Bipolar disorder is associated with an inflammation-triggered elevated catabolism of tryptophan to the kynurenine pathway, which impacts psychiatric symptoms and outcomes. The data indicate that lithium exerts anti-inflammatory effects by inhibiting indoleamine-2,3-dioxygenase (IDO)-1 activity. This exploratory study aimed to investigate the tryptophan catabolism in individuals with bipolar disorder (n = 48) compared to healthy controls (n = 48), and the associations with the response to mood stabilizers such as lithium, valproate, or lamotrigine rated with the Retrospective Assessment of the Lithium Response Phenotype Scale (or the Alda scale). The results demonstrate an association of a poorer response to lithium with higher levels of kynurenine, kynurenine/tryptophan ratio as a proxy for IDO-1 activity, as well as quinolinic acid, which, overall, indicates a pro-inflammatory state with a higher degradation of tryptophan towards the neurotoxic branch. The treatment response to valproate and lamotrigine was not associated with the levels of the tryptophan metabolites. These findings support the anti-inflammatory properties of lithium. Furthermore, since quinolinic acid has neurotoxic features via the glutamatergic pathway, they also strengthen the assumption that the clinical drug response might be associated with biochemical processes. The relationship between the lithium response and the measurements of the tryptophan to the kynurenine pathway is of clinical relevance and may potentially bring advantages towards a personalized medicine approach to bipolar disorder that allows for the selection of the most effective mood-stabilizing drug.
Lesbian, gay, bisexual, transgender, intersex, queer people and minority gender identities and sexualities (LGBTIQ+) are often stigmatised and experience discrimination in healthcare settings, leading to poorer mental health outcomes and unmet needs compared to heterosexual and cisgendered peers. It is thus imperative that mental health providers consider and address structural challenges in order to reduce mental health inequalities of this population. This narrative review assessed the barriers that may prevent access to care and the pathways for care in LGBTIQ+ communities. PubMed, PsycInfo, Embase, and Scopus were searched for papers published between December 2021 and February 2022. 107 papers were included with studies reflecting five themes: (1) Unmet mental health needs; (2) Young people; (3) Substance abuse and addiction; (4) Barriers and pathways to care; and (5) Interventions. Findings demonstrate that LGBTIQ+ people experience stigmatisation and higher rates of substance misuse and mental ill health, which may lead to barriers in accessing healthcare services, and fewer tailored interventions being provided. These findings have implications for policy, healthcare screening, and how specialist services are structured. Substantial gaps in the evidence-base exist, and future research should examine how mental healthcare providers can challenge social issues that maintain discriminatory and stigmatising practices, and support LGBTIQ+ individuals to sustain their resilience. Table 2. Characteristics of included studies (without a review design)*
Background and PurposeComorbidity between diabetes and depression, and diabetes and eating disorders (ED) conveys significant diagnostic, clinical and therapeutic implications. The present study was conducted on a sample of adult outpatients affected by Type 1 Diabetes (T1DM) to assess lifetime prevalence of ED; current prevalence of depression and Disturbed Eating Behaviors (DEB) and their impact on glycemic control. We hypothesized that patients with depression would have higher rates of lifetime ED and current DEB. We hypothesized a significant and independent association between DEB and the prevalence of depression.Materials and MethodsThe study was carried out using a cross-sectional design in a sample of 172 diabetic patients with T1DM aged from 17 to 55 years. Lifetime prevalence of ED according to DSM-5 criteria was assessed by means of the Module H modified of the Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I). The following questionnaires were used: Beck Depression Inventory–IA version (BDI-IA) and Diabetes Eating Problems Survey—Revised (DEPS-R), to assess respectively the current presence of depression and DEB. Socio-demographic, clinical, and laboratory data were also collected.ResultsHigh rates of depression (35.5%) and DEB (19.2%) were observed in our sample of 172 adult outpatients with T1DM. Lifetime history of ED was present in 20.9% of the sample and was more frequently diagnosed in patients with current depression (34.4% vs. 13.9%, p = 0.002). Higher levels of DEB at DEPS-R significantly increased the odds of depression (adjOR: 1.09; 95% CI: 1.03–1.15; p = 0.003). The presence of DEB was associated with poor glycemic control. On the other hand, no association was found between depression and metabolic compensation.ConclusionAdult patients with T1DM and depression should be screened for ED and DEB. Treating DEB could positively impact both mood and glycemic control in this population. Further studies should be carried out on a larger patient population using a longitudinal design and an accurate method of evaluation to explore the complex relationship between diabetes, depression, ED, and DEB. Future research should investigate treatment strategies for DEB in T1DM patients and their impact on both psychopathological and metabolic outcomes.
The kynurenine pathway (KP) may play a role in the pathophysiology of bipolar disorder (BD). We conducted a genome-wide association study (GWAS) to identify genetic variants associated with the plasma levels of the metabolites of tryptophan (TRP) via the serotonin (5-HT) and kynurenine (KYN) pathways in 44 patients with BD and 45 healthy controls. We assessed whether variants that were differentially associated with metabolite levels based on the diagnostic status improved the prediction accuracy of BD using penalized regression approaches. We identified several genetic variants that were significantly associated with metabolites (5-HT, 5-hydroxytryptophan (5-HTP), TRP, and quinolinic acid (QA) or metabolite ratios (5-HTP/TRP and KYN/TRP) and for which the diagnostic status exerted a significant effect. The inclusion of genetic variants led to increased accuracy in the prediction of the BD diagnostic status. Specifically, we obtained an accuracy of 0.77 using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The predictors retained as informative in this model included body mass index (BMI), the levels of TRP, QA, and 5-HT, the 5-HTP/TRP ratio, and genetic variants associated with the levels of QA (rs6827515, rs715692, rs425094, rs4645874, and rs77048355) and TRP (rs292212) or the 5-HTP/TRP ratio (rs7902231). In conclusion, our study identified statistically significant associations between metabolites of TRP via the 5-HT and KYN pathways and genetic variants at the genome-wide level. The discriminative performance of penalized regression models incorporating clinical, genetic, and metabolic predictors warrants a follow-up analysis of this panel of determinants.
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