Influence of repeated maximal exercise testing on biomarkers and fatigue in sarcoidosis

Fatigue in the immune mediated inflammatory disease sarcoidosis is thought to be associated with impaired exercise tolerance. This prospective study assessed fatigue and recuperative capacity after repeated exercise, and examined whether changing concentrations in biomarkers upon exercise are associated with fatigue.Twenty sarcoidosis patients and 10 healthy volunteers performed maximal cardiopulmonary exercise tests on two successive days. Concentrations of cytokines, stress hormones, ACE and CK were assessed before and after the two exercise tests, and 3 days thereafter. All participants completed a sleep diary.Severely fatigued patients showed significant lower VO₂ max (p = 0.038, p = 0.022) and maximal workload (p = 0.034, p = 0.028) on both exercise tests compared to healthy controls. No impairment of maximal exercise testing was demonstrated during the second cycling test in any group. Fatigue was not correlated with changes in concentrations of biomarkers upon exercise. Severely fatigued patients rated both tests as significantly more fatiguing, and reported significant lower mean subjective night sleeping time during the testing period.Fatigue in sarcoidosis patients cannot be objectified by reduction of exercise capacity after repeated maximal exercise testing, and is not correlated with significant changes in biomarkers. Severe fatigue is only and consistently featured by patient reported outcomes.     

Cerebrospinal fluid inflammatory markers in Parkinson’s disease – Associations with depression,fatigue, and cognitive impairment

Neuroinflammation may be involved in the pathophysiology of Parkinson’s disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. The aim of this study was to measure inflammatory markers in cerebrospinal fluid (CSF) samples from PD patients and a reference group, and to investigate correlations between non-motor symptoms and inflammation.We quantified C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein 1-β in CSF samples from PD patients (N = 87) and the reference group (N = 33). Sixteen of the PD patients had a dementia diagnosis (PDD). We assessed symptoms of fatigue, depression, anxiety and cognitive function using the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and the Mini Mental State Examination, respectively.There were no significant differences in mean levels of inflammatory markers between PD patients and the reference group. After controlling for age, gender and somatic illness, patients with PDD had significantly higher levels of CRP compared to non-demented PD patients (p = 0.032) and the reference group (p = 0.026). Increased levels of inflammatory markers in CSF were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition in the entire PD group. After controlling for PD duration, age, gender, somatic illness and dementia diagnosis, high CRP levels were significantly associated with more severe symptoms of depression (p = 0.010) and fatigue (p = 0.008), and high MCP-1 levels were significantly associated with more severe symptoms of depression (p = 0.032).Our results indicate that non-motor features of PD such as depression, fatigue, and cognitive impairment are associated with higher CSF levels of inflammatory markers.     

Evaluation of the psychometric properties of the PROMIS Cancer Fatigue Short Form with cancer patients

ObjectiveFatigue is common among cancer patients and adversely impacts quality of life. As such, it is important to measure fatigue accurately in a way that is not burdensome to patients. The 7-item Patient Reported Outcome Measurement Information System (PROMIS) Cancer Fatigue Short Form scale was recently developed using item response theory (IRT). The current study evaluated the psychometric properties of this scale in two samples of cancer patients using classical test theory (CTT).MethodsTwo samples were used: 121 men with prostate cancer and 136 patients scheduled to undergo hematopoietic cell transplantation (HCT) for hematologic cancer. All participants completed the PROMIS Cancer Fatigue Short Form as well as validated measures of fatigue, vitality, and depression. HCT patients also completed measures of anxiety, perceived stress, and a clinical interview designed to identify cases of cancer-related fatigue.ResultsPROMIS Cancer Fatigue Short Form items loaded on a single factor (CFI = 0.948) and the scale demonstrated good internal consistency reliability in both samples (Cronbach's alphas > 0.86). Correlations with psychosocial measures were significant (p values < .0001) and in the expected direction, offering evidence for convergent and concurrent validity. PROMIS Fatigue scores were significantly higher in patients who met case definition criteria for cancer-related fatigue (p < .0001), demonstrating criterion validity.ConclusionThe current study provides evidence that the PROMIS Cancer Fatigue Short Form is a reliable and valid measure of fatigue in cancer patients.     

Preoperative inflammatory biomarkers and neurovegetative symptoms in peritoneal carcinomatosis patients

BackgroundInflammation plays a central role in peritoneal carcinomatosis (PC) etiology and progression, and circulating levels of inflammatory biomarkers prior to surgery predict progression-free and overall survival in PC patients. Depression and fatigue are prevalent among PC patients, and experimental research shows that these symptoms may be mediated by proinflammatory cytokines. As yet unstudied is the possibility that the heightened levels of inflammatory markers in PC patients may contribute to their experience of common neurovegetative symptoms.MethodsValidated self-report measures of fatigue, depressive symptoms, and quality of life were administered to 64 patients scheduled to undergo aggressive surgical treatment for PC. Serum samples were collected the morning of surgery, and ELISAs were conducted to quantify circulating IL-6, CRP, and TNF-α levels.ResultsConsistent with hypotheses, higher IL-6 levels were associated with more severe fatigue (β = −.39, p < .01) and neurovegetative symptoms of depression (β = .30, p < .05). IL-6 was also related to poorer physical quality of life (β = −.28, p < .05). CRP showed similar significant relationships with fatigue and physical quality of life. Inflammatory biomarkers were not significantly related to emotional symptoms of depression or to emotional or social functioning aspects of quality of life, and TNF-α levels were not related to patient-reported measures.ConclusionPreoperative inflammatory activity may contribute to patients’ experiences of fatigue and neurovegetative depressive symptoms as well as impaired quality of life. These biological mechanisms warrant consideration in the clinical management of neurovegetative symptoms in PC patients.     

Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways

PurposeNeuroinflammatory mechanisms are associated with fatigue in neurodegenerative conditions such as Parkinson’s. The symptoms in Parkinson’s including fatigue are thought to be related to α-synuclein overexpression. This study investigated genomic correlates of fatigue experienced by men with prostate cancer receiving external beam radiation therapy (EBRT).Patients and methodsSixteen men with non-metastatic prostate cancer who were scheduled to receive EBRT were enrolled. Fatigue scores and blood were obtained at baseline (prior to EBRT, D0); one hour following initiation of EBRT (D1), day 7 (D7), day 14 (D14), midpoint (days 19–21, D21), completion (days 38–42, D42), and four weeks post-EBRT (days 68–72, D72). Gene expression profiling using microarray analysis was performed from peripheral blood and confirmatory qPCR and protein (ELISA) analyses verified the microarray results. Correlations between fatigue and gene/protein expressions were determined using a mixed model approach.ResultsMicroarray data showed significant, differential expression of 463 probesets following EBRT. SNCA had a 2.95-fold change at D21from baseline. SNCA expression was confirmed by qPCR (p < 0.001) and ELISA (p < 0.001) over time during EBRT. Fatigue scores were significantly correlated with SNCA gene expression on D14 (r = 0.55, p < 0.05) and plasma α-synuclein concentrations on D42 of EBRT (r = 0.54, p = 0.04).ConclusionFatigue experienced during EBRT may be mediated by α-synuclein overexpression. Alpha-synuclein may serve as a useful biomarker to understand the mechanisms and pathways related to the development of fatigue in this population.     

Sex differences in the relationship between obesity,C-reactive protein,physical activity,depression, sleep quality and fatigue in older adults

Fatigue is a serious health concern in the elderly. Sex differences exist in adiposity, systemic inflammation, physical activity/fitness and fatigue; however, the relations among these variables remain inadequately characterized impeding the development of fatigue prevention strategies. Measures of adiposity, C-reactive protein, physical activity, aerobic fitness, fatigue, sleep quality and depression were obtained from 127 community-dwelling older adults. Although similar in age (70 y) and BMI (28.0 kg/m²) women (n = 80) reported 63% greater fatigue than men (p = 0.04). Adiposity (r = 0.44), CRP (r = 0.29), physical activity (r = ?0.26) and fitness (r = ?0.41) were related to fatigue in women (all p < 0.05), but not in men. Depression was also related to fatigue in women (r = 0.37), and was the only variable related to fatigue in men (r = 0.42). In women, fatigue was independently explained (all p < 0.05) by CRP (6.6%), depression (6.3%), physical activity (5.8%), and adiposity (3.9%); however, in men, only depression explained variance in fatigue (12.0%). CRP was 40% higher and adiposity 12% higher in women reporting fatigue compared to those with no fatigue; no such differences existed in men. Obese women perceived a greater degree of fatigue than non-obese women, but this was not the case in men. Women report more fatigue than men which was independently associated with inflammation, depression, physical activity and adiposity, whereas in men the only independent predictor was depression. Strategies to prevent fatigue may differ in older women and men, especially with regard to inflammation, physical activity and adiposity.     

A role for inflammatory metabolites as modulators of the glutamate N-methyl-d-aspartate receptor in depression and suicidality

BackgroundPatients with depression and suicidality suffer from low-grade neuroinflammation. Pro-inflammatory cytokines activate indoleamine 2,3-dioxygenase, an initial enzyme of the kynurenine pathway. This pathway produces neuroactive metabolites, including quinolinic- and kynurenic acid, binding to the glutamate N-methyl-d-aspartate-receptor, which is hypothesized to be part of the neural mechanisms underlying symptoms of depression. We therefore hypothesized that symptoms of depression and suicidality would fluctuate over time in patients prone to suicidal behavior, depending on the degree of inflammation and kynurenine metabolite levels in the cerebrospinal fluid (CSF).MethodsWe measured cytokines and kynurenine metabolites in CSF, collected from suicide attempters at repeated occasions over 2 years (total patient samples n = 143, individuals n = 30) and healthy controls (n = 36). The association between the markers and psychiatric symptoms was assessed using the Montgomery Åsberg Depression Rating Scale and the Suicide Assessment Scale.ResultsQuinolinic acid was increased and kynurenic acid decreased over time in suicidal patients versus healthy controls. Furthermore, we found a significant association between low kynurenic acid and severe depressive symptoms, as well as between high interleukin-6 levels and more severe suicidal symptoms.ConclusionsWe demonstrate a long-term dysregulation of the kynurenine pathway in the central nervous system of suicide attempters. An increased load of inflammatory cytokines was coupled to more severe symptoms. We therefore suggest that patients with a dysregulated kynurenine pathway are vulnerable to develop depressive symptoms upon inflammatory conditions, as a result the excess production of the NMDA-receptor agonist quinolinic acid. This study provides a neurobiological framework supporting the use of NMDA-receptor antagonists in the treatment of suicidality and depression.     

Double blind trial of adjunctive valacyclovir in individuals with schizophrenia who are seropositive for cytomegalovirus

ObjectiveTo investigate if adjunctive valacyclovir, an antiviral medication, reduces symptoms of persistent schizophrenia in individuals who are seropositive for cytomegalovirus (CMV).MethodN = 47 CMV seropositive schizophrenia outpatients were randomly assigned to receive valacyclovir 1 g twice daily (n = 24) or placebo (n = 23) for 16 weeks after a 2-week placebo run-in. Symptoms were assessed biweekly.ResultsThere was no significant difference in the change of positive, negative, general, or total PANSS symptoms between the valacyclovir vs. the placebo group.ConclusionsThe study did not demonstrate benefit of adjunctive valacyclovir for schizophrenia individuals with persistent symptoms who are CMV seropositive.     

Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

PurposeTo examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy.MethodsData from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed.ResultsFatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square = 16.762; df = 3; p = 0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square = 11.462; df = 3; p = 0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square = 11.547; df = 3; p = 0.009).ConclusionsOne third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.     

Deployment-related severe fatigue with depressive symptoms is associated with increased glucocorticoid binding to peripheral blood mononuclear cells

Severe fatigue and co-morbid depressive symptoms are frequently reported by recently deployed military personnel. Stress can induce lasting changes in the negative feedback regulation of the hypothalamic–pituitary–adrenal axis (HPA-axis) and the regulation of the immune system by cortisol. Since these actions of cortisol are modulated via glucocorticoid receptors (GR), we investigated the effect of deployment and of deployment-related fatigue on glucocorticoid binding to peripheral blood mononuclear cells (PBMCs) in a prospective design. Psychological assessments and blood sample collection took place before and one and six months after deployment. Participants were selected from a larger group and assigned to three groups based on their level of fatigue and depressive symptoms six months after deployment. We compared fatigued participants without depressive symptoms (n = 21), fatigued participants with depressive symptoms (n = 14) and non-fatigued participants without depressive symptoms (n = 21). Fatigued participants with depressive symptoms at six months after deployment had higher glucocorticoid binding to PMBCs than the other two groups at all three time points. Notably, this difference was already present before deployment. There was no effect of deployment on glucocorticoid binding to PBMCs. The observed differences in glucocorticoid binding were not related to pre-existing group differences in psychological symptoms. No group differences were observed in the composition of the PBMC population and plasma cortisol levels. These results indicate that high glucocorticoid binding to PBMCs might represent a vulnerability factor for the development of severe fatigue with depressive symptoms after a sustained period of stress, such as deployment.     

Depression and anxiety among high-risk obstetric inpatients

ObjectiveTo assess the following among women hospitalized antenatally due to high-risk pregnancies: (1) rates of depression symptoms and anxiety symptoms, (2) changes in depression symptoms and anxiety symptoms and, (3) rates of mental health treatment.MethodsSixty-two participants hospitalized for high-risk obstetrical complications completed the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder 7-item scale (GAD-7) and Short-Form 12 weekly until delivery or discharge, and once postpartum.ResultsAverage length of total hospital stay was 8.3±7.6days for women who completed an initial admission survey (n= 62) and 16.3±8.9 (n= 34), 25.4±10.2 (n= 17) and 35±10.9 days (n= 9) for those who completed 2, 3 and 4 surveys, respectively. EPDS was ≥ 10 in 27% (n= 17) and GAD-7 was ≥ 10 in 13% (n= 8) of participants at initial survey. Mean anxiety (4.2±6.5 vs. 5.2±5.1, p= .011) and depression (4.4±5.6 vs. 6.9±4.8, p= .011) scores were lower postpartum compared to initial survey. Past mental health diagnosis predicted depression symptoms [odds ratio (OR)=4.54; 95% confidence interval (CI) 1.91–7.17] and anxiety symptoms (OR=5.95; 95% CI 3.04–8.86) at initial survey; however, 21% (n= 10) with no diagnostic history had EPDS ≥ 10. Five percent (n= 3) received mental health treatment during pregnancy.ConclusionHospitalized high-risk obstetrical patients may commonly experience depression symptoms and/or anxiety symptoms and not receive treatment. A history of mental health treatment or diagnosis was associated with depression symptoms or anxiety symptoms in pregnancy. Of women with an EPDS ≥ 10, > 50% did not report a past mental health diagnosis.     

Fatigue in primary Sjögren’s syndrome – A link to sickness behaviour in animals?

Interleukin-1β (IL-1β) is involved in the regulation of sickness behaviour in response to infection and inflammation in animals. Human fatigue can be considered an element of sickness behaviour and is a prominent and often disabling phenomenon in autoimmune diseases such as primary Sjögren’s syndrome (PSS). The role of the IL-1 system in the fatigue of patients with PSS was explored.A cerebrospinal fluid (CSF) analysis of IL-1β, IL-1Ra, and IL-1sRII was performed in 54 PSS patients and 53 control subjects. Fatigue was evaluated in the patients using the Fatigue Severity Scale (FSS) and a fatigue visual analogue scale (VAS); mood was evaluated using the Beck Depression Inventory (BDI).There were higher CSF levels of IL-1Ra pg/mL in PSS patients vs. controls (median 38.4: range 15.4–81.7 vs. 33.7: 7.3–163.1, p = 0.026). Fatigue VAS scores were associated with increasing CSF levels of IL-1Ra in PSS patients (R² = 0.11, p = 0.015). In a subgroup analysis of the non-depressed PSS patients (N = 37; 69%), the association between VAS scores and IL-1Ra was even stronger (R² = 0.20, p = 0.006). The positive association between VAS scores and IL-1Ra remained significant in a multiple regression analysis adjusting for age and BDI scores.Increased levels of IL-1Ra in the CSF are associated with increasing fatigue in PSS patients, indicating that the activated IL-1 system is a possible biological factor associated with fatigue.     

The effect of cigarette smoking on vitamin D level and depression in male patients with acute ischemic stroke

ObjectiveThe association between low vitamin D levels and depression has been well documented in nonstroke subjects. Accumulating evidence shows that low vitamin D levels may be also associated with depression post stroke. Cigarette smoking was associated with lower vitamin D levels. The purposes of this study were to compare vitamin D levels in smokers to nonsmokers and examine the association between vitamin D levels and depression symptoms in patients with acute ischemic stroke.Materials and methodsSerum levels of 25-hydroxyvitamin D [25(OH)D] were measured in 194 males within 24 h after admission: 116 smokers and 78 nonsmokers. Depression symptoms were assessed with the 17-item Hamilton Depression Scale (HAMD-17). Patients with the HAMD-17 score >7 were identified to have depression symptoms.ResultsThe chi-square test showed that the frequency of depression in the smoker group was 23.3% (27/116), which was significantly higher than that in the nonsmoker group (11.5% = 9/78), with an odds ratios (OR) of 2.33 (95% CI: 1.03–5.27; χ² = 4.25, df = 1, p = 0.039, φ = 0.15). Vitamin D levels were significantly lower in smokers than in nonsmokers (52.4 ± 20.8 vs 61.7 ± 19.2; F = 9.88, p = 0.002), with an effect size of 0.05 (η_p²). Patients with depression symptoms showed lower vitamin D levels than those with no depression symptoms (49.2 ± 19.6 vs 57.7 ± 20.6; F = 5.03, p = 0.03), with an effect size of 0.03 (η_p²).ConclusionHigher rates of depression in smokers with acute ischemic stroke may be associated with lower vitamin D levels induced by smoking.     

The link between emotion regulation,social functioning,and depression in boys with ASD

PurposeSymptoms of depression are common in children and adolescents with an autism spectrum disorder (ASD), but information about underlying developmental factors is limited. Depression is often linked to aspects of emotional functioning such as coping strategies, but in children with ASD difficulties with social interactions are also a likely contributor to depressive symptoms.MethodologyWe examined several aspects of emotional coping (approach, avoidant, maladaptive) and social functioning (victimization, negative friendship interactions) and their relation to depression symptoms in children with ASD (N = 63) and typically developing (TD) peers (N = 57). Children completed a battery of self-report questionnaires.ResultsLess approach and avoidant, but more maladaptive coping strategies, and poor social functioning were uniquely associated with more symptoms of depression in children with ASD. Only less approach and more maladaptive coping were uniquely associated with depression severity in TD boys.ConclusionsUnlike TD boys, boys with ASD who report using avoidant strategies to deal with stressful situations report fewer symptoms of depression, suggesting that this may be an adaptive emotion regulation strategy. However, understanding the role of over-arousal in this process, inferences about long-term effects of this strategy, its causality and direction of effects will require additional research.     

Stealing behavior and impulsivity in individuals with kleptomania who have been arrested for shoplifting

ObjectivesKleptomania is characterized by strong urges to steal and is one of only a few psychiatric disorders defined by illegal behaviors, but the clinical characteristics of individuals with kleptomania who have faced legal consequences due to their behavior are poorly understood.MethodFrom 2001 to 2012, we recruited 107 adult participants with DSM-IV kleptomania. Participants with a history of shoplifting-related arrest (N = 82) were compared with those who had no such history (N = 25) on demographics, clinical features, and a self-report measure of impulsivity.ResultsParticipants whose shoplifting had resulted in arrest had higher self-rated impulsivity on a weak trend level (Eysenck Impulsiveness Questionnaire), with large to very large effect size (Cohen's d = 1.12). Group comparisons showed no significant differences in terms of overall functioning (d = 0.60), time spent stealing (d = 0.73), frequency of stealing behavior (d = 0.33), psychiatric comorbidity, or severity of kleptomania symptoms.ConclusionsLegal problems in kleptomania may be associated with generalized deficits in inhibitory control independent of kleptomania symptom severity. These findings emphasize the need for treatment to improve functional status in individuals with kleptomania and reduce the social and economic costs associated with reoffending.     

Testing alternative factor models of PTSD and the robustness of the dysphoria factor

ObjectivesThis study first aimed to examine the structure of self-reported posttraumatic stress disorder (PTSD) symptoms using three different samples. The second aim of the paper was to test the robustness of the factor analytic model when depression scores were controlled for.DesignBased on previous factor analytic findings and the DSM-IV formulation, six confirmatory factor models were specified and estimated that reflected different symptom clusters. The best fitting model was subsequently re-fitted to the data after including a depression variable.MethodsThe analyses were based on responses from 973 participants across three samples. Sample 1 consisted of 633 parents who were members of ‘The National Association of Infant Death’ and who had lost a child. Sample 2 consisted of 227 victims of rape, who completed a questionnaire within 4 weeks of the rape. Each respondent had been in contact with the Centre for Rape Victims (CRV) at the Aarhus University Hospital, Denmark. Sample 3 consisted of 113 refugees resident in Denmark. All participants had been referred to a treatment centre which focused on rehabilitating refugees through treatment for psychosocial integration problems (RRCF: Rehabliterings og Revliderings Centre for Flygtninge). In total 500 participants received a diagnosis of PTSD/sub-clinical PTSD (Sample 1, N = 214; 2, N = 176; 3, N = 110).ResultsA correlated four-factor model with re-experiencing, avoidance, dysphoria, and arousal factors provided the best fit to the sample data. The average attenuation in the factor loadings was highest for the dysphoria factor (M = ?.26, SD = .11) compared to the re-experiencing (M = ?.14, SD = .18), avoidance (M = ?.10, SD = .21), and arousal (M = ?.09, SD = .13) factors.ConclusionsWith regards to the best fitting factor model these results concur with previous research findings using different trauma populations but do not reflect the current DSM-IV symptom groupings. The attenuation of dysphoria factor loadings suggests that dysphoria is a non-specific component of PTSD.     

Comparing how co-morbid depression affects individual domains of functioning and life satisfaction in schizophrenia

ObjectiveDepression in schizophrenia is often associated with reduced life satisfaction. Yet, it is not clear how depression influences different functioning domains. The relative impact across objective and subjective quality of life (QOL) has also not been clearly compared. This study sought to examine the differences in individual QOL indicators between schizophrenia patients with and without co-morbid depression. This was completed separately for objective and subjective QOL.Method57 patients with schizophrenia/schizoaffective disorder were classified into groups with (DP: N = 31, M = 45.81, SD = 10.29) and without depression (NDP: N = 26, M = 40.54, SD = 11.00) using MADRS scores. Objective and subjective QOL was assessed using Lehman's (1988) QOL Interview using five domains: daily activities and functioning, family relations, social relations, safety and health. z-scores were created for these domains (objective and subjective) based on responses from 44 healthy controls (M = 39.80, SD = 13.94).ResultsObjectively, DP patients had significantly reduced social interaction frequency compared to HCs. Subjectively, DP patients had significantly poorer scores than HCs on all five domains, and additionally reported poorer satisfaction with daily activities and health compared with the NDP group.ConclusionsPresence of depression in schizophrenia results in reduced self-reported life satisfaction across a broad spectrum of QOL domains. Objectively, depression resulted in decreased interactions with friends and peers, i.e. greater social isolation. The findings support the need to continue developing and implementing peer support groups in schizophrenia, a challenging task especially in the face of depression. More broadly, the assessment of depression in other illnesses is recommended.     

Evaluating the effects of amantadin,modafinil and acetyl-l-carnitine on fatigue in multiple sclerosis – result of a pilot randomized,blind study

ObjectiveFatigue affects more than 60% of multiple sclerosis (MS) patients and is one of the most troublesome symptoms of the disease. Current treatment options for MS fatigue include amantadine, modafinil and acetyl-l-carnitine (ALCAR). The aim of our study was to compare efficacy of amantadine, modafinil and ALCAR with placebo in patients with MS.MethodsPatients with MS and a disability level ≤5.5 on the Kurtzke Expanded Disability Status Scale (EDSS) and fatigue were included in the study. Patients were assigned to a one month treatment with either amantadine 200 mg, ALCAR 2 g, modafinil 200 mg or placebo. Efficacy of the treatment was evaluated by using the modified fatigue impact scale (MFIS).ResultsSixty patients were included in the study (39 females). The mean age of patients was 38 ± 6.7 years and the mean disease duration was 6.6 ± 1.2 years. Contrast analysis showed significantly lower mean MFIS score after one month in patients on amantadine compared to placebo (mean difference = 17.3, p = 0.001). There was also a trend of a lower MFIS score in ALCAR group in comparison to placebo (mean difference = 12.4, p = 0.05, with Keppel-corrected alpha of 0.046). The quality of life measured as SF 36 – PCS and SF 36 – MCS proved to be significantly influenced by treatment.ConclusionOne month treatment with amantadine improved fatigue in patients with relapsing-remitting MS as evaluated by MFIS. No or only a trend of improvement was seen in patients treated with modafinil or ALCAR, respectively.     

Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability

BackgroundTranscranial direct current stimulation (tDCS) is a potential alternative treatment option for major depressive episodes (MDE).ObjectivesWe address the efficacy and safety of tDCS in MDE.MethodsThe outcome measures were Hedges’ g for continuous depression ratings, and categorical response and remission rates.ResultsA random effects model indicated that tDCS was superior to sham tDCS (k = 11, N = 393, g = 0.30, 95% CI = [0.04, 0.57], p = 0.027). Adjunctive antidepressant medication and cognitive control training negatively impacted on the treatment effect. The pooled log odds ratios (LOR) for response and remission were positive, but statistically non-significant (response: k = 9, LOR = 0.36, 95% CI[−0.16, 0.88], p = 0.176, remission: k = 9, LOR = 0.25, 95% CI [−0.42, 0.91], p = 0.468). We estimated that for a study to detect the pooled continuous effect (g = 0.30) at 80% power (alpha = 0.05), a total N of at least 346 would be required (with the total N required to detect the upper and lower bound being 49 and 12,693, respectively).ConclusionstDCS may be efficacious for treatment of MDE. The data do not support the use of tDCS in treatment-resistant depression, or as an add-on augmentation treatment. Larger studies over longer treatment periods are needed.     

Mental health of caregivers of individuals with disabilities: Relation to Suicidal Ideation

ObjectiveThe mental health of caregivers of individuals with disabilities is frequently neglected. This study investigated mental health status and Suicidal Ideation (SI) among caregivers and examined the predictive factors for SI.MethodCaregivers of individuals with physical or mental disabilities in a tertiary hospital in southern Taiwan were recruited through snowball sampling. They were assessed by self-report questionnaires, consisting of the Taiwanese Depression Questionnaire and a subset of the three-item Chinese Health Questionnaire, to assess probable depression and common mental disorders (CMDs), with cutoff points of 19 and 3, respectively.ResultsAmong 255 caregivers, 32.9% had probable depression, 37.6% had probable CMDs, and 18.8% experienced SI. The level of SI was correlated with primary caregivers (p = 0.015), lack of support from co-caregivers (p = 0.023), caring for younger patients (p = 0.010), caring for patients with mental disability (p = 0.019) or catastrophic diseases (p = 0.005), and caregivers' probable depression (p < 0.001) and CMDs (p < 0.001). Regression analysis predicted the greatest SI among caregivers caring for younger patients (odds ratio [OR] = 0.98, p = 0.048) and for patients with catastrophic diseases (OR = 3.15, p = 0.008), as well as for caregivers with probable depression (OR = 3.90, p = 0.010) or CMDs (OR = 9.40, p < 0.001).ConclusionsWhen examining SI, clinicians should be aware of the mental health of caregivers who are responsible for people with disability. In particular, they should be vigilant regarding caregivers of individuals who are of younger age or have catastrophic diseases and regarding caregivers who exhibit probable depression and CMDs.