The Absence of Items Addressing Increased Appetite or Weight in Depressive-Symptom Questionnaires: Implications for Understanding the Link between Major Depressive Disorder, Antidepressants, and Obesity.

Major depressive disorder (MDD) and obesity have a complex bidirectional relationship. However, most studies do not assess increased appetite or weight as a depressive symptom due to limitations in rating scales. Here we aimed to analyze frequently employed depressive-symptom scales and discuss the relevance of weight and appetite assessment items. To elaborate this perspective, we searched for validated questionnaires and scales evaluating depressive symptoms in English. We analyzed appetite and weight items from 20 depressive-symptoms rating scales. Only 8 of 20 rating scales assessed for increased weight or appetite. The scales reported in the literature as the most employed in antidepressants efficacy trials do not assess increased appetite or weight. The current use of rating scales limits our understanding of the relationship between MDD, antidepressants, and obesity. It is necessary to improve our weight and appetite measurements in MDD to clarify the respective impact of depressive symptoms and antidepressants on weight change.

Bidirectional negative relationship between thyrotropin and kidney function during alcohol intoxication in males.

Introduction: Despite a well-established direct toxic effect of alcohol on renal cells, there is a salutary dose-dependent effect of alcohol consumption on common laboratory parameters related to kidney performance. Alcohol also impacts thyroid hormones, while thyroid status modulates kidney function. The modulation of kidney parameters with thyrotropin (TSH) and thyroid status indicates a possible interaction between alcohol, kidney, and thyroid functions. This retrospective study was conducted to test the hypothesis that the positive effect of alcohol use on the estimated glomerular filtration rate (eGFR) is mediated by alcohol's effect on thyroid hormones. Methods: We reviewed the electronic medical records of 767 hospitalized adult patients free of thyroid disorders who received medical care in the Mayo Clinic Health System from June 2019 through June 2022 and had blood alcohol concentration (BAC), serum TSH, and serum creatinine measured during the hospitalization. We calculated the eGFR using both the re-expressed Modification of Diet in Renal Disease (MDRD II) study equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine equation. Results: We found a significant relationship of BAC with eGFR (CKD-EPI) and TSH in males only. BAC had a positive association with eGFR (b = 0.24, p = 0.0001) and negative with TSH (b=-0.17, p = 0.006). The covariance between the two outcomes (eGFR and TSH) was negative (b = -0.12, p = 0.049). The path analyses using the eGFR MDRD II equation were not significant in males, whereas females had no significant path analyses with either of the eGFR equations. Discussion: We observed that BAC influences both eGFR and TSH, whereas eGFR and TSH influence each other. After considering important covariates (e.g., age, body mass index, diabetes mellitus, cardiovascular disease, chronic kidney disease, and chronic liver disease) and the negative bidirectional effect of TSH and eGFR, a positive impact of BAC on eGFR was observed in males.

Acid accumulation is associated with metabolic alterations; higher energy, fat, and protein intake; and energy expenditure.

OBJECTIVE: The objective of this study was to study how acid accumulation (lower plasma bicarbonate and higher anion gap [AG] and corrected anion gap [CAG]) correlates with metabolic parameters, food intake, and 24-h energy expenditure (EE). METHODS: Acid accumulation was measured in 286 healthy adults with estimated glomerular filtration rate > 60 mL/min/1.73 m2. Measurements included body composition by dual-energy x-ray absorptiometry scan, ad libitum energy intake by a vending machine paradigm over 3 days, and 24-h EE in a whole-room indirect calorimeter. RESULTS: Lower bicarbonate, higher AG, and higher CAG were correlated with higher waist and thigh circumferences, body fat (percentage), fat mass, triglycerides, and lower high-density lipoprotein cholesterol. Acid accumulation markers were correlated with higher total energy (CAG partial r = 0.17; p = 0.02), fat (CAG partial r = 0.17; p = 0.02), protein intake (CAG partial r = 0.20; p = 0.006), and 24-h EE (CAG partial r = 0.24; p = 0.0007). A mediation analysis of CAG and total energy intake found that 24-h EE was a partial mediator (40%), but the association remained significant (ß = 0.15; p < 0.0001). CONCLUSIONS: In healthy individuals, acid accumulation was associated with an unfavorable metabolic phenotype; higher 24-h EE; and increased total energy, fat, and protein intake. Acid accumulation markers, as putative markers of higher dietary acid load (e.g., from protein), may affect energy balance physiology promoting weight gain.

The Wnt signaling pathway in major depressive disorder: A systematic review of human studies.

Despite uncertainty about the specific molecular mechanisms driving major depressive disorder (MDD), the Wnt signaling pathway stands out as a potentially influential factor in the pathogenesis of MDD. Known for its role in intercellular communication, cell proliferation, and fate, Wnt signaling has been implicated in diverse biological phenomena associated with MDD, spanning neurodevelopmental to neurodegenerative processes. In this systematic review, we summarize the functional differences in protein and gene expression of the Wnt signaling pathway, and targeted genetic association studies, to provide an integrated synthesis of available human data examining Wnt signaling in MDD. Thirty-three studies evaluating protein expression (n = 15), gene expression (n = 9), or genetic associations (n = 9) were included. Only fifteen demonstrated a consistently low overall risk of bias in selection, comparability, and exposure. We found conflicting observations of limited and distinct Wnt signaling components across diverse tissue sources. These data do not demonstrate involvement of Wnt signaling dysregulation in MDD. Given the well-established role of Wnt signaling in antidepressant response, we propose that a more targeted and functional assessment of Wnt signaling is needed to understand its role in depression pathophysiology. Future studies should include more components, assess multiple tissues concurrently, and follow a standardized approach.

Dietary Adherence Is Associated with Perceived Stress, Anhedonia, and Food Insecurity Independent of Adiposity.

We examined whether perceived stress, anhedonia, and food insecurity were associated with dietary adherence during a 6-week intervention. Sixty participants (23 m; 53 ± 14 y) completed psychosocial measures and were provided with full meals. Individuals with obesity were randomized to a weight-maintaining energy needs (WMENs) (n = 18; BMI 33 ± 4) or a 35% calorie-reduced diet (n = 19; BMI 38 ± 9); normal-weight individuals (n = 23; BMI 23 ± 2) were assigned to a WMENs diet. Adherence scores were determined via weekly assessments and daily ecological momentary assessments (EMAs) of real-time behavior in a natural environment. Perceived stress and anhedonia were associated with % body fat (all r-values > 0.25, all p-values < 0.05), but food insecurity and adherence were not. Higher perceived stress (r = -0.31, p = 0.02), anhedonia (r = -0.34, p = 0.01), and food insecurity (r = -0.27, p = 0.04) were associated with lower adherence scores, even after adjusting for age, sex, and % body fat. In all adjusted models, % body fat was not associated with adherence. Higher measures of stress, anhedonia, and food insecurity predicted lower adherence independently of body fat, indicating that psychosocial factors are important targets for successful adherence to dietary interventions, regardless of body size.

Greater anhedonia scores in healthy individuals are associated with less decline in 24-hour energy expenditure with fasting: Evidence for a link between behavioral traits and spendthrift phenotype.

Obesity rates are increasing and affecting mental health. It is important to understand how behavioral traits such as anhedonia are associated with physiologic traits that may predict weight-change in clinical and non-clinical populations. We studied whether 24-hour energy expenditure (24hEE) changes with fasting and overfeeding are associated with anhedonia in a healthy cohort. We performed behavioral assessments (physical anhedonia scale (PAS) and inventory for depressive symptoms (IDS)) followed by measures of 24hEE and urinary catecholamines in a whole-room indirect calorimeter (respiratory chamber) during energy balance, and then randomly during fasting and 2 different overfeeding diets. Participants (n=98) were medically healthy, between 18 and 55 years of age, with normal glucose regulation and weight-stable 6 months before admission. Women were premenopausal and not pregnant. Higher PAS was significantly associated with lesser decrease in 24hEE with fasting and higher urinary catecholamine excretion rates - consistent with spendthrift metabolism. As IDS increased, the association between anhedonia and the change in 24hEE from energy balance to fasting decreased (B-values were lower for change in EE). Here, higher PAS scores may reflect the ability to respond with appropriate homeostatic reactions which balance energy needs. IDS scores blunting this response may explain how anhedonia and depression can lead to weight gain.