Thyrotropin-releasing hormone (TRH) is a tripeptide that produces endocrine and behavioral effects in animals and humans. Some studies have shown transient antidepressant activity after morning administration of TRH. We hypothesized that nocturnal administration of TRH, when the circadian sensitivity of the TRH receptor is at its peak, may result in a more robust antidepressant effect.
Twenty patients with bipolar (BP) type I or BP type II major depressive episode (MDE) were given nocturnal intravenous TRH 500 microg (n = 10) or saline (n = 10) at midnight in a randomized, double-blind fashion. Antidepressant activity was assessed using the Hamilton Depression Rating (HAM-D), Young Mania Rating (YMR), and Profile of Mood (POMS) scales over a 48-hour period. Thyrotropin (TSH), total T4, and free T3 concentrations were measured before and after TRH administration. Data were analyzed using chi test, Fisher exact test, and repeated-measures ANOVA.
Sixty percent of the TRH group and 10% of the saline group showed a > or =50% reduction in baseline total HAM-D score within 24 hours (P = 0.03). HAM-D ratings fell by an average of 52% after TRH administration versus 12% after saline administration (P = 0.038). There was a modest increase in YMR scores after TRH compared with saline (P < 0.032). No manic or hypomanic episodes were observed. Antidepressant effects of TRH lasted up to 48 hours. There was no correlation between DeltaTSH, DeltaT4, or DeltaT3 measures after TRH (or saline) administration and the change in HAM-D scores.
Nocturnal TRH administration may produce a rapid antidepressant effect in some patients with BP I and BP II MDE.
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"In light of the proposed role for myelin in the pathophysiology of multiple psychiatric disorders and common comorbid manifestations of these disorders (reviewed in Altamura et al., 2011; Bartzokis, 2004, 2005), it should not be surprising that treatment with T3, its prohormone T4, or TRH itself have been reported to have antidepressant properties (Bauer et al., 2008; Szuba et al., 2005). Furthermore, several reports suggest that heavily myelinated subcortical fibers are most clearly susceptible to thyroid deficiencies (Barradas et al., 2001; Harsan et al., 2008; Pinazo-Duran et al., 2011). "
[Show abstract][Hide abstract] ABSTRACT: Current psychiatric diagnostic schema segregate symptom clusters into discrete entities, however, large proportions of patients suffer from comorbid conditions that fit neither diagnostic nor therapeutic schema. Similarly, psychotropic treatments ranging from lithium and antipsychotics to serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors have been shown to be efficacious in a wide spectrum of psychiatric disorders ranging from autism, schizophrenia (SZ), depression, and bipolar disorder (BD) to Alzheimer's disease (AD). This apparent lack of specificity suggests that psychiatric symptoms as well as treatments may share aspects of pathophysiology and mechanisms of action that defy current symptom-based diagnostic and neuron-based therapeutic schema. A myelin-centered model of human brain function can help integrate these incongruities and provide novel insights into disease etiologies and treatment mechanisms. Available data are integrated herein to suggest that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair. These signaling pathways respond to neurotransmitters, neurotrophins, hormones, and nutrition, underlie intricate neuroglial communications, and may substantially contribute to the mechanisms of action and wide spectra of efficacy of current therapeutics by promoting myelination. Imaging and genetic technologies make it possible to safely and non-invasively test these hypotheses directly in humans and can help guide clinical trial efforts designed to correct myelination abnormalities. Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases.
"The hypothalamic-pituitary-thyroid (HPT)-axis is also thought to play a role in the pathophysiology of depression . Thyrotropin-releasing hormone-(TRH) has been shown to have antidepressant properties [30-32], and TRH-1 and -2 receptor deficient mice display an increased depression-like behavioral phenotype [33, 34]. Electroconvulsive therapy, which is an effective treatment of depression, increases TRH gene expression in the brain [35, 36], and the CART system regulates TRH activity [37-39]. "
[Show abstract][Hide abstract] ABSTRACT: CART peptides are endogenous neurotransmitters that are involved in a variety of physiologic functions. Injection of CART 55-102 into the nucleus accumbens produces no effect, but when co-administered with cocaine, it reduces the locomotor and rewarding properties of cocaine. In a human study, subjects carrying a missense mutation of the CART gene exhibited increased anxiety and depression. Also, several animal studies support the idea that CART is involved in anxiety and depression, and they also suggest several possible mechanisms by which this may occur. Thus, there is interesting evidence that CART peptides play a role in anxiety and depression, and that CART peptides may be endogenous antidepressants.
DNA research: an international journal for rapid publication of reports on genes and genomes 03/2011; 9(1):12-6. DOI:10.2174/157015911795017074 · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psoriasis has substantial psychological and emotional effects. We assessed the effect of etanercept, an effective treatment for the clinical symptoms of psoriasis, on fatigue and symptoms of depression associated with the condition.
618 patients with moderate to severe psoriasis received double-blind treatment with placebo or 50 mg twice-weekly etanercept. The primary efficacy endpoint was a 75% or greater improvement from baseline in psoriasis area and severity index score (PASI 75) at week 12. Secondary and other endpoints included the functional assessment of chronic illness therapy fatigue (FACIT-F) scale, the Hamilton rating scale for depression (Ham-D), the Beck depression inventory (BDI), and adverse events. Efficacy analyses were based on the allocated treatment. Analyses and summaries of safety data were based on the actual treatment received. This study is registered with with the identifier NCT00111449.
47% (147 of 311) of patients achieved PASI 75 at week 12, compared with 5% (15 of 306) of those receiving placebo (p<0.0001; difference 42%, 95% CI 36-48). Greater proportions of patients receiving etanercept had at least a 50% improvement in Ham-D or BDI at week 12 compared with the placebo group; patients treated with etanercept also had significant and clinically meaningful improvements in fatigue (mean FACIT-F improvement 5.0 vs 1.9; p<0.0001, difference 3.0, 95% CI 1.6-4.5). Improvements in fatigue were correlated with decreasing joint pain, whereas improvements in symptoms of depression were less correlated with objective measures of skin clearance or joint pain.
Etanercept treatment might relieve fatigue and symptoms of depression associated with this chronic disease.
The Lancet 01/2006; 367(9504):29-35. DOI:10.1016/S0140-6736(05)67763-X · 45.22 Impact Factor