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Focused Ultrasound and Exosomes to Treat Depression, Anxiety, and Dementias

Primary Purpose

Refractory Depression, Anxiety Disorders, Neurodegenerative Diseases

Status
Suspended
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exosomes
Sponsored by
Neurological Associates of West Los Angeles
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Depression

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

In order for a subject to be considered for the depression application of this study, the following criteria are required:

  • Diagnosis of Major Depressive Disorder
  • Score greater than 13 on the Beck Depression Inventory
  • Failure to remit with 3 antidepressants
  • At least 18 years of age

In order for a subject to be considered for the anxiety application of this study, the following criteria are required:

  • Diagnosis of Generalized or Acute Anxiety Disorder
  • Score greater than 22 on the Beck Anxiety Inventory
  • Failure to remit with 3 anxiolytics
  • At least 18 years of age

In order for a subject to be considered for the neurodegenerative application of this study, the following criteria are required:

  • Cognitive decline with mild cognitive impairment (Clinical Dementia Rating stage 0.5) through moderate dementia (CDR stage 2)
  • Lumbar puncture for Abeta 42 and Tau proteins evincing clinical correlation of neurodegenerative disease pathology
  • Advanced MRI of the brain including volume measurement of the hippocampus, BOLD, and ASL perfusion scans. On entry, patients will have CDR stage of at least 0.5 and at least one abnormal imaging biomarker. CSF studies have demonstrated good sensitivity and specificity for MCI and dementia of the Alzheimer's type (Tapiola et al., 2009). Additionally, MRI volumetrics and perfusion scans have shown to be useful in differentiating subgroups of AD, PDD/DLB, and FTLD; these values are also responsive to change as patients progress form MCI to dementia (Targosz-Gajniak et al., 2013).

Exclusion Criteria:

  • Cognitive decline clearly related to an acute illness
  • Subjects unable to give informed consent
  • Subjects who would not be able to lay down without excessive movement in a calm environment sufficiently long enough to be able to achieve sleep
  • Recent surgery or dental work within 3 months of the scheduled procedure.
  • Pregnancy, women who may become pregnant or are breastfeeding
  • Advanced terminal illness
  • Any active cancer or chemotherapy
  • Bone marrow disorder
  • Myeloproliferative disorder
  • Sickle cell disease
  • Primary pulmonary hypertension
  • Immunocompromising conditions and/or immunosuppressive therapies
  • Any other neoplastic illness or illness characterized by neovascularity
  • Macular degeneration
  • Subjects with scalp rash or open wounds on the scalp (for example from treatment of squamous cell cancer)
  • Advanced kidney, pulmonary, cardiac or liver failure

Sites / Locations

  • Neurological Associates of West Los Angeles

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Patients deemed potentially appropriate candidates for exosome and focused ultrasound therapy for either treatment refractory depression (trMDD), anxiety, or neurodegenerative dementia will be treated with exosomes derived from healthy, full-term Cesarean section amniotic fluid. Up to one hour of transcranial focused ultrasound will be administered immediately prior to exosome treatment in an attempt to facilitate enhanced deployment to the subgenual cingulate for trMDD, the amygdala for anxiety, or the hippocampus for dementia. Target location will be determined by the physician upon enrollment depending on the patient's specific syndrome. Patients will be given 15cc of unconcentrated solution allogenic exosomes (equivalent to 21 million stem cells, Kimera Corporation) intravenously in 200 ccs of normal saline dripped over thirty minutes to one hour.

Outcomes

Primary Outcome Measures

[trMDD] Beck Depression Inventory (BDI-II)
The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from "0" (this item does not apply) to "3" (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.
[Anxiety] Beck Anxiety Inventory (BAI)
The BAI is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety symptoms. Each of the 21 items asks whether the patient has experienced various anxiety symptoms in the last two weeks, and if so, how severely. Each question/answer is scored on a scale value of "0" (not at all) to "3" (severely). Higher total scores indicate more severe anxiety symptoms. The maximum total score possible is 63 points. The standard cutoff scores are: 0-7 = minimal anxiety; 8-15 = mild anxiety; 16-25 = moderate anxiety; 26-63 = severe anxiety. A reduction in score by at least 30% is considered clinically meaningful.
[Dementia] Quick Dementia Rating Scale (QDRS)
The Quick Dementia Rating Scale (QDRS) is an interview-based tool administered by study officials to participants' caregivers used to obtain observations from a consistent source. The QDRS form consists of 10 categorical questions (5 cognitive, 5 functional), each with 5 detailed options depicting the level of impairment as either 0 (normal), 0.5 (mild/inconsistent impairment), 1 (mild/consistent impairment), 2 (moderate impairment), or 3 (severe impairment). Based on the conversion table outlined in Dr. James Galvin's research (2015), total QDRS scores were converted to Clinical Dementia Rating (CDR) scale levels ranging from 0 (normal aging), 0.5 (mild cognitive impairment), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia).
[ALL] Global Rating of Change (GRC)
The GRC consists of a single likert-scale ranging from "-5" (very much worse) to "0" (neutral/no change) to "5" (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change.

Secondary Outcome Measures

[trMDD] Patient Depression Questionnaire (PDQ-9)
The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from "0" (not at all), "1" (several days/week), "2" (more than half of the days), and "3" (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.
[trMDD] Hamilton Depression Rating Scale (HAM-D)
The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of "0" (symptom absent) to "4" (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful.
[Anxiety] Hamilton Anxiety Rating Scale (HAM-A)
The HAM-A is an observer/rater scale consisting of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
[Dementia] Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D
RBANS assesses immediate memory, visuospatial skill, language, attention, and delayed memory. Patient performance on each subscale immediate memory, language, attention, visuospatial, and delayed memory are scored relative to validated norms for same-aged peers. A change of 8+ points in the Total Scale score, 11+ points in the Immediate Memory score, 9+ points in the Language score, 4+ points on the Attention score, 14+ points is considered significant for the Visuospatial score, and 10+ points for the Delayed Memory score are considered significant.
[Dementia] Montreal Cognitive Assessment (MoCA) versions 7.1-7.3
The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status.

Full Information

First Posted
December 16, 2019
Last Updated
September 26, 2022
Sponsor
Neurological Associates of West Los Angeles
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1. Study Identification

Unique Protocol Identification Number
NCT04202770
Brief Title
Focused Ultrasound and Exosomes to Treat Depression, Anxiety, and Dementias
Official Title
Focused Ultrasound Delivery of Exosomes for Treatment of Refractory Depression, Anxiety, and Neurodegenerative Dementias
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Suspended
Why Stopped
Pending COVID-19 pandemic; pending status of product development
Study Start Date
December 1, 2019 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neurological Associates of West Los Angeles

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is designed to evaluate the safety and efficacy of exosome deployment with concurrent transcranial ultrasound in patients with refractory, treatment resistant depression, anxiety, and neurodegenerative dementia.
Detailed Description
The present study is designed to enhance the delivery of growth factors and anti-inflammatory agents to localized targets (determined by specific condition) by using focused transcranial ultrasound prior to intravenous infusion of exosomes. Exosomes, which are ubiquitous in blood, body fluids, and tissues are thought to play a normal physiological role in intercellular signaling. Exosomes delivered intravenously can be demonstrated to cross the blood brain barrier naturally. Exosomes and mesenchymal signaling cells (MSC's) demonstrate anti-inflammatory and pro-growth effects in preclinical models and clinical cases reports and have been used intravenously and with intracerebral and intrathecal injection. Various clinical trials have claimed safety and clinical efficacy. Focused ultrasound has been demonstrated to enhance local blood flow and has been proposed as a non-invasive means of targeting delivery of therapeutic agents. The present paper was designed to use focused ultrasound as a means of enhancing delivery of intravenous exosomes to the subgenual target for patients with refractory depression, the amygdala for patients with anxiety, and the hippocampus for patients with cognitive impairment due to neurodegenerative disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Depression, Anxiety Disorders, Neurodegenerative Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
The present study is being undertaken as an open-label study to evaluate the safety and feasibility of exosomes and concurrent focused ultrasound as an intervention for patients with refractory depression, anxiety, and cognitive impairment due to a neurodegenerative disease (e.g., Alzheimer's).
Masking
None (Open Label)
Allocation
N/A
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Patients deemed potentially appropriate candidates for exosome and focused ultrasound therapy for either treatment refractory depression (trMDD), anxiety, or neurodegenerative dementia will be treated with exosomes derived from healthy, full-term Cesarean section amniotic fluid. Up to one hour of transcranial focused ultrasound will be administered immediately prior to exosome treatment in an attempt to facilitate enhanced deployment to the subgenual cingulate for trMDD, the amygdala for anxiety, or the hippocampus for dementia. Target location will be determined by the physician upon enrollment depending on the patient's specific syndrome. Patients will be given 15cc of unconcentrated solution allogenic exosomes (equivalent to 21 million stem cells, Kimera Corporation) intravenously in 200 ccs of normal saline dripped over thirty minutes to one hour.
Intervention Type
Other
Intervention Name(s)
Exosomes
Intervention Description
Focused ultrasound delivery of intravenously-infused exosomes
Primary Outcome Measure Information:
Title
[trMDD] Beck Depression Inventory (BDI-II)
Description
The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from "0" (this item does not apply) to "3" (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.
Time Frame
8 weeks from baseline
Title
[Anxiety] Beck Anxiety Inventory (BAI)
Description
The BAI is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety symptoms. Each of the 21 items asks whether the patient has experienced various anxiety symptoms in the last two weeks, and if so, how severely. Each question/answer is scored on a scale value of "0" (not at all) to "3" (severely). Higher total scores indicate more severe anxiety symptoms. The maximum total score possible is 63 points. The standard cutoff scores are: 0-7 = minimal anxiety; 8-15 = mild anxiety; 16-25 = moderate anxiety; 26-63 = severe anxiety. A reduction in score by at least 30% is considered clinically meaningful.
Time Frame
8 weeks from baseline
Title
[Dementia] Quick Dementia Rating Scale (QDRS)
Description
The Quick Dementia Rating Scale (QDRS) is an interview-based tool administered by study officials to participants' caregivers used to obtain observations from a consistent source. The QDRS form consists of 10 categorical questions (5 cognitive, 5 functional), each with 5 detailed options depicting the level of impairment as either 0 (normal), 0.5 (mild/inconsistent impairment), 1 (mild/consistent impairment), 2 (moderate impairment), or 3 (severe impairment). Based on the conversion table outlined in Dr. James Galvin's research (2015), total QDRS scores were converted to Clinical Dementia Rating (CDR) scale levels ranging from 0 (normal aging), 0.5 (mild cognitive impairment), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia).
Time Frame
8 weeks from baseline
Title
[ALL] Global Rating of Change (GRC)
Description
The GRC consists of a single likert-scale ranging from "-5" (very much worse) to "0" (neutral/no change) to "5" (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change.
Time Frame
8 weeks from baseline
Secondary Outcome Measure Information:
Title
[trMDD] Patient Depression Questionnaire (PDQ-9)
Description
The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from "0" (not at all), "1" (several days/week), "2" (more than half of the days), and "3" (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.
Time Frame
8 weeks from baseline
Title
[trMDD] Hamilton Depression Rating Scale (HAM-D)
Description
The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of "0" (symptom absent) to "4" (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful.
Time Frame
8 weeks from baseline
Title
[Anxiety] Hamilton Anxiety Rating Scale (HAM-A)
Description
The HAM-A is an observer/rater scale consisting of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Time Frame
8 weeks from baseline
Title
[Dementia] Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D
Description
RBANS assesses immediate memory, visuospatial skill, language, attention, and delayed memory. Patient performance on each subscale immediate memory, language, attention, visuospatial, and delayed memory are scored relative to validated norms for same-aged peers. A change of 8+ points in the Total Scale score, 11+ points in the Immediate Memory score, 9+ points in the Language score, 4+ points on the Attention score, 14+ points is considered significant for the Visuospatial score, and 10+ points for the Delayed Memory score are considered significant.
Time Frame
8 weeks from baseline
Title
[Dementia] Montreal Cognitive Assessment (MoCA) versions 7.1-7.3
Description
The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status.
Time Frame
8 weeks from baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: In order for a subject to be considered for the depression application of this study, the following criteria are required: Diagnosis of Major Depressive Disorder Score greater than 13 on the Beck Depression Inventory Failure to remit with 3 antidepressants At least 18 years of age In order for a subject to be considered for the anxiety application of this study, the following criteria are required: Diagnosis of Generalized or Acute Anxiety Disorder Score greater than 22 on the Beck Anxiety Inventory Failure to remit with 3 anxiolytics At least 18 years of age In order for a subject to be considered for the neurodegenerative application of this study, the following criteria are required: Cognitive decline with mild cognitive impairment (Clinical Dementia Rating stage 0.5) through moderate dementia (CDR stage 2) Lumbar puncture for Abeta 42 and Tau proteins evincing clinical correlation of neurodegenerative disease pathology Advanced MRI of the brain including volume measurement of the hippocampus, BOLD, and ASL perfusion scans. On entry, patients will have CDR stage of at least 0.5 and at least one abnormal imaging biomarker. CSF studies have demonstrated good sensitivity and specificity for MCI and dementia of the Alzheimer's type (Tapiola et al., 2009). Additionally, MRI volumetrics and perfusion scans have shown to be useful in differentiating subgroups of AD, PDD/DLB, and FTLD; these values are also responsive to change as patients progress form MCI to dementia (Targosz-Gajniak et al., 2013). Exclusion Criteria: Cognitive decline clearly related to an acute illness Subjects unable to give informed consent Subjects who would not be able to lay down without excessive movement in a calm environment sufficiently long enough to be able to achieve sleep Recent surgery or dental work within 3 months of the scheduled procedure. Pregnancy, women who may become pregnant or are breastfeeding Advanced terminal illness Any active cancer or chemotherapy Bone marrow disorder Myeloproliferative disorder Sickle cell disease Primary pulmonary hypertension Immunocompromising conditions and/or immunosuppressive therapies Any other neoplastic illness or illness characterized by neovascularity Macular degeneration Subjects with scalp rash or open wounds on the scalp (for example from treatment of squamous cell cancer) Advanced kidney, pulmonary, cardiac or liver failure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sheldon Jordan, M.D.
Organizational Affiliation
Neurological Associates of West Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
Neurological Associates of West Los Angeles
City
Santa Monica
State/Province
California
ZIP/Postal Code
90403
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data from this study will not be made publicly available due to ethical and privacy concerns. Anonymized data will be available upon reasonable request from any qualified investigator.
Citations:
PubMed Identifier
26487813
Citation
Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. 2015 Sep;17(3):327-35. doi: 10.31887/DCNS.2015.17.3/bbandelow.
Results Reference
background
PubMed Identifier
30850617
Citation
Coupe P, Manjon JV, Lanuza E, Catheline G. Lifespan Changes of the Human Brain In Alzheimer's Disease. Sci Rep. 2019 Mar 8;9(1):3998. doi: 10.1038/s41598-019-39809-8.
Results Reference
background
PubMed Identifier
24223526
Citation
Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, Vos T, Whiteford HA. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013 Nov;10(11):e1001547. doi: 10.1371/journal.pmed.1001547. Epub 2013 Nov 5.
Results Reference
background
PubMed Identifier
23666528
Citation
Hebron ML, Lonskaya I, Moussa CE. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of alpha-synuclein in Parkinson's disease models. Hum Mol Genet. 2013 Aug 15;22(16):3315-28. doi: 10.1093/hmg/ddt192. Epub 2013 May 10. Erratum In: Hum Mol Genet. 2023 Jan 1;32(1):172-176.
Results Reference
background
Citation
Pagan, F., Valadez, E., Torres-Yaghi, Y., Falconer, R., Mills, R., Rogers, S., Wilmarth, B., Hebron, M., & Moussa, C. (2016) Effects of nilotinib on safety in open-label phase I clinical trial in Parkinson's disease with dementia and Lewy body dementia. Movement Disorders, 31(2).
Results Reference
background
PubMed Identifier
12103459
Citation
Montgomery SA, Baldwin DS, Riley A. Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction. J Affect Disord. 2002 May;69(1-3):119-40. doi: 10.1016/s0165-0327(01)00313-5.
Results Reference
background
PubMed Identifier
17074942
Citation
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.
Results Reference
background
PubMed Identifier
19185342
Citation
Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, Watanabe N, Nakagawa A, Omori IM, McGuire H, Tansella M, Barbui C. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet. 2009 Feb 28;373(9665):746-58. doi: 10.1016/S0140-6736(09)60046-5.
Results Reference
background
PubMed Identifier
29496589
Citation
Setiawan E, Attwells S, Wilson AA, Mizrahi R, Rusjan PM, Miler L, Xu C, Sharma S, Kish S, Houle S, Meyer JH. Association of translocator protein total distribution volume with duration of untreated major depressive disorder: a cross-sectional study. Lancet Psychiatry. 2018 Apr;5(4):339-347. doi: 10.1016/S2215-0366(18)30048-8. Epub 2018 Feb 26.
Results Reference
background
PubMed Identifier
18704022
Citation
Drevets WC, Savitz J, Trimble M. The subgenual anterior cingulate cortex in mood disorders. CNS Spectr. 2008 Aug;13(8):663-81. doi: 10.1017/s1092852900013754.
Results Reference
background
PubMed Identifier
18639234
Citation
Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH. Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry. 2008 Sep 15;64(6):461-7. doi: 10.1016/j.biopsych.2008.05.034. Epub 2008 Jul 18.
Results Reference
background
PubMed Identifier
28274468
Citation
Jalbrzikowski M, Larsen B, Hallquist MN, Foran W, Calabro F, Luna B. Development of White Matter Microstructure and Intrinsic Functional Connectivity Between the Amygdala and Ventromedial Prefrontal Cortex: Associations With Anxiety and Depression. Biol Psychiatry. 2017 Oct 1;82(7):511-521. doi: 10.1016/j.biopsych.2017.01.008. Epub 2017 Jan 17.
Results Reference
background
PubMed Identifier
12450943
Citation
Mayberg H. Depression, II: localization of pathophysiology. Am J Psychiatry. 2002 Dec;159(12):1979. doi: 10.1176/appi.ajp.159.12.1979. No abstract available.
Results Reference
background
PubMed Identifier
9276848
Citation
Mayberg HS. Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci. 1997 Summer;9(3):471-81. doi: 10.1176/jnp.9.3.471.
Results Reference
background
PubMed Identifier
12382208
Citation
Mayberg HS. Modulating limbic-cortical circuits in depression: targets of antidepressant treatments. Semin Clin Neuropsychiatry. 2002 Oct;7(4):255-68. doi: 10.1053/scnp.2002.35223.
Results Reference
background
PubMed Identifier
12697626
Citation
Mayberg HS. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull. 2003;65:193-207. doi: 10.1093/bmb/65.1.193.
Results Reference
background
PubMed Identifier
15024963
Citation
Mayberg HS. Positron emission tomography imaging in depression: a neural systems perspective. Neuroimaging Clin N Am. 2003 Nov;13(4):805-15. doi: 10.1016/s1052-5149(03)00104-7.
Results Reference
background
PubMed Identifier
17338903
Citation
Mayberg HS. Defining the neural circuitry of depression: toward a new nosology with therapeutic implications. Biol Psychiatry. 2007 Mar 15;61(6):729-30. doi: 10.1016/j.biopsych.2007.01.013. No abstract available.
Results Reference
background
PubMed Identifier
19339763
Citation
Mayberg HS. Targeted electrode-based modulation of neural circuits for depression. J Clin Invest. 2009 Apr;119(4):717-25. doi: 10.1172/JCI38454.
Results Reference
background
PubMed Identifier
9141092
Citation
Mayberg HS, Brannan SK, Mahurin RK, Jerabek PA, Brickman JS, Tekell JL, Silva JA, McGinnis S, Glass TG, Martin CC, Fox PT. Cingulate function in depression: a potential predictor of treatment response. Neuroreport. 1997 Mar 3;8(4):1057-61. doi: 10.1097/00001756-199703030-00048.
Results Reference
background
PubMed Identifier
10327898
Citation
Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, Silva JA, Tekell JL, Martin CC, Lancaster JL, Fox PT. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry. 1999 May;156(5):675-82. doi: 10.1176/ajp.156.5.675.
Results Reference
background
PubMed Identifier
15748841
Citation
Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3;45(5):651-60. doi: 10.1016/j.neuron.2005.02.014.
Results Reference
background
PubMed Identifier
11958786
Citation
Botteron KN, Raichle ME, Drevets WC, Heath AC, Todd RD. Volumetric reduction in left subgenual prefrontal cortex in early onset depression. Biol Psychiatry. 2002 Feb 15;51(4):342-4. doi: 10.1016/s0006-3223(01)01280-x.
Results Reference
background
PubMed Identifier
19464154
Citation
Yucel K, McKinnon M, Chahal R, Taylor V, Macdonald K, Joffe R, Macqueen G. Increased subgenual prefrontal cortex size in remitted patients with major depressive disorder. Psychiatry Res. 2009 Jul 15;173(1):71-6. doi: 10.1016/j.pscychresns.2008.07.013. Epub 2009 May 21.
Results Reference
background
PubMed Identifier
28397839
Citation
Riva-Posse P, Choi KS, Holtzheimer PE, Crowell AL, Garlow SJ, Rajendra JK, McIntyre CC, Gross RE, Mayberg HS. A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression. Mol Psychiatry. 2018 Apr;23(4):843-849. doi: 10.1038/mp.2017.59. Epub 2017 Apr 11.
Results Reference
background
PubMed Identifier
28715655
Citation
Yuan D, Zhao Y, Banks WA, Bullock KM, Haney M, Batrakova E, Kabanov AV. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials. 2017 Oct;142:1-12. doi: 10.1016/j.biomaterials.2017.07.011. Epub 2017 Jul 10.
Results Reference
background
PubMed Identifier
29724892
Citation
Boshuizen MCS, Steinberg GK. Stem Cell-Based Immunomodulation After Stroke: Effects on Brain Repair Processes. Stroke. 2018 Jun;49(6):1563-1570. doi: 10.1161/STROKEAHA.117.020465. Epub 2018 May 3. No abstract available.
Results Reference
background
PubMed Identifier
29033030
Citation
Detante O, Rome C, Papassin J. How to use stem cells for repair in stroke patients. Rev Neurol (Paris). 2017 Nov;173(9):572-576. doi: 10.1016/j.neurol.2017.09.003. Epub 2017 Oct 21.
Results Reference
background
PubMed Identifier
28941317
Citation
Doeppner TR, Bahr M, Hermann DM, Giebel B. Concise Review: Extracellular Vesicles Overcoming Limitations of Cell Therapies in Ischemic Stroke. Stem Cells Transl Med. 2017 Nov;6(11):2044-2052. doi: 10.1002/sctm.17-0081. Epub 2017 Sep 23.
Results Reference
background
PubMed Identifier
29090465
Citation
Sarmah D, Agrawal V, Rane P, Bhute S, Watanabe M, Kalia K, Ghosh Z, Dave KR, Yavagal DR, Bhattacharya P. Mesenchymal Stem Cell Therapy in Ischemic Stroke: A Meta-analysis of Preclinical Studies. Clin Pharmacol Ther. 2018 Jun;103(6):990-998. doi: 10.1002/cpt.927. Epub 2017 Dec 14.
Results Reference
background
PubMed Identifier
28743464
Citation
Stonesifer C, Corey S, Ghanekar S, Diamandis Z, Acosta SA, Borlongan CV. Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms. Prog Neurobiol. 2017 Nov;158:94-131. doi: 10.1016/j.pneurobio.2017.07.004. Epub 2017 Jul 23.
Results Reference
background
PubMed Identifier
28899062
Citation
Sussman ES, Steinberg GK. A Focused Review of Clinical and Preclinical Studies of Cell-Based Therapies in Stroke. Neurosurgery. 2017 Sep 1;64(CN_suppl_1):92-96. doi: 10.1093/neuros/nyx329. No abstract available.
Results Reference
background
PubMed Identifier
28936740
Citation
Suzuki E, Fujita D, Takahashi M, Oba S, Nishimatsu H. Therapeutic Effects of Mesenchymal Stem Cell-Derived Exosomes in Cardiovascular Disease. Adv Exp Med Biol. 2017;998:179-185. doi: 10.1007/978-981-10-4397-0_12.
Results Reference
background
PubMed Identifier
19273758
Citation
Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H, Pirttila T. Cerebrospinal fluid beta-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol. 2009 Mar;66(3):382-9. doi: 10.1001/archneurol.2008.596.
Results Reference
background
PubMed Identifier
24035276
Citation
Targosz-Gajniak MG, Siuda JS, Wicher MM, Banasik TJ, Bujak MA, Augusciak-Duma AM, Opala G. Magnetic resonance spectroscopy as a predictor of conversion of mild cognitive impairment to dementia. J Neurol Sci. 2013 Dec 15;335(1-2):58-63. doi: 10.1016/j.jns.2013.08.023. Epub 2013 Aug 27.
Results Reference
background
PubMed Identifier
28824181
Citation
Toyoshima A, Yasuhara T, Date I. Mesenchymal Stem Cell Therapy for Ischemic Stroke. Acta Med Okayama. 2017 Aug;71(4):263-268. doi: 10.18926/AMO/55302.
Results Reference
background
PubMed Identifier
26651008
Citation
Mah L, Szabuniewicz C, Fiocco AJ. Can anxiety damage the brain? Curr Opin Psychiatry. 2016 Jan;29(1):56-63. doi: 10.1097/YCO.0000000000000223.
Results Reference
background
PubMed Identifier
18207311
Citation
McDannold N, Vykhodtseva N, Hynynen K. Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. Ultrasound Med Biol. 2008 May;34(5):834-40. doi: 10.1016/j.ultrasmedbio.2007.10.016. Epub 2008 Jan 22.
Results Reference
background

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Focused Ultrasound and Exosomes to Treat Depression, Anxiety, and Dementias

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