A new case-control study reveals an association between obesity, depression, and decreased levels of the protein neuregulin-1 (NRG-1).
The research suggests NRG-1 may serve as a biomarker linking depression and obesity.
Key facts:
- Depressive symptoms were more common in obese individuals compared to normal weight controls.
- After bariatric surgery, most obese patients saw an improvement in depressive symptoms along with weight loss.
- Levels of NRG-1 were significantly lower in obese patients versus controls.
- Severely depressed obese patients had the lowest NRG-1 levels.
- There was a correlation between lower NRG-1 levels and higher depression scores both before and after surgery.
- NRG-1 showed potential as a diagnostic marker for pre-operative depression and for predicting depression prognosis after surgery.
Source: BMC Psychiatry 2023
The Link Between Obesity and Depression
Obesity and depression are two major public health issues that often co-occur.
Research increasingly suggests bi-directional relationships between the two conditions – obesity may increase depression risk, while depression can also predispose to obesity.
Some key factors thought to link obesity and depression include:
- Shared genetic risks
- Obesity-related conditions like inflammation, metabolic changes, and cardiovascular disease
- Reduced efficacy of antidepressants in obese individuals
- Psychosocial effects of obesity like poor body image and stigma
This new study aimed to explore the connection between obesity and depression further by evaluating levels of the protein neuregulin-1 (NRG-1).
Past studies have hinted NRG-1 may play roles in both depression and metabolic conditions.
About Neuregulin-1 (NRG-1) Biomarker
Neuregulin-1 (NRG-1) is a protein involved in cell growth and development in the nervous system.
It signals through ErbB receptor tyrosine kinases.
NRG-1 has several functions related to brain health, including:
- Promoting development and myelination of neurons
- Supporting synaptic plasticity
- Regulating neurotransmission
- Mediating immunomodulatory and anti-inflammatory effects
Research shows NRG-1 is decreased in animal models of chronic stress and depression.
Its deficiency can lead to impaired inhibitory signaling in the brain.
As a nerve growth factor, NRG-1 helps maintain plasticity which is reduced in depression.
Interestingly, NRG-1 may also impact metabolic health.
Studies demonstrate NRG-1 can improve glucose tolerance and insulin sensitivity in obese mouse models.
It’s been proposed as a possible therapy for diabetes and obesity-related insulin resistance.
Overall, NRG-1’s dual roles in mental and metabolic health make it an intriguing candidate biomarker for linking depression and obesity.
Study: NRG-1 Levels Lower in Obese Patients
The recent study was conducted by researchers at Alexandria University in Egypt.
It involved 208 participants:
- 108 obese patients undergoing laparoscopic sleeve gastrectomy
- 100 normal weight controls
Participants were assessed for depressive symptoms using the Beck Depression Inventory (BDI) before and one month after bariatric surgery.
Blood levels of NRG-1 were measured and compared between groups.
Notable findings included:
- Before surgery, 50% of obese patients had depressive symptoms (BDI score ≥14) compared to 18% of controls.
- One month after surgery, the percentage with depressive symptoms dropped to 32%, indicating an improvement for most patients.
- However, a small subset of patients (6%) showed worsening depressive symptoms after surgery.
- Mean NRG-1 levels were significantly lower in obese patients (3.13 ng/mL) versus controls (7.09 ng/mL).
- Among obese patients, NRG-1 levels progressively declined with worsening depressive symptoms. Severely depressed patients had the lowest levels (1.28 ng/mL).
- There was a strong negative correlation between NRG-1 levels and depression scores before and after surgery.
NRG-1 as a Biomarker Linking Obesity & Depression
This study highlights depleted NRG-1 levels as a possible blood biomarker connecting obesity and depression.
Analysis of NRG-1’s predictive capacity for diagnosing depression revealed:
- 92% sensitivity and 69% specificity prior to surgery at a cut-off of ≤3.5 ng/mL
- 53% sensitivity and 80% specificity after surgery at a cut-off of ≤2.5 ng/mL
The researchers conclude NRG-1 shows promise as a biomarker for identifying depression pre-operatively.
It may also help predict postoperative depression prognosis in bariatric surgery patients based on pre-operative levels.
Future studies with longer follow-up are needed to clarify NRG-1’s role as a prognostic marker for depression after bariatric surgery-induced weight loss.
Mechanisms Linking NRG-1, Obesity, and Depression
While this study establishes a relationship between NRG-1, obesity, and depression, the underlying mechanisms remain to be fully elucidated.
Some hypotheses include:
- Inflammation – Obesity involves chronic low-grade inflammation. Pro-inflammatory cytokines may inhibit NRG-1 expression. Inflammation also likely contributes to obesity-related depression.
- Insulin resistance – NRG-1 improves insulin sensitivity and glucose metabolism. Obesity-driven insulin resistance may reduce NRG-1 activity.
- Neuroplasticity – NRG-1 promotes structural and functional plasticity in the brain, which is impaired in depression. Obesity may exacerbate these effects.
Further research is required to uncover the causal pathways involved.
However, manipulating NRG-1 levels directly could have implications for treating both obesity and depression.
The Big Picture: Obesity, Depression, NRG-1
Identifying biomarkers that link obesity and depression is an important step towards precision medicine and improved treatment outcomes.
For obese individuals, screening for biochemical markers like NRG-1 may help predict those most susceptible to pre-operative depression or postoperative depressive symptoms following bariatric surgery.
This allows for earlier targeted intervention.
In the future, boosting NRG-1 activity through novel therapeutics could benefit both obesity and depression.
More studies are first needed to fully establish NRG-1’s clinical utility as a prognostic and diagnostic biomarker.
For now, this research significantly advances our understanding of the complex interplay between obesity, depression, and metabolic-inflammatory factors like NRG-1.
It provides clues to the shared biological basis behind these major public health challenges.
Continuing to elucidate the mechanisms linking excess weight and mood disorders is crucial for developing new prevention and treatment strategies.
Finding improved ways to address the obesity-depression intersection has far-reaching implications for improving health on a societal level.
References
- Study: Is neuregulin-1 (NRG-1) a potential blood biomarker linking depression to obesity?
- Authors: Heba Ahmed Abdelaziz et al. (2023)
