Bidirectional link between mood disorders and diabetic retinopathy

Abstract

The recently published article by Gao et al identifies risk factors for anxiety and depression in patients with diabetic retinopathy. We supplement that there is pathophysiological evidence to show a complex and possibly bidirectional relation between diabetes, diabetic retinopathy, and mood disorders, especially depression. Longitudinal studies may strengthen proof of a causal relationship between these diseases. A better understanding can help in the holistic management of these patients.

Key Words: Diabetic retinopathy; Diabetes; Depression; Anxiety; Mood disorders; Bidirectional; Correlation

Core Tip: There is a complex relationship between diabetic retinopathy and mood disorders like anxiety and depression. The diseases have a similar interplay of biochemical and physiological changes as discussed further. This may also link the severity and progression of retinopathy to mood disorders. Further research can build on the intersection between the potential molecular mechanisms of mental illness and diabetic retinopathy.

INTRODUCTION

We read with great interest the article by Gao et al[1] regarding the anxiety and depression status in diabetic retinopathy (DR) recently published. The authors have made an exhaustive effort to explore the prevalence and factors influencing anxiety and depression among patients with DR using robust tools and strong statistical analysis. We commend the authors on establishing a positive correlation between a family history of diabetes and hypertension with increased psychiatric disturbance, which was a lacuna in many other studies. A strength of the study is that it comprehensively evaluates the prevalence of anxiety and depression separately via specific questionnaires whereas, in many previous studies the diseases and symptoms are combined as a single entity[2].

We further add that evidence suggests a bidirectional association between diabetes and depression, a complex relation that might share biological including neuroimmune mechanisms. DR may increase the future risk of depression, especially with progressive and severe forms of disease[3,4]. Diabetes is accompanied by neurodegeneration and inflammation, as is also prevalent in depressive disorders. The multifunctional neurotransmitter 5-hydroxytryptamine is suppressed in both diseases. Diabetic state of hyperglycemia can reduce neurotransmitter activity leading to impairment of synaptic plasticity, neurogenesis, etc.[4,5]. This can cause pathological changes in hippocampal function, hypothalamic-pituitary axis, and emotional function[6]. Diabetes and depression, both have increased proinflammatory cytokines like C-reactive protein, tumor necrosis factor α, interferon α, etc., and reactive oxygen species[3]. These have been linked with neurocognitive defects and microvascular changes which are further complicated by hypoglycemia. Retinal vessels are particularly sensitive to glycemic fluctuations and have different calibers in patients with both diseases[3]. Other shared etio-pathological mechanisms between DR and mood disorders include endothelial dysfunction, endocrine abnormalities, behavioral and environmental factors like obesity, and medication-related factors[7]. DR affects the photosensitive retinal ganglion cells essential for circadian rhythms. The progression of retinopathy severity could worsen sleep quality and mood through the hypothalamic-pituitary axis[8]. The retinal microvasculature and nerve fiber layer changes studied in patients with psychiatric disorders point toward a possible association between the diseases, grounded in shared embryological and physiological features between the eye and brain[3,7,9]. All of this may help open a new avenue for the discovery of novel endocrine biomarkers of depression and DR and potential treatment targets.

On another note, regarding the management interventions - as stressed by the authors, the social environment plays a key role in the prevention of mood disorders and also, in delaying progression of retinopathy, and control of diabetic macular edema[1,7]. We found that most studies evaluating anxiety/depression in ocular diseases are designed as cross-sectional studies, which by their study design cannot determine causal relationships. In the future, a longitudinal study design may help us explore the possibility of a bidirectional nature of the disease. Such evidence may help us quantify the risk of the development of anxiety and depression because of the ongoing management of diabetes and its complications. One may also observe whether individuals with pre-existing anxiety and depression are more likely to experience DR due to poor diabetic control and quantitatively assess the impact of social supportive measures.

CONCLUSION

In conclusion, there is complex relationship between diabetes and mental disorders linked by inflammatory, neural and endocrine factors. Further study of these mechanisms may help in research for biomarkers and possible interventions for prevention or reversal. The diseases are interlinked and patient screening for these diseases in high-risk patients at first contact point may help in more holistic management. We commend the authors for highlighting the mental health needs of patients with DR and hope that future research will build on these findings to integrate mental health check-ups and support into diabetes management programs.