROUND: The study aimed to compare purgative anorexia and bulimia nervosa patients in regard of their level of aggression and impulsivity traits, as well as dynamics of selected impulsive behaviours over time-course of eating disorder treatment. SUBJECTS AND METHODS: 30 females with purgative anorexia nervosa, 33 females with purgative bulimia nervosa and 31 controls were included. Impulsive behaviours were assessed upon hospital admission, discharge, and three and six months after, using the internal ward questionnaire. Aggression and impulsivity traits were evaluated three months after discharge using Buss-Durkee Hostility Inventory and Barratt Impulsiveness Scale, 11th Revision. RESULTS: In all patients, the expressed impulsive behaviours were most frequent upon admission, when bingeing, striking and quarrelling were more expressed in bulimic patients. Later, patient groups did not differ regarding any impulsive behaviour. These all substantially resolved till discharge, and showed further decline at later assessments. All patients had a higher level of aggression and impulsivity traits and lower overt and higher covert aggression than controls. Patient groups had similar within group distribution of aggression and impulsivity intensity levels. Regarding individual dimensions of these traits no difference was found between them, except for the higher level of suspiciousness in anorectic individuals. CONCLUSIONS: Purgative anorectic and bulimic patients show similar dynamics of impulsive behaviours which substantially decline over time-course of eating disorder treatment. They both present similarly heightened levels of aggression and impulsivity traits, with some minor differences regarding their individual dimensions, possibly reflecting higher overt aggression in bulimic and higher covert aggression in anorectic patients.

Effect of management of patients with Anorexia and Bulimia nervosa on symptoms and impulsive behavior.

The aim of the study was to provide further and up to date information on the evaluation of the management of Anorexia and Bulimia nervosa at the Eating Disorders Unit (EDU) of the Ljubljana Psychiatric Clinic, based upon detailed assessment of the eating disorders specific and non specific symptoms of impulsive behaviors, highly correlated with these entities. 34 female patients with anorexia (restrictive or purgative type) and 38 female patients with Bulimia nervosa (purgative or non-purgative type) undergoing hospital treatment at the EDU were evaluated upon admission, as well as upon discharge and three and six months after discharge, using the Eating Disorder Questionnaire. Upon discharge a marked decrease in the overall symptoms was noted. The differences in symptoms incidences between the two groups were significantly specific for the individual form of eating disorder, especially upon admission, and were more pronounced in anorexia group. In later measurements, performed during the period of three and six months after discharge, a mild trend of increase in the disorder specific symptoms was detected in both groups, but was not statistically significant. In addition to binging on food, striking, quarreling and spending sprees are characteristics of patients with eating disorders, which in particular apply to the Bulimia nervosa group. Apart from the disorder specific symptoms, impulsive behavior was also reduced during study period, while the difference in its occurrence between the two groups gradually became non-significant. The management of patients with eating disorders at the EDU was successful in both groups, confirmed by an intense reduction of the disorder specific symptoms, impulsive behavior and increased stability recorded three and six months after discharge. The study strongly suggests that the effect of treatment regime for eating disorders can be predicted by careful assessment of the relevant symptoms and impulsive behavioral patterns.

Stress, coping and social support in three groups of university students.

BACKGROUND: The paper presents the findings of our study researching the differences in strategies for coping with stress, social support, hassles and uplifts of sport, medical and psychology students at the University of Ljubljana, Slovenia. SUBJECTS AND METHODS: A random sample of 237 Slovene undergraduate university students was studied. The three groups were chosen among students of medicine, sport and psychology. RESULTS: It was found that there were no significant differences in strategies for coping with stress between the three groups of students. Significant differences between the groups were found in the number of uplifts and hassles, but not in the mean of both variables. Sport students had less social support compared with the other two groups of students, but the difference between actual and ideal social support is not significant. DISCUSSION: The results were interpreted according to our hypothesis and compared with findings of research in students' stress. CONCLUSION: Some suggestions for further research are given on the basis of the present research.

CYP 2D6 polymorphism and antipsychotic therapy.

One of the most challenging problems in clinical psychiatry are inter-individual differences in clinical response to antipsychotic treatment. Several studies were investigating the impact of the polymorphic cytochrome P450 2D6 gene (CYP 2D6) on the psychopathological and extrapyramidal symptoms, but the results were conflicting. There is a lack of clinical studies of the impact of CYP2D6 polymorphism on therapeutic efficacy, especially in the long-term treatment of schizophrenia. The aim of the presentation was to evaluate the impact of CYP2D6 genotype on psychopathological and extrapyramidal symptoms in a group of Slovenian outpatients with schizophrenia or schizoaffective disorder in stable remission, who were receiving long-term maintenance therapy.

Adult metachromatic leukodystrophy: a new mutation in the schizophrenia-like phenotype with early neurological signs.

OBJECTIVES: The adult type of metachromatic leukodystrophy can manifest itself as motor or as psycho-cognitive form, the latter is very similar to schizophrenia. We report on two sisters with adult metachromatic leukodystrophy who display symptoms of both forms. METHODS: Presented are genotype analyses and 4-year follow-up data regarding clinical manifestations as well as neurocognitive and neuroimaging results for two adult sisters with metachromatic leukodystrophy. RESULTS: Whereas the younger sister developed disorganized schizophrenia-like symptoms, the other exhibited schizophrenia-like, negative symptoms. In both sisters, neurological signs were already present at the onset of the disease and progression towards dementia was documented within 1-2 years. In peripheral leukocytes, the activity of arylsulphatase A was reduced to 2 and 5% of the mean normal activity in both women. Genotype analysis revealed compound heterozygosity for a known severe splice site mutation, (c.459+1G>A) together with two known polymorphisms, [(c.937G>T), (p.Trp193Asp)] and [(c.1530C>G), (p.Thr391Ser)], and a novel missense mutation, (c.1194C>T). The latter results in the exchange of a conserved polar amino acid, threonine 279, to hydrophobic isoleucine (Thr279Ileu), which could not be found among >100 control alleles. A family analysis identified T279I as the paternal allele, whereas (c.459+1G>A) as well as the two polymorphisms were inherited from the mother. This is consistent with a disease-causing effect of the novel mutation. CONCLUSIONS: The novel mutation, T279I detected in our patients, correlates with a specific phenotype with schizophrenia-like symptoms, neurological signs and cognitive impairment early in the course of the disease and a relatively fast progression towards dementia. This is in contrast to previous reports on adult metachromatic leukodystrophy patients with the psycho-cognitive phenotype who did not show any neurological signs for decades, however, most of these patients were heterozygous for another specific missense mutation, I179S.

Polymorphisms in dopamine receptor DRD1 and DRD2 genes and psychopathological and extrapyramidal symptoms in patients on long-term antipsychotic treatment.

DRD(1) and DRD(2) receptor gene variants have been associated with clinical aspects of schizophrenia; however only specific features were analyzed in different samples. To assess the complex interaction between genetic and clinical factors, we studied the possible cross-interactions between DRD1 and DRD2 dopamine receptor gene polymorphisms, symptomatology of schizophrenia and schizoaffective disorders, and the occurrence of treatment induced side effects taking into consideration possible clinical confounding variables. One hundred thirty one outpatients in stable remission meeting the DSMIV criteria for schizophrenia spectrum disorders and receiving long-term maintenance therapy with haloperidol, fluphenazine, zuclopenthixole, or risperidone were genotyped for DRD1 A-48G, DRD2 Ins-141CDel, and DRD2 Ser311Cys polymorphisms. Psychopathological symptoms were assessed with the positive and negative syndrome scale for schizophrenia (PANSS). Extrapyramidal side effects were assessed with the Simpson-Angus extrapyramidal side effects scale (EPS), the Barnes Akathisia scale (BARS), and the abnormal involuntary movement scale (AIMS). Drug dosage was included as covariant because it was associated with the severity of symptomatology, akathisia, and parkinsonism. No association was observed for DRD1 and DRD2 polymorphisms and extrapyramidal side effects, or with the other clinical variables considered. Our study suggests that DRD1 and DRD2 variants are not liability factors for tardive dyskinesia.

Trait aggression and hostility in recovered alcoholics.

There is a long-recognized association between alcohol consumption and aggressive behavior. This study was designed to examine aggression in a group of socially well-adapted recovered alcoholics (RA). The question addressed was whether the treatment, together with long-term abstinence from alcohol, could reduce aggression and hostility in RA. A group of male RA (n = 64), who did not meet the DSM-IV criteria for any psychiatric or personality disorder, were recruited to the study from aftercare groups. According to data from their group therapists, they were reliably abstinent for at least 3 years and socially well adapted. The study participants representing the control group (n = 69), diagnosed as being 'reliable nonalcoholics' (NA) by the Munich Alcoholism Test, were recruited from general practice. Data were derived from an in-house questionnaire on general characteristics of both groups, and aggressive and hostility traits were assessed using the Buss-Durkee Hostility Inventory (BDHI). The univariate and multivariate between-groups design was used for data analysis. Taking into account the BDHI dimensions of aggression and hostility, the difference between RA and NA groups was statistically significant [Wilks' lambda (8, 125) = 0.769; p = 0.00004]. There were statistically significant differences in the BDHI scales for indirect aggression, irritability, negativism, suspicion, resentment, and guilt. Both RA and Na groups did not differ significantly in variables that assessed physical and verbal aggression. After a 3-year abstinence, subjects from the RA group displayed signs of hostility and covert aggression.

The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment.

Poor response to antipsychotics treatment and extrapyramidal side effects (EPS) are the most challenging problems in the treatment of schizophrenia. Several studies were investigating the impact of polymorphic cytochrome P450 2D6 gene (CYP2D6) on EPS but the results were conflicting. There are practically no clinical studies of long-term treatment of schizophrenia and CYP2D6 polymorphism. Our aim was to evaluate the influence of CYP2D6 genotype on psychopathological symptoms and the occurrence of EPS in Slovenian outpatients with schizophrenia or schizoaffective disorder in stable remission, receiving long-term maintenance antipsychotic treatment. In total 131 outpatients meeting the DSM IV criteria for schizophrenia or schizoaffective disorder and receiving maintenance therapy with haloperidol, fluphenazine, zuclopethixole or risperidone were genotyped for 14 polymorphic CYP2D6 alleles. Psychopathological symptoms were assessed with the Positive and Negative Symptom Scale for Schizophrenia (PANSS). EPS were assessed with the Simpson Angus Scale (SAS), the Barnes Akathisia Scale and the Abnormal Involuntary Movement Scale (AIMS). Six patients (4.6%) were genotyped as poor metabolizers (PMs). PMs scored significantly higher on the negative subscale for PANSS. There were no statistically significant differences between the group of PMs and the group of patients with at least one functional CYP2D6 allele in view of patient's characteristics or any of the items of the AIMS, the SAS or the Barnes Akathisia Scale. CYP2D6 genotype may not be the major factor that determines the susceptibility to antipsychotic-induced EPS in Slovenian patients in stable remission and on maintenance therapy with antipsychotics that are mainly CYP2D6 substrates. However, CYP2D6 genotype might be a factor contributing to the persistent negative symptoms of schizophrenia.