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.

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.

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.

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.

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.

Highly discrepant proportions of female and male Scandinavian and British Isles ancestry within the isolated population of the Faroe Islands.

The Faroe Islands in the North Atlantic Ocean are inhabited by a small population, whose origin is thought to date back to the Viking Age. Historical, archaeological and linguistic evidence indicates that the present population of the Faroe Islands may have a mixture of Scandinavian and British Isles ancestry. In the present study we used 122 new and 19 previously published hypervariable region I sequences of the mitochondrial control region to analyse the genetic diversity of the Faroese population and compare it with other populations in the North Atlantic region. The analyses suggested that the Faroese mtDNA pool has been affected by genetic drift, and is among the most homogenous and isolated in the North Atlantic region. This will have implications for attempts to locate genes for complex disorders. To obtain estimates of Scandinavian vs British Isles ancestry proportions, we applied a frequency-based admixture approach taking private haplotypes into account by the use of phylogenetic information. While previous studies have suggested an excess of Scandinavian ancestry among the male settlers of the Faroe Islands, the current study indicates an excess of British Isles ancestry among the female settlers of the Faroe Islands. Compared to other admixed populations of the North Atlantic region, the population of the Faroe Islands appears to have the highest level of asymmetry in Scandinavian vs British Isles ancestry proportions among female and male settlers of the archipelago.

Association between the CCR5 32-bp deletion allele and late onset of schizophrenia.

OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission to a psychiatric hospital department served as a measure of disease onset. RESULTS: Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher age at first admission. After age at first admission was analyzed as a continuous variable, it was dichotomized using 40 years as the cutoff. With this approach the authors found that genotype distributions of patients with age at first admission above the cutoff (possible cases of late-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without affecting the disease susceptibility.

Analysis of coding-polymorphisms in NOTCH-related genes reveals NUMBL poly-glutamine repeat to be associated with schizophrenia in Brazilian and Danish subjects.

Abnormality in neurodevelopment is one of the most robust hypotheses on the etiology of schizophrenia and has found substantial support from brain imaging and genetic studies. Neurodevelopmental processes involve several signaling pathways, including the Notch, but little is known at present regarding their possible involvement in schizophrenia. In the present study we investigated the link of non-synonymous variants of five genes of the Notch pathway (NOTCH2, NOTCH3, JAGGED2, ASCL1 and NUMBL) to schizophrenia in a group of 200 Brazilian patients and 200-paired controls. Also, we replicated the association of the NUMBL variant, our most promising finding, in an unrelated set of 684 Danish patients and controls. When the Brazilian and Danish cohorts were merged, a total of 1084 subjects, we found the allele 18 CAG of NUMBL (p=0.003, x2=8.88, OR=1.30, 95% CI 1.09-1.56) as well as the 18/18 CAG genotype (p=0.002, x2=9.46, OR=1.46, 95% CI 1.15-1.87) to be associated with schizophrenia. The consistency of this finding in two independent and unrelated populations reinforces the veracity of this association.

No significant association of the 5' end of neuregulin 1 and schizophrenia in a large Danish sample.

Neuregulin 1 has been implicated as a susceptibility gene in schizophrenia. Several research groups have reported association with the 5' end of the gene although no causative variant has been reported. We have investigated whether there is association with the 5' end of the gene in Danish schizophrenia patients. We found that the at-risk haplotype initially reported in the Icelandic population was not found in significant excess (or = 1.4, p = 0.12). The haplotype structure in the Danish sample was similar to that of other reported in other Caucasian populations and highly different from that of Chinese.