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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.

Background: Alcohol-related morbidity may involve changes in the gut microbiota and immune dysregulation. We have previously demonstrated alterations in gut microbiota composition and functions in patients with alcohol overconsumption, and now aimed to investigate possible associations between cytokine levels, gut microbiota, and clinical symptoms., Methods: We included hospital inpatients with a history of chronic alcohol overconsumption. For comparison, we included control patients with a low alcohol intake. Cytokine levels (TGF-β1, TNF-α, IL-10, IL-8, IL-6, IFN-γ, MCP-1, IL-1RA, IL-1β, and IL-17) were determined using a customized V-plex assay. We then examined associations of cytokine levels with the abundance of Proteobacteria and Faecalibacterium, percentage of the short-chain fatty acid butyrate, psychiatric symptoms (Hospital Anxiety and Depression Scale), and biochemical liver variables., Results: We included 28 patients with alcohol overconsumption (79% men), and 25 control patients (72% men). Patients with alcohol overconsumption had higher levels of IL-6 (p = 0.002), IFN-γ (p = 0.018), and MCP-1 (p = 0.006), and lower levels of TGF-β1 (p = 0.017) compared with control patients. Inverse correlations were found between Proteobacteria abundance and TNF-α (R s  = -0.55, p = 0.02) and IL-8 (R s  = -0.58, p = 0.014), and between Faecalibacterium and MCP-1 levels (R s  = -0.56, p = 0.02) in the control patients, but not in patients with alcohol overconsumption. Patients with alcohol overconsumption reported more psychiatric symptoms, and these symptoms were inversely correlated with IL-10 levels. There were positive correlations between several of the assessed cytokines and biochemical liver variables, and negative correlations between cytokine levels and albumin., Conclusion: Patients with alcohol overconsumption had a cytokine profile suggestive of increased systemic inflammatory activity, with higher levels of pro-inflammatory cytokines (IL-6, IFN-γ, and MCP-1) and lower levels of anti-inflammatory cytokines (TGF-β1). The findings may represent a link between alcohol use and alcohol-related morbidity., Competing Interests: Declaration of competing interest There are no potential conflicts of interest to be disclosed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Background: Psychological distress is common among people with a substance abuse disorder in treatment. Identifying correlates of psychological distress may serve as points of intervention to improve substance abuse treatment outcomes. Immune function measured as cytokine levels have been associated with psychological distress, but this association remains unexplored among people with a substance abuse disorder in treatment. This study aimed to examine whether cytokine levels in patients treated for a substance use disorder were related to depression, anxiety, and overall psychological distress, and to observe these associations separately among people with a past year alcohol use disorder and those with a past year drug use disorder., Methods: We collected cross-sectional data from 80 inpatients at five alcohol and substance abuse treatment centers in Norway. We determined alcohol and drug diagnoses, and assessed symptoms of depression, anxiety, and overall psychological distress. We tested blood samples for IL-1, IL-6, TNF-α, INF-γ, and IL-10. We used multivariate linear regressions to examine the associations between cytokine levels and psychological distress measures., Results: All cytokines were significantly and positively associated with depression score. INF-γ was significantly and negatively associated with anxiety, and IL-6 was significantly and positively associated psychological distress. Among people with only an alcohol use disorder, IL-6 was positively associated with depression and psychological distress scores, and IL-10 was negatively associated with anxiety score. Among people with only a drug use disorder, TNF-α was positively associated with depression score., Conclusion: The relationship between immune function and psychological distress is robust in the context of substance abuse, and further research is warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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-1β (IL-1β), 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.

Alcohol is a known modulator of the innate immune system. Owing to the absence of human studies, alcohol's effect on circulating cytokine profile remains unclear. We investigated the effect of acute high dose alcohol consumption on systemic cytokine release. After an overnight fasting, alcohol-experienced healthy male volunteers ( N = 20) aged 25-45 years were given oral ethanol in the form of vodka (4.28 mL/kg) which they drank over a period of 30 minutes reaching peak blood alcohol concentration of 0.12% (SD 0.028). Blood samples were obtained prior to alcohol intake as well as 2, 7, and 12 hours thereafter. Serum levels of the inflammatory cytokines IL-1 β , IL-1Ra, IL-6, IL-10, IL-17, IFN- γ , MCP-1, and TNF- α were determined by the multibead-based assay. Baseline cytokine levels were not related to BMI, hepatic parameters, electrolytes, glucose, or morning cortisol levels. Within 2 hours of alcohol intake, levels of IL-1Ra were elevated and remained so throughout the assessment period ( p for trend = 0.015). In contrast, the levels of the chemokine MCP-1 dropped acutely followed by steadily increasing levels during the observation period ( p < 0.001). The impact of sustained elevated levels of MCP-1 even after the clearance of blood alcohol content deserves attention., Competing Interests: All other authors, except Andreas Skulberg and Knut Ragnvald Skulberg, report no conflict of interests related to this work.

Neurodegenerative and inflammatory processes are involved separately in major depression (MD) and alcohol-use disorders (AUD). Little is known about the nature of this relationship in the context of comorbid AUD and depression disorders. In this study, we determined brain-derived neurotrophic factor (BDNF) serum levels in patients with AUD and tested whether BDNF levels were related to history of major depression, recent depressive symptoms, AUD severity, and TNF-α and IL-6 levels. Nepalese male AUD inpatients (N=152) abstinent from alcohol for an average of 34 days were administered structured interviews to assess depression symptoms and pattern and extent of alcohol use, and to generate research diagnoses for AUD and MD. AUD severity was assessed by scores on the Alcohol Use Disorder Identification Test. Serum BDNF and cytokines were measured using ELISA and multiplex technology, respectively. Although serum BDNF levels were unrelated to MD history, patients with recent depressive symptoms (n=42) had lower (mean±SD) BDNF serum levels compared to those without (n=110) (21.6±8.1 ng/mL vs. 26.0±9.6 ng/mL; p=0.010), and patients with higher AUD severity and binge-drinking patterns had higher mean serum BDNF levels compared to lower AUD severity and non-binging (25.9±9.7 ng/mL vs. 22.1±8.7 ng/mL; p=0.022 and 25.7±9.3 vs. 21.8±9.7 ng/mL; p=0.029, respectively). Positive correlations were present between BDNF and TNF-α (r=0.39, p<0.001) and IL-6 (r=0.2, p=0.027). In particular, TNF-α levels were predictive of BDNF levels after controlling for confounders (B=0.3 [95% CI=0.2-0.5], p<0.001). These findings show that in alcohol-using populations, peripheral BDNF levels are related to severity of AUD as well as presence of depressive symptoms. The significant associations between inflammatory and neurotrophic factors may have implications for neuroadaptive changes during recovery from AUD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: As major depression (MD) is often comorbid with alcohol-use disorders (AUD) and alcohol itself modulates the immune system, we examined serum levels of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF), and interferon (IFN)-γ in AUD patients with and without MD. Putative interactions between alcohol variables and MD on cytokine levels were also assessed., Methods: A consecutive sample of inpatients with AUD (N = 176) from eight alcohol treatment centers in Kathmandu, Nepal, was assessed for alcohol use and depression by administering fully structured psychiatric interviews. Serum cytokine levels were determined using multiplex technology., Results: Alcohol-use disorders patients with a positive history of MD had higher levels of the inflammatory cytokines IL-6 (P = 0.019), TNF (P = 0.020), and IFN-γ (P = 0.001), but not of IL-10 (P = 0.853). AUD patients with MD had higher concentrations of cytokines compared with those without, regardless of the severity of the alcohol problem, but the difference was greater among those drinking in lower frequency and intensity., Conclusion: These findings provide evidence for altered functioning of the immune system in AUD patients with comorbid MD. However, frequent and intense drinking may attenuate the difference in the cytokine profiles between AUD patients with and without MD., (© 2014 John Wiley & Sons Ltd.)

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. [ABSTRACT FROM AUTHOR]

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‐1β, 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‐1β, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-1β, 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-1β (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. [ABSTRACT FROM AUTHOR]

Background: This study examined how alcohol use disorder (AUD) patients with post-traumatic stress disorder (PTSD) differed from those without PTSD in terms of demography, drinking patterns and C-reactive protein, inflammatory cytokines, tryptophan metabolism parameters, and brain-derived neurotrophic factor (BDNF). Methods: A consecutive sample (N = 187) of treatment-receiving AUD individuals were recruited from Nepalese facilities. They underwent fully structured psychiatric interviews. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-1 Receptor antagonist (IL-1Ra), IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ)] were determined by a multiplex assay, kynurenine and tryptophan levels by high-performance liquid chromatography, and BDNF by enzyme-linked immunosorbent assay (ELISA). Results: The prevalence of exposure to severe trauma and PTSD was 74% and 17%, respectively. PTSD comorbidity was not associated with age, gender, or socioeconomic status, but with co-occurring major depression, history of attempted suicide, earlier peak of drinking problems, higher drinking quantity and withdrawal symptoms, experiencing alcoholic blackouts, and drinking problems among parents. None of the assessed neuroimmune parameters was related to comorbid PTSD. Conclusions: The findings support routine trauma screening in AUD treatment samples and screening for risky drinking in trauma populations to help guide interventions. The expected aberrations in neuroimmune functioning may not be found when examined in a sample with multiple psychiatric morbidities. [ABSTRACT FROM AUTHOR]