Perceptions and practices among students, parents, and teachers of the Human Papillomavirus (HPV) Vaccination: A pilot feasibility study from Rural Kerala.

Anxiety‐depressive disorder (ADD) is a common subtype of major depressive disorder (MDD). According to the diagnostic criteria system, DSM‐5 classifies it as “Major Depressive Disorder with Anxious Distress,” accounting for about 40% of patients with clinical depression at first diagnosis. Compared to uncomplicated depression, patients with ADD typically exhibit a higher disease burden, longer duration of illness, and more frequent relapses, and they respond poorly to classic antidepressants such as SSRIs, presenting greater clinical heterogeneity and complexity of neural network dysregulation, making diagnosis and treatment more challenging. In contrast to uncomplicated depression, ADD exhibits unique neuroimmune dysregulation characteristics in its pathological mechanisms, particularly the activation of inflammatory pathways in key brain regions involved in emotional regulation, such as the hippocampus and amygdala. Patients with uncomplicated depression show more hippocampus‐dominant neuroinflammation, while ADD presents elevated inflammation levels in both the hippocampus and amygdala. Chronic restraint combined with corticosterone stress is a well‐established model for ADD. In model animals, the levels of monoamine neurotransmitters serotonin (5‐HT), dopamine (DA), and norepinephrine (NE) in the hippocampus and amygdala decrease, while the levels of IL‐1β, IL‐6, and IL‐18 in the hippocampus increase. Anti‐inflammatory treatment can significantly alleviate anxiety‐like and depression‐like behaviors in rats. Circadian rhythms are closely related to diurnal fluctuations in physiological indicators such as sleep–wake cycles, cognitive function, blood pressure, heart rate, and hormone levels, regulated by core clock genes and clock‐controlled genes. Numerous studies have confirmed that abnormal expression of circadian rhythm genes (CCGs) is associated with emotional disorders and is related to the onset of mental illnesses such as sleep disorders, delirium, and schizophrenia, hinting at a possible link to ADD. Research indicates that abnormalities in circadian rhythm genes mediate the disruption of microglial clocks, impairing the activity of tissue protease S and interfering with sleep and social abilities. Individuals with mutations in the PER3 gene exhibit more pronounced hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis and increased scores on depression scales., Additionally, circadian rhythm genes influence the homeostasis of glial cells, the metabolism of monoamine neurotransmitters, and the diurnal variations of the HPA axis, forming a shared genetic basis for depression‐anxiety‐insomnia. For instance, patients with sleep phase delays caused by abnormalities in CLOCK and CRY family genes have an increased risk of depression and anxiety; compared to uncomplicated depression, symptoms such as difficulty falling asleep, early awakening, and reduced sleep efficiency are more pronounced in anxiety‐depressive patients, who also have a higher risk of suicidal ideation and suicide attempts, further suggesting that abnormalities in circadian rhythm genes may have a complex interplay with ADD.