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Background The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19). Methods A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination. Results The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56–1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found. Conclusions The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.

Objective: Seasonal and non-seasonal depression are prevalent conditions in visual impairment (VI). We assessed the effects and side effects of light therapy in persons with severe VI/blindness who experienced recurrent depressive symptoms in winter corresponding to seasonal affective disorder (SAD) or subsyndromal SAD (sSAD). Results: We included 18 persons (11 with severe VI, 3 with light perception and 4 with no light perception) who met screening criteria for sSAD/SAD in a single-arm, assessor-blinded trial of 6 weeks light therapy. In the 12 persons who completed the 6 weeks of treatment, the post-treatment depression score was reduced (p < 0.001), and subjective wellbeing (p = 0.01) and sleep quality were improved (p = 0.03). In 6/12 participants (50%), the post-treatment depression score was below the cut-off set for remission. In four participants with VI, side effects (glare or transiently altered visual function) led to dropout or exclusion. Conclusion: Light therapy was associated with a reduction in depressive symptoms in persons with severe VI/blindness. Eye safety remains a concern in persons with residual sight.

Objective To investigate (1) if antidepressant use among women in assisted reproductive technology (ART) treatment and among women without ART treatment influences cumulative live birth rates (CLBR) and number of initiated treatment cycles per woman, (2) whether women undergoing ART treatment are at higher risk of initiating use of antidepressants compared to women not having undergone ART, (3) if mothers after ART treatment have higher risk for postpartum use of antidepressants after ART treatment compared to mothers not having used ART treatment. Study design A Danish nation-wide register-based cohort study including all women in ART treatment between 1995 through 2009 and an age-matched comparison group of women not having initiated ART treatment. In both groups, women had no previous children before study entry. The women were followed from time of initiating first ART treatment until time of permanent emigration (> 6 months), date of death, or end of follow-up by 31st of December 2009. Chi-square test was used to assess whether observed differences in CLBR between groups were significant. Adjusted incidence rates (IR) and incidence rate ratio (IRR) with 95 % confidence interval (CI) were calculated using Poisson regression analysis. The main outcome measures were: CLBR, number of initiated ART treatment cycles and IRR of initiating antidepressant use. Results Women using antidepressants before, during or after ART treatment were significantly older, had a lower CLBR and a lower mean number of initiated ART treatment cycles compared to women in ART treatment with no use of antidepressants. No significant difference was found in the incidence of initiating antidepressant use between women in ART treatment and the comparison group. However, when comparing only women with a live birth, significantly more women in ART treatment initiated antidepressant use in the postpartum period (adjusted incidence rate ratio (IRR) = 2.56 (95 % CI 1.98−3.30; p Conclusion Generally, women undergoing ART treatment are not at higher risk of initiating use of antidepressants compared with an age-matched comparison group not treated with ART. However, women with antidepressant medication use prior to ART initiate fewer ART treatments and have lower CLBR. Even though it has not been possible to adjust for all relevant confounders and our follow-up period only runs until the end of 2009, we still believe the results of this study to be highly relevant. According to our study, clinicians should be aware that women conceiving after ART treatment might experience an increased level of psychological strain during the postpartum period compared to mothers who conceived without ART.

Introduction: Valid and reliable methods for diagnosing depression are essential. The present study aimed to test the performance of a new diagnostic interview for depression focusing on the core symptoms of depression. Method: We developed a diagnostic interview for depression: the CORE Diagnostic Interview, CORE-DI, which assesses each of the core features of depression on the four dimensions: quality, reactivity, globality, and fluctuations over time. The diagnostic performance of this interview was tested in a clinical study including 83 individuals presenting with various depressive symptoms, who were interviewed independently (1) by means of the CORE-DI and the Mini-International Neuropsychiatric Interview (M.I.N.I.), and (2) by highly skilled specialists in depression representing gold standard diagnoses. Results: We compared the outcome of the CORE-DI, the M.I.N.I., and the diagnosis made by clinicians, respectively, versus the gold standard diagnosis, using diagnostic efficiency statistics. The CORE-DI diagnosed depression with a high specificity (0.91, 95% CI: 0.85–0.97, for International Classification of Diseases [ICD]-10 criteria and 0.88, 95% CI: 0.81–0.95, for Diagnostic and Statistical Manual of Mental Disorders [DSM-5] criteria) compared to both M.I.N.I (specificity 0.44, 95% CI: 0.33–0.55) and clinical diagnoses (specificity 0.76, 95% CI: 0.67–0.85). The sensitivity of the CORE-DI was 0.61 (95% CI: 0.55–0.72) for ICD-10 criteria and 0.67 (95% CI: 0.57–0.77) for DSM-5 criteria. Discussion/Conclusion: The CORE-DI increased the specificity of the depression diagnosis substantially compared to clinical diagnoses and the diagnoses obtained by M.I.N.I. The results point to the usefulness of an elaborated and systematic assessment of the core symptoms in the examination of patients with depressive symptoms and thereby indicate a way for further development of specific diagnostic tools for depression in both clinical and research settings. However, it should be noted that the sensitivity of the CORE-DI was modest, and the psychometric properties of the CORE-DI might be different in other settings with higher or lower prevalence or severity of depressive symptoms.

Background The gut microbiota of children delivered by cesarean section differs from that of children delivered vaginally. In light of the gut-brain axis hypothesis, cesarean section may influence risk of affective disorders. Methods Population based prospective cohort study included Danish children born 1982 through 2001, with follow-up until 2015. The effect of delivery mode on the risk of affective disorders was assessed using a standard Cox model and two types of Cox sibling models. Diagnostic codes or prescriptions for antidepressants and lithium were used to define cases of affective disorders. Results 1,009,444 children were followed for 8,880,794 person-years from the age of 13 years, with relevant covariates available from birth. There are strong calendar time trends in the occurrence of affective disorders with an increasingly younger age at first diagnosis and with a hotspot between the years 2007–2012. Fully adjusted standard Cox models showed an increased risk of affective disorders for both pre-labor (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.08–1.15) and intrapartum (HR, 1.07; 95% CI, 1.05–1.10) cesarean section, compared to vaginal delivery. This effect disappeared in the between–within sibling model for pre-labor (HR, 1.00; 95% CI, 0.94–1.07) but not intrapartum (HR, 1.05; 95% CI, 1.00–1.12) cesarean section. Limitations Interpretation of results from sibling models may not be relevant to children without siblings. Conclusions These results do not support the hypothesis that a delivery-mode dependent change in gut microbiota is a cause of subsequent affective disorders, despite an apparent association with delivery mode.

Objectives: Antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are a key factor in protecting against coronavirus disease 2019 (COVID-19). We examined longitudinal changes in seroprevalence in healthcare workers (HCWs) in Copenhagen and the protective effect of antibodies against SARS-CoV-2. Methods: In this prospective study, screening for antibodies against SARS-CoV-2 (ELISA) was offered to HCWs three times over 6 months. HCW characteristics were obtained by questionnaires. The study was registered at ClinicalTrials.gov, NCT04346186. Results: From April to October 2020 we screened 44 698 HCWs, of whom 2811 were seropositive at least once. The seroprevalence increased from 4.0% (1501/37 452) to 7.4% (2022/27 457) during the period (p < 0.001) and was significantly higher than in non-HCWs. Frontline HCWs had a significantly increased risk of seropositivity compared to non-frontline HCWs, with risk ratios (RRs) at the three rounds of 1.49 (95%CI 1.34–1.65, p < 0.001), 1.52 (1.39–1.68, p < 0.001) and 1.50 (1.38–1.64, p < 0.001). The seroprevalence was 1.42- to 2.25-fold higher (p < 0.001) in HCWs from dedicated COVID-19 wards than in other frontline HCWs. Seropositive HCWs had an RR of 0.35 (0.15–0.85, p 0.012) of reinfection during the following 6 months, and 2115 out of 2248 (95%) of those who were seropositive during rounds one or two remained seropositive after 4–6 months. The 133 of 2248 participants (5.0%) who seroreverted were slightly older and reported fewer symptoms than other seropositive participants. Conclusions: HCWs remained at increased risk of infection with SARS-CoV-2 during the 6-month period. Seropositivity against SARS-CoV-2 persisted for at least 6 months in the vast majority of HCWs and was associated with a significantly lower risk of reinfection.

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants’ PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.

Primary open angle glaucoma is associated with an increased risk of mood and sleep disorders. These adversities have been suggested to relate to a disrupted function of the intrinsically photosensitive retinal ganglion cells (ipRGCs). The ipRGCs are key components in the nonvisual photoreceptive system that mediates light effects on mood, sleep and circadian rhythm. We assessed the diurnal hormone levels, pupillary responses and mood and sleep under seasons with different photoperiods in 24 patients with glaucoma and 24 age- and sex-matched healthy controls to investigate responses to naturalistic seasonal changes in daylight. The patients had moderate-to-advanced glaucoma with substantial visual field defects and reductions in the ipRGC-mediated pupillary responses (

Summary Background Health-care workers are thought to be highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the prevalence of antibodies against SARS-CoV-2 in health-care workers and the proportion of seroconverted health-care workers with previous symptoms of COVID-19. Methods In this observational cohort study, screening was offered to health-care workers in the Capital Region of Denmark, including medical, nursing, and other students who were associated with hospitals in the region. Screening included point-of-care tests for IgM and IgG antibodies against SARS-CoV-2. Test results and participant characteristics were recorded. Results were compared with findings in blood donors in the Capital Region in the study period. Findings Between April 15 and April 23, 2020, we screened 29 295 health-care workers, of whom 28 792 (98·28%) provided their test results. We identified 1163 (4·04% [95% CI 3·82–4·27]) seropositive health-care workers. Seroprevalence was higher in health-care workers than in blood donors (142 [3·04%] of 4672; risk ratio [RR] 1·33 [95% CI 1·12–1·58]; p

This is a case report of a 42-year-old patient, who was admitted to hospital with clinical pneumonia. The only positive test result was for SARS-CoV-2. After a few days of treatment, the patient was discharged in stable condition for isolation at home. The patient had previously had contact with the mental health services and was diagnosed with catatonic schizophrenia but had been without outpatient contact or treatment for the last four years. After seven days he was admitted in a state of severe psychosis. This begs the question if the psychotic relapse was triggered by a neuroinflammatory response caused by SARS-CoV-2.

In previous studies, investigators have reported reduced mortality among women undergoing assisted reproductive technology (ART) treatment, possibly related to selection of healthy women into ART treatment. Our aim in this study was to explore the impact of relevant selection factors on the association between ART treatment and mortality and to explore effect modification by parity. Women treated with ART in fertility clinics in Denmark during 1994-2009 (n = 42,897) were age-matched with untreated women from the background population (n = 204,514) and followed until December 31, 2010. With adjustment for relevant confounders, the risk of death was lower among ART-treated women during the first 2 years after ART treatment (hazard ratio (HR) = 0.68, 95% confidence interval (CI): 0.63, 0.74), but there was no apparent difference after 10 years (HR = 0.92, 95% CI: 0.79, 1.07). Having children prior to ART treatment was associated with markedly reduced mortality (HR = 0.45, 95% CI: 0.38, 0.53), possibly due to better health among fertile women. While the frequencies of previous medical and psychiatric diagnoses among ART-treated and untreated women were similar, differences in disease severity could explain the reduced mortality among ART-treated women, as poor prognosis would make initiation of ART treatment unlikely. The survival advantage among ART-treated women is likely a selection phenomenon rather than a biological phenomenon.

Background Seasonal affective disorder (SAD) is characterized by seasonally recurring depression. Heightened amygdala activation to aversive stimuli is associated with major depressive disorder but its relation to SAD is unclear. We evaluated seasonal variation in amygdala activation in SAD and healthy controls (HC) using a longitudinal design targeting the asymptomatic/symptomatic phases of SAD. We hypothesized increased amygdala activation to aversive stimuli in the winter in SAD individuals (season-by-group interaction). Methods Seventeen SAD individuals and 15 HCs completed an implicit emotional faces BOLD-fMRI paradigm during summer and winter. We computed amygdala activation (SPM5) to an aversive contrast (angry & fearful minus neutral) and angry, fearful and neutral faces, separately. Season-by-group and main effects were evaluated using Generalized Least Squares. In SAD individuals, we correlated change in symptom severity, assessed with The Hamilton Rating Scale for Depression – Seasonal Affective Disorder version (SIGH-SAD), with change in amygdala activation. Results We found no season-by-group, season or group effect on our aversive contrast. Independent of season, SAD individuals showed significantly lower amygdala activation to all faces compared to healthy controls, with no evidence for a season-by-group interaction. Seasonal change in amygdala activation was unrelated to change in SIGH-SAD. Limitations Small sample size, lack of positive valence stimuli. Conclusions Amygdala activation to aversive faces is not increased in symptomatic SAD individuals. Instead, we observed decreased amygdala activation across faces, independent of season. Our findings suggest that amygdala activation to angry, fearful and neutral faces is altered in SAD individuals, independent of the presence of depressive symptoms.

Objective: Approximately, 50% of all individuals with anxiety disorders do not benefit from the "gold standard" treatment, namely cognitive behavioral therapy (CBT). Reliable predictors of treatment effect are lacking. The primary aim of this study was to investigate the predictive value of emotion regulation, attentional control, and attachment style for group-based CBT outcomes in routine clinical settings. Method: A total of 76 patients with anxiety disorders received manual-based group CBT at psychiatric outpatient clinics. Emotion regulation, attachment style, and attentional control were assessed with self-report measures and with an experimental computer-based attentional control task at baseline. The severity of anxiety was assessed at intake, post-treatment, and at a 6-month follow-up. Results: Attentional control, emotion regulation, and attachment avoidance did not predict treatment outcomes. Higher attachment anxiety at baseline was significantly related to poorer outcome. Conclusion: In routine clinical settings, high attachment anxiety may predict poorer outcomes for group-based CBT.

Background Although there is substantial evidence for the role of emotion regulation in the etiology and maintenance of anxiety disorders, knowledge about what contributes to emotion dysregulation is sparse. Attachment style is related to emotion regulation and anxiety symptoms, but these variables have rarely been examined together. Examining emotion dysregulation within the context of anxiety disorders through an attachment theory framework will lead to a better understanding of the etiology and maintenance of anxiety disorders. In the present study we combined theoretically and empirically derived knowledge to examine the mediating role of emotion regulation between attachment dimensions (avoidance and anxiety) and anxiety symptoms. Methods A total of 147 individuals were assessed with Beck Anxiety Inventory (BAI), Experiences in Close Relationships-Revised (ECR-R) and Difficulties in Emotion Regulation Scale (DERS), and statistical mediation analyses were conducted. Results Our results indicate that the significant association between anxiety and attachment anxiety was mediated by emotion dysregulation, whereas attachment avoidance was not significantly related to anxiety when covarying for attachment anxiety. The primary limitation of our study is that data is cross-sectional and so causation cannot be inferred. Secondly, all measures used in this study were derived from self-reported questionnaires, which may be more susceptible to bias. Conclusions Our results suggest that it is not insecure attachment in general that is important in anxiety disorders, but that attachment anxiety is specifically relevant. Thus, clinical interventions for anxiety disorders may improve by targeting attachment related difficulties.

Background Oral clefts (OCs) are among the most common congenital malformations and can have a large impact on the life of the affected individual. Research findings regarding the psychological and psychosocial consequences of OC are inconclusive. Methods Using Danish nationwide registers, we investigated redeemed prescriptions of psychotropic medication during 1996 to 2012 and visits to psychiatrists and psychologists during 1996 to 2011 among individuals born with nonsyndromic OC in Denmark between 1936 and 2009 and a comparison cohort of individuals without OC. This includes 8244 individuals with OC and 82,665 individuals without OC. Results The Cox regression analysis revealed 12% (95% confidence interval [CI], 7 to 16%) increased risk of using any psychotropic medication for individuals with OC. When examining by cleft type, higher risks for medication use were observed in individuals with cleft lip and palate (CLP) or cleft palate (CP) only. The largest increased relative risk was found for use of antipsychotics and stimulants for individuals with CP followed by use of antipsychotics for individuals with CLP. We found increased risk of visits to psychiatrists for individuals with CP and no increased risk for visits to psychologists for either group. Conclusions This study indicates that a small group of individuals with nonsyndromic OC, in particular those with palatal involvement, have greater risk of using psychotropic medications. However, elevated use was also observed among younger individuals with cleft lip (CL) only. There seems to be only a modest increase in visits to health professionals for psychological reasons. Undiagnosed syndromes (e.g., 22q11 deletion syndrome), may, however, contribute to an overestimation of the associations. Birth Defects Research 00:000–000, 2017. © 2017 Wiley Periodicals, Inc.

STUDY QUESTION Are male factor infertility or remaining childless risk factors for unipolar depression among men in assisted reproductive technology (ART) treatment? SUMMARY ANSWER Male factor infertility was not associated with a significantly increased risk of unipolar depression and men remaining childless did not have a significantly increased risk of developing unipolar depression compared to men in ART treatment who became fathers. WHAT IS KNOWN ALREADY Men in medically assisted reproduction due to male factor infertility are more distressed and have more negative emotions such as feelings of loss, stigma and low self-esteem compared to men in fertility treatment due to other infertility diagnosis. Stress is in general a risk factor for depression. However, previous studies show conflicting results whether male factor infertility is a risk factor for depression. STUDY DESIGN, SIZE, DURATION This national, register-based cohort study consisted of 37 913 cohabitant male partners of women in ART treatment recorded in the Danish IVF register (1994–2009). Via a national register, the men’s personal identification number data were linked to the Danish Psychiatric Central Research Register (PCRR) (1969–2009) which records psychiatric diagnoses including unipolar depression, based on the ICD-8 and ICD-10 classification system. PARTICIPANTS/MATERIALS, SETTING, METHODS The full cohort of male partners (n = 37 913) was included in the initial analysis on prevalence of unipolar depression before or after ART treatment initiation. The association between male factor infertility and unipolar depression diagnosis after initiating ART treatment was analysed with Cox regression analysis in a sub-study population of men with the exclusion of men having a depression prior to ART treatment or not having full data on educational level and infertility diagnosis (n = 34 817). MAIN RESULTS AND THE ROLE OF CHANCE Overall, 1.2% (n = 446) of the men were diagnosed with unipolar depression either before initiating ART treatment (n = 146) or during follow-up (n = 300). In all, 76.0% of men with depression prior to or after ART treatment achieved fatherhood compared to 82.3% of men without depression (P LIMITATIONS, REASONS FOR CAUTIONS Only severe cases of depression are recorded and included in this national register-based study given that only men with clinically diagnosed unipolar depression recorded in a psychiatric hospital (in-patient and out-patient) are included in the Danish PCRR. It is difficult to completely rule out an association between the exposures and depression as this outcome is so rare, and therefore the results are still statistically uncertain despite a large cohort. Furthermore, only men in ART treatment were included in this study, and caution should be taken in generalising findings to the total population of men in all areas of medically assisted reproduction or infertile men who have not sought treatment. WIDER IMPLICATIONS OT THE FINDINGS This large national cohort study suggests that despite evidence showing that male factor infertility is a potential severe stressor for men, which can increase psychological distress and negative emotions, infertile men in ART treatment and men remaining childless after ART are not at a significantly increased risk of developing clinically diagnosed unipolar depression. STUDY FUNDING/COMPETING INTERESTS C.S.S. was funded by unrestricted research grants received by Lone Schmidt from The Danish Health Insurance Foundation (J.nr. 2008B105) and Merck Sharp & Dohme (MSD). The sponsors had no influence on how data were retrieved and analysed or on the conclusions of the study. C.S.S. and L.S. have declared conflicts of interests; the remaining co-authors have no conflicts of interests to declare. TRIAL REGISTRATION NUMBER Not applicable.

Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P < 0.001). Further, the change in serotonin transporter was sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract.

Electroconvulsive therapy (ECT) is the most effective and fast-acting treatment for severe depression but associated with troublesome cognitive side-effects. Systemically administered erythropoietin (EPO) crosses the blood-brain-barrier and is a promising treatment for cognitive dysfunction in a wide array of neuropsychiatric and neurological disorders. In this study we trained rats to locate a submerged platform in a water maze and then subjected them to electroconvulsive stimulations (ECS, the rodent equivalent to ECT) and EPO treatment. We then analysed their ability to remember and relearn the location of the platform. In addition, we examined "wall-clinging" (thigmotaxis), a behavioural indicator of stress. ECS caused significant deficit in a probe trial administered after three weeks (nine stimulations) as well as one week (six stimulations) of treatment, indicative of induction of retrograde amnesia. ECS had no effect on relearning of the water maze task or performance in a subsequent probe trial. EPO treatment did not ameliorate the ECS-induced retrograde amnesia, but after nine ECS stimulations the animals that had received EPO relearned the position of the hidden platform faster than the animals that had not. We also found EPO to decrease "wall-clinging" behaviour, suggesting an effect of EPO on the stress response in rats. Thus, we establish the Morris Water Maze as a suitable model for ECS-induced memory loss in rats and provide some evidence for potential beneficial effects of EPO.

Circadian and seasonal rhythm disturbances are prominent in patients with psychiatric disorders. Properly timed and dosed light of specific spectral composition stabilises mood and sleep through serotonergic mechanisms and through input to the master circadian clock in the hypothalamus. Correctly administered, light can be used as an effective treatment for seasonal and non-seasonal depression and for stabilising the sleep-wake cycle. Blocking blue light in the evening may provide a non-pharmacological anti-manic tool. Current developments use dynamic lighting built into somatic and psychiatric hospitals to maximise the beneficial effects of light.

Background Hypotheses concerning adverse effects of changes in microbiota have received much recent attention, but unobserved confounding makes them difficult to test. We investigated whether surrogate markers for potential adverse microbiota change in infancy affected autism risk, addressing unobserved confounding using a sibling study design. Methods This is a population-based, prospective cohort study including all singleton live births in Denmark from 1997 to 2010. The exposure variables were cesarean delivery and antibiotic use in the first 2 years of life. The outcome was a subsequent autism diagnosis. We used the between- and within-sibling model and compared it with sibling-stratified Cox models and simpler standard Cox models that ignored sibship. Results Of our study population including 671,606 children, who were followed for up to 15 years (7,341,133 person-years), 72% received antibiotics, 17.5% were delivered by cesarean, and 1.2% (8,267) developed autism. The standard Cox models predicted that both cesarean (compared with vaginal) delivery and antibiotics increased the risk of autism. In the sibling-stratified Cox model, only broader spectrum antibiotics were associated with increased risk of autism: hazard ratio (HR) = 1.16 (95% confidence interval = 1.01, 1.36). The between-within model estimated no exposure effects: intrapartum cesarean HR = 1.06 (0.89, 1.26); prelabor cesarean HR = 0.97 (0.83, 1.15); exclusively penicillin HR = 1.05 (0.93, 1.18); and broader spectrum antibiotics HR = 1.05 (0.95, 1.16). Conclusions The between-within model rendered more precise estimates than sibling-stratified Cox models, and we believe that it also provided more valid estimates. Results from these preferred models do not support a causal relation between antibiotic treatment during infancy, cesarean delivery, and autism. See video abstract at, http://links.lww.com/EDE/B432.

Background Increasing attention deficit hyperactivity disorder (ADHD) incidence has been proposed to be caused by factors influencing microbiota in early life. We investigated the potential causality between ADHD and two surrogate markers for changes in children's microbiota: birth delivery mode and early childhood antibiotic use. Method This population-based, prospective cohort study linked nationwide registers of data for native Danish singleton live births in Denmark from 1997 to 2010. Exposure variables were delivery mode and antibiotic use during the first 2 years of life. The main outcome measure was ADHD diagnosis or redeemed ADHD medication prescriptions. For statistical analysis, we used both advanced sibling models and a more traditional approach. Results We included 671,592 children, followed from their second birthday in the period 1999-2014 for 7,300,522 person-years. ADHD was diagnosed in 17,971. In total, 17.5% were born by cesarean delivery, and 72% received antibiotic treatment within their first 2 years of life. In the adjusted between-within sibling survival model, mode of delivery or antibiotics had no effect on ADHD when compared with vaginal delivery or no antibiotic treatment as hazard ratios were 1.09 (95% confidence interval 0.97-1.24) for intrapartum cesarean, 1.03 (0.91-1.16) for prelabor cesarean, 0.98 (0.90-1.07) for penicillin, and 0.99 (0.92-1.06) for broader spectrum antibiotics. In a sibling-stratified Cox regression, intrapartum cesarean was associated with increased ADHD risk, but other exposures were not. In a descriptive, nonstratified Cox model, we found increased risk for ADHD for all exposures. Conclusions Detailed family confounder control using the superior between-within model indicates that cesarean delivery or use of antibiotics during the first 2 years of life does not increase ADHD risk. Therefore, our study suggests that changes in children's microbiota related to cesarean delivery or antibiotic use, do not cause ADHD.

To investigate whether administration of an oral dose of 6 mg melatonin before bedtime perioperatively in breast cancer surgery could change sleep outcomes measured by actigraphy.This paper reports secondary outcomes from a double-blind, placebo-controlled, randomized clinical trial where patients received 6 mg melatonin (n = 27) or placebo (n = 21) approximately 60 minutes before bedtime 3 nights preoperatively until at least one week postoperatively. Participants were monitored in the entire period with actigraphy, and were instructed to complete visual analogue scale (VAS) for sleep, and the Karolinska Sleepiness Scale (KSS) each morning.Administration of 6 mg oral melatonin approximately 1 hour before bedtime resulted in significantly increased sleep efficiency and reduced wake after sleep onset for the entire 2-week postoperative period. No other significant differences for actigraphy determined sleep outcomes or subjective outcome parameters in the perioperative period were found between the groups. Overall, the patients sleep outcomes were within normal ranges and no participants had pathological sleep disturbances.Melatonin significantly changed sleep efficiency and wake after sleep onset after surgery, but had no effects on other objective sleep outcomes or on subjective sleep quality (VAS and KSS).

Background and Aim: Improvement in patients admitted to inpatient wards with severe depression is slow, and such patients are often discharged with residual symptoms which put them at risk for relapse. New treatments that can speed up recovery are highly desired. This naturalistic follow-up study in a specialized affective disorders unit investigated the impact of daylight on the length of hospital stay and improvement of depression. Methods: For a period of 1 year, we collected data on sociodemographics, length of stay, vitamin D, and depression severity for patients in an inpatient affective disorders unit. The ward is located with one facade that faces southeast (SE); the opposite one faces northwest (NW) and receives far less light and no direct sunlight during winter. Results: SE-facing rooms received far more daylight than NW-facing rooms. The length of stay was significantly lower in the SE rooms, i.e., 29.2 (±26.8) versus 58.8 (±42.0) days in the NW rooms (p = 0.01). There was a statistically nonsignificant greater reduction of 52.2% in depression severity for the patients staying in the SE rooms compared to 42.2% in the NW rooms, which may nevertheless be clinically relevant. Conclusion: Due to the study design, no causality for the observed difference in length of stay can be given, but the results support findings in previous studies of the importance of architectural orientation providing natural daylight as a factor for improvement.

BackgroundLight severely affects the occurrence of seasonal affective disorder (SAD).AimsTo compare the prevalence of SAD in persons with severe visual impairment and persons with full sight, and in persons with severe visual impairment with or without light perception.MethodThis cross-sectional study assessed the Global Seasonality Score (GSS) and the prevalence of SAD among 2781 persons with visual impairment and 4099 persons with full sight using the Seasonal Pattern Assessment Questionnaire (SPAQ).ResultsRespondents with visual impairment had significantly higher GSS and prevalence of SAD compared with full sight controls, PConclusionsThe study showed a highly significant association between visual impairment and SPAQ-defined SAD parameters, supporting the hypothesis that decreased retinal light input plays a role in the pathogenesis of SAD.

Stress-induced allostatic load affects a variety of biological processes including synaptic plasticity, angiogenesis, oxidative stress, and inflammation in the brain, especially in the hippocampus. Erythropoietin (EPO) is a pleiotropic cytokine that has shown promising neuroprotective effects. Recombinant human EPO is currently highlighted as a new candidate treatment for cognitive impairment in neuropsychiatric disorders. Because EPO enhances synaptic plasticity, attenuates oxidative stress, and inhibits generation of proinflammatory cytokines, EPO may be able to modulate the effects of stress-induced allostatic load at the molecular level. The aim of this study was therefore to investigate how EPO and repeated restraint stress, separately and combined, influence (i) behavior in the novelty-suppressed feeding test of depression/anxiety-related behavior; (ii) mRNA levels of genes encoding proteins involved in synaptic plasticity, angiogenesis, oxidative stress, and inflammation; and (iii) remodeling of the dendritic structure of the CA3c area of the hippocampus in male rats. As expected, chronic restraint stress lowered the number of CA3c apical dendritic terminals, and EPO treatment reversed this effect. Interestingly, these effects seemed to be mechanistically distinct, as stress and EPO had differential effects on gene expression. While chronic restraint stress lowered the expression of spinophilin, tumor necrosis factor α, and heat shock protein 72, EPO increased expression of hypoxia-inducible factor-2α and lowered the expression of vascular endothelial growth factor in hippocampus. These findings indicate that the effects of treatment with EPO follow different molecular pathways and do not directly counteract the effects of stress in the hippocampus.

Neuronal genotoxic insults from oxidative stress constitute a putative molecular link between stress and depression on the one hand, and cognitive dysfunction and dementia risk on the other. Oxidative modifications to DNA are repaired by specific enzymes; a process that plays a critical role for maintaining genomic integrity. The aim of the present study was to characterize the pattern of cerebral DNA repair enzyme regulation after stress through the quantification of a targeted range of gene products involved in different types of DNA repair. 72 male Sprague–Dawley rats were subjected to either restraint stress (6 h/day) or daily handling (controls), and sacrificed after 1, 7 or 21 stress sessions. The mRNA expression of seven genes ( Ogg1, Ape1, Ung1, Neil1, Xrcc1, Ercc1, Nudt1 ) involved in the repair of oxidatively damaged DNA was determined by quantitative real time polymerase chain reaction in the prefrontal cortex (PFC) and hippocampus (HC). DNA repair gene expression in PFC exhibited a general trend towards an induction after acute stress and a decrease after subchronic exposure compared to control animals. After chronic stress, a normalization towards control levels was observed. A similar pattern was seen in HC, but with overall smaller effects and without the induction after acute stress. Nuclear DNA damage from oxidation as measured by the comet assay was unaffected by stress in both regions. We conclude that psychological stress have a dynamic influence on brain DNA repair gene expression; however, since we were unable to identify concurrent changes in DNA damage from oxidation, the down-stream consequences of this regulation, if any, remains unclear.

Cognitive dysfunction is a core feature in a range of neuropsychiatric disorders which reduces patients' workforce capacity - the largest socio-economic cost of these disorders. Nevertheless, there is no clinically available medical treatment with robust and enduring efficacy on cognitive deficits in most neuropsychiatric conditions. Recent research has shown that erythropoietin may have beneficial effects on cognitive dysfunction across neuropsychiatric disorders, including bipolar and unipolar disorders, schizophrenia, Parkinson's disease and multiple sclerosis.