A Diagnosis and Treatment Optimization Study of Depression Based on the Neurological Mechanism of Reward System

Study Overview
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Brief Summary
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Major depressive disorder (MDD) is a high-disabling disease. But its etiology and pathogenesis is not clear, and early recognition, diagnosis and treatment still has many challenges. Among numerous clinical manifestations of MDD, anhedonia is an important core symptom of MDD, especially in patients with melancholic features. Our previous studies and studies abroad have shown that MDD patients had functional abnormality in reward circuit. The abnormalities of reward-related core areas, such as the prefrontal cortex - nucleus accumbens - ventral tegmental area were closely associated with the development of MDD, and is an important neural basis of anhedonia. This study would take the reward circuit as mainline to carry out the etiology, diagnosis and therapeutic intervention studies of MDD. We would collect MDD patients with melancholic features and other populations with reward dysfunction. The neuroimaging techniques, stress assessment, genetic testing and drug intervention methods would be mainly used in this study. The functional connectivity of reward regions, such as the ventral striatum, nucleus accumben, and ventral medial prefrontal cortex, would be analyzed to identify the dysfunction of reward circuit of MDD, and its implication for early recognition, diagnosis and prediction of treatment efficacy of antidepressants. We would also investigate the effect of genetic and environmental factors on reward function of MDD and its biological basis. Finally, through modulating the reward circuit activity using animal experiments, we would verify and investigate reward dysfunction of MDD and its biological mechanisms. The project is expected to provide for new evidence for the establishment of reward mechanism - based objective diagnosis and treatment optimization strategy of MDD.

Official Title
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Clinical Psychopharmacology Division,Institute of Mental Health,Peking University

Conditions
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Diagnosis and Treatment of Depression

Intervention / Treatment
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* Drug: Escitalopram
* Drug: Duloxetine
* Drug: Mirtazapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: first-episode, drug naive melancholic depression; remitted depression; schizophrenia patients; first-degree relatives of depressed patients. Exclusion Criteria: major somatic diseases; DSM-IV axis I other mental illness; personality disorder, mental retardation; drug and / or alcohol dependence; serious suicidal tendencies or suicidal behavior; pregnant or lactating women; MRI contraindications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: escitalopram<br>Eligible patients were assigned to escitalopram treatment based on investigators' clinical practice. | Drug: Escitalopram<br>* receive escitalopram<br>|
| Experimental: duloxetine<br>Eligible patients were assigned to duloxetine treatment based on investigators' clinical practice. | Drug: Duloxetine<br>* receive duloxetine<br>|
| Experimental: mirtazapine<br>Eligible patients were assigned to mirtazapine treatment based on investigators' clinical practice. | Drug: Mirtazapine<br>* receive mirtazapine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Depression | remission defined by Hamilton Rating Scale for Depression < 7 | 8 weeks |