Neurochemical, Metabonomics and Neuroimaging Characterization of TCM Diagnostic Subtypes of Major Depression Disorder

Study Overview
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Brief Summary
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There is heterogeneity in patients with depression. Many scholars propose that individualization of antidepressant achieves better outcomes. However, the scientific theoretical basis of individualized treatment is still quite weak. Different clinical subtypes of depression and their possible biomarkers are critically needed to provide the individualization with theoretical base. Diagnostic types of major depression disorder (MDD) based on the Theory of Traditional Chinese Medicine (TCM) and possible differentiations in neurobiochemistry, metabonomics and neuroimaging could be one of ways to explore the biomarkers and support the theory of the individualized treatment. The hypothesized results will be of help to clarify the biological basis of MDD with LDQS and with DBHS, to provide the TCM with further scientific evidence, to explore the pathogenesis of depression, to improve the objective diagnosis of depression, and to promote targeted interventions by Western medicine, TCM or both.

Detailed Description
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The objectives of this study is to explore if there are any differences in neurobiochemistry, metabonomics and neuroimaging (1) at the baseline, between the subjects who are the normal controls (C Group) and who both meet diagnostic criteria of the Diagnostic and Statistical Manual of 5th edition (DSM-V) on MDD and TCM criteria of 'pattern of Liver Depression and Qi Stagnation (LDQS)' or'pattern of Deficiency of Both Heart and Spleen (DBHS)' (T Group); (2) at the baseline, between the MDD subjects of LDQS and DBHS; (3) after 6-week venlafaxine administration, between the MDD subjects of LDQS and DBHS. 50 subjects in T Group and 25 in C Group are recruited in the study and the main laboratory tests include High Performance Liquid Chromatography(HPLC), Gas Chromatography-Mass Spectrum(GCMS) and neuroimaging DTI technology.

Official Title
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Neurochemical,Metabonomics and Neuroimaging Characterization of TCM Diagnostic Subtypes of Major Depression Disorder

Conditions
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Severe Major Depression Disorder

Intervention / Treatment
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* Drug: venlafaxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Had a diagnosis of major depressive disorder according to DSM-V and TCM criteria of 'pattern of Liver Depression and Qi Stagnation (LDQS)' or'pattern of Deficiency of Both Heart and Spleen (DBHS) The severity of the symptoms is moderate or severe, confirmed by a 35 or greater of Hamilton Rating Scale for Depression(HAMD) score Absence of brain and/or severe physical diseases 18-65years old Exclusion Criteria: In pregnancy，brain and other severe medical conditions Psychoactive substance abuse Had a diagnosis of bipolar disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LDQS group<br>Liver Depression and Qi Stagnation (LDQS)group,Liver Depression and Qi Stagnation Syndrome should include at least the following 5 symptoms and signs: emotional depression or sadness, pessimism, short breath, sigh, dysphoria，thin coating，stringy pulse Drugs use generic name :Venlafaxine; Dosage form:capsule Dosage, frequency and duration:Venlafaxine dose was initiated at 75 mg/day and escalated to an optimal dose (150-225 mg/day in most cases) within 2 week, depending upon individual patient response, but the maximum dose could not exceed 300 mg/day during the next 4 weeks. The biomarkers of neurobiochemistry, metabonomics and neuroimaging would be tested at the baseline and after 6-week venlafaxine administration. | Drug: venlafaxine<br>* Venlafaxine dose was initiated at 75 mg/day and escalated to an optimal dose (150-225 mg/day in most cases) within 2 week, depending upon individual patient response, but the maximum dose could not exceed 300 mg/day during the next 4 weeks. Patients were prescribed a combination of venlafaxine and Benzodiazepines for sleep disturbance.<br>* Other names: clonazepam;|
| Active Comparator: DBHS group<br>Deficiency of Both Heart and Spleen (DBHS) group,Deficiency of Both Heart and Spleen Syndrome should include at least following 6 symptoms and signs: emotional depression, thinking torpidity, tiredness, forgetfulness, insomnia, loose stool, sweating, pale tongue body, thin tongue coating, and thin and deep pulse Drugs use generic name :Venlafaxine; Dosage form:capsule Dosage, frequency and duration:Venlafaxine dose was initiated at 75 mg/day and escalated to an optimal dose (150-225 mg/day in most cases) within 2 week, depending upon individual patient response, but the maximum dose could not exceed 300 mg/day during the next 4 weeks. The biomarkers of neurobiochemistry, metabonomics and neuroimaging would be tested at the baseline and after 6-week . | Drug: venlafaxine<br>* Venlafaxine dose was initiated at 75 mg/day and escalated to an optimal dose (150-225 mg/day in most cases) within 2 week, depending upon individual patient response, but the maximum dose could not exceed 300 mg/day during the next 4 weeks. Patients were prescribed a combination of venlafaxine and Benzodiazepines for sleep disturbance.<br>* Other names: clonazepam;|
| No Intervention: the normal controls group<br>The normal controls group including the healthy volunteer None drug The biomarkers of neurobiochemistry, metabonomics and neuroimaging would be tested at the baseline . | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain neuroimaging | Diffusion Tensor Imaging(DTI) is used to detect changes in FA maps of brain white matter fiber in major depressive patients | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical tests | Gas Chromatography-Mass Spectrum is used to test blood and urine samples for: lactic acid, alanine, 3 - hydroxy butyric acid, valine, carbamide, glycerinum, phosphoric acid, isoleucine, glycine, succinic acid, threonine, malic acid, glutamic acid, citric acid, stearic acid, GABA, methionine, cysteine, lysine, tryptophan, leucine, methionine and tyrosine. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuroimaging, major depression disorder, biochemistry, TCM diagnosis, Neurological, metabonomics