•The role of adipose tissue in the manifestation of MDD has been proposed.•The current study explored and quantified the relationship between different adipokines (i.e., leptin and adiponectin) and ...MDD.•For exploring the mechanistic role of leptin and adiponectin in the pathological process of MDD, sex-related differences also were taken into consideration.
To explore differences in adipokine levels (i.e., leptin and adiponectin levels) between adults with Major Depressive Disorder (MDD) and healthy controls (HC), and to discuss the possible role of adipokine regulation in the development and progression of MDD.
A systematic review and meta-analysis were conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic search was conducted for all English and Chinese peer-reviewed articles from inception to November 2017. A random effects model was used to calculate the standardized mean difference (SMD) of leptin and/or adiponectin levels in subjects diagnosed with MDD versus HC within a 95% confidence interval (CI).
Thirty-three studies were included in this meta-analysis. In total, 4,372 (52.3%) subjects with MDD and 3,984 (47.7%) HC were compared. We identified significant lower adiponectin levels in MDD compared to HC with a small effect size (ES) (SMD = −0.25; 95% CI: −0.48, −0.02; P < 0.001). However, no significant difference was observed in leptin levels between MDD subjects and HC (SMD = 0.13; 95% CI: −0.06, 0.31; P = 0.170). The heterogeneity in the results of our meta-analysis could not be completely explained by dividing subjects into subgroups. Results from subgroup analyses suggested that studies involving samples with BMI ≥ 25 had lower adiponectin levels in subjects with MDD compared to HC, and older age samples (i.e., age ≥ 40) with BMI ≥ 25 had both higher leptin levels and lower adiponectin levels in MDD subjects as compared to HC.
The heterogeneity of included studies, small sample sizes, and potential publication bias were significant limitations.
The current systematic review and meta-analysis indicated that lower adiponectin levels may be associated with MDD. Moreover, the results suggest that males expressing lower adiponectin and leptin levels have an increased likelihood of developing MDD. Future studies should aim to investigate the manifestation of depressive phenotypes in older, obese populations with altered metabolic profiles resulting from adipokine dysregulation.
The review has been registered with PROSPERO (registration number CRD42018082733).
It is well established that deficits in motivation, reward, and cognition are common during and in between syndromal episodes of depression as part of Major Depressive Disorder (MDD). Informed by ...evidence indicating functional and structural interconnectivity between cognitive and reward brain circuits, we preliminarily evaluate the association between measures of cognitive performance and reward/motivation.
This is a post-hoc analysis of a primary study (i.e. the THINC-it sensitivity to change study). Adults (18–65 years of age) meeting DSM-5 criteria for MDD, single-episode or recurrent confirmed by M.I.N.I. with moderate severity or greater (i.e. Montgomery Asberg Depression Rating Scale ≥20). All eligible subjects received vortioxetine 10–20 mg open-label for 8 weeks. The Effort Expenditure Reward Task (EEfRT) was the principal measure of motivation and reward. We directly compare the effects of cognitive measures and depressive symptoms on effort-based decision-making using the THINC-it composite score and MADRS total score.
Twenty-one participants with MDD (Mean age = 38.47, SD = 12.85) and 20 healthy volunteers (Mean age = 41.50, SD = 14.21) completed the optional EEfRT task. Amongst individuals with MDD, performance in processing speed, executive function (i.e. Trails B) and overall composite cognitive score was positively associated with the proportion of hard-task choices in the high reward condition (i.e. greater reward valuation). Across both groups, a greater probability (χ2 = 1.137) and magnitude of reward (χ2 = 0.045) was associated with increased effort (i.e. choosing the hard task more frequently). Using fully factored GEE models, we observed a positive association between performance on the Trails test (β = 2.223, SE = 0.928, p = 0.017) as well as the composite score (β = 0.978, SE = 0.0.459, p = 0.033), and greater effort for high rewards. In addition, it was observed that a positive association (i.e. greater effort for reward in higher probability) was observed with depressive symptoms and overall cognitive measures.
Herein, we observed that an association exists between overall cognitive function, notably processing speed and executive function and reward function. Specifically, a greater effort for hard task rewards (using the EEfRT task) was manifested in individuals exhibiting higher levels of cognitive performance in a well-characterized sample of MDD treated with Vortioxetine.
•Cognitive function highly correlates with measures of reward and motivation in adults with major depressive disorder (MDD)•Processing speed, executive function and overall cognition was positively associated with greater reward valuation•Overall cognition positively correlated (i.e. greater effort for reward in higher probability) with depressive symptoms•Self-reported measures of anhedonia and reward valuation are distinct domains of psychopathology in those with MDD
Treating to target in chronic diseases e.g. Major Depressive Disorder (MDD) fosters precision, consistency, and appropriateness of treatment selection and sequencing. Therapeutic target ...definitions/endpoints in MDD should satisfy patient-, provider-, and societal expectations. Functional recovery in depression and return to both physical and mental health are the overarching therapeutic objectives. Treating to target in MDD implies multidimensional symptomatic remission, with a particular emphasis on cognitive function and aspects of positive mental health. Several atypical antipsychotic agents (i.e. brexpiprazole, aripiprazole, quetiapine) are FDA-approved as augmentation agents in MDD. Vortioxetine, duloxetine, and psychostimulants have evidence of independent, direct, and robust effects on cognitive function in MDD. Vortioxetine is the only agent that demonstrates efficacy across multiple cognitive domains in MDD associated with functional recovery. Measurement-based care, health information technology/systems, and integrated care models (e.g. medical homes) provide requisite tools and health environments for optimal health outcomes in MDD. Achieving remission in MDD does not equate to health. Return to positive mental health as well as full functioning provide the impetus to pivot away from traditional provider-defined outcomes toward an inclusive perspective involving patient- and society-defined outcomes (i.e. optimization of human capital). As in other chronic diseases, treating to target (e.g. cognitive function) further increases the probability of achieving optimal health outcomes.
Psychotropic Drug-Related Weight Gain and Its Treatment McIntyre, Roger S; Kwan, Angela T H; Rosenblat, Joshua D ...
The American journal of psychiatry,
2024-Jan-01, 2024-01-01, 20240101, Letnik:
181, Številka:
1
Journal Article
Recenzirano
Psychotropic drug-related weight gain (PDWG) is a common occurrence and is highly associated with non-initiation, discontinuation, and dissatisfaction with psychiatric drugs. Moreover, PDWG ...intersects with the elevated risk for obesity and associated morbidity that has been amply reported in the psychiatric population. Evidence indicates that differential liability for PDWG exists for antipsychotics, antidepressants, and anticonvulsants. During the past two decades, agents within these classes have become available with significantly lower or no liability for PDWG and as such should be prioritized. Although lithium is associated with weight gain, the overall extent of weight gain is significantly lower than previously estimated. The benefit of lifestyle and behavioral modification for obesity and/or PDWG in psychiatric populations is established, with effectiveness similar to that in the general population. Metformin is the most studied pharmacological treatment in the prevention and treatment of PDWG, and promising data are emerging for glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, semaglutide). Most pharmacologic antidotes for PDWG are supported with low-confidence data (e.g., topiramate, histamine-2 receptor antagonists). Future vistas for pharmacologic treatment for PDWG include large, adequately controlled studies with GLP-1 receptor agonists and possibly GLP-1/glucose-dependent insulinotropic polypeptide co-agonists (e.g., tirzepatide) as well as specific dietary modifications.
There is a paucity of treatments that are capable of reliably and robustly improving cognitive function in adults with mood disorders. Glucagon-like peptide-1 is synthesized centrally and its ...receptors are abundantly expressed in neural circuits subserving cognitive function. We aimed to determine the effects of liraglutide, a GLP-1 receptor (GLP-1R) agonist, on objective measures of cognition in adults with a depressive or bipolar disorder.
In this 4-week, pilot, open-label, domain-based study (e.g. cognition), we recruited 19 individuals with major depressive disorder (MDD) or bipolar disorder (BD) and an impairment in executive function, defined as a below-average performance in the Trail Making Test-B (TMTB). Liraglutide 1.8mg/day was added as an adjunct to existing pharmacotherapy.
Participants had significant increases from baseline to week 4 in the TMTB standard score (age and education corrected) (Cohen's d=0.64, p=0.009) and in a composite Z-score comprising multiple cognitive tests (i.e. Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop test) (Cohen's d=0.77, p<0.001). Neither changes in mood rating scales nor metabolic parameters were associated with changes in cognitive performance (all p>0.05); however baseline insulin resistance (IR) and body mass index (BMI) moderated the changes in the composite Z-score (p=0.021 and p=0.046, respectively), indicating larger responses in individuals with higher IR and BMI at baseline. There was a significant increase in lipase (p<0.001), but individual values were above the upper limit of normality.
Small sample size, open-label design, lack of a placebo group.
Liraglutide was safe and well tolerated by a sample of non-diabetic individuals with mood disorders and had beneficial effects on objective measures of cognitive function. Larger studies with controlled trial designs are necessary to confirm and expand the results described herein.
•Cognitive deficits in mood disorders are highly prevalent and impactful.•Few interventions have evidence of pro-cognitive effects in mood disorders.•In this pilot study we explored the cognitive effect of a GLP-1R agonist.•4-week treatment with liraglutide was associated with cognitive improvements.•Liraglutide was also safe and well tolerated by individuals with mood disorders.
Abstract Background Previous studies showed that the insulin resistance (IR) could be related to depression. However, this association is still equivocal in the general population. Herein, we aimed ...to investigate the association between IR and depressive symptoms in a large sample in South Korea. Methods A cross-sectional study was carried out for 165,443 Korean men and women who received a health checkup including various clinical parameters and the Center for Epidemiologic Studies Depression scales (CES-D). Subjects were stratified into subgroups by CES-D score, sex, age, and presence of diabetes. The odd ratios (ORs) for homeostasis model assessment of insulin resistance (HOMA-IR) were compared between groups using multivariable logistic regression analyses. Results After adjusting covariates (e.g. smoking, family income, marriage state, unemployment status, average alcohol use, BMI, physical activity, systolic blood pressure, diabetes), increased IR was weakly associated with greater depressive symptoms (adjusted OR = 1.01 95% CI 1.0001 - 1.03). Subgroup analysis revealed this association was statistically significant in females (adjusted OR = 1.03, 95% CI 1.001 – 1.06), non-diabetic group (adjusted OR = 1.04, 95% CI 1.02 – 1.06), and young participants under the age of thirty (adjusted OR =1.17, 95% CI 1.07 – 1.27). But we couldn’t find significant association in diabetic and middle to elderly participants. Conclusions This study demonstrates that there is a relationship between IR and depressive symptoms in the Korean general population. Results from this epidemiological study revealed that young adults and non-diabetic individuals with increased IR may be related with depressive symptoms.
To validate the THINC-integrated tool (THINC-it)-a freely available, patient-administered, computerized screening tool integrating subjective and objective measures of cognitive function in adults ...with major depressive disorder (MDD).
Subjects aged 18 to 65 years (n = 100) with recurrent MDD experiencing a major depressive episode of at least moderate severity were evaluated and compared to age-, sex-, and education-matched healthy controls (n = 100). Between January and June 2016, subjects completed the THINC-it, which includes variants of the Choice Reaction Time Identification Task (IDN), One-Back Test, Digit Symbol Substitution Test, Trail Making Test-Part B, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D).
The THINC-it required approximately 10 to 15 minutes for administration and was capable of detecting cognitive deficits in adults with MDD. A total of 44.4% of adults with MDD exhibited cognitive performance at ≥ 1.0 SD below that of healthy controls on standardized mean scores of the THINC-it. Concurrent validity of the overall tool, based on a calculated composite score, was acceptable (r = 0.539, P < .001). Concurrent validity of the component tests ranged from -0.083 (IDN) to 0.929 (PDQ-5-D). Qualitative survey results indicated that there was a high level of satisfaction and perceived value in administering the THINC-it regarding its impact on the appropriateness and quality of care being received.
The THINC-it is a valid and sensitive tool for detecting cognitive dysfunction in adults with MDD that is free, easy to use, and rapidly administered. The THINC-it should be incorporated into the assessment and measurement of all patients with MDD, particularly among those with enduring functional impairment.
ClinicalTrials.gov identifier: NCT02508493.
Orexins are neuropeptides that are postulated to play a central role in the regulation of the sleep-wake cycle, appetite, affect, and reward circuitry. The objectives of the current review are to ...comprehensively evaluate (1) the potential role of orexins in the pathophysiology of major depressive disorders (MDD) and (2) the orexin system as a novel target in the treatment of MDD. Dysfunction of the sleep-wake cycle is observed as a central feature of MDD pathophysiology. Orexin system disturbances produce sleep-wake dysfunction, as observed in MDD. Orexin antagonists have been shown to treat insomnia effectively without disrupting normal sleep architecture in both preclinical (e.g., animal models) and clinical studies. Orexin antagonists are generally safe, well-tolerated, and associated with an acceptable long-term adverse effect profile with relatively low propensity for tolerance or dependence. Orexin antagonists have also been shown to possess antidepressant-like properties in some animal models of MDD. Extant evidence indicates that orexin-modulating treatments exert pleiotropic effects on multiple neural systems implicated in the phenomenology of mood disorders and suggests orexins as a promising target for investigation and intervention in mood disorders. To date, no human clinical trials evaluating the antidepressant effects of orexin antagonists in MDD have been completed. Given the promising results from preclinical studies, clinical trials are merited to evaluate the antidepressant effects of orexin antagonists in MDD.
•Orexins are neuropeptides that are postulated to play a central role in the regulation of the sleep-wake cycle, appetite, affect, and reward circuitry•Dysfunction of the sleep-wake cycle is observed as a central feature of MDD pathophysiology•Orexin system disturbances produce sleep-wake dysfunction, as observed in MDD•Orexin antagonists are generally safe, well-tolerated, and associated with an acceptable long-term adverse effect profile with relatively low propensity for tolerance or dependence and has shown to possess antidepressant properties•The objectives are to evaluate (1) the potential role of orexins in the pathophysiology of major depressive disorders (MDD) and (2) the orexin system as a novel target in the treatment of MDD
•Patients with bipolar disorder are at higher risk of developing type 2 diabetes (T2DM), impaired fasting glucose (IFG), general obesity, and abdominal obesity.•The relative risk of T2DM among ...patients with bipolar disorder is 1.57 compared to the age- and gender-matched non-psychiatric controls.•The relative risk of general obesity among patients with bipolar disorder is 1.67 compared to the age- and gender-matched non-psychiatric controls.
The study herein aimed to assess the prevalence of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), as well as general and abdominal obesity in patients with bipolar disorder (BD). We also compared the prevalence of T2DM and general obesity in patients with BD with age- and gender-matched healthy controls.
A systematic search of Embase, Medline, PubMed, and APA PsycArticles was conducted from inception to June 2021 without language restrictions. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) modified for case-control studies.
A total of forty-nine studies were included in this analysis. The pooled prevalence of T2DM was 9.6% (95% CI, 7.3-12.2%). Patients with BD had a nearly 1.6 times greater risk of developing T2DM compared to their age- and gender-matched controls (RR=1.57, 95% CI 1.36-1.81, p<0.001). In the present analysis, IFG is defined as a fasting plasma glucose (FPG) ≥ 100 mg/dL (FPG≥100) with a prevalence of 22.4% (95% CI, 16.7-28.7%), or as an FPG equal to or greater than 110 mg/d (FPG≥110) with a prevalence of 14.8% (95% CI, 10.8-19.3%). The prevalence of general obesity (BMI≥30 kg/m2) was 29.0% (95% CI, 22.8-35.6%); the risk of obesity was almost twice the rate reported in patients with BD compared to controls (RR=1.67, 95% CI 1.32-2.12, p<0.001). We also observed that more than half of the BD participants had abdominal obesity (i.e., prevalence of 51.1%; 95% CI, 45.0-57.3%).
A significant degree of heterogeneity was detected. Sources of heterogeneity included differences in study designs, inclusion criteria, measurement tools, and data analysis methods.
Bipolar disorder is associated with a higher prevalence of T2DM, IFG, general obesity, and abdominal obesity. Type 2 diabetes mellitus and obesity are significantly more prevalent in patients with BD than in their age- and gender-matched controls.
: CRD42021258431
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