Sleep-related breathing disturbances in adolescents with treatment resistant depression.

OBJECTIVE/BACKGROUND: A considerable subgroup of adolescents does not respond to standard antidepressant treatments. There are some indications that sleep disordered breathing may contribute to refractory depression in adults, but little is known about how it may relate to the course of depressive disorders in adolescents. Focussing on a group of Canadian adolescents with treatment resistant depression (TRD), this study aimed to investigate how the severity of residual depressive symptoms following unsuccessful antidepressant trials relates to breathing disturbances during sleep. PATIENTS/METHODS: A retrospective chart review was conducted at a tertiary mental health facility. Polysomnography, the Beck Depression Inventory-II (BDI-II), and the Epworth Sleepiness Scale (ESS) were collated from 18 adolescents (15-18 years old, 44% females) patients with depressive disorders who did not respond to at least two 4-week trials of antidepressant medications. RESULTS: Of this sample, 39% reported at least mild levels of excessive daytime sleepiness, and 55% had an apnea/hypopnea index ≥1. Worse depressive symptoms correlated with higher RDI (r = 0.53, p = 0.022). This was mainly driven by respiratory effort-related arousals occurring during NREM sleep (r = 0.52, p = 0.029). No significant correlation was found between depressive symptoms and other respiratory or sleep variables. Higher daytime sleepiness correlated significantly with lower minimum oxygen desaturation (r = -0.51, p = 0.030). CONCLUSIONS: These results suggest that even subtle respiratory disturbances during sleep may play a role in persistent depressive symptoms and treatment resistance. Early screening for sleep-related breathing disturbances in adolescents with TRD may be relevant, since previous work suggests that treating sleep-related breathing disturbances can attenuate depressive symptoms.

Daily methylphenidate administration attenuates c-fos expression in the striatum of prepubertal rats.

Methylphenidate (Ritalin) is a psychostimulant drug used to treat children with attention deficit hyperactivity disorder. Despite its widespread and increasing clinical use, little is known about the long-term consequences of drug treatment. We compared the effects of a single injection of methylphenidate with that of long-term methylphenidate injections (one/day; 14 days) on immediate-early gene expression (c-fos) in the striatum of prepubertal male rats. Rats (25 days old) were injected once daily for 14 days with either saline or methylphenidate (1, 2 or 10 mg/kg), or for 13 days with saline followed by one injection of methylphenidate (1, 2 or 10 mg/kg) on day 14, and were sacrificed 2 h post-injection. Methylphenidate dose-dependently increased FOS immunoreactivity in the striatum. A single injection of methylphenidate (2 or 10 mg/kg) on day 14, following saline treatment for 13 days, caused a dramatic elevation in c-fos expression. This effect was significantly attenuated in animals treated chronically with methylphenidate (2 or 10 mg/kg) for the entire 14 days. Our data suggest that repeated methylphenidate treatment, at a clinically relevant dose (2 mg/kg), markedly inhibits immediate-early gene expression in the brain. This is the first demonstration of methylphenidate-induced modification of gene expression in developing rat striatum and may have implications for chronic methylphenidate use in children.

Peripheral amitriptyline suppresses formalin-induced Fos expression in the rat spinal cord.

UNLABELLED: We examined the effects of systemically, spinally, and peripherally administered amitriptyline on formalin-induced Fos immunoreactivity in the lumbar spinal cord. Formalin (2.5%), injected subcutaneously into the rat hindpaw, increased Fos immunoreactivity in laminae I-II, III-IV, and V-VI of the dorsal L5 spinal cord. Amitriptyline, administered both systemically and spinally before formalin, increased flinching and concurrently decreased biting/licking behaviors, but neither route of administration produced any statistically significant change in Fos immunoreactivity. Amitriptyline coadministered with the formalin reduced both flinching and biting/licking behaviors, and significantly reduced Fos immunoreactivity, particularly in laminae I-II. These immunohistochemical changes reflect the net behavioral effects observed after the different routes of drug administration. The profile of amitriptyline action after peripheral administration may be of clinical importance because of the potential use of antidepressants as topical analgesics. IMPLICATIONS: In the formalin test, amitriptyline produces different effects on pain behaviors after systemic, spinal administration and peripheral administration. Fos protein, an indicator of neuronal activity after noxious stimulation, is upregulated after formalin injection. We examined the effects of amitriptyline on such expression and observed a reduction in expression with peripheral administration.