Neuropeptide Y and corticotropin-releasing hormone in CSF mark response to antidepressive treatment with citalopram

Abstract

Neuropeptides appear to play a role in the pathophysiology of depression and electroconvulsive treatment and lithium affect these compounds in human cerebrospinal fluid (CSF) and rodent brain. Consequently, we investigated whether long-term treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram (Cit) would also affect neuropeptides in CSF of depressed patients. Changes in CSF monoamine metabolites were also explored. CSF concentrations of corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI), neuropeptide Y (NPY)-LI, and Cit were determined in 21 patients with major depression. Lumbar puncture was performed in the morning at baseline and was repeated after at least 4 wk of Cit treatment (40 mg/d). The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAMD). Cit treatment was associated with a significant increase in NPY-LI and decrease in CRH-LI. An evaluation of the relationship between changes in concentrations of NPY-LI, CRH-LI, and the clinical response showed significant correlations between these parameters. Significant NPY and CRH changes in CSF following treatment as well as correlations to changes in HAMD support the hypothesis that these two peptides play a role in affective disorders and are markers of therapeutic response.

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

“…Significantly, it (1) contributes additional evidence to the experimental results both that NPY has a central role in conditions of 'disturbed emotionality', such as depression (Heilig, 2004;Heilig et al, 2004;Husum et al, 2006;Jiménez-Vasquez et al, 2007;Mathé et al, 2007;Nikisch et al, 2005), anxiety (Thorsell et al, 2000;Neumann et al, 2011), ethanol preference (Ehlers et al, 1998), chronic stress (Sergeyev et al, 2005), and early life adverse events (Jiménez-Vasquez et al, 2001;Husum and Mathé, 2002) and (2) reinforces the proposition that NPY and the NPY Y1-receptor agonists are potential novel therapeutic targets for the stress-related disorders, of importance in light of the insufficient efficacy of current drugs targeting monoamines.…”

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

“…In fact, the current pharmacotherapy of depression is also mainly based on use of compounds correcting dysfunctions in monoaminergic transmission, including selective serotonin reuptake inhibitors (SSRIs) (see Frazer, 1997;Millan, 2004). However, recent studies have also implicated several neuropeptides in the pathophysiology of depression and in the action of antidepressant drugs (see Heilig, 2004;Lu et al, 2005aLu et al, , 2007Nikisch et al, 2005;Ö gren et al, 2006).…”

Cerebrospinal fluid neuropeptide Y in combat veterans with and without posttraumatic stress disorder

“…CSF NPY concentrations have been found to be reduced Nikisch et al, 2005;Widerlov et al, 1988) or elevated (Martinez et al, 2012) in studies of patients with major depression in comparison with healthy subjects. In our entire cohort of combat veterans, CSF NPY did not significantly correlate with depression ratings, but did with PTSD symptom scores, suggesting that reduced CSF NPY may be more tightly associated with PTSD than with accompanying depression.…”