Abstract
Objective
Evidence suggests that stressful life experiences contribute significantly to the aetiology of mood disorders. Hypothalamic neuropeptides are thought to be biomarkers used to differentiate patients with mood disorders. In our study, we aimed to evaluate the concentrations of hypothalamic neuropeptides NPY and POMC in patients with bipolar (BP) and unipolar (UP) depression.
Methods
The study included 26 UP and 28 BP patients, 27 healthy controls.NPY and POMC concentrations were quantified in peripheral blood specimens.The Hamilton Depression Rating Scale(HAM-D), Epworth Sleepiness Scale and Three-Factor Eating Questionnaire were administered.
Results
Serum NPY and POMC levels were significantly lower in UP and BP patients compared to the control group (p = 0.001).NPY level was lower in the depression group compared to the bipolar group but not statistically significant (p˃0.05).POMC level was decreased in the bipolar group compared to the depression group, but the results were not statistically significant (p˃0.05). No significant correlation was found between any scale score and NPY and POMC(p>0.05).
Conclusion
This study suggests that changes in serum NPY and POMC levels in UP and BP patients may have a potential role in disease pathophysiology. In particular, it is the first study to investigate the interaction between NPY, POMC and changes in eating behaviour in depressed patients, highlighting the need for further research in this area.
Keywords: Unipolar depression, Bipolar depression, Neuropeptide Y, Pro-opiomelanocortin, Biomarkers
Introduction
Bipolar disorder (BD) is a chronic and serious psychiatric condition characterised by complex manic and depressive episodes that can be triggered by psychosocial, environmental and biological stressors [1] and affects approximately 1% of the world population [2]. Depressive symptoms frequently precede manic episodes by several years. Conversion to mania happens in 4–33% of individuals with depression. The majority of improvements were documented within 18 months following the initial depressive episode. Bipolar conversions are rather frequent one or more decades following the initial depressed episode [3]. Given that depressed mood frequently represents the initial and most enduring symptom in BD patients, differentiating BD from unipolar depression (UD) based solely on clinical manifestations is challenging. Consequently, BD is frequently misidentified as UD, resulting in considerable diagnostic delays. In as many as one-third of instances, BD remains undiagnosed for a decade following the emergence of symptoms [4].
Major depression is a common disorder that significantly impairs psychosocial functioning and reduces quality of life. The World Health Organisation predicts that by 2030 depression will be the primary cause of the global burden of disease [5–8]. Major depressive disorder (MDD) is characterised by a variety of physical and cognitive symptoms, including persistent sadness, decreased interest, anxiety and irregular sleep patterns [8, 9]. Various variables contribute to the pathophysiology of MDD, including inflammation, alterations in neuroendocrinology, neurotransmitter imbalances, synaptic dysfunction, compromised brain regeneration, and microbiome abnormalities. MDD should be understood as a systemic disorder characterised by numerous dysfunctions, rather than being examined in isolation [10]. The activation of neuroinflammation is intricately associated with the neuroendocrine system, particularly under conditions of chronic stress. Persistent psychological or environmental stress leads to considerable dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, culminating in elevated secretion of stress hormones, particularly glucocorticoids [11]. The hypothalamic-pituitary-adrenal (HPA) axis has been the subject of depression studies for many years. A notable biological finding in severe depression with melancholic features associated with changes in the HPA axis is elevated plasma cortisol levels. This physiological difference results from a combination of increased cortisol release due to stress and impaired feedback inhibition mediated by glucocorticoid receptors. Changes in the HPA axis are also associated with decreased cognitive function [7].
Research has revealed that stress contributes significantly to the onset and progression of bipolar disorder [12]. Real or perceived stress activates multiple neuronal circuits, including the prefrontal cortex, hippocampus, amygdala, septum and hypothalamus, ultimately leading to activation of the HPA axis through stimulation of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) production in the paraventricular nuclei (PVN) of the hypothalamus. Subsequently, both neuropeptides travel via small blood arteries CRH or neuronal projections (AVP) to the pituitary, leading to the secretion and subsequent re-release of corticotropin (adrenocorticotropic) [11]. The control of the stress response through proteolytic conversion of pro-opiomelanocortin (POMC) to adrenocorticotropin (ACTH) in the anterior pituitary is one of the most extensively investigated aspects of the HPA axis. The anorexigenic hormone POMC, a precursor polypeptide, plays a crucial role in appetite regulation within the CNS. It generates several products, including ACTH, α-, β-, and γ-melanocyte stimulating hormones (α-MSH, β-MSH, and γ-MSH), β-lipotrophin, and endorphins. ACTH, produced by the pituitary gland, interacts with adrenal melanocortin receptors (MC2Rs) to modulate cortisol secretion from the adrenal cortex [13].
Neuropeptide Y (NPY) is a 36 amino acid peptide produced in neurons of the arcuate nucleus, which extends to the paraventricular nucleus of the hypothalamus [14]. NPY participates in numerous physiological activities, including stress response, circadian rhythms, eating behaviour, sexual behaviour, memory and blood pressure regulation [5, 14, 15]. In the central nervous system, various stressors can cause changes in NPY levels in specific brain regions [14]. Studies on the correlation between MDD and NPY levels have revealed ambiguous findings. Although many studies have shown that patients with MDD have decreased NPY levels, numerous studies have failed to establish a significant relationship between MDD and NPY levels [5]. Recent studies on mood disorders examining peripheral biomarkers have focused on three areas: cellular growth, survival and synaptic plasticity, particularly brain-derived neurotrophic factor; inflammation, pro- and anti-inflammatory cytokines; and energy metabolism, oxidative stress and mitochondrial function. Research on hypothalamic neuropeptides that regulate processes such as hunger and sleep is also believed to advance the field [5]. These neuropeptides are believed to offer valuable insights to differentiate depression in bipolar and unipolar patients. Our study aimed to evaluate the concentrations of the orexigenic peptide NPY and the anorexigenic peptide POMC, which are hypothalamic neuropeptides important for the regulation of food intake, in patients diagnosed with unipolar and bipolar depression. To our knowledge, this study represents the first comparison of serum NPY and POMC levels between patients with bipolar and unipolar depression.
Materials and methods
Study sample
This research was performed in the psychiatry clinic of a university hospital, sanctioned by the ethics committee (Ethics Committee Decision No: 2024/02–32, dated 13.02.2024). The study was performed in compliance with the Declaration of Helsinki, and informed consent was secured from all participants. Patients who were followed up in the psychiatry outpatient clinic and ward using the semi-structured interview method and diagnosed with bipolar disorder and major depression according to DSM-5 criteria were included in the study.
The study comprised 81 patients: 27 in the control group, 28 diagnosed with bipolar illness, and 26 diagnosed with serious depression. All participants were scheduled to complete the sociodemographic data form developed by the researcher. The study group consisted of healthy adults comparable to the patient group in terms of age, gender and BMI, with no history of psychiatric follow-up and treatment, who presented to the examination for administrative purposes for control. Body Mass Index (BMI) was determined as weight in kilograms divided by the square of height in metres. Conditions that could influence food and sleep, hence impacting neuropeptide levels, were established as exclusion criteria. Mental illnesses other than generalised anxiety disorder, the most common comorbidity in patients with depression, were excluded. Exclusion criteria encompassed obesity, hyperlipidaemia, diabetes, hypertension, cardiovascular disease, recent administration of corticosteroids or immunosuppressants, cancer, neuroinflammatory or neurodegenerative disorders, significant medical conditions, active infections, or ongoing treatment for infectious or chronic systemic diseases.
The Hamilton Depression Rating Scale and the Young-Mania Scale were administered to the patients who consented to participate in the study. The criteria for inclusion in the patient groups were as follows: MDD, also known as UP. Bipolar patients were designated as BP. fulfil DSM-5 criteria for a major depressive episode; (b) achieve a score of 16 on the 17-item Hamilton Depression Scale (HAM-D). To establish a more stable UP group, we included patients with a psychiatric history of several depressive episodes and no manic episodes, as a diagnosis conversion favouring BP may occur in patients diagnosed with UP during follow-up.
The Hamilton Depression Rating Scale is a widely used scale for measuring the severity of depression symptoms, and its Turkish validity and reliability have been performed [16]. Young-Mania Scale was used to determine the symptoms of mania and hypomania. Its Turkish validity and reliability was performed [17]. The three-factor eating questionnaire and Epworth sleepiness scale were also administered to the patients. It was developed to measure the behavioural and cognitive components of eating [18]. Turkish validity and reliability was performed. It is a 4-point Likert-type scale consisting of 21 questions and three sub-dimensions: ‘Uncontrolled Eating’, ‘Cognitive Restraint’ and ‘Emotional Eating’ [19]. The Epworth Sleepiness Scale (ESS) was employed to evaluate hypersomnia. The ESS is a 4-point Likert scale designed to assess excessive daytime sleepiness over the preceding month, with each item scoring between 0 and 3 points. The exam yields a total score between 0 and 24, with elevated results signifying greater tiredness. A score beyond 10 is deemed abnormal [20].
Measurement of serum levels of NPY and POMC
Blood samples were collected from all three groups after at least 8. The samples were placed in biochemical serum tubes and allowed to coagulate for 20 min at room temperature. Subsequently, the specimens were centrifuged at 4000 revolutions per minute for 10 min. Serum levels of Human neuropeptide Y and Human pro-opiomelanocortin were determined using ELISA kits (Bioassay Technology Laboratory [BT LAB], catalogue no: E1285Hu for NPY; E3425Hu for POMC). All sera were analyzed collectively and simultaneously, under the supervision of the same specialist. Serum NPY and POMC levels were expressed in ng/L.
Statistical analysis
Data analysis was performed using SPSS software, version 26 (IBM Corp., Armonk, NY, USA). Normality of the data was assessed using the Kolmogorov-Smirnov and Shapiro-Wilk tests and histograms. For normally distributed variables, differences between groups were evaluated by independent t-test and presented as mean ± standard deviation (SD). For non-normally distributed variables, Mann-Whitney U test was used to compare medians and presented as median (minimum - maximum). Categorical variables were compared using the chi-square test and expressed as number and percentage (n, %). The distributions of variables and log-transformed variables were analysed by histogram plots and descriptive statistics. Serum POMC and NPY levels which did not show normal distribution were log-transformed. One way ANOVA was used to compare the three groups. Bonferroni correction was used as a posthoc test. ANCOVA analysis was performed by adding gender, age and BMI as covariates. p-value less than 0.05 was considered statistically significant. All tests were performed as two-tailed.
Results
The study involved 81 people, comprising 27 in the control group, 28 individuals diagnosed with bipolar illness, and 26 individuals diagnosed with major depression. No substantial differences were seen among the three groups for age, BMI, gender, marital status, and education. There is a significant difference in terms of employment (Table 1).
Table 1.
Sociodemographic and clinical features of people with unipolar depression, bipolar disorder, and healthy controls
| UP (n = 26) | BP (n = 28) | HC (n = 27) | p-value | ||
|---|---|---|---|---|---|
| Age | 44.08 ± 11.940 | 44.07 ± 10.95 | 41.59 ± 6.95 | 0.587 α | |
| BMI (kg/m2) | 26.04 ± 3.12 | 26.72 ± 2.22 | 26.06 ± 2.23 | 0.535 α | |
| Smoking | 16 (61.5%) | 17 (60.7%) | 15 (55.6%) | 0.890 β | |
| Marriage Status | Married | 22 (84.6%) | 21 (75.0%) | 23 (85.2%) | 0.550 β |
| Single | 4 (15.4%) | 7 (25.0%) | 4 (14.8%) | ||
| Education Status | Primary school | 12 (46.2%) | 16 (57.1%) | 17 (63.0%) | 0.271 β |
| High school | 10 (38.5%) | 8 (28.6%) | 10 (37.0%) | ||
| University | 4 (15.4%) | 4 (14.3%) | 0 (0.0%) | ||
| Working Status | Unemployed | 11 (42.3%) a, b | 17 (60.7%) b | 5 (18.5%) a | 0.006 β |
| Employed | 15 (57.7%) a, b | 11 (39.3%) b | 22 (81.5%) a | ||
| Gender | Male | 12 (46.2%) | 14 (50.0%) | 12 (44.4%) | 0.914 β |
| Female | 14 (53.8%) | 14 (50.0%) | 15 (55.6%) | ||
| Medication use | Not receiving treatment | 9 (34.6%)a | 2 (7.1%)b | N/A | 0.001 β |
| Antidepressants | 13 (50.0%)a | 0 (0.0%)b | |||
| Antipsychotics | 0 (0.0%)a | 1 (3.6%)a | |||
| AD + AP | 4 (15.4%)a | 2 (7.1%)a | |||
| MD | 0 (0.0%)a | 6 (21.4%)b | |||
| MD + AP | 0 (0.0%)a | 8 (28.6%)b | |||
| MD + AD | 0 (0.0%)a | 6 (21.4%)b | |||
| MD + AD + AP | 0 (0.0%)a | 3 (10.7%)a | |||
| Comorbid psychiatric diseases | 4 (15.4%) | 0 (0.0%) | N/A | 0.031 β | |
| Increased appetite in atypical depression | 6 (23.1%) | 13 (46.4%) | N/A | 0.073 β | |
| Increased sleep in atypical depression | 4 (15.4%) | 8 (28.6%) | N/A | 0.244 β | |
UP unipolar depression, BP bipolar depression, HC healthy control, AD Antidepressants, AP Antipsychotics, MS Mood stabilizers
αOne way ANOVA (Mean ± SD)
βChi Square test
Note: Different supersript letters in the same row indicate significant differences between groups (p < 0.05)
The sole significant disparity in scale scores between the UP and BP groups was noted in the juvenile mania rating scale score. Patients with bipolar disorder exhibited significantly higher scores on the Young Mania Rating Scale compared to the unipolar depression group (p < 0.001). The ESS scale exhibited no statistically significant difference (p = 0.177). The average HAM-D total score for patients in the UP group was 24.65 ± 7.27, whereas in the BP group it was 24.5 ± 5.71. No significant difference was seen between the groups in the three-factor eating questionnaire (p > 0.005) (Table 2).
Table 2.
Comparative analysis of the unipolar and bipolar cohorts for HAM-D, ESS, and young mania rating scale
| UP (n = 26) | BP (n = 28) | p-value | |
|---|---|---|---|
| HAM-D | 24.65 ± 7.27 | 24.50 ± 5.71 | 0.931 * |
| Young Mania Rating Scale | 0.5 (0.0–2.0) | 2.0 (0.0–8.0) | 0.001 ¥ |
| Eating cognitive | 9.81 ± 4.20 | 11.04 ± 4.88 | 0.328 * |
| Eating emotional | 10.50 ± 5.57 | 11.68 ± 5.14 | 0.422 * |
| Eating control | 14.15 ± 5.80 | 16.96 ± 5.99 | 0.086 * |
| ESS | 3.5 (0.0–24.0) | 4.5 (0.0–29.0) | 0.177 ¥ |
UP unipolar depression, BP bipolar depression, HC healthy control, HAM-D Hamilton depression rating scala, ESS epworth sleepiness scale, TFEQ-R Three- factor eating questionnaire
*Independent t test
¥Mann Whitney U test (Mean ± SD)
A notable disparity was seen in serum NPY (p < 0.001) and serum POMC (p < 0.001) concentrations across the groups. NPY levels were significantly decreased in the UP and BP groups relative to healthy controls. In the comparison between UP and BP groups, NPY levels were lower in UP, although the difference was not statistically significant. The POMC level was statistically lower in the UP and BP groups compared to healthy controls. In the comparison between UP and BP groups, POMC levels were lower in BP; however, this difference was not statistically significant (Table 3; Figs. 1 and 2).
Table 3.
Comparative NPY and POMC levels in UP, BP and healthy controls
| UP (n = 26) | BP (n = 28) | HC (n = 27) | p-value | |
|---|---|---|---|---|
| POMC (ng/L) | 1499.04 ± 708.28 | 1390.89 ± 574.69 | 3117.13 ± 2663.56 | 0.001 α |
| NPY (ng/L) | 438.52 ± 238.61 | 634.13 ± 606.35 | 1198.17 ± 817.54 | 0.001 α |
Log-transformation was performed for both variables
For POMC; K > D (p = 0.003); K > B (p = 0.001); D = B (p = 1.00)
For NPY; K > B (p = 0.002); K > D (p = 0.001); B = D (p = 0.826)
Age, BMI, Gender, Smoking were identified as covariates in the ANCOVA analysis
For POMC [F(2,74) = 7.978 partial η² = 0.220 p = 0.001]; K > D (p = 0.005); K > B (p = 0.002); D = B (p = 1.00)
For NPY [F(2,74) = 10.804 partial η² = 0.267 p = 0.001]; K > B (p = 0.001); K > D (p = 0.005); B = D (p = 0.636)
αOne way ANOVA (Post-hoc test: performed with Bonferroni test), (Mean ± SD)
Fig. 1.
Box plot showing the distribution of serum Log POMC levels in Bipolar Disorder, Depression and Control groups
Fig. 2.
Box plot showing the distribution of serum Log NPY levels in Bipolar Disorder, Depression and Control groups
ROC analysis was performed to evaluate the diagnostic performance of POMC and NPY biomarkers in differentiating bipolar depression and unipolar depression from controls (Table 4). For bipolar depression, the optimal cut-off value for POMC was determined as < 1507.5 and a sensitivity of 78.57%, specificity of 55.56%, PPV of 64.71% and NPV of 71.43% were obtained. The area under the curve (AUC) was 0.729 (95% CI: 0.598–0.860) with a statistically significant p-value of 0.004. Similarly, the best cut-off for NPY was < 790.71, providing 85.71% sensitivity, 62.96% specificity, 70.59% PPV and 80.95% NPV. The AUC was 0.731 (95% CI: 0.592–0.870) and the p-value was 0.003 (Fig. 3).
Table 4.
Performance of POMC and NPY biomarkers in the diagnosis of bipolar depression and depression
| Variables | Cutpoint | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | AUC | p-value | |
|---|---|---|---|---|---|---|---|---|
| BP | POMC | <1507.5 | 78.57 | 55.56 | 64.71 | 71.43 | 0.729(0.598-0.860) | 0.004 |
| NPY | <790.71 | 85.71 | 62.96 | 70.59 | 80.95 | 0.731(0.592-0.870) | 0.003 | |
| UP | POMC | <2172.5 | 92.31 | 40.74 | 60.00 | 84.62 | 0.694(0.553-0.836) | 0.015 |
| NPY | <959.29 | 96.15 | 55.56 | 67.57 | 93.75 | 0.809(0.690-0.928) | 0.001 | |
Fig. 3.
ROC curves of POMC and NPY biomarkers in the diagnosis of bipolar disorder
In the depression group, POMC < 2172.5 showed a sensitivity of 92.31% and specificity of 40.74% at the cut-off value, with a PPV of 60.00% and NPV of 84.62%. The corresponding AUC was 0.694 (95% CI: 0.553–0.836) and the p-value was 0.015. With a cut-off value of NPY < 959.29, it demonstrated superior diagnostic performance, achieving 96.15% sensitivity, 55.56% specificity, 67.57% PPV and 93.75% NPV. The AUC was 0.809 (95% CI: 0.690–0.928) and the result was statistically significant (p = 0.001) (Fig. 4).
Fig. 4.
ROC curves of POMC and NPY biomarkers in the diagnosis of depression
Discussion
To our knowledge, this is the first study to investigate the relationship between POMC, an anorexigenic peptide, and NPY, an orexigenic peptide, in patients with bipolar and major depressive disorder. In our study, patients with bipolar and MDD were found to have significantly lower levels of POMC and NPY than controls.
Research has shown that the POMC gene may be associated with the pathological process of depression [21, 22]. Zheng et al. investigated the relationship between POMC gene and depressive disorder in adolescent depression patients. They showed that POMC gene expression decreased with increasing POMC promoter methylation. They argued that this led to a decrease in the level of POMC and its derivatives [21]. Another study showed that depressive disorders were strongly associated with methylation of the POMC gene in both blood and saliva of regularly abused children [23]. Maier et al. showed that POMC levels after electroconvulsive therapy in MDD patients had an increased DNAm ratio compared with the control group [22]. Myung et al. reported that fluoxetine, one of the antidepressant drugs, may lead to a decrease in POMC levels in the hypothalamus [24]. Another study showed that lithium, a mood stabiliser, did not change the level of POMC-related peptides [25]. In our study, similar to the literature, POMC levels were decreased in UP and BP patient cohort compared to healthy controls. The decrease in POMC levels compared with the literature may be related to the rapid use of POMC to increase alpha MSH synthesis.
NPY is proposed to inhibit HPA axis activity by reducing CRH, ACTH, and cortisol levels [26]. Chronic stress in depression leads to HPA activation and a decrease in NPY levels [5]. NPY is believed to play a role in the pathophysiology of some mood disorders and in the mechanism of action of antidepressant medications [26]. In animal models of depression, site-specific changes in central NPY levels have been reported and antidepressant treatment has been shown to alter central NPY synthesis [27]. This coincides with the results of previous studies showing that NPY levels are decreased in the brain of rats exposed to prolonged stress [28, 29]. While brain NPY activity seems more correlated with psychopathology, plasma NPY levels are frequently utilised to examine NPY activity in human stress and mental health studies. The link between central and peripheral NPY remains inadequately comprehended. Nonetheless, peripheral NPY has been proposed as an indicator of stress resilience and is correlated with psychopathology in stress-related diseases [27]. Research by Heiling et al. demonstrated reduced cerebrospinal fluid (CSF) and plasma NPY levels in individuals with depression [30]. Unler et al. showed that NPY levels were decreased in BP patients compared to UP patients [5].
Certain investigations have noted no substantial alteration in plasma NPY levels in cases of depression. In humans, a spontaneous episode of MDD is associated with a reduction in cerebrospinal fluid and NPY concentrations, irrespective of medication status [27]. Besides NPY in prior research, substantial evidence exists for the altered expression of NPY receptors in depression. The NPY receptor subtypes NPY1R, NPY2R, and NPY5R are documented as functional inside the limbic brain and implicated in chronic stress, anxiety, and depression-like behaviours [31–33]. Sharma et al. examined whether depression and suicidal behaviour are associated with changes in the expression of NPY and its four receptors NPY1R, NPY2R, NPY4R and NPY5R in the PFC and hippocampal regions of the postmortem brains of adult control and depression-suicide group (n = 24) subjects. The study revealed that NPY protein levels and mRNA expression in the PFC and hippocampus of depressed persons who committed suicide were markedly lower than those of healthy individuals. Conversely, substantial elevations were noted in the mRNA levels of NPY1R and NPY2R among NPY receptors, whereas no significant alterations were detected in other receptor types. Although some of the individuals who died due to depression (n = 12) were using antidepressants, no statistically significant difference was found between this condition and NPY mRNA expression. Moreover, the researchers explicitly observed that the presence of antidepressants in the participants’ blood at the moment of death did not influence the outcomes [34]. In another study using a substantial sample. Using functional connectivity techniques, correlational relationships between brain regions of npy were examined. They detected changes in functional connectivity when imaging brain networks in anxiety and depression. They emphasised that by changing the intrinsic functional connectivity of the NPY network, it may affect the risk of mood and anxiety disorders [35]. In the light of all these data, the decrease in NPY levels in UP and BP patients in our study coincides with the literature data.
Certain research have investigated the impact of psychiatric medications on NPY, yielding incongruous results [36]– [37]. Ozsoy et al. demonstrated an elevation in serum NPY levels associated with venlafaxine, whereas fluoxetine and sertraline were not associated with any significant alterations in NPY levels [38]. Previous research has highlighted that lithium, a mood stabiliser, elevates NPY levels [37]. Another research study indicated that NPY levels were lower in BP patients treated with a combination of mood stabilisers and either antidepressants or antipsychotics, in comparison to the control group [5]. In our study, patients with bipolar disorder predominantly used a combination of mood stabilisers with antidepressants or antipsychotics. Similarly, NPY levels decreased in the BP group in our study. Nine of the UP patients in our study were untreated at the time of sample collection. NPY levels decreased in both treated and untreated patient cohorts compared to the control group. In conclusion, it can be concluded that reduced NPY levels in the patient cohort are predominantly related to disease pathogenesis rather than therapeutic interventions.
Nwafor et al. reported that the severity of eating disorder symptoms measured by scales assessing eating behaviour can predict NPY levels. The finding indicates that the NPY receptor system may be involved in brain processes associated with eating.
NPY receptor localisation in the brain coincides with neuronal networks associated with cue-conditioned feeding in limbic and cortical regions [39]. Conversely, another study indicated a substantial negative connection between serum NPY levels and Emotional Eating subscale scores of the TFEQ-R in persons with BP [5]. In the current study, no statistically significant correlation was observed between serum NPY levels and clinical eating behaviour scales. This result suggested that the effect of NPY on eating behavior may be complex and situation specific.
The present study has some limitations. First, central NPY and POMC levels were assessed instead of peripheral ones; nevertheless, the correlation between central and peripheral NPY/POMC levels remains inadequately clarified, potentially constraining the generalisability of the results. Secondly, the absence of precise equivalence in certain clinical and sociodemographic characteristics raises concerns regarding the influence of confounding variables on the interpretation of biomarker levels across bipolar and unipolar depression groups. Consequently, it may be inappropriate to ascribe the observed differences exclusively to disease type, which is seen as an important limitation of the study. Furthermore, differences in psychiatric medication use between BP and UP groups constitute a potential confounding factor that may affect biomarker levels. The study’s sample size restricts the generalisability of the results to a broader population.
Acknowledgments
Disclosure statement
All authors declare that they approve of the final version.
Authors’ contributions
HS: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Resources; Software; Supervision; Validation; Visualization; Roles/Writing - original draft; and Writing - review & editing.OG: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Resources; Software; Supervision; Validation; Writing - review & editing.
Funding
This research did not receive any specifc grant from funding agencies in the public, commercial or not-for-proft sectors.
Data availability
The data that support the findings of this study are not publicly available due to privacy reasons, but are available from the corresponding author upon reasonable request.
Declarations
Ethics approval and consent to participate
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are not publicly available due to privacy reasons, but are available from the corresponding author upon reasonable request.