Altered serum interleukin-17A and interleukin-23A levels may be associated with the pathophysiology and development of generalized anxiety disorder.

In recent times, the pathogenesis of generalized anxiety disorder (GAD) and the influence of pro- and anti-inflammatory cytokines on it have garnered considerable interest. Cytokine research, especially Th-17 cytokine research on GAD patients, is limited. Here, we aim to assess the role of interleukin-17A (IL-17A) and interleukin-23A (IL-23A) in the pathophysiology and development of GAD. This investigation included 50 GAD patients and 38 age-sex-matched healthy controls (HCs). A psychiatrist diagnosed patients with GAD and assessed symptom severity using the DSM-5 and the GAD-7 scales. The serum concentrations of IL-17A and IL-23A were determined using commercially available ELISA kits. GAD patients exhibited elevated levels of IL-17A (77.14 ± 58.30 pg/ml) and IL-23A (644.90 ± 296.70 pg/ml) compared to HCs (43.50 ± 25.54 pg/ml and 334.40 ± 176.0 pg/ml). We observed a positive correlation between disease severity and cytokine changes (IL-23A: r = 0.359, p = 0.039; IL-17A: r = 0.397, p = 0.032). These findings indicate that IL-17A and IL-23A may be associated with the pathophysiology of GAD. ROC analysis revealed moderately higher AUC values (IL-23A: 0.824 and IL-17A: 0.710), demonstrating their potential to discriminate between patients and HCs. Also, the sensitivity values of both cytokines were relatively higher (IL-23A: 80.49% and IL-17A: 77.27%). According to the present findings, there may be an association between peripheral serum levels of IL-17A and IL-23A and the pathophysiology and development of GAD. These altered serum IL-17A and IL-23A levels may play a role in directing the early risk of developing GAD. We recommend further research to ascertain their exact role in the pathophysiology and their performance as risk assessment markers of GAD.

Association of interleukin-2 and interleukin-10 with the pathophysiology and development of generalized anxiety disorder: a case-control study.

BACKGROUND: Generalized anxiety disorder (GAD) is a devastating mental health condition characterized by constant, uncontrolled worrying. Recent hypotheses indicate that pro-inflammatory cytokines and chemokines are potential contributors to the pathogenesis of GAD. Here, we aimed to assess the role of interleukin-2 (IL-2) and interleukin-10 (IL-10) in the pathophysiology and development of GAD. METHODS: This study recruited 50 GAD patients diagnosed according to the DSM-5 criteria and 38 age-sex-matched healthy controls (HCs). A qualified psychiatrist evaluated all study subjects. The socio-demographic and clinical characteristics of the study population were determined using pre-structured questionnaires or interviews, and cytokine serum levels were estimated using commercially available ELISA kits. RESULTS: We observed reduced serum IL-10 levels in GAD patients compared to HCs (33.69 ± 1.37 pg/ml vs. 44.12 ± 3.16 pg/ml). Also, we observed a significant negative correlation between altered IL-10 levels and GAD-7 scores (r=-0.315, p = 0.039). Moreover, IL-10 serum measurement exhibited good predictive value in receiver operating characteristics (ROC) analysis with an area under the curve (AUC) value of 0.793 (p < 0.001) with 80.65% sensitivity and 62.79% specificity at a cutoff value of 33.93 pg/ml. Conversely, we noticed elevated serum IL-2 levels in GAD patients than in HCs (14.81 ± 2.88 pg/ml vs. 8.08 ± 1.1 pg/ml); however, it failed to maintain any significant association with GAD-7 scores, implying that IL-2 might not be involved in GAD pathogenesis. The lower AUC value (0.640; p > 0.05) exhibited by IL-2 serum measurement in ROC analysis further supported that IL-2 might not be associated with GAD. CONCLUSION: This study provides new insights into the complex interplay between anti-inflammatory cytokines and GAD pathogenesis. Based on the present findings, we can assume that IL-10 but not IL-2 may be associated with the pathophysiology and development of GAD. However, further research with a larger population size and longitudinal design is required to confirm the potential diagnostic efficacy of IL-10.

Prevalence, demographic characteristics, and clinical features of suicide risk in first episode drug-naïve schizophrenia patients with comorbid severe anxiety.

BACKGROUND: Both anxiety symptoms and suicide risk are common in schizophrenia. However, previous findings about the association between anxiety and suicide risk in schizophrenia were controversial. This study is the first to examine the prevalence of suicide risk and related demographic, clinical features in a large sample of first episode drug-naïve (FEDN) schizophrenia patients with comorbid severe anxiety. METHODS: In total, 316 patients with FEDN schizophrenia were enrolled in this study. Patients' symptoms were assessed using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS). Serum levels of glucose, insulin, uric acid, and lipids including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), were evaluated. RESULTS: In the current study, 56.3% patients presented comorbid severe anxiety. The rate of suicide risk was higher in the severe anxiety group (55.6%) than in the mild-moderate anxiety group (33.3%). The interactions among severe anxiety, uric acid and HDL-C were associated with suicide risk. Compared with patients with normal uric acid, those with abnormal uric acid exhibited a stronger association between HAMA scores and HAMD-suicide item scores. This enhanced association was also observed for patients with abnormal HDL-C levels. CONCLUSIONS: In FEDN schizophrenia patients with comorbid severe anxiety, our findings suggested a high incidence of suicide risk. Abnormal levels of uric acid and low levels of HDL-C, as well as high depression may be associated with an increased risk of suicide in FEDN schizophrenia patients with comorbid severe anxiety.

C-reactive protein concentrations diverge as a function of substance use disorder: A pre-registered replication in a clinical sample.

BACKGROUND: Inflammatory biomarkers may differentiate clinical disorders, which could lead to more targeted interventions. Analyses within a clinical sample (May et al., 2021) revealed that females with substance use disorders (SUD) exhibited lower C-reactive protein (CRP) and higher interleukin (IL)-8 and -10 concentrations than females without SUD who met criteria for mood/anxiety disorders. We aimed to replicate these findings in a new sample. METHODS: Hypotheses and analyses were preregistered. Treatment-seeking individuals with mood/anxiety disorders and/or SUD (N = 184) completed a blood draw, clinical interview, and questionnaires. Participants were categorized as SUD+ (45F, 43M) and SUD- (78F, 18M). Principal component analysis (PCA) of questionnaire data resulted in two factors reflecting appetitive and aversive emotional states. SUD group and nuisance covariates (PCA factors, age, body mass index [BMI], medication, nicotine [and hormones in females]) predicted biomarker concentrations (CRP, IL-8, and IL-10) in regressions. RESULTS: In females, the omnibus CRP model [F(8, 114) = 8.02, p <.001, R²-adjusted =.32] indicated that SUD+ exhibited lower CRP concentrations than SUD- (ß = -.33, t = -3.09, p =.002, 95% CI [-.54, -.12]) and greater BMI was associated with higher CRP levels (ß =.58, t = 7.17, p <.001, 95% CI [.42,.74]). SUD+ exhibited higher IL-8 levels than SUD- in simple but not omnibus regression models. CONCLUSION: Findings across two samples bolster confidence that females with SUD show attenuated CRP-indexed inflammation. As SUD+ comorbidity was high, replication is warranted with respect to specific SUD classes (i.e., stimulants versus cannabis).

Stages of hyperglycemia and common mental disorders in adults - The Brazilian Study of Adult Health (ELSA-Brasil) / Estágios de hiperglicemia e transtornos mentais comuns em adultos - Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil)

ABSTRACT CONTEXT AND OBJECTIVE: Diabetes mellitus and depressive disorders frequently coexist. However, this relationship has been little evaluated across stages of hyperglycemia and for a broad range of common mental disorders (CMDs). The objective here was to investigate the association between CMDs and stages of glycemia. DESIGN AND SETTING: Cross-sectional study conducted among civil servants aged 35-74 years participating in the ELSA-Brasil cohort. METHODS: CMDs were classified using the Clinical Interview Schedule - Revised (CIS-R). Glycemia was classified in stages as normal, intermediate hyperglycemia, newly classified diabetes or previously known diabetes, based on oral glucose tolerance testing, glycated hemoglobin (HbA1c), self-reported diabetes and medication use. Blood glucose control was assessed according to HbA1c. RESULTS: CMDs were most prevalent in individuals with previously known diabetes. After adjustments, associations weakened considerably and remained significant only for those with a CIS-R score ≥ 12 (prevalence ratio, PR: 1.15; 95% confidence interval, CI: 1.03-1.29). Intermediate hyperglycemia did not show any association with CMDs. For individuals with previously known diabetes and newly classified diabetes, for every 1% increase in HbA1c, the prevalence of depressive disorders became, respectively, 12% and 23% greater (PR: 1.12; 95% CI: 1.00-1.26; and PR: 1.23; 95% CI: 1.04-1.44). CONCLUSION: Individuals with previously known diabetes had higher CIS-R scores. Among all individuals with diabetes, worse blood glucose control was correlated with depressive disorder. No relationship between intermediate hyperglycemia and CMDs was observed, thus suggesting that causal processes relating to CMDs, if present, must act more proximally to diabetes onset.

RESUMO CONTEXTO E OBJETIVO: Diabetes mellitus e transtornos depressivos frequentemente coexistem. No entanto, essa relação tem sido pouco avaliada nos estágios hiperglicêmicos e em uma amplitude maior de transtornos mentais comuns (TMCs). O objetivo foi investigar a associação entre TMCs e estágios de glicemia. TIPO DE ESTUDO E LOCAL: Estudo transversal realizado com funcionários públicos com idade entre 35-74 anos participantes da coorte ELSA-Brasil. MÉTODOS: TMCs foram classificados usando o instrumento Clinical Interview Schedule - Revised (CIS-R). Para a classificação dos estágios de glicemia, foi utilizado o teste de tolerância a glicose, hemoglobina glicada (HbA1c), relato pessoal de diabetes e uso de medicamentos. A glicemia foi categorizada como: normal, hiperglicemia intermediária, classificação nova de diabetes, e diabetes prévio. Controle glicêmico foi avaliado pela HbA1c. RESULTADOS: TMCs foram mais prevalentes nos pacientes com diabetes prévio. Após ajustes, as associações foram consideravelmente enfraquecidas, permanecendo significativas somente para aqueles com escore do CIS-R ≥ 12 (razão de prevalência, RP: 1,15; intervalo de confiança de 95%, IC: 1,03-1,29). Hiperglicemia intermediária não teve associação com CMDs. Para aqueles com diabetes prévio e classificação nova de diabetes, para cada aumento de 1% na HbA1c, a prevalência de transtorno depressivo foi, respectivamente, 12% e 23% maior (RP: 1,12; IC: 1,00-1,26 e RP: 1,23; IC: 1,04-1,44). CONCLUSÃO: Aqueles com diabetes prévio tiveram escore do CIS-R mais elevado. Entre todos com diabetes, o controle glicêmico pior foi relacionado ao transtorno depressivo. Não foi observada relação entre hiperglicemia intermediária e TMCs, sugerindo que a relação causal relacionada aos TMCs, se presente, deve agir de forma mais próxima ao início de diabetes.

Cholesterol levels in panic disorder, generalized anxiety disorder and major depression

Serum plasma total cholesterol levels were measured in 85 male or female outpatients with panic disorder (PD; N=41), generalized anxiety disorder (GAD; N=23) and major depression (MD; N=21) according to DSM-IV criteria. All the patients had a mean cholesterol level within the normal range; males (N=22) and females (N=63) had approximately the same serum cholesterol levels (p > .05). No significant differences in cholesterol levels emerged between PD, GAD and MD patient groups. Both female PD and female GAD subjects had a mean cholesterol level similar to their male counterparts (p>.05). It is concluded that both Hayward and colleagues and Bajwa et al. findings could not be replicated by our study.