Bariatric surgery patients in AUD treatment in Norway-an exploratory cross-sectional study.

AIMS: Patients who have undergone some forms of bariatric surgery have increased risk of developing alcohol use disorder (AUD). In the present observational study, we compared patients with AUD who themselves reported to having undergone bariatric surgery with other patients in treatment for AUD. MATERIALS: One-hundred-and-six consecutively enrolled patients in residential treatment for AUD were asked if they had undergone bariatric surgery. Sociodemographics, mental health-related, and alcohol use-related parameters were compared between those who had and those who had not undergone bariatric surgery. RESULTS: Of the 106 patients with AUD, seven (6.6%; 95% confidence interval, 2.7%-13.1%) had undergone bariatric surgery. Six of seven patients had undergone such surgery were women (P < .001). The patients with AUD who had undergone bariatric surgery were similar to other patients with AUD on most other parameters, the exception being a larger number of alcohol units ingested to feel an effect of alcohol (adjusted odds ratio 7.1; 95% confidence interval 2.0-12.2; P = .007). CONCLUSION: The high number of patients with AUD that reported having undergone bariatric surgery emphasizes the risks following such a procedure. The overrepresentation of women may reflect than more women undergo such procedures. The unexpected finding that patients with AUD having undergone bariatric surgery seemed to need more alcohol to feel intoxicated warrants further research.

Levels of IL-6 are Associated with Lifetime Attempted Suicide in Alcohol Use Disorder Patients.

Background: Patients with alcohol use disorder (AUD) have an increased risk of suicide. Neuroimmunological measures, such as cytokines, are shown to deviate in people with attempted suicide. Few studies have investigated this among AUD patients. Patients and Methods: One-hundred and fourteen patients undergoing residential treatment for AUD were interviewed on lifetime suicide attempts (SA) along with several other background variables and clinical characteristics. Serum blood samples were drawn for analysis of cytokines. Results: Thirty-one patients (27%) reported at least one SA. These patients had more symptoms of current affective disorders and more severe dependence. In bivariate analysis only IL-6 and IL-10 appeared to be associated with lifetime SA but without reaching statistical significance. In multivariate linear regression, adjusting for sex, nicotine use, somatic illness, and the use of anti-inflammatory drugs, IL-6 was associated to SA (p = 0.033). Conclusion: The cytokine IL-6 has repeatedly been found to be associated with suicidality. The present study concurs with this role of IL-6 in a naturalistic observational study of AUD patients.

Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco.

BACKGROUND: Smoking and alcohol use often co-occur, and the use of nicotine-containing products is particularly common among persons with alcohol use disorder (AUD). Recent evidence shows that chronic alcohol use leads to inflammation through increased gut permeability and dysregulated cytokine levels. While cigarette smoking also has detrimental health effects, nicotine has immune dampening effects in some settings. Preclinical evidence demonstrates that nicotine can dampen alcohol-induced inflammation, but inflammatory responses after nicotine use has not been studied in persons with AUD. This study compared the level of circulating cytokines in abstinent AUD inpatients who were non-tobacco users, smokers, users of Swedish snus, or dual tobacco users. METHODS: We collected blood samples and information about somatic and mental health and tobacco habits from 111 patients in residential treatment for AUD and 69 healthy controls. Levels of interferon (IFN)-γ, interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-17a, IL-1ß, IL-6, IL-8, IL-1 receptor antagonist (ra), and monocyte chemoattractant protein (MCP)-1 were examined using a multiplex assay. RESULTS: Patients with AUD had higher levels of seven cytokines than healthy controls. Among the AUD patients, nicotine users had lower levels of IL-10, TNF-α, IL-17a, IL-1ß, IL-8, and MCP-1 (all p < 0.05). CONCLUSIONS: Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD. Nonetheless, nicotine use cannot be recommended as a viable therapeutic option to reduce alcohol-induced inflammation because of its other adverse effects. Additional studies of the effects of tobacco or nicotine products on cytokine patterns in relation to mental or somatic health conditions are warranted.

Longitudinal determinants of insomnia among patients with alcohol use disorder.

Insomnia is common among patients with AUD and can impair quality of life and cognitive functioning, as well as cause psycho-social problems and increased risk of relapse. Nonetheless, determinants of insomnia in patients with AUD have scarcely been studied. We aimed to examine prevalence and development of self-perceived insomnia among inpatients in treatment for AUD, and to examine factors in this group known to be associated with sleep disturbance in the general population. We examined self-reported information about sleep from 94 AUD inpatients in long-term treatment (up to 9 months) using a questionnaire identifying probable insomnia. Potential predictors identified in bivariate tests were used in binomial logistic regressions to examine the effect on sleep at baseline and at 6-week follow-up. Longitudinal multilevel analyses were used to examine factors affecting development of sleep quality during the treatment stay. At baseline, 54% of the patients reported sleep problems indicating insomnia. This was reduced to 35% at 6-week follow-up. In a cross-sectional analysis of sleep at baseline, we found that being male (OR 0.18, p = 0.042) and engaging in physical activity (OR 0.09, p < 0.001) were negatively associated with insomnia, while a high level of depressive symptoms (OR 1.10, p = 0.010) was positively associated after adjustment for age, history of trauma, and severity of dependence. Multilevel analyses of data over a 6-month period showed time interactions with physical activity, such that sleep improvement was greater in patients who initially had a low level of physical activity. This longitudinal study corroborates findings of high prevalence of insomnia among AUD patients and identifies factors in this group associated with insomnia, such as sex, depression, and physical activity. Future longitudinal studies are needed to examine the causal directions between sleep, depression, and physical activity and how these might be targeted in clinical settings.

History of Delirium Tremens in AUD Patients in Treatment: Relationship to AUD Severity and Other Factors.

Introduction: Delirium tremens (DT) occurs after stopping prolonged, high alcohol intake and may be life-threatening if untreated. We need to know about clinical correlates of DT in order to provide the best clinical care. Methods: At admission to inpatient treatment a cohort of 114 alcohol use disorder (AUD) patients were interviewed and examined concerning psychiatric diagnosis and symptoms, trauma experiences and alcohol related measures and if they had experienced DT. Results: Twenty-four percent of the patients reported a life-time experience of DT. These patients were predominantly males and had lower educational level. More of the patients in the DT than the non-DT group reported at least one suicide attempt, were diagnosed with PTSD, and dropped out of treatment. Also, having parents with alcohol problems was more common among these patients, and they reported a longer duration of problematic drinking and a higher number of drinks needed to feel an effect of drinking. In the multivariable adjusted analysis only a diagnosis of PTSD (OR=5.71; 95% confidence interval (CI): 1.34-24.31) and duration of problematic drinking with a 6% increase in risk for every year (OR=1.06; 95% CI: 1.01-1.11) remained significant risk factors for having DT experience. Discussion and conclusion: Having experienced DT was more prevalent in the current investigation than in earlier studies. Patients that had experienced DT seemed to have more serious AUD, especially signified by a longer duration of drinking. These patients seemed to have many clinical disadvantages including more drop-out and higher suicide rate. PTSD could be a risk factor for DT but may also follow the DT experience.

Levels of Peripheral Circulating IL-6 and IL-10 Decrease Over Time Despite High Depression Burden in PTSD Patients.

Background: Patients with combined depression symptoms and post-traumatic stress disorder (PTSD) often exhibit high levels of circulating inflammatory biomarkers as either a cause or consequence of their disease. We aimed to investigate how cytokines and depression symptoms develop with one-year follow-up and compare them with non-PTSD patients. Methods: The study had a longitudinal design with one-year follow-up measurements in an inpatient treatment setting at a psychiatric center in Norway. PTSD diagnoses were set using the Mini International Neuropsychiatric Interview (MINI). The first three measurements were at baseline (T0), halfway (T1) and at discharge (T2) from a 12-week main stay, followed by a final measurement one year after discharge (T3). Serum blood samples were collected on all four occasions. The Beck Depression Inventory-II (BDI-II) was administered at T0, T2 and T3. Results: Levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) in PTSD patients were higher than in patients without PTSD at T0 (p = 0.005 and 0.042). The PTSD patients had a higher average level of IL-10 across all four measurements (B = 1.62, Standard Error (SE) = 0.78, p = 0.037). The IL-10 levels in PTSD patients declined from T0 to T3 (p = 0.039). The PTSD patients were more depressed than non-PTSD patients at T3 (p = 0.019). Conclusions: The levels of IL-10 and IL-6 in PTSD patients more closely resembled the levels in non-PTSD patients at one-year follow-up, despite level of depression being unchanged in the PTSD patients. This calls into question the close relationship between level of circulating cytokines and depressive symptoms, at least in PTSD patients. Further research is needed to investigate what appears to be a complex relationship between immune markers and depression in patients with PTSD.

Persistent level of mental distress in PTSD patients is not reflected in cytokine levels 1 year after the treatment.

OBJECTIVE: Cross-sectional data show that post-traumatic stress disorder (PTSD) patients often have increased levels of circulating inflammatory markers. There is, however, still a paucity of longitudinal studies with long follow-up times on levels of cytokines in such patients. The current study assesses patients with and without PTSD diagnosis 1 year after discharge from inpatient treatment. METHODS: Patients in treatment for serious non-psychotic mental disorders were recruited at the beginning of their treatment stay at a psychiatric centre in Norway. Ninety patients submitted serum samples and filled out the Hopkins Symptom Checklist-90 Revised Global Severity Index (HSCL-90R GSI) questionnaire during their mainstay and at a follow-up stay 1 year after discharge. Of these patients, 33 were diagnosed with PTSD, 48 with anxiety, depression, or eating disorder, while 9 patients had missing data. The patients were diagnosed using the Mini-International Neuropsychiatric Interview (MINI). RESULTS: At the follow-up stay (T3), PTSD patients had higher levels of GSI scores than non-PTSD patients (p = 0.048). These levels were unchanged from the year before (T2) in both groups. The levels of circulating cytokines/chemokine did not differ between the PTSD and non-PTSD patients at T3. At T2, however, the PTSD and non-PTSD groups exhibited different levels of interleukin 1ß (IL-1ß) (p = 0.053), IL-1RA (p = 0.042), and TNF-α (p = 0.037), with the PTSD patients having the higher levels. CONCLUSION: Despite exhibiting different mental distress scores, the PTSD and non-PTSD patients did not differ regarding levels of circulating inflammatory markers at 1-year follow-up.

Circulating cytokine levels in the treatment of comorbid anxiety disorders.

Psychotherapy research aims to investigate predictors and moderators of treatment outcome, but there are few consistent findings. This study aimed to investigate cytokines in patients undergoing treatment for anxiety disorders and whether the level of cytokines moderated the treatment outcome. Thirty-seven patients with comorbid and treatment-resistant anxiety disorders were investigated using multilevel modelling. Serum cytokine levels were measured three times: pretreatment, in the middle of treatment, and at the end of treatment. Anxiety and metacognitions were measured weekly throughout treatment by self-report. The levels of monocyte chemoattractant protein-1, tumour necrosis factor-alpha, and interleukin-1 receptor antagonist did not change during therapy or were not related to the level of anxiety. Metacognitive beliefs predicted anxiety, but the relationship between metacognitions and anxiety was not moderated by cytokines. Limitations of the study include that the patients were not fasting at blood sampling, and we did not assess body mass index, which may affect cytokine levels. The lack of significance for cytokines as a predictor or moderator may be due to a lack of power for testing moderation hypotheses, a problem associated with many psychotherapy studies. Cytokines did not predict the outcome in the treatment of comorbid anxiety disorders in our sample. Furthermore, cytokines did not moderate the relationship between metacognitions and anxiety.

Cytokine concentrations are related to level of mental distress in inpatients not using anti-inflammatory drugs.

OBJECTIVE: Cross-sectional data show elevated levels of circulating cytokines in psychiatric patients. The literature is divided concerning anti-inflammatory drugs' ability to relieve symptoms, questioning a causal link between inflammatory pathways and psychiatric conditions. We hypothesised that the development of circulating cytokine levels is related to mental distress, and that this relationship is affected by the use of anti-inflammatory drugs. METHODS: The study was a longitudinal assessment of 12-week inpatient treatment at Modum Bad Psychiatric Center, Norway. Sera and self-reported Global Severity Index (GSI) scores, which measure psychological distress, were collected at admission (T0), halfway (T1) and before discharge (T2). Other variables known to distort the neuroimmune interplay were included. These were age, gender, diagnosis of PTSD, antidepressants and anti-inflammatory drugs. A total of 128 patients (92 women and 36 men) were included, and 28 were using anti-inflammatory medication. Multilevel modelling was used for data analysis. RESULTS: Patients with higher levels of IL-1RA and MCP-1 had higher GSI scores (p = 0.005 and p = 0.020). PTSD patients scored higher on GSI than non-PTSD patients (p = 0.002). These relationships were mostly present among those not using anti-inflammatory drugs (n = 99), with higher levels of IL-1RA and MCP-1 being related to higher GSI score (p = 0.023 and 0.018, respectively). Again, PTSD patients showed higher GSI levels than non-PTSD patients (p = 0.014). CONCLUSIONS: Cytokine levels were associated with level of mental distress as measured by the GSI scores, but this relationship was not present among those using anti-inflammatory drugs. We found no association between cytokine levels and development of GSI score over time.

PTSD patients show increasing cytokine levels during treatment despite reduced psychological distress.

BACKGROUND: A reciprocal relationship between activated innate immune system and changes in mood and behavior has been established. There is still a paucity of knowledge on how the immune system responds during psychiatric treatment. We aimed to explore circulating cytokines and assess psychiatric symptom severity scores during 12 weeks of inpatient psychiatric treatment. METHODS: The study was a longitudinal assessment of 124 patients (88 women and 36 men) in treatment at Modum Psychiatric Center, Norway. The patient sample comprised a mixed psychiatric population of whom 39 were diagnosed with posttraumatic stress disorder (PTSD). Serum blood samples for cytokine analysis and measures of mental distress using Global Severity Index were collected at admission (T0), halfway (T1), and before discharge (T2). Other factors assessed were age, gender, and the use of antidepressants and anti-inflammatory drugs. Multilevel modeling was used for longitudinal analyses to assess the repeated cytokine samples within each patient. RESULTS: Overall level of IL-1RA was higher in PTSD patients when compared to those without PTSD (P=0.021). The level of IL-1ß, MCP-1, and TNF-α increased over time in PTSD compared to non-PTSD patients (P=0.025, P=0.011 and P=0.008, respectively). All patients experienced reduced mental distress as measured by self-reported Global Severity Index scores. Stratified analysis showed that PTSD patients who used anti-inflammatory drugs had higher levels of IL-1ß (P=0.007) and TNF-α (P=0.049) than PTSD patients who did not use such drugs. CONCLUSION: The study indicates that traumatized patients may have a distinct neuroimmune development during recovery. Their activated immune system shows even further activation during their rehabilitation despite symptom reduction.

The effect of trauma and alcohol on the relationship between level of cytokines and depression among patients entering psychiatric treatment.

BACKGROUND: Depression is associated with immunological responses as reflected by altered levels of circulating cytokines. Alcohol use and trauma may modulate immune activity, and few studies have investigated these factors in depressed patients. We aimed to explore the association between circulating peripheral cytokine levels and degree of depressive symptoms, taking trauma and alcohol into account. METHODS: The study was a cross-sectional assessment of patients at admission to a specialized psychiatric center in Norway. A total of 128 patients were included. Information was gathered using the self-administered questionnaires Beck Depression Inventory-II (BDI-II) and the Alcohol Use Disorders Identification Test (AUDIT), in addition to clinical interviews recording childhood or adult life trauma. Serum levels of the cytokines Interleukin-1ß (IL-1ß), Interleukin-1 Receptor Antagonist (IL-1RA), Tumor Necrosis Factor-α (TNF-α) and the chemokine Monocyte Chemoattractant Protein-1 (MCP-1) were assessed. A Luminex bead-based multiplex assay was used for cytokine measurements. Patient cytokine levels were compared to those of healthy volunteers by the Mann-Whitney U test. RESULTS: Levels of cytokines did not differ across patients with mild, moderate and severe depression. AUDIT score was not related to cytokine levels, but to level of depression. A history of trauma was related to higher levels of IL-1RA and TNF-α (p = 0.048 and p = 0.033, respectively), especially among the severely depressed. Serum levels of MCP-1 and TNF-α were significantly higher among psychiatric patients than in healthy volunteers. CONCLUSIONS: Findings indicate that depression was not related to levels of circulating cytokines among patients in treatment, but that traumatized patients had higher levels of IL-1RA and TNF-α than patients without trauma experience. The lack of relationship between cytokine level and depression was evident both in those without and with trauma.

Opioid dependency rehabilitation with the opioid maintenance treatment programme - a qualitative study from the clients' perspective.

BACKGROUND: Opioid maintenance treatment (OMT) is the most widely used treatment for opioid dependence. The opioid maintenance treatment (OMT) programme represents an opportunity for people who are opioid users to minimize the many negative health and societal outcomes associated with opioid use through meeting the physiological need of their bodies for opioids. The purpose of this study is to shed some light on how clients in the Norwegian OMT programme see their level of influence on their own treatment. METHOD: It is a qualitative enquiry using semi-structured interviews of seven OMT clients living in various locations in Norway. The analysis of the material utilized a grounded theory-inspired approach. RESULTS: This study show that the clients who were part of the OMT programme had better lives than people with untreated addictions did. However, the participants experienced having to play by the rules of the OMT programme if they wanted to have successful treatment. This resulted in varying degrees of dissatisfaction with the treatment. CONCLUSIONS: The results indicated that the clients felt objectified and disenfranchised in the OMT programme, and points out the low level of influence on their own treatment felt by the OMT clients.