Prosody and schizophrenia. Objective acoustic measurements of monotonous and flat intonation in young Danish people with a schizophrenia diagnosis. A pilot study.

PURPOSE: Patients with schizophrenia have a flat and monotonous intonation. The purpose of the study was to find the variables of flat speech that differed in patients from those in healthy controls in Danish. MATERIALS AND METHODS: We compared drug-naïve schizophrenic patients 5 men, 13 women and 18 controls, aged 18-35 years, which had all grown up in Copenhagen speaking modern Danish standard (rigsdansk). We used two different tasks that lay different demands on the speaker to elicit spontaneous speech: a retelling of a film clip and telling a story from pictures in a book. A linguist used the computer program Praat to extract the phonetic linguistic parameters. RESULTS: We found different results for the two elicitation tasks (Task 1: a retelling of a film clip, task 2: telling a story from pictures in a book). There was higher intensity variation in task one in controls and higher pitch variation in task two in controls. We found a difference in intensity with higher intensity variation in the stresses in the controls in task one and fewer syllables between each stress in the controls. We also found higher F1 variation in task one and two in the patient group and higher F2 variation in the control group in both tasks. CONCLUSIONS: The results varied between patients and controls, but the demands also made a difference. Further research is needed to elucidate the possibilities of acoustic measures in diagnostics or linguistic treatment related to schizophrenia.

The Amager Project IV: suicidal behavior and aftercare: real world data (RWD) from a prospective observational project.

BACKGROUND: In an RCT study, OPAC (outreach, problem solving, adherence, continuity) approach to aftercare after suicide attempts had an effect. The present study used the OPAC method in a clinical setting on Amager Copenhagen to patients after suicide attempt (Group 1) and patients with suicide ideation (Group 2) in a real-world data (RWD) study. AIM: To study whether the OPAC method could provide real world evidence (RWE) for results from the RCT study and long-time prospects. METHOD: This RWD study included 506 patients and followed them for 5 years. Kaplan-Meyer showed 5 years results. Risk factors for 5 years were calculated. RESULTS: 206 males (mean age 37.9) and 300 females (mean age 35.2) participated. A decline in survival accelerated after 3 years. After a 2-year follow-up, Group 1 had an attempted suicide rate of 12,2% and Group 2 5,4%. After 5 years the numbers were 18% and 10%. There were 3 completed suicides. Risk factors were: earlier suicide attempts, one or both parents or they themselves were alcohol/drug abusers, and a poor social network. Group 1 showed the same result as the intervention group in our earlier RCT study. Group 2 did better. Both groups did better than the control group from our RCT study. CONCLUSION: The OPAC effect was translated into the daily clinic. Risk factors were previous suicide attempts, alcohol and drug abuse and poor social networks. More specific therapy is needed for some patients to prevent relapse. Focus on enhancing a sense of belongingness and/or treating substance abuse.

Hope pictured in drawings by patients newly diagnosed with advanced cancer.

BACKGROUND: Hope is an integral part of a dying person's needs and an important phenomenon that has not been satisfactorily explored. The tension between hope for a cure and the reality of being terminally ill is a paradox, which in the context of palliative cancer care, nurses and health care professionals must take into consideration. OBJECTIVE: The purpose of this study was to elucidate the phenomenon of hope and to investigate the lived experiences of hope among newly diagnosed patients with advanced cancer. METHOD: The study used a phenomenological-visual method where drawings and post-drawing interviews were used. The participants were six patients who recently had been offered specialised palliative care treatment. They were five women and one man with different cancer diagnoses and between 30 and 82 years of age (median 65 years). The data consisted of six drawings and individual post-drawing interviews with the participants. The study was reported using the COREQ checklist. RESULTS: The study revealed one main concern 'Being in hope' and hope appeared in four different dimensions; internal, external, relational and transcendental. Hopelessness was present at all times. CONCLUSION: Hope pictured in drawings was expressed through colour, shape, lines, symbols and metaphors, and hope incorporated internal, external, relational and transcendental aspects. Hope was constantly fighting against hopelessness and hope integrated with past, present and future. RELEVANCE TO CLINICAL PRACTICE: Drawings, as well as other visual representations, are suitable tools when trying to understand an ineffable phenomenon such as hope experienced by people newly diagnosed with cancer.

Variability between psychiatrists on domains of the mental status examination.

Background: The Mental Status Examination (MSE) is a core element of the psychiatric assessment. To investigate the current level of psychopathological knowledge, the reliability of the MSE can be used as a proxy as it is based on descriptive psychopathology.Methods: Three psychiatrists wrote their MSE based on 27 video recordings. The variability and inter-rater agreement were evaluated using an agreement scale from 1 to 5, made by several psychiatrists. The agreement was analysed by mean values, stratified mean values and Cronbach's alpha.Results: The total agreement had a Cronbach's alpha of 0.87 (p < 0.000). The grand mean of variability was 4.1 (SD = 0.8). The domains with the highest variability were Attitude (Est. = 3.5, SD = 0.9), Affect (Est. = 3.8, SD = 0.8) and Motor activity (3.7, SD = 0.9). The videos with the highest variability were #2 (Est.=3.3, SD = 1,1) and #21 (Est. = 3.6, SD = 1.1).Conclusions: The overall reliability of the MSE based on Cronbach's alpha was good and the mean variability was low. This indicates that the MSE performed by three psychiatrists is reliable. The main reason for variability was due to individual interpretation and discrepancies in literature. The literature-driven variability could possibly be reduced by approaching national tradition to international practise. The individual variability maybe reduced by increasing the opportunities for clinical group rating.

The treatment in the Danish suicide prevention clinics: a clinician perspective.

Background: Few qualitative studies have focused on clinicians' perspectives regarding treatment of suicidal people. Despite limited evidence and imperfect risk-assessment tools, the psychosocial therapy at the Danish suicide prevention clinics has been linked to reductions in numbers of repeated self-harm, deaths by suicide, and other causes. This merits an investigation into how clinicians describe their practice.Methods: Using a qualitative design, 10 semi-structured interviews were conducted and analyzed to describe the psychosocial therapy.Results: The practices that the therapists described could be categorized along four dichotomous continuums. These illustrated dilemmas encountered during treatment of suicidal patients: 1) intuitive vs. specific risk assessment, 2) meaningful vs. formal, 3) patient-oriented vs. therapist-oriented and 4) direct vs. indirect approach to suicide prevention.Conclusions: Treatment in the Danish Suicide Prevention Clinics is characterized by methodological flexibility and diversity and with an emphasis on a patient-oriented approach. Furthermore, clinicians balance knowledge available by switching between a direct and an indirect approach according to the perceived suicide risk. If suicide risk was perceived as high, they would administer a direct approach and if low, an indirect approach. Finally, there seems to be differences as to how effective therapeutic methodologies work in the practice of suicide prevention.

E-Library of Authentic Patient Videos Improves Medical Students' Mental Status Examination.

OBJECTIVE: During psychiatric rotation, clerkship students must learn the clinical skill of recording an accurate Mental Status Examination (MSE). The authors built a video e-library consisting of 23 authentic patient videos that were accessible on a secure website during the rotation period, aimed at assisting students' acquisition of MSE skills. METHODS: The authors conducted a prospective case comparison study investigating the impact of the video e-library as "add-on" intervention, on acquisition of MSE skills, as measured by a test consisting of three videos with adjoining forced choice questionnaires. Eighty-five clerkship students had instructions and access to the video e-library whereas 82 did not. A group of clinicians, unfamiliar with the video e-library, was also subjected to the new MSE skills test and they served as a reference group. Outcome was defined as scores of MSE skills measured by the purpose made MSE skills test and entailed evaluation questions on the students' use of the e-library. RESULTS: The MSE skill test score differed between the three groups, and the clinicians scored higher than both student groups (clinicians mean score (M) 12.6; p < 0.001). However, the students with video access scored higher compared to students without access (M 10.7 versus M 9.9, p = 0.04). The e-library was appreciated by the students as helpful (83.6%) and they used it not only for practicing the MSE but also for observation of interviewing techniques. CONCLUSION: The e-library with video vignettes of authentic patients strengthens MSE skills as "add-on" to the psychiatric rotation, and evaluations by the students were positive.

Preventing repetition of attempted suicide-III. The Amager Project, 5-year follow-up of a randomized controlled trial.

BACKGROUND: The Amager Project was initiated as a quasi-experimental study in 2005, based on an active outreach suicide preventive intervention inspired by the Norwegian Baerum Model. A 1-year follow-up study was conducted as a randomized controlled trial showing that this kind of active outreach to suicide attempters had a significant preventive effect on the prevalence of suicide attempts and significantly reduced the number of patients repeating a suicide attempt. AIMS: In this 5-year RCT follow-up the aim was to investigate the sustainability of the suicide preventive effect shown in a 1-year follow-up study. METHOD: One hundred and thirty-three suicide attempters were included at this 5-year follow-up RCT study at Copenhagen University Hospital, Amager, and randomized to a rapid outreach suicide preventive intervention (OPAC) or TAU. RESULTS: Offering OPAC intervention to patients after a suicide attempt has a significant preventive effect on the total of suicide attempts and significantly reduces the number of patients repeating a suicide attempt. The suicide preventive effect lasts up to 265 weeks. After 3-4 years the effect on the number of patients repeating a suicide attempt is no longer sustainable, while the effect on the number of repetitive events remains significant. CONCLUSION: This study emphasizes the importance of a rapid and active outreach intervention and points out that the effect on the number of patients repeating a suicide attempt wears off and is no longer sustainable after 3-4 years, suggesting the need for a follow-up intervention.

Whole-exome sequencing implicates DGKH as a risk gene for panic disorder in the Faroese population.

The demographic history of the isolated population of the Faroe Islands may have induced enrichment of variants rarely seen in outbred European populations, including enrichment of risk variants for panic disorder (PD). PD is a common mental disorder, characterized by recurring and unprovoked panic attacks, and genetic factors have been estimated to explain around 40% of the risk. In this study the potential enrichment of PD risk variants was explored based on whole-exome sequencing of 54 patients with PD and 211 control individuals from the Faroese population. No genome-wide significant associations were found, however several single variants and genes showed strong association with PD, where DGKH was found to be the strongest PD associated gene. Interestingly DGKH has previously demonstrated genome-wide significant association with bipolar disorder as well as evidence of association to other mental disorders. Additionally, we found an enrichment of PD risk variants in the Faroese population; variants with otherwise low frequency in more outbreed European populations. © 2016 Wiley Periodicals, Inc.

Efforts to Prevent Railway Suicides in Denmark.

Background: Reviews of camera surveillance systems have demonstrated ambivalent behaviors among people who die by railway suicide. Yet, only few preventive measures have been evaluated. Aims: We aimed to review incidents of suicidal behavior at a Danish railway station, install preventive measures, and monitor subsequent calls to a telephone helpline and reports of suicidal incidences. Method: Suicide incidents at Valby Station during 2012-2018 were reviewed to identify options for preventive measures. Based on these findings, signs encouraging help-seeking and other measures were implemented. Calls to the Danish helpline for suicide prevention and suicidal events at the station were subsequently monitored. Results: The review revealed locations where measures were meaningful and signs, physical barriers, and motion-sensitive lights were installed. Over the following 14 months, no suicide deaths occurred, and the signs were mentioned in 14 calls to the helpline, some of which were made by callers who were evaluated to be at high risk of suicide. Limitations: No direct link between implemented measures and observed outcomes could be established. Conclusion: Installing measures, including signs, at appropriate locations at railway platforms may encourage people in crisis to seek support.

Preventing repetition of attempted suicide--II. The Amager project, a randomized controlled trial.

Repetition after attempted suicide is high but only few effect studies have been carried out. The Baerum Model from Norway offers practical and affordable intervention for those not being offered psychiatric treatment. During a period from 2005-2007, all attempted suicide patients except those with major psychiatric diagnoses (schizophrenia, bipolar disorder, severe/psychotic depression), were offered participation. The intervention group received the OPAC programme (outreach, problem solving, adherence, continuity) and the control group received treatment as usual (TAU). The intervention period was 6 months. After this intervention period, all patients were followed passively for an extra 6 months. The design was an intent-to-treat one. The outcomes were: 1) repetition of attempted suicide or suicide, and 2) total number of suicidal acts. A total of 200 patients were offered participation, 67 refused. Of the 133 participants, 69 were randomized to the OPAC programme and 64 to the (non-intervention) control group. Four in each group dropped out after initial participation. There was a significant lower proportion who repeated a suicide attempt the intervention group (proportion 8.7%) than in the control group (proportion 21.9%) and the number of repetitive acts was also significant lower (eight repetitions in the intervention group vs. 22 in the control group). In conclusion, our findings suggest a protective effect of the OPAC programme on the proportion who repeated a suicide attempt and on the total number of repetitions during the follow-up.

The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis.

Serotonin (5-hydroxytryptamin; 5-HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5-monooxygenase; TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT, and sequence variation in intron 6 of the TPH1 gene has been associated with schizophrenia. The minor allele (A) of this polymorphism (A218C) is also more frequent in patients who have attempted suicide and individuals who died by suicide, than in healthy control individuals. In an attempt to replicate previous findings, five single nucleotide polymorphisms (SNPs) were genotyped in 837 Scandinavian schizophrenia patients and 1,473 controls. Three SNPs spanning intron 6 and 7, including the A218C and A779C polymorphisms, were associated with schizophrenia susceptibility (P = 0.019). However there were no differences in allele frequencies of these loci between affected individuals having attempted suicide at least once and patients with no history of suicide attempts (P = 0.84). A systematic literature review and meta-analysis support the A218C polymorphism as a susceptibility locus for schizophrenia (odds ratio 1.17, 95% confidence interval 1.07-1.29). Association studies on suicide attempts are however conflicting (heterogeneity index I(2) = 0.54) and do not support the A218C/A779C polymorphisms being a susceptibility locus for suicidal behavior among individuals diagnosed with a psychiatric disorder (OR = 0.96 [0.80-1.16]). We conclude that the TPH1 A218/A779 locus increases the susceptibility of schizophrenia in Caucasian and Asian populations. In addition, the data at hand suggest that the locus contributes to the liability of psychiatric disorders characterized by elevated suicidal rates, rather than affecting suicidal behavior of individuals suffering from a psychiatric disorder.

Association of MCTP2 gene variants with schizophrenia in three independent samples of Scandinavian origin (SCOPE).

The MCTP2 gene is involved in intercellular signal transduction and synapse function. We genotyped 37 tagging SNPs across the MCTP2 gene to study a possible association with schizophrenia in three independent Scandinavian samples. We report, for the first time, a possible involvement of MCTP2 as a potential novel susceptibility gene for schizophrenia.

Suicide and mental illness in parents and risk of suicide in offspring: a birth cohort study.

BACKGROUND: A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide. AIMS: To examine the risk of offspring suicide in relation to parental history of suicide and other parental risk factors. METHOD: The study population consisted of 7,177 adult offspring born 1959-1961 and their parents from the Copenhagen Perinatal Cohort. Cohort members and their parents who had committed suicide were identified in the Danish Causes of Death Registry (follow-up until December 31, 2005), while information on psychiatric hospitalisation history was obtained from the Danish Psychiatric Central Research Register. RESULTS: Forty-eight cohort members, 77 mothers and 133 fathers had committed suicide during the follow-up. Independent of parental psychiatric illness and social status, parental suicide significantly increased suicide risk in offspring (hazard ratio 4.40 with 95% CI 1.81-10.69). A stronger effect of parental suicide was observed in offspring without a history of psychiatric hospitalisation. CONCLUSION: Parental history of suicide is a risk factor for suicide in offspring, but primarily in offspring without psychiatric hospitalisation.

Core features of suicide. Gender, age, alcohol and other putative risk factors in a low-incidence population.

The aim of the study was to elucidate some supposed core features of suicide through a study of suicide in a low-incidence population. The material covered all suicides and undetermined deaths 1945-2004 in the Faroe Islands (a low-incidence population) and the study made use of all available information. Results showed that suicide rate had been low since the Second World War. However, there was an increase throughout the 1970s and 1980s. Supposed core features of suicide, such as gender, marital status, former psychiatric admittance, former suicidal behaviour, alcohol and method preference were confirmed. Others were not, such as an increasing rate with old age. In diagnostics, the role of psychiatric disorders was confirmed, but so was a substantial role of "no disorder". Increase period revealed a high proportion of cases with alcohol involved and a substantial part included males, in age groups 25-64 years, unmarried, divorced and alcohol intoxicated. The main conclusion was that a low-incidence population of suicide population confirmed some supposed core features of the suicide phenomenon. Others, related to age and psychiatric disorders, were only partially confirmed. In periods of increase, the most vulnerable were the young and middle-aged males, unmarried, divorced, and alcohol played a crucial role.

Preventing repetition of attempted suicide--I. Feasibility (acceptability, adherence, and effectiveness) of a Baerum-model like aftercare.

Repetition after attempted suicide is high with only limited research been put into effect studies. The Baerum-model from Norway offers a practical and affordable intervention. Our aim was to study the acceptability and effectiveness of a Baerum-model like intervention after attempted suicide using a quasi-experimental design. During a period in 2004, attempted suicide patients were offered follow-up care by a rapid-response outreach programme, an intervention lasting 6 months; a control group was established prospectively from a similar period in 2002. The design was an intent-to-treat analysis. The outcome was measured by: 1) participation by acceptance and adherence, 2) repetition of suicide attempt and suicide, and 3) including the number of repetitive acts in 1 year after the attempted suicide episode. Follow-up period was 1 year. Participation was 70%. There was a significant lower repetition rate in the intervention group, where the proportion of repetitive patients fell from 34% to 14%. There were also fewer suicidal acts, in total 37 acts in 58 patients in the control group and 22 acts in 93 patients for the intervention group. We have concluded that the outreach programme has a good feasibility because of high acceptability and adherence, and has an acceptable effectiveness in the follow up period of 1 year. We have therefore initiated a similar study using a randomization design in order to study efficacy.

A pilot study on high amplitude low frequency-music impulse stimulation as an add-on treatment for depression.

OBJECTIVE: High Amplitude Low Frequency-Music Impulse Stimulation (HALF-MIS) is a form of Vagus Nerve Stimulation (VNS). The aim of the study was to determine the feasibility, efficacy, and potential side effects of HALF-MIS, used as an add-on treatment for depression. METHODS: This is an open randomized controlled pilot study. Patients with depressive disorder were randomly allocated to either a HALF-MIS group with eight add-on HALF-MIS sessions (over a period of 3-4 weeks) or a control group which received treatment as usual. Seated in a specially designed chair() embedded with a transducer, their central nervous system was stimulated through the abdomen, () using music and vibration. Hamilton rating was performed. Side effects were registered. RESULTS: Eighteen patients were randomized to the add-on treatment and 20 patients to the control group. Both groups show in Hamilton Depression Rating Scale (HDRS)-17 and in HDRS-6, although the HALF-MIS group had a greater decline of symptoms. This was a significant difference in intergroup analysis (p = .011, CI 95% for the HALF-MIS group 3.0588-8.5327 and CI 95% for the control group 0.2384-3.0). The (HDRS)-6 difference was also significant (p = .020, CI 95% for the HALF-MIS group 1.5911-5.0487 and for the control group -0.297 to 1.7058). No side effects were observed. CONCLUSIONS: High Amplitude Low Frequency-Music Impulse Stimulation treatment seems to give beneficial effect as an add-on treatment for depression. HALF-MIS appears to be a safe and effective add-on treatment for depression.

The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples.

BACKGROUND: Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene- and protein expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia or at least with gender-associated aspects of the illness. RESULTS: We genotyped 185 SNPs in three independent case-control samples of Scandinavian origin (a total of 765 patients and 1274 control subjects). Variants of the mitogen-activated protein kinase 14 gene (MAPK14) and the phosphoenolpyruvate carboxykinase 1 (PCK1) and fructose-1,6-biphosphatase (FBP1) were nominal significantly associated with schizophrenia, and several haplotypes within enolase 2 gene (ENO2) consist of the same SNP allele having elevated risk of schizophrenia. Importantly, we find no evidence of stratification due to nationality or gender. CONCLUSION: Several gene variants in the Glycolysis were associated with schizophrenia in three independent samples. However, the findings are weak and not resistant to correction for multiple testing, which may indicate that they are either spurious or may relate to a particular subtype or aspect of the illness.

Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder: an association study.

Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single gene polymorphisms (SNPs; C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences. The present Scandinavian results do not verify previous associations between the putative functional MTHFR gene polymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism and schizophrenia. Additional studies are warranted to shed further light on these relationships.

Aspects of Additional Psychiatric Disorders in Severe Depression/Melancholia: A Comparison between Suicides and Controls and General Pattern.

OBJECTIVE: Additional and comorbid diagnoses are common among suicide victims with major depressive disorder (MDD) and have been shown to increase the suicide risk. The aim of the present study was first, to investigate whether patients with severe depression/melancholia who had died by suicide showed more additional psychiatric disorders than a matched control group. Second, general rates of comorbid and additional diagnoses in the total group of patients were estimated and compared with literature on MDD. METHOD: A blind record evaluation was performed on 100 suicide victims with severe depression/melancholia (MDD with melancholic and/or psychotic features: MDD-M/P) and matched controls admitted to the Department of Psychiatry, Lund, Sweden between 1956 and 1969 and monitored to 2010. Diagnoses in addition to severe depression were noted. RESULTS: Less than half of both the suicides and controls had just one psychiatric disorder (47% in the suicide and 46% in the control group). The average number of diagnoses was 1.80 and 1.82, respectively. Additional diagnoses were not related to an increased suicide risk. Anxiety was the most common diagnosis. Occurrence of suspected schizophrenia/schizotypal or additional obsessive-compulsive symptoms were more common than expected, but alcohol use disorders did not appear very frequent. CONCLUSIONS: The known increased risk of suicide in MDD with comorbid/additional diagnoses does not seem to apply to persons with MDD-M/P (major depressive disorder-depression/Melancholia). Some diagnoses, such as schizophrenia/schizotypal disorders, were more frequent than expected, which is discussed, and a genetic overlap with MDD-M/P is proposed.