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A complex pathogenesis involving several physiological systems is theorized to underline the development of depressive disorders. Depression is accompanied by circadian regulation disruption and interaction with the functioning of both central and peripheral oscillators. Many aspects of melatonin function unite these systems. The use of drugs for circadian rhythm disorders could inspire a potential treatment strategy for depression. Melatonin plays an essential role in the regulation of circadian rhythms. It exerts effect by activating two types of melatonin receptors, type 1A (MT1) and 1B (MT2). These are G-protein-coupled receptors, predominantly located in the central nervous system. MT1/MT2 agonists could be a useful treatment approach according to all three prevalent theories of the pathogenesis of depression involving either monoamines, synaptic remodeling, or immune/inflammatory events. MT1/MT2 receptors can be a potential target for novel antidepressants with impact on concentrations of neurotrophins or neurotransmitters, and reducing levels of pro-inflammatory cytokines. There is an interesting cross-talk mediated via the physical association of melatonin and serotonin receptors into functional heteromers. The antidepressive and neurogenetic effects of MT1/MT2 agonists can also be caused by the inhibition of the acid sphingomyelinase, leading to reduced ceramide, or increasing monoamine oxidase A levels in the hippocampus. Compounds targeting MT1 and MT2 receptors could have potential for new anti-depressants that may improve the quality of therapeutic interventions in treating depression and relieving symptoms. In particular, a combined effect on MT1 and/or MT2 receptors and neurotransmitter systems may be useful, since the normalization of the circadian rhythm through the melatonergic system will probably contribute to improved treatment. In this review, we discuss melatonergic receptors as a potential additional target for novel drugs for depression.

Background We sought to determine the utility of PET-MRI in diagnosing Idiopathic Inflammatory Myositis (IIM), and look for association between FDG uptake and clinical, pathological and laboratory parameters. Methods A retrospective, observational study was conducted on IIM patients having positive serum autoantibodies and who underwent PET-MRI (3-Tesla SIEMENS Biograph MR scanner) between 2017 and 2021. Thirty patients who underwent PET-MRI to detect systemic metastasis without muscle involvement formed the control group. Results In the IIM cohort, female: male sex ratio was 1.73, mean age at diagnosis was 40.33 years, and the mean duration of illness was 7 months. 33.33% of patients had severe limb weakness. Mi2B (43.33%), Mi2A (43.33%), PL-7(10%), PL-12(6.67%), SRP (16.67%), Tif1gamma (3.33%), NxP2 (3.33%), Ro-52(40%), PM-Scl, U1-RNP, ANA (26.67%) were the serum autoantibodies identified. Using SUV max Ratio to quantify FDG uptake, PET-MRI showed a sensitivity of 100% with 93.3% specificity in diagnosing IIM.FDG uptake was maximum in proximal lower limb region followed by proximal upper limb. Multivariate regression analysis showed that the severity of muscle weakness, serum Mi2B antibody positivity and serum creatinine kinase levels had a significant positive correlation with FDG uptake (value of 0.005, 0.043, 0.042, respectively for whole-body FDG uptake). FDG uptake also showed good correlation with histopathological features and muscle MRI, but there was no significant association with treatment response. Three female patients in our cohort had primary malignancy involving the breast, uterus, and cervix. Conclusions PET-MRI is a promising diagnostic modality for IIM. PET-MRI reflects the severity of muscle inflammation, showing good association with various clinical/laboratory parameters, histopathology, and muscle MRI. Parameters associated with severe muscle inflammation in PET-MRI—clinical severity of muscle weakness, Mi2B positivity, and serum creatine kinase levels—may be used as clinical/laboratory markers of disease severity in IIM. PET-MRI has the added advantage of detection of systemic malignancy.

Megaconial congenital muscular dystrophy (CMD)(OMIM #602541), related to CHKB mutation, is a rare autosomal recessive disorder. To date, only 35 confirmed patients are recorded. We present a detailed description of the clinical, histopathological, imaging, and genetic findings of five children from four Indian families. The children had moderate-to-severe autistic behavior, hand stereotypies, and global developmental delay mimicking atypical Rett syndrome. In addition, generalized hypotonia was a common initial finding. The progression of muscle weakness was variable, with two patients having a milder phenotype and three having a severe form. Interestingly, the majority did not attain sphincter control. Only patient 1 had classical ichthyotic skin changes. Muscle biopsy in two patients showed a myopathic pattern with characteristic peripherally placed enlarged mitochondria on modified Gomori trichrome stain and electron microscopy. Genetic analysis in these patients identified three novel null mutations in CHKB [c.1027dupA (p.Ser343LysfsTer86);c.224 + 1G > T (5' splice site); c.1123C > T (p.Gln375Ter)] and one reported missense mutation, c.581G > A (p.Arg194Gln), all in the homozygous state. Megaconial CMD, although rare, forms an important group with a complex phenotypic presentation and accounted for 5.5% of our genetically confirmed CMD patients. Atypical Rett syndrome-like presentation may be a clue towards CHKB-related disorder.