Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism

Heilig, Markus; Zachrisson, Olof; Thorsell, Annika; Ehnvall, Anna; Mottagui‐Tabar, Salim; Sjögren, Magnus; Åsberg, Marie; Ekman, Rolf; Wahlestedt, Claes; Ågren, Hans

doi:10.1016/s0022-3956(03)00101-8

Cited by 164 publications

(139 citation statements)

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“…Several studies have shown that plasma and cerebrospinal (CSF) NPY levels were found to be lower in MDD patients compared to healthy controls (22)(23)(24)(25)(26). Our results were consistent with this finding.…”

Section: Discussionsupporting

confidence: 92%

“…Many clinical studies have demonstrated decreased NPY levels in the CSF and plasma of depressed patients when compared to healthy control subjects (22)(23)(24)(25)(26). According to preclinical studies, three lines of evidence from animal work supported the relevance of NPY in depression: (1) animal models of depression and NPY levels; (2) potentiation of NPY expression by antidepressant treatments; (3) administration of NPY compounds reduce depressive behavior (3,27,28).…”

Section: Introductionmentioning

confidence: 99%

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Plasma Neuropeptide Y Levels in Medication Naive Adolescents with Major Depressive Disorder

Güleç

Ozalmete

Öztürk³

et al. 2010

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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ÖZET:‹laç tedavisi almayan majör depresif bozukluklu ergenlerde plasma nöropeptid Y düzeyleri Amaç: Neuropeptide Y (NPY), anksiyete ve depresyon patofizyolojisinde önemli bir maddedir. NPY'nin emosyonel düzenlemeyi sürdürmesi için kortikotropin sal›n›m›n› sa¤-layan faktör (CRF) taraf›ndan arac›l›k edilen stres etkilerini giderdi¤i ileri sürülmüfltür. Bu çal›flmada ilk kez depresyon tan›s› alan ergenlerde NPY düzeyleri, hastalar›n intihar giriflimi öyküleri gözününde bulundurularak araflt›r›lm›flt›r. Yöntem: Majör depresif bozukluk (MDB) tan›l› 33 ergen ça-l›flmaya al›nd›. 11 hasta, baflka bir psikiyatrik hastal›¤›n varl›¤› nedeniyle çal›flma d›fl›nda tutuldu. MDB tan›l› 22 ergende, NPY'nin plazma konsantrasyonlar› ölçüldü. Beck Depresyon Envanteri-Türkçe uyarlamas› ve Beck Anksiyete Envanteri-Türkçe uyarlamas›, depresyon ve anksiyete düzey-lerini ölçmek için kullan›ld›. Bulgular: Depresyonlu ergenlerde sa¤l›kl› kontrollere oranla anlaml› derecede düflük NPY düzeyleri bulundu. Hastalar intihar giriflimi öykülerine göre s›n›fland›r›ld›¤›nda her iki grup aras›nda NPY düzeyleri aç›s›ndan anlaml› bir fark bulunmad›. NPY düzeyleri, hastal›¤›n süresiyle ve suç-luluk duygular› ile negatif yönde, anksiyeteyle pozitif yön-de korelasyon gösterdi. Aksiyete, bir eflde¤iflken olarak al›nd›¤› zaman, NPY ile suçluluk duygular› aras›ndaki korelasyonlar kayboluyor, hastal›¤›n süresi bir eflde¤iflken olarak al›nd›¤›nda aradaki korelasyon anlaml›l›¤›n› koruyordu. Tart›flma: Ergen depresif hastalar sa¤l›kl› kontrollere oranla daha düflük NPY plazma düzeylerine sahipti. Plazma NPY düzeyleri, hastal›¤›n süresiyle azal›yor, suçluluk duygusu ve anksiyetenin fliddetiyle art›yordu. NPY'nin, ergenlerde gö-rülen MDB'de anksiyete ile ilgili depresyona bir e¤ilim için belirleyici oldu¤u ileri sürülebilir. Plasma neuropeptide Y levels in medication naive adolescents with major depressive disorder Objective: Neuropeptide Y (NPY) has been implicated in pathophysiology of anxiety and depression. It was proposed that NPY counteracts corticotropin-releasing factor-mediated stress effects to maintain emotional regulation. We investigated NPY concentrations in a sample of first episode medication-naive adolescent patients with MDD with regards to their history of suicide attempts. Method: 33 adolescents with MDD were enrolled. 11 patients were excluded due to comorbidity of another psychiatric illness. In 22 adolescents with MDD patients, the plasma concentrations of NPY were assessed. The Beck Depression Inventory-Turkish Version and the Beck Anxiety Scale-Turkish Version were used to rate the severity of depressive and anxiety symptoms. Results: Our sample of depressed patients showed lower levels of NPY compared to healthy controlsWhen the depressed patients were grouped with regards to suicidality, both groups did not show any significant differences. NPY levels were negatively correlated with duration of illness and feelings of guilt, and positively correlated with anxiety. When anxiety was taken as a covariate, significant correlations between ...

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Plasma Neuropeptide Y Levels in Medication Naive Adolescents with Major Depressive Disorder

Güleç

Ozalmete

Öztürk³

et al. 2010

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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“…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.…”

Section: Discussionmentioning

confidence: 87%

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

Cohen

Liu

Kozlovsky

et al. 2011

Neuropsychopharmacol

242

190

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Converging evidence implicates the regulatory neuropeptide Y (NPY) in anxiety-and depression-related behaviors. The present study sought to assess whether there is an association between the magnitude of behavioral responses to stress and patterns of NPY in selected brain areas, and subsequently, whether pharmacological manipulations of NPY levels affect behavior in an animal model of PTSD. Animals were exposed to predator-scent stress for 15 min. Behaviors were assessed with the elevated plus maze and acoustic startle response tests 7 days later. Preset cutoff criteria classified exposed animals according to their individual behavioral responses. NPY protein levels were assessed in specific brain regions 8 days after the exposure. The behavioral effects of NPY agonist, NPY-Y1-receptor antagonist, or placebo administered centrally 1 h post-exposure were evaluated in the same manner. Immunohistochemical technique was used to detect the expression of the NPY, NPY-Y1 receptor, brain-derived neurotrophic factor, and GR 1 day after the behavioral tests. Animals whose behavior was extremely disrupted (EBR) selectively displayed significant downregulation of NPY in the hippocampus, periaqueductal gray, and amygdala, compared with animals whose behavior was minimally (MBR) or partially (PBR) disrupted, and with unexposed controls. One-hour post-exposure treatment with NPY significantly reduced prevalence rates of EBR and reduced trauma-cue freezing responses, compared with vehicle controls. The distinctive pattern of NPY downregulation that correlated with EBR as well as the resounding behavioral effects of pharmacological manipulation of NPY indicates an intimate association between NPY and behavioral responses to stress, and potentially between molecular and psychopathological processes, which underlie the observed changes in behavior. The protective qualities attributed to NPY are supported by the extreme reduction of its expression in animals severely affected by the stressor and imply a role in promoting resilience and/or recovery.

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“…Five patients were free from medication for less than 1 week (one with SSRI, four with other antidepressants), and eight patients were under medication (five with SSRI, three with other antidepressants). CSF was obtained under standardized conditions as described previously (Heilig et al, 2004). Briefly, lumbar punctures were performed in the morning with the patients remaining in bed after the night, in the L3/L4 or L4/L5 interspace.…”

Section: Lumbar Puncture and Analyses Of Monoamine Metabolites In Csfmentioning

confidence: 99%

Monoamine Metabolites Level in CSF is Related to the 5-HTT Gene Polymorphism in Treatment-Resistant Depression

Kishida

Aklillu

Kawanishi

et al. 2007

Neuropsychopharmacol

Self Cite

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The serotonin (5-hydroxytryptamine) transporter (5-HTT) is considered to affect the pathogenesis of mood disorders. Large number of genetic association studies between 5-HTT functional polymorphisms and vulnerability of mood disorders and therapeutic response to antidepressants has been carried out. We investigated the influence of 5-HTT-linked polymorphic region (5-HTTLPR) and 5-HTT 17 bp variable number of tandem repeat polymorphism (5-HTTVNTR) polymorphisms on concentrations of monoamine metabolites in cerebrospinal fluid (CSF) among treatment-resistant patients with mood disorders. Subjects were 119 Swedish patients with persistent mood disorders and 141 healthy subjects. In 112 of these patients, we measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol in CSF. Genotyping for 5-HTT polymorphisms from genomic DNA was carried out by PCR. There was no significant difference in allele/genotype frequency between patients and healthy subjects. In patients with mood disorders, we found significant difference in mean 5-HIAA concentration between 5-HTTLPR genotypes (p ¼ 0.03). Although the 5-HIAA concentration showed a tendency to be higher in short (S) carriers than in non-S carriers of the 5-HTTLPR in patients (p ¼ 0.06), when considering patients with major depressive disorder (MDD), the 5-HIAA concentration was significantly higher among S carriers than among non-S carriers (p ¼ 0.02). Moreover, the 5-HIAA concentration was higher in S/S subjects compared to long (L)/L (p ¼ 0.0001) and L/S (p ¼ 0.002) subjects in patients with MDD. Similarly, there was higher HVA concentration in S/S subjects compared to L/L (p ¼ 0.002) and L/S subjects (p ¼ 0.002). There was no effect of 5-HTTVNTR. Our findings show that the 5-HTTLPR polymorphism affects 5-HIAA and HVA concentrations among treatment-resistant patients with mood disorders.

show abstract

Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism

Cited by 164 publications

References 51 publications

Plasma Neuropeptide Y Levels in Medication Naive Adolescents with Major Depressive Disorder

Plasma Neuropeptide Y Levels in Medication Naive Adolescents with Major Depressive Disorder

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

Monoamine Metabolites Level in CSF is Related to the 5-HTT Gene Polymorphism in Treatment-Resistant Depression

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