Changes in pain during a depressive episode and relationship to cytokine levels in major depressive disorder.

BACKGROUND: Depressed patients have an increased incidence of pain. A pathophysiological connection between depression and pain is still not revealed. Immunological activation has been found in both depression and pain. There are few studies of pain and immune activation in patients with depression, without inflammatory and autoimmune disorders. METHODS: This is a naturalistic follow-up study of 50 patients with a major depressive disorder (MDD) depressive episode, without any inflammatory or autoimmune conditions. We have previously reported on the relationship between depression and cytokine levels. In this study, we obtained data of depression, pain and cytokine levels before and after 12 weeks of depression treatment. All patients were medication-free at inclusion. RESULTS: At inclusion three out of four patients experienced pain, and the pain scores correlated with the depression scores. After treatment, as depression was relieved, the pain scores dropped significantly and were no longer correlated to the depression scores. There were no correlations between pain scores and cytokine levels. Pain level at inclusion did not correlate with depression treatment outcome. CONCLUSION: Our findings indicate that pain is a feature of depression. Pain levels and cytokine values didn't correlate. Pain at inclusion did not predict depression treatment outcome.

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

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

Chronic fatigue syndromes: real illnesses that people can recover from.

The 'Oslo Chronic Fatigue Consortium' consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation.

BACKGROUND: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to systemic inflammasome activation, and elevated atherogenic lipid ratios have been shown to correlate with circulating levels of inflammatory biomarkers in SMI. It is, however, not yet known if increased systemic cholesterol load leads to inflammasome activation in these patients. METHODS: We tested the hypothesis that patients with SCZ and BD display higher circulating levels compared to healthy individuals of key members of the IL-18 system using a large patient cohort (n = 1632; including 737 SCZ and 895 BD), and healthy controls (CTRL; n = 1070). In addition, we assessed associations with coronary artery disease risk factors in SMI, focusing on relevant inflammasome-related, neuroendocrine, and lipid markers. RESULTS: We report higher baseline levels of circulating IL-18 system components (IL-18, IL-18BPA, IL-18R1), and increased expression of inflammasome-related genes (NLRP3 and NLRC4) in the blood of patients relative to CTRL. We demonstrate a cholesterol dyslipidemia pattern in psychotic disorders, and report correlations between levels of blood cholesterol types and the expression of inflammasome system elements in SMI. CONCLUSIONS: Based on these results, we suggest a role for inflammasome activation/dysregulation in SMI. Our findings further the understanding of possible underlying inflammatory mechanisms and may expose important therapeutic targets in SMI.

Psychiatric outcome after severe cardio-respiratory failure treated with extracorporeal membrane oxygenation: a case-series.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used to save patients with severe cardiopulmonary failure at high risk of dying, but the long-term psychiatric outcome of the treatment has not been studied. METHODS: Twenty-eight adults who survived ECMO were subjected to psychiatric assessment 5 years after ECMO by means of interviews (MINI-Neuropsychiatric Interview and Montgomery-Åsberg Depression Rating Scale) and psychometrics [Neuroticism and social conformity (EPQ-N+L); General Health Questionnaire (GHQ), Hospital Anxiety Depression Scale; Aggression Questionnaire, Toronto Alexithymia Scale, and Giessener somatic symptom checklist (GBB)]. RESULTS: Fifteen patients (54%) suffered lifetime psychiatric disorders prior to ECMO. After ECMO, 11 subjects (39%) developed new psychiatric disorders, mostly organic mental (18%), obsessive-compulsive disorders (OCD) 15%, and/or post-traumatic stress disorders (PTSD) 11%. These 11 patients reported higher scores on Montgomery-Åsberg Depression Rating Scale (MADRS), GHQ, EPQ-N, and GBB. Disregarding the presence of psychiatric disorders at follow-up, ECMO patients reported high levels of distress, physical aggression, anger, and alexithymic traits. CONCLUSIONS: Severe life-threatening cardiovascular or pulmonary failure with subsequent ECMO is associated with an increased prevalence of long-term psychiatric disorders and distress. Studies addressing the etiology and prevalence of psychiatric consequences after ECMO are needed.

Paternal psychological response after ultrasonographic detection of structural fetal anomalies with a comparison to maternal response: a cohort study.

BACKGROUND: In Norway almost all pregnant women attend one routine ultrasound examination. Detection of fetal structural anomalies triggers psychological stress responses in the women affected. Despite the frequent use of ultrasound examination in pregnancy, little attention has been devoted to the psychological response of the expectant father following the detection of fetal anomalies. This is important for later fatherhood and the psychological interaction within the couple. We aimed to describe paternal psychological responses shortly after detection of structural fetal anomalies by ultrasonography, and to compare paternal and maternal responses within the same couple. METHODS: A prospective observational study was performed at a tertiary referral centre for fetal medicine. Pregnant women with a structural fetal anomaly detected by ultrasound and their partners (study group,n=155) and 100 with normal ultrasound findings (comparison group) were included shortly after sonographic examination (inclusion period: May 2006-February 2009). Gestational age was >12 weeks. We used psychometric questionnaires to assess self-reported social dysfunction, health perception, and psychological distress (intrusion, avoidance, arousal, anxiety, and depression): Impact of Event Scale. General Health Questionnaire and Edinburgh Postnatal Depression Scale. Fetal anomalies were classified according to severity and diagnostic or prognostic ambiguity at the time of assessment. RESULTS: Median (range) gestational age at inclusion in the study and comparison group was 19 (12-38) and 19 (13-22) weeks, respectively. Men and women in the study group had significantly higher levels of psychological distress than men and women in the comparison group on all psychometric endpoints. The lowest level of distress in the study group was associated with the least severe anomalies with no diagnostic or prognostic ambiguity (p < 0.033). Men had lower scores than women on all psychometric outcome variables. The correlation in distress scores between men and women was high in the fetal anomaly group (p < 0.001), but non-significant in the comparison group. CONCLUSION: Severity of the anomaly including ambiguity significantly influenced paternal response. Men reported lower scores on all psychometric outcomes than women. This knowledge may facilitate support for both expectant parents to reduce strain within the family after detectionof a fetal anomaly.

No effect of combined coenzyme Q10 and selenium supplementation on atorvastatin-induced myopathy.

OBJECTIVE: The aim of the present study was to evaluate the possible effects of Q10 and selenium supplementation on statin-induced myopathy (SIM), both for subjective symptoms and muscle function. DESIGN: Patients (N = 43) who had experienced previous or ongoing SIM on atorvastatin therapy were recruited. Following a 6-week washout period during which no statins were administered, the patients were re-challenged with 10 mg of atorvastatin. Patients (N = 41) who experienced SIM continued the atorvastatin treatment and were in addition randomized to receive 12 weeks supplement of 400 mg Q10 and 200 µg selenium per day or a matching double placebo. SIM was assessed using 3 validated symptom questionnaires, and a muscle function test was performed at the beginning and at the end of the study. RESULTS: The patients receiving the active supplement experienced significant increases in their serum Q10 and selenium concentrations compared with the group receiving placebo. No statistically significant differences in symptom questionnaire scores or muscle function tests were revealed between the groups. CONCLUSIONS: Despite substantial increases in the serum Q10 and selenium levels following the oral supplementation, this study revealed no significant effects on SIM compared with the placebo.

Maternal psychological distress and parenting stress after gastrostomy placement in children.

OBJECTIVES: The aim of the study was to evaluate stress in mothers of children with feeding problems before and after gastrostomy placement, and to identify changes in child health and variables affecting maternal stress. METHODS: Psychological distress and parenting stress in 34 mothers of children referred for gastrostomy were assessed using general health questionnaire (GHQ) (overall psychological distress), impact of event scale (IES) (intrusive stress related to child's feeding problems), and parenting stress index (PSI) (stress related to parenting) before, 6, and 18 months after placement of a gastrostomy. Information of child health and long-term gastrostomy complications were recorded. A semistructured interview constructed for the present study explored maternal preoperative expectations and child's quality of life. RESULTS: Insertion of a gastrostomy did not significantly influence vomiting or the number of children with a low weight-for-height percentile. All of the children experienced peristomal complications. Despite this, mothers' overall psychological distress was significantly reduced after 6 and 18 months, and the majority of mothers (85%) reported that their preoperative expectations were fulfilled and that the child's quality of life was improved after gastrostomy placement. Maternal concerns for the child's feeding problems, measured as intrusive stress, had effect on maternal overall psychological distress. CONCLUSIONS: Despite frequent stomal complications the gastrostomy significantly reduced the mothers' psychological distress and improved the child's quality of life as reported by the mother.

In-depth study of personality disorders in first-admission patients with substance use disorders.

BACKGROUND: Assessment of comorbid personality disorders (PDs) in patients with substance use disorders (SUDs) is challenging due to symptom overlap, additional mental and physical disorders, and limitations of the assessment methods. Our in-depth study applied methods to overcome these difficulties. METHOD: A complete catchment area sample of 61 consecutively admitted patients with SUDs, with no previous history of specialized treatment (addiction clinics, psychiatry) were studied, addressing PDs and associated clinical and demographic variables. The thorough assessments included the Psychiatric Research Interview for Substance and Mental Disorders and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders. RESULTS: Forty-six percent of the SUD patients had at least one PD (16% antisocial [males only]; 13% borderline; and 8% paranoid, avoidant, and obsessive-compulsive, respectively). Cluster C disorders were as prevalent as Cluster B disorders. SUD patients with PDs were younger at the onset of their first SUD and at admission; used more illicit drugs; had more anxiety disorders, particularly social phobia; had more severe depressive symptoms; were more distressed; and less often attended work or school. CONCLUSION: The psychiatric comorbidity and symptom load of SUD patients with PDs differed from those of SUD patients without PDs, suggesting different treatment needs, and stressing the value of the assessment of PDs in SUD patients.

Substance use disorders and comorbid mental disorders in first-time admitted patients from a catchment area.

AIM: To describe lifetime mental disorders in patients with substance use disorders (SUD) admitted for the first time to specialized treatment for psychiatric or addiction problems from a catchment area. METHODS: Special efforts were made to include all eligible patients and secure completion of thorough assessments, including the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) and the Structured Clinical Interview for DSM-IV axis II personality disorders (SCID-II). The strength of this study lies in its rigorous patient recruitment and assessment methods. RESULTS: Of 61 patients, 53 had alcohol use disorder (AUD). Of these, 28 had AUD only, and 25 had an additional drug use disorder (DUD). 89% had comorbid axis I (85%) or axis II (46%) disorders. The most prevalent axis I disorders were major depressive disorder (71%), social phobia (31%) and posttraumatic stress disorder (18%). Among those with comorbid psychiatric disorders (n = 54), 25 (41% of the sample) had disorders considered to be independent of their substance use only, 4 patients (7%) had substance-induced disorders only, and 23 patients (38%) had both independent and substance-induced disorders. CONCLUSION: Comorbid mental disorders were remarkably prevalent in these SUD patients who were admitted for the first time.

Plasma Levels of the Cytokines B Cell-Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL) in Schizophrenia, Bipolar, and Major Depressive Disorder: A Cross Sectional, Multisite Study.

BACKGROUND: Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection. METHODS: We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP. RESULTS: Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen's d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10). CONCLUSIONS: These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders.

Coping Patterns and Emotional Distress in Patients With Chronic Obstructive Lung Disease Who Are Undergoing Lung Transplant Evaluation.

OBJECTIVES: Living with severe lung disease like chronic obstructive pulmonary disease (COPD) is a very stressful situation. The way patients cope may impact their symptoms of anxiety and depression and physical function as well. We studied how ways of coping are associated with levels of emotional distress and lung function in patients with COPD being evaluated for lung transplantation. METHODS: Sixty-five (mean age 57 years, 46% females) patients completed the General Health Questionnaire-30 (GHQ-30) assessing emotional distress and the Ways of Coping Questionnaire. Measurements of lung function and 6-minute walk test were included. RESULTS: Seventeen (26%) patients had elevated emotional distress. Logistic regression of chronic GHQ score with gender, age, body mass index, lung function, and coping scales as covariates showed that escape avoidance and self-controlling coping and forced vital lung capacity were significantly associated with high emotional distress. Odds ratio of emotional distress increased with 5.2 per tertile (P = .011) in escape avoidance coping score. Moreover, we revealed that emotionally distressed patients cope with their current situation by refusing to believe the current situation and taking their distress out on other people. CONCLUSION: Among patients with COPD, a high level of emotional distress was uniquely associated with escape-avoidance coping and lung function. Future work should ascertain whether coping style predicts distress or whether distress increases the use of escape-avoidance coping. Nevertheless, our findings indicate that if either element is present, health care professionals should be attentive to the need for interventions to improve patients' well-being.