Lack of Association Between Depression and Subclinical Hypothyroidism in Adolescents Presenting for Routine Physical Examinations.

Background: There are conflicting results in the existing studies regarding the association between depression and subclinical hypothyroidism in adolescents. Subclinical hypothyroidism is defined as elevated thyroid stimulating hormone (TSH) levels above the reference range without signs or symptoms of hypothyroidism. Objectives: The focus of this study is to determine whether there is any association between depression and subclinical hypothyroidism, (as defined by the serum TSH levels) in a population of healthy adolescents. Design: Quantitative-based cross-sectional study of a representative subset of the adolescent population. Methods: We carried out a cross-sectional study to determine the association between major depressive disorder (MDD) and subclinical hypothyroidism, in adolescents presenting for annual physical examinations during the peak period of the COVID-19 pandemic in the USA, a period deemed high for adolescent depression. All the adolescents were screened for depression by the PHQ-9 screening tool and had their TSH measured. Results: Of the 304 subjects analyzed, 179 (58.88%) were minimally or not depressed according to the Patient Health Questionnaire (PHQ-9) screening tool (mean PHQ 1.80 ± 1.49). 70 (23.03%) had mild depression (mean PHQ 6.59 ± 1.46), 50 (16.45%) had moderate depression (mean PHQ 13.70 ± 2.75), and 5 (1.64%) had severe depression (mean PHQ 21.40 ± 1.67). Mean TSH values were 1.93 ± 0.99, 1.77 ± 1.05, 2.10 ± 0.98, and 1.57 ± 0.32 mIU/L, respectively in the four groups. All values were within the recommended range of 0.50 to 4.30 mIU/L, without statistically significant inter-group differences. Conclusion: We conclude that there is no statistically significant association between depression and subclinical hypothyroidism, in a population of adolescents presenting for physical examinations, and if the screening for depression by the PHQ-9 tool indicates depression, a screening TSH test for subclinical hypothyroidism is not justified.

Live cell microscopy of mitochondria-lysosome contact site formation and tethering dynamics.

Mitochondria-lysosome contact sites are critical for maintaining cellular homeostasis by regulating mitochondrial and lysosomal network dynamics and mediating metabolite exchange. Here, we present a protocol to quantitatively analyze the formation and tethering duration of mitochondria-lysosome contact sites by using time-lapse live confocal microscopy of LAMP1 and TOMM20. Although this protocol focuses on mammalian HeLa cells, it can be applied to other cell types for further studies on mitochondria-lysosome contact regulation and function, and elucidation of their role in human disorders. For complete details on the use and execution of this protocol, please refer to Wong et al. (2018) and Wong et al. (2019b).

Mitochondria-lysosome contact site dynamics and misregulation in neurodegenerative diseases.

Neurons rely heavily on properly regulated mitochondrial and lysosomal homeostasis, with multiple neurodegenerative diseases linked to dysfunction in these two organelles. Interestingly, mitochondria-lysosome membrane contact sites have been identified as a key pathway mediating their crosstalk in neurons. Recent studies have further elucidated the regulation of mitochondria-lysosome contact dynamics via distinct tethering/untethering protein machinery. Moreover, this pathway has been shown to have additional functions in regulating organelle network dynamics and metabolite transfer between lysosomes and mitochondria. In this review, we highlight recent advances in the field of mitochondria-lysosome contact sites and their misregulation across multiple neurodegenerative disorders, which further underscore a potential role for this pathway in neuronal homeostasis and disease.

Mid51/Fis1 mitochondrial oligomerization complex drives lysosomal untethering and network dynamics.

Lysosomes are highly dynamic organelles implicated in multiple diseases. Using live super-resolution microscopy, we found that lysosomal tethering events rarely undergo lysosomal fusion, but rather untether over time to reorganize the lysosomal network. Inter-lysosomal untethering events are driven by a mitochondrial Mid51/Fis1 complex that undergoes coupled oligomerization on the outer mitochondrial membrane. Importantly, Fis1 oligomerization mediates TBC1D15 (Rab7-GAP) mitochondrial recruitment to drive inter-lysosomal untethering via Rab7 GTP hydrolysis. Moreover, inhibiting Fis1 oligomerization by either mutant Fis1 or a Mid51 oligomerization mutant potentially associated with Parkinson's disease prevents lysosomal untethering events, resulting in misregulated lysosomal network dynamics. In contrast, dominant optic atrophy-linked mutant Mid51, which does not inhibit Mid51/Fis1 coupled oligomerization, does not disrupt downstream lysosomal dynamics. As Fis1 conversely also regulates Mid51 oligomerization, our work further highlights an oligomeric Mid51/Fis1 mitochondrial complex that mechanistically couples together both Drp1 and Rab7 GTP hydrolysis machinery at mitochondria-lysosome contact sites. These findings have significant implications for organelle networks in cellular homeostasis and human disease.

Treatment with Vitamin D3 in Vitamin D Deficient Adolescents: A Pilot Study.

Multiple epidemiological studies have shown that vitamin D deficiency is highly prevalent amongst adolescents in the USA. However, recommendations regarding the treatment of vitamin D deficiency in healthy adolescents are not well defined. We carried out a prospective pilot study, to determine whether treatment with 2000 international units of vitamin D3 daily for 3 months, would normalize the vitamin D levels in vitamin D deficient adolescents. Following treatment there was a 56.02% increase in the vitamin D levels from the mean baseline values and 80.39% of the subjects normalized their vitamin D levels. There were no adverse effects associated with this intervention. This study offers complementary guidelines to the existing recommendations from the American Academy of Pediatrics on the optimal dose and duration of vitamin D3 therapy in vitamin D deficient, but otherwise healthy adolescents. Further prospective, large scale, case control studies are indicated to validate our results.

Vitamin D Deficiency and Association With Body Mass Index and Lipid Levels in Hispanic American Adolescents.

In this retrospective study, vitamin D deficiency was examined with body mass index (BMI) and lipid levels in a sample of Hispanic American adolescents. The prevalence of vitamin D deficiency among 234 subjects aged 13 to 19 years was 27.8%. Vitamin D deficiency was significantly associated with a BMI of 85 kg/m2 or higher (odds ratio = 2.02, 95% confidence interval = 1.11-3.69, χ2 = 5.37, P = .021), and 55.6% of the sample were overweight or obese (BMI ≥ 85%). In the overweight or obese subjects, vitamin D deficiency was significantly associated with higher mean lipid levels compared with those with adequate vitamin D levels: total cholesterol = 165 ± 28.6 mg/dL versus 145.7 ± 27.5 mg/dL, P = .0003; low-density lipoprotein = 92.7 ± 25.7 mg/dL versus 80.8 ± 21.4 mg/dL, P = .007; and triglycerides = 148.9 ± 97.1 mg/dL versus 90.6 ± 40.7 mg/dL, P = .0000. The mean triglyceride level of 148.9 mg/dL in the overweight or obese subjects was in the dyslipidemic range. In the underweight and healthy weight subjects (BMI ≤ 84), there was no statistically different lipid levels between the vitamin D adequate and vitamin D deficient groups. The effect of vitamin D on lipid levels was confirmed by regression analysis. Elevated lipids and dyslipidemic triglyceride levels, associated with vitamin D deficiency in overweight or obese Hispanic American adolescents, indicates a need for clinical monitoring and appropriate intervention.