Swedish nationwide time series analysis of influenza and suicide deaths from 1910 to 1978.

OBJECTIVES: There is concern that the COVID-19 pandemic will be associated with an increase in suicides, but evidence supporting a link between pandemics and suicide is limited. Using data from the three influenza pandemics of the 20th century, we aimed to investigate whether an association exists between influenza deaths and suicide deaths. DESIGN: Time series analysis. SETTING: Sweden. PARTICIPANTS: Deaths from influenza and suicides extracted from the Statistical Yearbook of Sweden for 1910-1978, covering three pandemics (the Spanish influenza, the Asian influenza and the Hong Kong influenza). MAIN OUTCOME MEASURES: Annual suicide rates in Sweden among the whole population, men and women. Non-linear autoregressive distributed lag models was implemented to explore if there is a short-term and/or long-term relationship of increases and decreases in influenza death rates with suicide rates during 1910-1978. RESULTS: Between 1910 and 1978, there was no evidence of either short-term or long-term significant associations between influenza death rates and changes in suicides (ß coefficients of 0.00002, p=0.931 and ß=0.00103, p=0.764 for short-term relationship of increases and decreases in influenza death rates, respectively, with suicide rates, and ß=-0.0002, p=0.998 and ß=0.00211, p=0.962 for long-term relationship of increases and decreases in influenza death rates, respectively, with suicide rates). The same pattern emerged in separate analyses for men and women. CONCLUSIONS: We found no evidence of short-term or long-term association between influenza death rates and suicide death rates across three 20th century pandemics.

Repetitive transcranial magnetic stimulation in major depression: A three-arm parallel-group dose-response randomized pilot trial.

BACKGROUND: The optimal dose (number of pulses per session) of repetitive transcranial magnetic stimulation (rTMS), using the H-coil, in major depressive disorder (MDD) has not previously been reported. OBJECTIVE: To explore the relationship between rTMS dose and antidepressant effect, and collect data for the design of a definitive trial. METHODS: This was a double-blind, three-arm parallel-group, randomized [1:1:1], pilot trial conducted in Stockholm, Sweden (September 2014 to September 2016). The primary outcome was change in depression severity measured with the Montgomery Åsberg Depression Rating Scale (MADRS) after 4 weeks. Participants (n = 29) with MDD were randomized to 1000, 2000, or 4000 pulses of rTMS for 20 sessions during 4 weeks. RESULTS: At 4 weeks, the 3 treatment groups reduced the mean MADRS (95% CI) by 11.6 (4.0-19.2), 9.1 (5.0-13.3), and 11.3 (4.1-18.5) points respectively. Eleven participants met criteria for response and 10 for remission. No serious adverse events occurred. Ratings of subjective memory improved in all groups. Exploring the effect of dose and time, 4000 pulses had the largest reduction in MADRS during the first 2 weeks. A comparison of change in MADRS between 2000 and 4000 pulses after 2 weeks will require a sample size of 66 patients at power .80 and alpha .05. CONCLUSIONS: It is feasible to conduct a definitive trial investigating whether a higher number of magnetic pulses per treatment session gives a more rapid antidepressive response.

A randomized controlled study of weighted chain blankets for insomnia in psychiatric disorders.

STUDY OBJECTIVES: This study aimed to evaluate the effect of weighted chain blankets on insomnia and sleep-related daytime symptoms for patients with major depressive disorder, bipolar disorder, generalized anxiety disorder, and attention deficit hyperactivity disorder. METHODS: One hundred twenty patients were randomized (1:1) to either a weighted metal chain blanket or a light plastic chain blanket for 4 weeks. The outcome was evaluated using the Insomnia Severity Index as primary outcome measure and day and night diaries, Fatigue Symptom Inventory, and Hospital Anxiety and Depression Scale as secondary outcome measures. Sleep and daytime activity levels were evaluated by wrist actigraphy. RESULTS: At 4 weeks, there was a significant advantage in Insomnia Severity Index ratings of the weighted blanket intervention over the light blanket (P < .001) with a large effect size (Cohen's d 1.90). The intervention by the weighted blanket resulted in a significantly better sleep-maintenance, a higher daytime activity level, and reduced daytime symptoms of fatigue, depression, and anxiety. No serious adverse events occurred. During a 12-month open follow-up phase of the study, participants continuing to use weighted blankets maintained the effect on sleep, while patients switching from a light to a weighted blanket experienced an effect on Insomnia Severity Index ratings similar to that of participants using the weighted blanket from the beginning. CONCLUSIONS: Weighted chain blankets are an effective and safe intervention for insomnia in patients with major depressive disorder, bipolar disorder, generalized anxiety disorder, or attention deficit hyperactivity disorder, also improving daytime symptoms and levels of activity. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Controlled Study of Chain Blanket for Insomnia; URL: https://clinicaltrials.gov/ct2/show/NCT03546036; Identifier: NCT03546036.

Physician estimated vs. self-reported subjective memory in depressed patients treated with electroconvulsive therapy.

Background: Subjective memory deficits are common in depression and during series of treatment with electroconvulsive therapy (ECT). There is a need for feasible assessment of memory deficit. In the Swedish National Quality Register for ECT, patients' subjective memory function is rated by a clinician. Self-ratings would be easier to administer.Objectives: The aim of this study was to analyze the consistency between self-reported and physician estimated subjective memory in depressed patients treated with ECT.Methods: Fifty-two inpatients treated with ECT for major- or bipolar depression were recruited and 41 of them completed the study protocol. Each patient rated their own subjective memory and had it rated in an interview by a physician both before/in the beginning of the ECT series and after the ECT series. The patients' memory was rated and self-rated with the memory item in the Comprehensive Psychopathological Rating Scale (CPRS). We then analyzed correlations, and differences in distributions, between self-reported assessment and physician estimates of patients' subjective memory.Results: The correlations between the self-reported and the physician estimated ratings of subjective memory were 0.699 (p < .01) in baseline ratings and 0.651 (p < .01) in post-treatment ratings. These correlations were relatively high compared to a previous study on self-reported vs. physician estimated CPRS ratings.Conclusions: Based on the results in this study, we propose that patients' self-ratings of subjective memory in association with ECT can be used instead of a physician's rating of patients' subjective memory.

Group acceptance and commitment therapy (ACT) for bipolar disorder and co-existing anxiety - an open pilot study.

Previous studies have supported acceptance and commitment therapy (ACT) for reducing impairment related to various chronic conditions. ACT may possibly be beneficial for bipolar disorder (BD) with co-existing anxiety, which is associated with a poorer treatment outcome. Efforts are needed to identify suitable psychological interventions for BD and co-existing anxiety. In this open clinical trial, we included 26 patients with BD type 1 or 2 at an outpatient psychiatric unit specializing in affective disorders. The intervention consisted of a 12-session manualized group treatment that included psychoeducation, mindfulness, engaging in values-based behaviour, cognitive defusion, acceptance and relapse prevention modules. Participants completed four self-report questionnaires covering anxiety symptoms (Beck Anxiety Inventory - BAI), depressive symptoms (Beck Depression Inventory - BDI-II), quality of life (Quality of Life Inventory - QOLI) and psychological flexibility (Acceptance and Action Questionnaire - AAQ-2) before, during and after the treatment. At post-treatment, the participants reported significant improvements in all outcome measures, with large effects (Cohen's d between 0.73 and 1.98). The mean reduction in anxiety symptoms was 45%. At post-treatment, 96% of the patients were classified as responders on at least one of the outcome measures. A limitation is that the trial is uncontrolled. The results suggest that ACT has the potential to be an effective treatment for BD patients with co-existing anxiety. Further randomized studies are warranted.

Functional and structural alterations in the cingulate motor area relate to decreased fronto-striatal coupling in major depressive disorder with psychomotor disturbances.

Psychomotor disturbances are a classic feature of major depressive disorders. These can manifest as lack of facial expressions and decreased speech production, reduced body posture and mobility, and slowed voluntary movement. The neural correlates of psychomotor disturbances in depression are poorly understood but it has been suggested that outputs from the cingulate motor area (CMA) to striatal motor regions, including the putamen, could be involved. We used functional and structural magnetic resonance imaging to conduct a region-of-interest analysis to test the hypotheses that neural activation patterns related to motor production and gray matter volumes in the CMA would be different between depressed subjects displaying psychomotor disturbances (n = 13) and matched healthy controls (n = 13). In addition, we conducted a psychophysiological interaction analysis to assess the functional coupling related to self-paced finger-tapping between the caudal CMA and the posterior putamen in patients compared to controls. We found a cluster of increased neural activation, adjacent to a cluster of decreased gray matter volume in the caudal CMA in patients compared to controls. The functional coupling between the left caudal CMA and the left putamen during finger-tapping task performance was additionally decreased in patients compared to controls. In addition, the strength of the functional coupling between the left caudal CMA and the left putamen was negatively correlated with the severity of psychomotor disturbances in the patient group. In conclusion, we found converging evidence for involvement of the caudal CMA and putamen in the generation of psychomotor disturbances in depression.

A comparison of three methods of assessing differential item functioning (DIF) in the Hospital Anxiety Depression Scale: ordinal logistic regression, Rasch analysis and the Mantel chi-square procedure.

PURPOSE: It is important for clinical practice and research that measurement scales of well-being and quality of life exhibit only minimal differential item functioning (DIF). DIF occurs where different groups of people endorse items in a scale to different extents after being matched by the intended scale attribute. We investigate the equivalence or otherwise of common methods of assessing DIF. METHOD: Three methods of measuring age- and sex-related DIF (ordinal logistic regression, Rasch analysis and Mantel χ(2) procedure) were applied to Hospital Anxiety Depression Scale (HADS) data pertaining to a sample of 1,068 patients consulting primary care practitioners. RESULTS: Three items were flagged by all three approaches as having either age- or sex-related DIF with a consistent direction of effect; a further three items identified did not meet stricter criteria for important DIF using at least one method. When applying strict criteria for significant DIF, ordinal logistic regression was slightly less sensitive. CONCLUSIONS: Ordinal logistic regression, Rasch analysis and contingency table methods yielded consistent results when identifying DIF in the HADS depression and HADS anxiety scales. Regardless of methods applied, investigators should use a combination of statistical significance, magnitude of the DIF effect and investigator judgement when interpreting the results.

Motor imagery in bipolar depression with slowed movement.

We hypothesized that motor retardation in bipolar depression is mediated by disruption of the pre-executive stages of motor production. We used functional magnetic resonance imaging to investigate neural activity during motor imagery and motor execution to elucidate whether brain regions that mediate planning, preparation, and control of movement are activated differently in subjects with bipolar depression (n = 9) compared with healthy controls (n = 12). We found significant between-group differences. During motor imagery, the patients activated the posterior medial parietal cortex, the posterior cingulate cortex, the premotor cortex, the prefrontal cortex, and the frontal poles more than the controls did. Activation in the brain areas involved in motor selection, planning, and preparation was altered. In addition, limbic and prefrontal regions associated with self-reference and the default mode network were altered during motor imagery in bipolar depression with motor retardation.

Activation of kynurenine pathway in ex vivo fibroblasts from patients with bipolar disorder or schizophrenia: cytokine challenge increases production of 3-hydroxykynurenine.

Accumulating data suggest a causative link between immune stimulation, disturbed metabolism of tryptophan, and pathogenesis of bipolar disorder and schizophrenia. The goal of this study was to examine the production of kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK) and the expression of kynurenine pathway enzymes involved in their synthesis and metabolism in cultured skin fibroblasts obtained from patients with bipolar disorder, schizophrenia or from healthy control individuals. The assessment was performed under basal conditions or following treatment with interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, or their combinations, in cells exposed to exogenous kynurenine. In both groups of patients, the baseline production of KYNA and 3-HK was increased, as compared to control subjects. Case-treatment analyses revealed significant interactions between bipolar case status and IL-1ß, IL-6, IFN-γ + TNF-α, or IFN-γ + IL-1ß, as well as between schizophrenia case status and IL-1ß, IFN-γ + TNF-α, or IFN-γ + IL-1ß, in terms of higher 3-HK. Noteworthy, no case-treatment interactions in terms of KYNA production were found. Observed changes did not appear to correlate with the expression of genes encoding kynurenine aminotransferases (KATs), kynureninase (KYNU) or kynurenine-3-monooxygenase (KMO). The single nucleotide polymorphisms (SNPs), rs1053230 and rs2275163, in KMO influenced KYNA levels yet did not explain the case-treatment discrepancies. In conclusion, our present findings indicate the utility of skin-derived fibroblasts for kynurenines research and support the concept of kynurenine pathway alterations in bipolar disorder and schizophrenia. The increase in ratio between neurotoxic 3-HK and neuroinhibitory/neuroprotective KYNA following exposure to cytokines may account for altered neurogenesis and structural abnormalities characteristic for both diseases.

[Affective disorders and their treatment during pregnancy and after birth -- a review]. / Hangulati betegségek és azok kezelése a terhesség alatt és a szülés után -- áttekintés.

Treatment and management of affective disorders associated with pregnancy is still an underemphasized field receiving little attention, furthermore, it is burdened with misinformation as well as incomplete or missing knowledge. Professionals of related fields (psychiatrists, obstetrician-gynecologists) often provide patients with contradicting information or, due to their lack of sufficient knowledge, keep referring the patient for information between different services. However, there is an increasing amount of data and information available, suitable for drawing conclusions and making it possible to provide adequate and credible counselling and information for pregnant women or family planning couples. In the present paper we aim to facilitate this process by reviewing the currently available information.

The neural correlates of self-paced finger tapping in bipolar depression with motor retardation.

OBJECTIVE: Motor retardation is a characteristic feature of bipolar depression, and is also a core feature of Parkinson's disease. Within the framework of the functional deafferentiation theory in Parkinson's disease, we hypothesised that motor retardation in bipolar depression is mediated by disrupted subcortical activation, leading to decreased activation of cortical motor areas during finger tapping. METHODS: We used functional magnetic resonance imaging to investigate neural activity during self-paced finger tapping to elucidate whether brain regions that mediate preparation, control and execution of movement are activated differently in subjects with bipolar depression (n = 9) compared to healthy controls (n = 12). RESULTS: An uncorrected whole-brain analysis revealed significant group differences in dorsolateral and ventromedial prefrontal cortex. Corrected analyses showed non-significant differences in patients compared to controls: decreased and less widespread activation of the left putamen and left pallidum; increased activity in the left thalamus and supplementary motor area; decreased activation in the left lateral pre- and primary motor cortices; absence of activation in the pre-supplementary motor area; activation of the bilateral rostral cingulate motor area. CONCLUSION: Both movement preparation and execution may be affected in motor retardation, and the activity in the whole left-side motor circuit is altered during self-initiated motor performance in bipolar depression.

An item response theory evaluation of three depression assessment instruments in a clinical sample.

BACKGROUND: This study investigates whether an analysis, based on Item Response Theory (IRT), can be used for initial evaluations of depression assessment instruments in a limited patient sample from an affective disorder outpatient clinic, with the aim to finding major advantages and deficiencies of the instruments. METHODS: Three depression assessment instruments, the depression module from the Patient Health Questionnaire (PHQ9), the depression subscale of Affective Self Rating Scale (AS-18-D) and the Montgomery-Åsberg Depression Rating Scale (MADRS) were evaluated in a sample of 61 patients with affective disorder diagnoses, mainly bipolar disorder. A '3- step IRT strategy' was used. RESULTS: In a first step, the Mokken non-parametric analysis showed that PHQ9 and AS-18-D had strong overall scalabilities of 0.510 [C.I. 0.42, 0.61] and 0,513 [C.I. 0.41, 0.63] respectively, while MADRS had a weak scalability of 0.339 [C.I. 0.25, 0.43]. In a second step, a Rasch model analysis indicated large differences concerning the item discriminating capacity and was therefore considered not suitable for the data. In third step, applying a more flexible two parameter model, all three instruments showed large differences in item information and items had a low capacity to reliably measure respondents at low levels of depression severity. CONCLUSIONS: We conclude that a stepwise IRT-approach, as performed in this study, is a suitable tool for studying assessment instruments at early stages of development. Such an analysis can give useful information, even in small samples, in order to construct more precise measurements or to evaluate existing assessment instruments. The study suggests that the PHQ9 and AS-18-D can be useful for measurement of depression severity in an outpatient clinic for affective disorder, while the MADRS shows weak measurement properties for this type of patients.

Symptoms and treatment of bipolar patients in Sweden.

OBJECTIVE: The objective of the study was to investigate affective symptoms and pharmacological treatment in bipolar I disorder patients, and to test whether self-rated symptoms could predict hospital admissions during a 12-month follow-up period. METHODS: A total of 231 outpatients with clinical bipolar I disorder were recruited. The clinical diagnoses were reassessed by a semi-structured interview. Twenty-four patients (10%) was reclassified as bipolar disorder type II or schizoaffective disorder (bipolar type). Medication status was recorded and symptoms were assessed with the self-rating scale AS-18. Patients were prospectively followed for 12 months and hospitalizations during that time were recorded. RESULTS: More than half (60%) rated themselves as normothymic. Mixed affective symptoms were more common than either depressive or manic/hypomanic symptoms. The admission rate during 1 year of follow-up was 13% (95% C.I. 8-17%). Patients which at baseline rated themselves high in either mania or in depression had a significantly increased risk for hospitalization (OR = 3.15; 95% C.I. 1.38-7.19). CONCLUSIONS: The findings should encourage clinicians to use patient self ratings in order to identify patients with a high risk for hospitalization for targeted interventions.

An IRT validation of the Affective Self Rating Scale.

BACKGROUND: The Affective Self Rating Scale (AS-18) is intended for the use in bipolar outpatients. It includes subscales for the rating of depressive and manic-type symptoms. It has previously been validated using methods from Classical Test Theory. AIMS: The aim of this study was to evaluate the psychometric properties of the AS-18 when used at an outpatient clinic for patients with bipolar disorder at routine visits, and to analyze the potential for improvement of the scale. METHODS: 231 patients with mainly bipolar I disorder doing ratings on routine visits at an affective disorder outpatient clinic were included. Ratings were analyzed using the Mokken non-parametric and the Rasch parametric model statistical methods. RESULTS: In the Mokken analysis, both subscales of the AS-18 showed a strong ability to rank respondents according to their total score and all items contributed adequately to the measurement. In the Rasch model, there were no indications of disturbing influence from secondary dimensions in the subscales. The depression subscale had the capacity reliably to separate the sample in at most three levels and the mania subscale in two levels. The limited capacity to separate respondents can mainly be explained by a lack of items reflecting lower levels of depressive and manic symptoms. CONCLUSIONS: AS-18 has good basic psychometric properties for use of rating of symptoms in bipolar I patients at routine visits, but there is also room for improvement. Item Response Theory (IRT) methods are suitable tools for evaluation and construction of rating scales.

Development and validation of the Affective Self Rating Scale for manic, depressive, and mixed affective states.

Most rating scales for affective disorders measure either depressive or hypomanic/manic symptoms and there are few scales for hypomania/mania in a self-rating format. We wanted to develop and validate a self-rating scale for comprehensive assessment of depressive, manic/hypomanic and mixed affective states. We developed an 18-item self-rating scale starting with the DSM-IV criteria for depression and mania, with subscales for depression and mania. The scale was evaluated on 61 patients with a diagnosis of affective disorder, predominantly bipolar disorder type I, using Montgomery-Asberg Depression Rating Scale (MADRS), Hypomania Interview Guide-Clinical version (HIGH-C) and Clinical Global Impression scale, modified for bipolar patients (CGI-BP) as reference scales. Internal consistency of the scale measured by Cronbach's alpha was 0.89 for the depression subscale and 0.91 for the mania subscale. Spearman's correlation coefficients (two-tailed) between the depression subscale and MADRS was 0.74 (P<0.01) and between mania subscale and HIGH-C 0.80 (P<0.01). A rotated factor analysis of the scale supported the separation of symptoms in the mania and depression subscale. We established that the self-rating scales sensitivity to identify mixed states, with combined cut-offs on the MADRS and HIGH-C as reference, was 0.90 with a specificity of 0.71. The study shows that the Affective Self Rating Scale is highly correlated with ratings of established interview scales for depression and mania and that it may aid the detection of mixed affective states.

Pulse Intravenous Clomipramine as an alternative antidepressant treatment to ECT. A pilot study

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Background and Objectives: The aim of the study was to examine the antidepressant effect of a single pulse dose of intravenous clomipramine (200 mg i.v.) followed by oral administration as an alternative method to electroconvulsive therapy. Methods: Twenty-one inpatients (8 male, 13 female) with major depression were included. Depression severity was measured by Montgomery Asberg Rating Scale (MADRS) and Clinical Global Impression severity scale (CGI-S) before the pulse dose and 1 week after. The day after the pulse dose, the patient was medicated with 75 mg of oral clomipramine and from day two with 150 mg clomipramine daily. Results: The MADRS score dropped with 39% ± 22% and the CGI score with 28% ± 19% in one week. The improvement of the MADRS score after one week was 13.1(C.I.9.5-17.0). CGI-ratings dropped from a mean of 5.5 (SD 1.2) to 3.9 (SD 1.1), an improvement of 28% ± 19%.(C.I. 1.0-2.1). Both improvements were significant (p<000.1).Conclusions: Single pulse dose clomipramine administration ameliorates depressive symptoms, and may be an alternative to ECT (AU)