Lipid metabolism and functional somatic disorders in the general population. The DanFunD study.

OBJECTIVES: Earlier studies on the association between plasma lipid profiles and functional somatic disorders (FSD) are mainly small case control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study was to investigate the associations between various FSDs and plasma lipid profiles (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) in a large, unselected population. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Somatic Disorders (DanFunD) conducted in 2011-2015 in 10 municipalities in the western part of greater Copenhagen, Denmark. PARTICIPANTS: A total of 8,608 men and women aged 18-76 years were included in the analyses. Various delimitations of FSD such as chronic fatigue, chronic widespread pain, irritable bowel, and bodily distress syndrome were measured using validated self-administrated questionnaires. Lipid parameters were measured from fasting plasma samples using colorimetric slide methods with Vitros 4600/5600 Ortho Clinical Diagnostics. OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between plasma lipids and the various delimitations of FSD. Associations are presented by OR (95% CI) and shown in boxplots. RESULTS: We found a positive association between bodily distress syndrome and triglycerides and non-HDL cholesterol and a negative association with HDL-cholesterol, but no consistent association with total cholesterol. A similar pattern was observed for persons with chronic fatigue, and to some degree for persons with chronic widespread pain, whereas persons with irritable bowel did not show a clear association with the lipid profiles. CONCLUSION: This is the first major study on plasma lipid profiles and FSD indicating an association between some delimitations of FSD and an unfavorable lipid profile. Due to the cross-sectional design, it cannot be determined whether the findings are consequences or determinants of FSD. Further studies-preferable prospective studies-are needed.

Anomalies of Imagination, Self-Disorders, and Schizophrenia Spectrum Psychopathology: A Network Analysis.

BACKGROUND: Anomalies of imagination encompass disturbances of the basic experiential structure of fantasies and imagery that can be explored in a semi-structured way with the Examination of Anomalous Fantasy and Imagination (EAFI). We aimed (1) to examine the distribution of anomalies of imagination among different diagnostic groups and a group of healthy controls, and (2) to examine their relation with disorders of basic self, perceptual disturbances and canonical state psychopathology of the schizophrenia-spectrum (positive, negative and general symptoms). METHODS: The 81 participants included patients with schizophrenia or other non-affective psychosis (N = 32), schizotypal personality disorder (N = 15) or other mental illness (N = 16) and healthy controls (N = 18). The assessment encompassed EAFI, Examination of Anomalous Self-Experience (EASE), parts of Bonn Scale for the Assessment of Basic Symptoms (BSABS) and Positive and Negative Syndrome Scale (PANSS). For network analysis, the associations of EAFI with the other psychopathological variables were tested by Pearson's correlation coefficient and graphically represented using multidimensional clustering. Comparisons between correlations in the network were tested with Steiger's test. RESULTS: Anomalies of imagination aggregated significantly in schizophrenia-spectrum disorders compared to other mental illness and healthy controls with no difference between schizophrenia and schizotypal disorder. In the network analysis, anomalies of imagination were closely inter-connected with self-disorders. Although, the anomalies of imagination correlated moderately with perceptual disturbance and positive, negative and general state symptomatology, these dimensions aggregated separately and relatively distant in the network. CONCLUSIONS: The results support that anomalies of imagination are highly characteristic of schizophrenia-spectrum disorders and closely related to self-disorders.

UGT polymorphisms and lamotrigine clearance during pregnancy.

OBJECTIVE: To evaluate the impact of maternal UGT1A4 and UGT2B7 genetic polymorphisms and sex of foetus on gestation-induced changes in lamotrigine (LTG) clearance during pregnancy and post-partum (PP). METHODS: Single nucleotide polymorphisms UGT1A4 142T > G, L48V (*3), UGT1A4 70C > A, P24T (*2) and UGT2B7 802C > T, H268Y (*2) were determined in 40 women (47 pregnancies) with epilepsy treated with LTG. Retrospectively collected data included LTG dosage and LTG plasma levels before pregnancy (T0), and LTG dosage and LTG plasma level changes in the first (T1), second (T2) and third trimester (T3), and post-partum (PP) as well as the sex of the foetus. RESULTS: Reductions in the LTG concentration-to-dose ratio (C/D ratio) during pregnancy were seen in all genotype panels and varied between -53% and -74% in T3. Genetic polymorphism of UGT1A4 T142G (*3) and UGT2B7 C802T (*2) had the most pronounced influence on LTG clearance. Women with UGT1A4 142TG had a lower decrease in the C/D ratio in T3 than those with wild type: -53% (95%CI: -68% to -39%) versus -65% (95%CI: -69% to -60%) (p = 0.04). In homozygous carriers of UGT2B7 802TT the LTG C/D ratio was reduced significantly already in T1 (p = 0.015) as well as in T3 compared to the heterozygous carriers (802CT) (p = 0.04). Multiple regression analysis demonstrated that women who carried a female foetus had a significantly higher reductions in the LTG C/D ratio from T0 to the end of pregnancy than those with a male foetus (p = 0.003). In the univariate analysis the reductions in LTG C/D ratio were -64% in T2 (95%CI: -69% to -59%) and -67% in T3 (95%CI: -71% to -63%) in women who expected a female child compared to whose with a male child -58% in T2 (p = 0.002, 95%CI: -67% to -48%) and -57% in T3 (p < 0.001, 95%CI: -65% to -48%). CONCLUSION: Genetic polymorphism in UGT1A4 and UGT2B7 may play a modest role in LTG clearance changes during pregnancy. In addition, our study indicates that the sex of the foetus influenced significantly the change in LTG clearance.

Timing of surgical site infection and pulmonary complications after laparotomy.

BACKGROUND: Surgical site infection (SSI) and other postoperative complications are associated with high costs, morbidity, secondary surgery, and mortality. Many studies have identified factors that may prevent SSI and pulmonary complications, but it is important to know when they in fact occur. The aim of this study was to investigate the diagnostic timing of surgical site infections and pulmonary complications after laparotomy. MATERIAL AND METHODS: This is a secondary analysis of the PROXI trial which was a randomized clinical trial conducted in 1400 patients undergoing elective or emergent laparotomy. Patients were randomly allocated to either 80% or 30% perioperative inspiratory oxygen fraction. RESULTS: SSI or pulmonary complications were diagnosed in 24.2% (95% CI: 22.0%-26.5%) of the patients at a median of 9 days [IQR: 5-15] after surgery. Most common was surgical site infection (19.6%); median time 10 days after surgery [IQR: 7-18]. The corresponding figures for anastomotic leakage was 5.7%, 8 days [IQR: 6-10]; pneumonia 3.5%, 5 days [IQR: 3-9]; and respiratory failure 2.3%, 3 days [IQR: 1-8]. The oxygen allocation was not significantly related to time of diagnosis for postoperative surgical site infections or pulmonary complications. CONCLUSION: A high percentage of patients undergoing laparotomy develop a postoperative complication. This study adds new knowledge by identifying time intervals within which medical professionals should be aware of surgical site infections and pulmonary complications in order to initiate appropriate treatment of the patients.

Self-disorders in schizophrenia-spectrum disorders: a 5-year follow-up study.

Self-disorders have been hypothesized to be an underlying and trait-like core feature of schizophrenia-spectrum disorders and a certain degree of temporal stability of self-disorders would therefore be expected. The aim of the study was to examine the persistence of self-disorders measured by the Examination of Anomalous Self Experiences over a time span of 5 years. 48 patients with schizophrenia-spectrum disorders were thoroughly assessed for psychopathology at baseline and 5 years later. Self-disorders were assessed by the Examination of Anomalous Self Experiences. The level of self-disorders was same at the two occasions for the full Examination of Anomalous Self Disorders and for four out of the five domains. For one domain, the level of self-disorders increased slightly from baseline to follow-up. The correlations between baseline and follow-up were moderate. 9 out of the 13 most-frequently rated items at baseline showed equal frequencies at follow-up. The baseline level of self-disorders predicted global symptomatic, but not functional outcome. Self-disorders measured by the Examination of Anomalous Self Experiences show a high level of temporal persistence over 5 years and predict symptomatic outcome.

Triage in psychiatric emergency services in Copenhagen: results from a descriptive 1-year evaluation study.

Inspired by the Australasian triage system, a regional psychiatric triage system was introduced in the psychiatric emergency units (PEUs) in Copenhagen in 2011. Our aim of the study is to determine the characteristics of the patient according to the defined triage criteria and check if this is in accordance with recommendations. A random 10% data sample was obtained throughout 2012 in three PEUs of Copenhagen. Triage category, demographic, social and clinically relevant variables were collected. A total of 929 contacts were registered. We found significant associations between triage category and several clinical parameters. Time of visit was correlated to diagnoses. The results indicate that use of the new triage system in emergency psychiatry has facilitated urgency categorization, reduced waiting time, and optimized clinical decisions. These goals are important clinical implications of the service in PEUs. The need for PEUs out-of-daytime (when all Community Mental Health Centers are closed) has also been demonstrated.

Variability in clinical diagnoses during the ICD-8 and ICD-10 era.

AIMS: To explore whether the diagnostic homogeneity in a daily, routine clinical activity changed visibly over two historical periods (the ICD-8 and the ICD-10 era) across and within five psychiatric in-patient clinics. METHODS: In this register study, we analyzed the discharge diagnoses from five university-affiliated departments of psychiatry in Denmark in two time periods: 1980-1985 (ICD-8) and 2001-2010 (ICD-10). RESULTS: The synchronic inter-departmental diagnostic differences did not decrease in the ICD-10 era compared with ICD-8 era. Nor did the diachronic stability within each department become more homogeneous. CONCLUSION: The diagnostic variability reflected by the diagnostic differences between the departments and by the diagnostic homogeneity within each department remained similar in the two historical periods with no evidence of an increased homogeneity of diagnostic habits after the introduction of the ICD-10. LIMITATIONS: There is a myriad of variables that affects the diagnostic variability over time that we were not able to control.

The use of COPD maintenance therapy following spirometry in General Practice.

BACKGROUND: Several studies have shown that the use of pulmonary medication is widespread and often initiated without initial spirometry. Early detection of chronic obstructive pulmonary disease (COPD) by spirometry in General Practice is essential for an early and correct implementation of medical treatment. AIM: The aim of the present study was to evaluate the use of regular therapy following diagnostic spirometry for COPD in General Practice from February 2008 to February 2009. METHOD: Spirometry data and results were linked through Statistics Denmark with information from the Register of Medicinal Product Statistics using the unique personal identification code. Data were analysed to evaluate the impact of screening on use of regular COPD therapy. Primary outcome was initiation of regular therapy following COPD diagnosis with spirometry. RESULTS: In a population of 3,376 individuals at risk, 1,458 underwent spirometric assessment with 631 being diagnosed with COPD; 110 of those received regular therapy before assessment with this figure increasing to 161 after spirometry. Of 827 participants not receiving a COPD diagnosis, 36 received regular therapy prior to assessment and 42 received regular therapy after spirometry despite no established COPD diagnosis. CONCLUSION: There is a significant chance of receiving regular therapy after being diagnosed with COPD. However, a large proportion of subjects diagnosed with COPD did not receive regular therapy following diagnosis. Efforts should be made to ensure correct diagnosis and correct medical treatment according to guidelines in individuals with COPD.

Psychiatric emergency services in Copenhagen 2012: A 27-year psychiatric and demographic follow-up study.

BACKGROUND: Since the first publication of the psychiatric emergency units (PEUs) in Copenhagen 1985, outpatient facilities have undergone considerable changes. Our aim is to examine how these changes have influenced the activities in the PEUs in the same catchment area. METHODS: We conducted a follow-up study to describe this development in the past 27 years by comparing 1985 variables with same measures in 2012. A random sample of all visits every 10 days in 2012 to three PEUs in Copenhagen were registered and compared with data collected, using the same study design in 1985. MAIN RESULTS: The number of visits has decreased significantly from 367 visits/year/10,000 inhabitants in 1985 to 225 in 2012. Apart from a considerable number (15.6%) of visitors with non-Danish background, the demographic variables have not changed significantly since 1985. Compared with 1985, the diagnostic distribution among the 2012 visitors shows an increased frequency of affective disorders and neurotic and stress disorders, while schizophrenia spectrum and personality disorders show almost the same frequencies in 1985 and 2012. Rates of alcoholism and organic mental disorders show a minor reduction during the 27-year follow-up period. In 1985, 20.7% of the visits ended up without any referrals, compared with 4.8% in 2012. The rate of acute admissions into a psychiatric ward was 60.8% in 2012 compared with 35.65% in 1985. CONCLUSION: The extension of the psychiatric outpatients' facilities since 1985 has reduced the number of visits in the PEUs considerably. The results have shown a change of diagnostic distribution and more severe conditions requiring acute admissions for emergency treatment. Close collaboration with the patients' families, GPs, social authorities and specialized psychiatric outpatient clinics is emphasized.

Exploring rationality in schizophrenia.

BACKGROUND: Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. AIMS: To explore syllogism-based rationality in schizophrenia. METHOD: Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 29 syllogisms that varied in presentation content (ordinary v. unusual) and validity (valid v. invalid). Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence and neuropsychological test performance. RESULTS: Controls outperformed patients on all syllogism types, but the difference between the two groups was only significant for valid syllogisms presented with unusual content. However, when adjusting for intelligence and neuropsychological test performance, all group differences became non-significant. CONCLUSIONS: When taking intelligence and neuropsychological performance into account, patients with schizophrenia and controls perform similarly on syllogism tests of rationality. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Body water distribution and risk of cardiovascular morbidity and mortality in a healthy population: a prospective cohort study.

BACKGROUND: Early alterations in the cardiovascular structure and function may change normal body water distribution. The resulting fluid shifts may thus serve as an early marker for cardiovascular disease. However, studies examining this in healthy populations are absent. OBJECTIVE: This study examined the association between the proportion of total body water that is extracellular water and subsequent development of non-fatal or fatal cardiovascular disease in a healthy population. METHOD: Bioelectrical impedance spectroscopy is an easy-to-use, non-invasive and relatively inexpensive technique to evaluate changes in body water distribution. A random subset (n = 2120) of Danes aged 41-71 years, examined in 1993-1994 for body water distribution by bioelectrical impedance spectroscopy was included. Cox-proportional hazard models and linear splines were performed. The ratio between resistance estimates from an infinite-frequency and from no-frequency (R∞/R0) was used as a surrogate measure of ratio between extracellular water and total body water. The outcome was 13.5 years of follow-up for cardiovascular morbidity and mortality. RESULTS: A high proportion of total body water that is extracellular water was associated with increased risk of incident cardiovascular disease. A threshold effect was evident, with greatly increased risk of cardiovascular morbidity and mortality above R∞/R0 = 0.68. Below the threshold there seemed to be no additional benefit of having a low ratio. CONCLUSION: Our findings suggest that non-clinically evident oedema, measured as an increased proportion of total body water that is extracellular, above a threshold of 0.68, may be an early marker of pre-clinical cardiovascular disease. This simple, safe, cheap and easily obtainable measure of R∞/R0 from bioelectrical impedance may help the early identification of these otherwise clinically healthy individuals who are at an increased risk of future cardiovascular disease. However, more studies are needed before it can be concluded that bioelectrical impedance spectroscopy improves clinical risk prediction.

The Mediterranean diet in relation to mortality and CVD: a Danish cohort study.

The aim of the present study was to determine whether the Mediterranean Diet Score (MDS) is associated with reduced total mortality, cardiovascular incidence and mortality in a Danish population. Analyses were performed on 1849 men and women sampled during the 1982-83 Danish MONICA (MONItoring trends and determinants of Cardiovascular disease) population study, whose diet was assessed by means of a validated 7 d food record. The adherence to a Mediterranean dietary pattern was calculated by three different scores: one based on a classification excluding ingredients from mixed dishes and recipes (score 1); another based on a classification including ingredients (score 2); the last one based on a variant of the latter including wine instead of alcohol intake (score 3). The association between these scores and, respectively, total mortality, cardiovascular incidence and mortality was tested by a Cox proportional hazards model adjusted for several potential confounders of the association. Generally, all three scores were inversely associated with the endpoints, although associations with score 1 did not reach statistical significance. Score 2 was inversely associated with total mortality (hazard ratio 0·94; 95 % CI 0·88, 0·99). This association was confirmed for total cardiovascular as well as myocardial infarction (MI) incidence and mortality, but not for stroke. Score 3 was slightly more associated with the same outcomes. All associations were also resistant to adjustment for covariates related to potential CVD pathways, such as blood lipids, blood pressure and weight change after 11 years of follow-up. In a Danish cohort, the MDS was inversely associated with total mortality and with cardiovascular and MI incidence and mortality, but not with stroke incidence or mortality.

Assessing the diagnostic validity of a structured psychiatric interview in a first-admission hospital sample.

The use of structured psychiatric interviews performed by non-clinicians is frequent for research purposes and is becoming increasingly common in clini-cal practice. The validity of such interviews has rarely been evaluated empirically. In this study of a sample of 100 diagnostically heterogeneous, first-admitted inpatients, the results of an assessment with the Structured Clinical Interview for DSM-IV (SCID), yielding a DSM-IV diagnosis and performed by a trained non-clinician, were compared with a consensus lifetime best diagnostic estimate (DSM-IV) by two experienced research clinicians, based on multiple sources of information, which included videotaped comprehensive semi-structured narrative interviews. The overall kappa agreement was 0.18. The sensitivity and specificity for the diagnosis of schizophrenia by SCID were 19% and 100%, respectively. It is concluded that structured interviews performed by non-clinicians are not recommendable for clinical work and should only be used in research with certain precautions. It is suggested that a revival of systematic theoretical and practical training in psychopathology is an obvious way forward in order to improve the validity and therapeutic utility of psychiatric diagnosis.

Premorbid intelligence and educational level in bipolar and unipolar disorders: a Danish draft board study.

BACKGROUND: Registry-based studies have found no or weak associations between premorbid intelligence and the broad entity of affective spectrum disorder, but none of the studies compared bipolar/unipolar subgroups. METHODS: IQ and educational level were assessed at the draft board, and hospital diagnoses were followed up to the ages 43-54 years for 294 individuals hospitalized with bipolar disorder and 1434 with unipolar or depressive disorder. Controls comprised 20,531 individuals without psychiatric registration. RESULTS: Mean IQs of 98.32 and 96.71 were observed for patients with bipolar and depressive disorder respectively. For both patient groups a unimodal, slightly negatively skewed distribution was observed. The difference between the two patient samples was not statistically significant (p=0.10), but both obtained lower mean scores than the controls (p<0.0001 for unipolar and p=0.057 for bipolar patients). The means of the index of educational level were 5.22 and 4.82 for bipolar and unipolar patients (p=0.0006). The mean educational level was similar to the controls in bipolar disorder (p=0.15), while it was significantly lower compared to the controls in the unipolar group (p=0.0005). When possible prodromal patients were excluded, essentially the same results were observed. LIMITATIONS: The study was based on clinical hospital admission diagnoses. CONCLUSIONS: Clinicians should be aware of the relatively high intelligence and educational level in patients with bipolar disorder compared with patients with unipolar disorder. However, we were unable to confirm distinct subgroups of bipolar disorder with high and low premorbid intelligence and educational level.

Self-experience in the early phases of schizophrenia: 5-year follow-up of the Copenhagen Prodromal Study.

Despite the avalanche of empirical data on prodromal/"at risk" conditions, the essential aspects of the vulnerability to the schizophrenia spectrum remain largely unaddressed. We report here the results of the Copenhagen Schizophrenia Prodromal Study, a prospective, observational study of first admission patients in putative state of beginning psychosis (N=151) with a follow-up length of 60 months. At follow-up, the rate of conversion to schizophrenia spectrum diagnosis was 37%, whereas the conversion rate from schizotypal disorder to schizophrenia was 25%. High levels of perplexity and self-disorders baseline scores yielded the best prediction of the subsequent development of schizophrenia spectrum disorders. Escalating transitions within the spectrum (i.e., from schizotypal disorder to schizophrenia) were not associated to any candidate psychopathological predictor.

Looking at the schizophrenia spectrum through the prism of self-disorders: an empirical study.

Nonpsychotic anomalies of subjective experience were emphasized in both classic literature and phenomenological psychiatry as essential clinical features of schizophrenia. However, only in recent years, their topicality with respect to the construct validity of the concept of the schizophrenia spectrum has been explicitly acknowledged, mainly as a consequence of the increasing focus on early detection and prevention of psychosis. The current study tested the hypothesis of a specific aggregation of self-disorders (SDs, various anomalies of self-awareness) in schizophrenia-spectrum conditions, comparing different diagnostic groups; 305 subjects, previously assessed in the Copenhagen Schizophrenia Linkage Study, were grouped into 4 experimental samples, according to their Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) main diagnosis: schizophrenia, (n = 29), schizotypal personality disorder (n = 61), other mental illness not belonging to the schizophrenia spectrum (n = 112), and no mental illness (n = 103). The effect of diagnostic grouping on the level of SDs was explored via general linear model and logistic regression. The diagnosis of schizophrenia and schizotypy predicted higher levels of SDs, and SDs scores were significantly different between spectrum and nonspectrum samples; the likelihood of experiencing SDs increased as well with the diagnostic severity. The findings support the assumption that SDs are a discriminant psychopathological feature of the schizophrenia spectrum and suggest their incorporation to strengthen its construct validity, with potential benefit for both early detection and pathogenetic research.

Premorbid IQ varies across different definitions of schizophrenia.

The nature of the association between IQ and schizophrenia is still unclear. So far no study addressed this issue in relation to the breadth or scope of the very concept of schizophrenia. We examined the premorbid IQ in a polydiagnostic study with four classifications of schizophrenia: ICD-8/9, ICD-10, St. Louis and Flexible System-Wide. Only the ICD-10 schizophrenia patients exhibited a significantly lower premorbid IQ. There were suggestive differences between the four examined systems as well as between the ICD-10 paranoid and non-paranoid subtypes. Exploration of crucial diagnostic features of schizophrenia in relation to IQ revealed associations between low premorbid IQ and hallucinations as well as negative symptoms. It is concluded that premorbid IQ varies across different definitions of schizophrenia.

Anomalous subjective experience among first-admitted schizophrenia spectrum patients: empirical investigation.

Our research group has for several years conducted philosophically informed, phenomenological-empirical studies of morbid alterations of conscious experience (subjectivity) in schizophrenia (Sz) and its spectrum of disorders. Some of these experiential alterations constitute, in our view, the vulnerability markers to Sz--indicators that are intrinsic to this disorder and which were historically considered as constituting the phenotypic anchor of the very concept and the diagnostic validity of Sz spectrum disorders. In a more pragmatic clinical context, these indicators, considered here as symptoms, may be potentially effective for early differential diagnosis. In this study, 151 consecutive first-admitted patients (with bipolar, melancholic and organic patients excluded) diagnosed according to the ICD-10, were evaluated on a number of expressive and experiential psychopathological dimensions, with special emphasis on the experiences of perplexity, disorders of self-awareness, perceptual disorders and anomalous bodily experiences. The a priori scales derived from the item pool of a slightly modified OPCRIT and BSABS were used for analyses. Sz and schizotypal disorder scored equally on the subjective dimensions, suggesting a basic phenomenological affinity of these disorders. In contrast, anomalies of subjective experience were clearly more pronounced among the patients within, as compared to those outside the Sz spectrum.