Lower circulating neuron-specific enolase concentrations in adults and adolescents with severe mental illness.

BACKGROUND: Both neurodegenerative and neurodevelopmental abnormalities have been suggested to be part of the etiopathology of severe mental illness (SMI). Neuron-specific enolase (NSE), mainly located in the neuronal cytoplasm, may indicate the process as it is upregulated after neuronal injury while a switch from non-neuronal enolase to NSE occurs during neuronal maturation. METHODS: We included 1132 adult patients with SMI [schizophrenia (SZ) or bipolar spectrum disorders], 903 adult healthy controls (HC), 32 adolescent patients with SMI and 67 adolescent HC. Plasma NSE concentrations were measured by enzyme immunoassay. For 842 adults and 85 adolescents, we used total grey matter volume (TGMV) based on T1-weighted magnetic resonance images processed in FreeSurfer v6.0. We explored NSE case-control differences in adults and adolescents separately. To investigate whether putative case-control differences in NSE were TGMV-dependent we controlled for TGMV. RESULTS: We found significantly lower NSE concentrations in both adult (p < 0.001) and adolescent patients with SMI (p = 0.007) compared to HC. The results remained significant after controlling for TGMV. Among adults, both patients with SZ spectrum (p < 0.001) and bipolar spectrum disorders (p = 0.005) had lower NSE than HC. In both patient subgroups, lower NSE levels were associated with increased symptom severity. Among adults (p < 0.001) and adolescents (p = 0.040), females had lower NSE concentrations than males. CONCLUSION: We found lower NSE concentrations in adult and adolescent patients with SMI compared to HC. The results suggest the lack of progressive neuronal injury, and may reflect abnormal neuronal maturation. This provides further support of a neurodevelopmental rather than a neurodegenerative mechanism in SMI.

Blood-borne extracellular vesicles of bacteria and intestinal cells in patients with psychotic disorders.

BACKGROUND: Human cells and bacteria secrete extracellular vesicles (EV) which play a role in intercellular communication. EV from the host intestinal epithelium are involved in the regulation of bacterial gene expression and growth. Bacterial EV (bactEV) produced in the intestine can pass to various tissues where they deliver biomolecules to many kinds of cells, including neurons. Emerging data indicate that gut microbiota is altered in patients with psychotic disorders. We hypothesized that the amount and content of blood-borne EV from intestinal cells and bactEV in psychotic patients would differ from healthy controls. METHODS: We analyzed for human intestinal proteins by proteomics, for bactEV by metaproteomic analysis, and by measuring the level of lipopolysaccharide (LPS) in blood-borne EV from patients with psychotic disorders (n = 25), tested twice, in the acute phase of psychosis and after improvement, with age- and sex-matched healthy controls (n = 25). RESULTS: Patients with psychotic disorders had lower LPS levels in their EV compared to healthy controls (p = .027). Metaproteome analyses confirmed LPS finding and identified Firmicutes and Bacteroidetes as dominating phyla. Total amounts of human intestine proteins in EV isolated from blood was lower in patients compared to controls (p = .02). CONCLUSIONS: Our results suggest that bactEV and host intestinal EV are decreased in patients with psychosis and that this topic is worthy of further investigation given potential pathophysiological implications. Possible mechanisms involve dysregulation of the gut microbiota by host EV, altered translocation of bactEV to systemic circulation where bactEV can interact with both the brain and the immune system.

Exploring associations between the Modular Assessment of Risk for Imminent Suicide (MARIS) questionnaire and recent suicidal ideation and behavior among patients admitted at an acute psychiatric inpatient department.

PURPOSE: The aim of the present study was to investigate the psychometric validity of the Modular Assessment of Risk for Imminent Suicide (MARIS) questionnaire in relation to recent suicidal ideation and behavior among a sample of patients admitted to an acute psychiatric inpatient department in Norway. METHODS: The MARIS was completed within the first 24 h after admission by 338 patients and their clinicians. Information on recent suicidal ideation and behavior was extracted from patients' medical charts. Two out of four MARIS modules, the Suicide Trigger Scale Short-Form (STS-SF; modified version), and the Therapist Response Questionnaire Short-Form (TRQ-SF) demonstrated good internal consistency. The relationships between the STS-SF, addressing symptoms of the suicide crisis syndrome, and the TRQ-SF, exploring therapist emotional responses, and recent suicidal ideation was investigated by logistic regression analysis. RESULTS: In the logistic regression analysis including pre-selected diagnoses, age, and gender as covariates, both STS-SF and TRQ-SF showed significant associations with recent suicidal ideation (inclusive of suicidal behavior in 27% of the patients with suicidal ideation). CONCLUSION: Both the STS-SF and the TRQ-SF showed concurrent and incremental validity with regard to suicidal ideation. This is the first study showing the cross-cultural validity of the MARIS and supports its clinical utility as a suicide risk assessment tool in inpatient settings. Additionally, this study adds to the literature supporting the value of assessing clinicians' emotional responses to high risk patients.

Identification of unhealthy alcohol use by self-report and phosphatidylethanol (PEth) blood concentrations in an acute psychiatric department.

BACKGROUND: The use of standard screening methods could improve the detection rate of unhealthy alcohol use in patients admitted to psychiatric acute and emergency departments. The aim of the present study was to investigate the ability of the alcohol biomarker phosphatidylethanol (PEth) to identify patients with high levels of alcohol consumption prior to admission. METHODS: The data were prospectively collected at admittance to an acute psychiatric department in the period January 2016 to June 2017. A blood sample for the analysis of PEth was available from 177 patients. We compared the PEth concentrations with the Alcohol Use Disorders Identification Test (AUDIT) scores during the hospital stay, and psychiatric diagnoses at discharge. RESULTS: A total of 45.8% of the patients had a PEth concentration ≥ 0.03 µmol/L, indicating significant alcohol consumption. AUDIT scores consistent with unhealthy alcohol use were present in 51.7%. There was a significant positive correlation between PEth concentrations and AUDIT scores (r = 0.631, p < 0.001). PEth was above the detection limit of 0.03 µmol/L in 19% of those reporting an average daily intake of zero alcohol units per day during the last week before admission. PEth concentrations were significantly higher among those with an alcohol diagnosis than among those without such a diagnosis (0.82 µmol/L vs. 0.09 µmol/L, p = 0.001). CONCLUSION: PEth provides supplementary information on recent alcohol consumption in a psychiatric population and would be particularly helpful in patients unable or unwilling to give such information at admission.

Research based on existing clinical data and biospecimens: a systematic study of patients' opinions.

BACKGROUND: The aim of the present survey was to investigate newly discharged hospital patients' opinions on secondary use of their hospital data and biospecimens within the context of health research in general and, more specifically, on genetic research, data sharing across borders and cooperation with the health industry. METHODS: A paper questionnaire was sent to 1049 consecutive newly discharged hospital patients. RESULTS: The vast majority of the respondents preferred to be informed (passive consent) or to receive no notification at all for secondary research on their health data and biospecimens (88% and 91% for data and biospecimens respectively). The rest wanted to be asked for active consent. The same trend applied for the other aspects also. 81% of respondents were positive towards genetic research without active consent. 95% were positive towards cooperating with the health industry, and 90% were positive towards data sharing. CONCLUSIONS: These results suggest that hospital patients generally are very positive to secondary research and support the concept of opting out rather than opting in.

Non-disclosure of suicidal ideation in psychiatric inpatients: Rates and correlates.

The study explored how common non-disclosure of suicidal ideation is in a sample of adult psychiatric inpatients (N = 171) plus associated patient characteristics. A large percentage (51.5%) withheld some information on suicidal ideation during admission. In multivariable analyses, correlates of non-disclosure included a diagnosis of emotionally unstable personality disorder, low satisfaction with stay, and symptoms of the suicide crisis syndrome. In univariate analyses, therapists' emotional response to the patient was also a correlate. Findings indicate that among acute psychiatric inpatients, non-disclosure of suicidal ideation is quite common, requiring awareness from clinicians relying on this parameter in suicide risk assessments.

Quality of clinical management of cardiometabolic risk factors in patients with severe mental illness in a specialist mental health care setting.

PURPOSE: Cardiometabolic disease in patients with severe mental illness is a major cause of shortened life expectancy. There is sparse evidence of real-world clinical risk prevention practice. We investigated levels of assessments of cardiometabolic risk factors and risk management interventions in patients with severe mental illness in the Norwegian mental health service according to an acknowledged international standard. METHODS: We collected data from 264 patients residing in six country-wide health trusts for: (a) assessments of cardiometabolic risk and (b) assessments of levels of risk reducing interventions. Logistic regressions were employed to investigate associations between risk and interventions. RESULTS: Complete assessments of all cardiometabolic risk variables were performed in 50% of the participants and 88% thereof had risk levels requiring intervention according to the standard. Smoking cessation advice was provided to 45% of daily smokers and 4% were referred to an intervention program. Obesity was identified in 62% and was associated with lifestyle interventions. Reassessment of psychotropic medication was done in 28% of the obese patients. Women with obesity were less likely to receive dietary advice, and use of clozapine or olanzapine reduced the chances for patients with obesity of getting weight reducing interventions. CONCLUSIONS: Nearly nine out of the ten participants were identified as being at cardiometabolic high risk and only half of the participants were adequately screened. Women with obesity and patients using antipsychotics with higher levels of cardiometabolic side effects had fewer adequate interventions. The findings underscore the need for standardized recommendations for identification and provision of cardiometabolic risk reducing interventions in all patients with severe mental illness.

Epilepsy and other seizure disorders in acute psychiatric inpatients.

BACKGROUND: It is well known that patients with epilepsy have a high rate of psychiatric comorbidity. However, studies exploring epilepsy in psychiatric cohorts are scarce. The aim of this study was to examine the prevalence of seizure disorders in acute psychiatric inpatients. METHODS: This is a cross-sectional study performed in a catchment-area based acute psychiatric department. All patients (age > 18) admitted during September 2011 - March 2012 were eligible for inclusion. Consenting patients were screened for a life-time history of epilepsy or seizures using self-reported questionnaire data and diagnostic codes for epilepsy in hospital and National registries. Patients scoring positive to one or more of these screening criteria underwent a thorough diagnostic validation (chart review), and the seizure disorders were classified as epilepsy, acute symptomatic seizures and/or psychogenic non-epileptic seizures according to current definitions. RESULTS: A total of 380 out of 591 (64.3%) consecutively admitted patients consented to participate in the study. Eighty-nine patients (23.4%) scored positive to one or more screening criteria. Fifteen (3.9%) were classified with epilepsy, 21 (5.5%) with acute symptomatic seizures and 9 (2.4%) with psychogenic non-epileptic seizures. CONCLUSIONS: This is the first study to report on the prevalence of seizure disorders in acute psychiatric inpatients. The life-time prevalence of epilepsy in this cohort of patients is five - six times as high as reports in the general population. These findings underscore the need for the clinical psychiatrist to have comprehensive knowledge on the interface between epileptology and psychiatry. TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT01415323 .

Biomarkers of Autoimmunity in Acute Psychiatric Disorders.

OBJECTIVE: Previous studies have suggested that autoantibodies associated with systemic autoimmune disorders are more prevalent in patients with psychotic and affective disorders compared with healthy control subjects. However, most positive studies addressing this issue have been limited by small sample sizes and lack of correction for confounding factors. The authors aimed to assess the prevalence of several autoantibodies in patients admitted to acute psychiatric inpatient care and investigate whether patients with psychotic and affective disorders have an increased prevalence of autoantibodies compared with psychiatric patients admitted for other reasons. METHODS: Five hundred eighty-five patients were screened for the presence of antinuclear antibodies (ANA), anticardiolipin and antibeta2-glycoprotein, antithyroid peroxidase (anti-TPO), antitissue transglutaminase IgA, antigliadin deamidated peptide IgG, and rheumatoid factor IgM (RF). Differences in prevalence between patients with nonaffective psychoses (N=105), bipolar disorders (N=78), unipolar depressive disorders (N=146), and other reasons for admission (N=256) were assessed using chi-square tests and logistic regression models. RESULTS: One or more autoantibodies were present in 26.2% of the patients, including ANA (9.4%), RF (9.2%), and anti-TPO (5.6%). Autoantibody prevalence increased with age (odds ratio=1.21, 95% CI=1.09-1.35) and smoking status (odds ratio=1.99, 95% CI=1.04-3.82) but was not associated with a diagnosis of a psychotic or affective disorder. CONCLUSIONS: Autoimmune autoantibodies seem to be equally prevalent in patients with acute psychiatric conditions with and without psychotic and affective disorders. This result challenges the idea that these autoantibodies have specificity for certain psychiatric disorders.

The significance of anti-neuronal antibodies for acute psychiatric disorders: a retrospective case-controlled study.

BACKGROUND: The clinical significance of anti-neuronal antibodies in patients with psychiatric disorders, but without encephalitis, remains unknown. In patients admitted to acute psychiatric inpatient care we aimed to identify clinical features distinguishing anti-neuronal antibody positive patients from matched controls. RESULTS: Patients who were serum-positive to N-methyl D-aspartate receptor (NMDAR) (n = 21), contactin-associated protein 2 (CASPR2) (n = 14) and/or glutamic acid decarboxylase 65 (GAD65) (n = 9) antibodies (cases) were age and sex matched (1:2) with serum-negative patients from the same cohort (controls). The prevalence and severity of psychiatric symptoms frequently encountered in NMDAR, CASPR2 and GAD65 antibody associated disorders were compared in cases and controls. NMDAR, CASPR2 and GAD65 antibody positive patients did not differ in their clinical presentation from matched serum negative controls. CONCLUSION: In this cohort, patients with and without NMDAR, CASPR2 and GAD65 antibodies admitted to acute psychiatric inpatient care had similar psychiatric phenotypes. This does not exclude their clinical relevance in subgroups of patients, and studies further investigating the clinical significance of anti-neuronal antibodies in patients with psychiatric symptomatology are needed.

Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study.

OBJECTIVES: Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment. METHODS: In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm-based pharmacologic treatment or right unilateral electroconvulsive therapy. After the 6-week treatment period, all of the patients received maintenance pharmacotherapy as recommended by their clinician guided by a relevant treatment algorithm. Patients were assessed at baseline and at 6 months. Neurocognitive functions were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and autobiographical memory consistency was assessed using the Autobiographical Memory Interview-Short Form. RESULTS: Seventy-three patients entered the trial, of whom 51 and 26 completed neurocognitive assessments at baseline and 6 months, respectively. The MATRICS Consensus Cognitive Battery composite score improved by 4.1 points in both groups (P = .042) from baseline to 6 months (from 40.8 to 44.9 and from 41.9 to 46.0 in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively). The Autobiographical Memory Interview-Short Form consistency scores were reduced in both groups (72.3% vs 64.3% in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively; P = .085). CONCLUSIONS: This study did not find that right unilateral electroconvulsive therapy caused long-term impairment in neurocognitive functions compared to algorithm-based pharmacologic treatment in bipolar depression as measured using standard neuropsychological tests, but due to the low number of patients in the study the results should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00664976.

Onconeural Antibodies in Acute Psychiatric Inpatient Care.

Paraneoplastic neurological disorders associated with onconeural antibodies often appear with neuropsychiatric symptoms. To study the prevalence of onconeural antibodies in patients admitted to acute psychiatric inpatient care, the serum of 585 such patients was tested for antibodies targeting MOG, GLRA1B, DPPX, GRM1, GRM5, DNER, Yo, ZIC4, GAD67, amphiphysin, CV2, Hu, Ri, Ma2, and recoverin. Only one sample was positive (antirecoverin IgG). The present findings suggest that serum onconeural antibody positivity is rare among patients acutely admitted for inpatient psychiatric care. The clinical implications of this finding are discussed.

Variability of activity patterns across mood disorders and time of day.

BACKGROUND: Few actigraphy studies in mood disorders have simultaneously included unipolar (UP) and bipolar (BD) depression or BD mixed states as a separate subgroup from mania. This study compared objectively measured activity in UP, BD depression, mania and mixed states and examined if patterns differed according to time of day and/or diagnostic group. METHODS: Eighty -eight acutely admitted inpatients with mood disorders (52 UP; 18 mania; 12 BD depression; 6 mixed states) underwent 24 hours of actigraphy monitoring. Non-parametric analyses were used to compare median activity level over 24 h (counts per minute), two time series (64-min periods of continuous motor activity) in the morning and evening, and variability in activity across and within groups. RESULTS: There was no between-group difference in 24-h median level of activity, but significant differences emerged between BD depression compared to mania in the active morning period, and between UP and mania and mixed states in the active evening period. Within-group analyses revealed that UP cases showed several significant changes between morning and evening activity, with fewer changes in the BD groups. CONCLUSIONS: Mean activity over 24 hours has limited utility in differentiating UP and BD. In contrast, analysis of non-linear variability measures of activity at different times of day could help objectively distinguish between mood disorder subgroups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01415323 , first registration July 6, 2011.

Challenges in detecting and diagnosing substance use in women in the acute psychiatric department: a naturalistic cohort study.

BACKGROUND: This study examines sex differences in substance use and substance use disorder in the acute psychiatric department, and possible interactions between sex and clinical and social factors associated with this phenomenon. METHODS: Data concerning substance use were collected in a naturalistic cohort study (n = 384, 51.6% male, 48.4% female) in an acute psychiatric department. Recent intake of substances at admission, diagnosis of substance use disorder and demographic and socioeconomic information were recorded. At admission, serum and urine samples were analysed for substance use and breath analysis was performed for alcohol levels. RESULTS: Twice as many men as women were diagnosed with substance use disorder, whereas there were no gender differences in the number of positive toxicology screenings. Toxicology screening revealed the use of non-prescribed medication with addiction potential in 40% of both female and male patients many of whom did not report this in the admission interview. A low level of education in men and absence of parental responsibility in women showed a statistically significant interaction with a current diagnosis of substance use disorder. CONCLUSIONS: Despite no sex differences in positive toxicology screenings in the acute psychiatric department, twice as many men as women are diagnosed with substance use disorders. The use of prescription drugs with addiction potential was widely under-reported by both sexes, in patients with no prescriptions for the medications. Women with no parental responsibility are overrepresented among those diagnosed with substance use disorder, as are men with a low level of education. TRIAL REGISTRATION: The study is registered with the ClinicalTrials.gov identifier NCT01415323.

Religious convictions in patients with epilepsy-associated affective disorders: a controlled study from a psychiatric acute department.

Patients with epilepsy often have different mood symptoms and behavioral trait characteristics compared to the non-epileptic population. In the present prospective study, we aimed to assess differences in behavioral trait characteristics between acutely admitted, psychiatric in-patients with epilepsy-associated depressive symptoms and gender/age-matched patients with major depression. Patients with epilepsy-associated depression had significantly higher scores for "religious convictions," "philosophical and intellectual interests" and "sense of personal destiny." These behavioral trait characteristics at admission or in clinical history should alert the psychiatrist and lead to closer examination for a possible convulsive disorder.