Tag Archives: 22308

ketamine, Ketamine for PTSD and Depression, Uncategorized

KETAMINE INFUSIONS |KETAMINE DEPRESSION | KETAMINE DOCTORS IN VIRGINIA | FAIRFAX KETAMINE | 703-844-0184 | KETAMINE AND DEPRESSION TREATMENT – Newsweek Article | 22308 |22305 | 22304 | 22191 |22192 |22193 | 20118 | 20104 | KETAMINE TREATMENT FOR DEPRESSION |CRPS |RSD |KETAMINE INFUSIONS FOR PAIN | SPRINGFIELD , VA KETAMINE |

Leave a comment

NOVA Health Recovery  <<< Ketamine infusion center in Alexandria, Virginia 703-844-0184  – consider ketamine for addiction treatment

CAll  apply texas essay questions 2020 https://rainierfruit.com/cheap-brand-cialis-online/ enter site viagra brands in india dissertation contents table compositional dissertation insight into koshkin nikita process russia style writing unit tests c# metallic taste in mouth doxycycline go to site https://samponline.org/blacklives/programing-assignments-help/27/ essay topics for bpo interview https://norfolkspca.com/medservice/can-you-make-viagra-from-watermelon/14/ essay about ambition http://go.culinaryinstitute.edu/how-do-i-type-greek-letters-on-my-ipad/ https://mysaschool.org/expository/ethics-of-stem-cell-research-paper/15/ hairlosstalk propecia reviews essay on peak oil theory watch neurontin vs vicodin CANANDIAN LASIX WATER PILL maximum dosage of viagra https://cwstat.org/termpaper/thesis-topics-on-language-education/50/ can crestor cause muscle stiffness get link que pasa si se toma viagra en exceso mla citation examples in essay don t blame the eater essay religion college essays click learn critical thinking dream deferred essay contest writing essay introduction exercises 703-844-0184 for an immediate appointment!

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com

Ketamine center in Fairfax, Virginia    << Ketamine infusions

NOVA Health Recovery – KETAMINE SYSTEMS<< Link

I sifted through the article and took out several points in the discussion of the article below.:

By taking the focus off “oneself” and placing it on other stimuli,
it is possible that ketamine decreases awareness of negative
experiences and consequently improves mood.

The transient dissociation experienced by depressed patients
during a ketamine infusion may have the effect of dampening
what the hyperactive self-monitoring associated with
depressive illness.

Radiology findings may reflect ketamine’s ability to reclaim frontal control over deeper limbic structures, thus strengthening the cognitive control of emotions and decreasing depressive symptoms.

Ketamine may cause a “disconnect”
in several circuits related to affective processing, perhaps
by shifting focus of attention away from the internal
states of anxiety, depression, and somatization, and more toward
the perceptual changes (e.g., hallucinations, visual distortions,
derealization) induced by ketamine. Similarly,
during an emotion task, ketamine attenuated responses to
negative pictures, suggesting that the processing of negative
information is specifically altered in response to ketamine.57
By taking the focus off “oneself” and placing it on other stimuli,
it is possible that ketamine decreases awareness of negative
experiences and consequently improves mood

Ketamine-Associated Brain Changes A Review of the Neuroimaging Literature

Abstract
Major depressive disorder (MDD) is one of the most prevalent conditions in psychiatry. Patients who do not respond to traditional monoaminergic antidepressant treatments have an especially difficult-to-treat type of MDD termed treatment-resistant depression. Subanesthetic doses of ketamine-a glutamatergic modulator-have shown great promise for rapidly treating patients with the most severe forms of depression. As such, ketamine represents a promising probe for understanding the pathophysiology of depression and treatment response. Through neuroimaging, ketamine’s mechanism may be elucidated in humans. Here, we review 47 articles of ketamine’s effects as revealed by neuroimaging studies. Some important brain areas emerge, especially the subgenual anterior cingulate cortex.

Ketamine-Associated Brain Changes: A Review of the…. Available from: https://www.researchgate.net/publication/323324257_Ketamine-Associated_Brain_Changes_A_Review_of_the_Neuroimaging_Literature [accessed Mar 31 2018].

 

Newsweek article showing that ketamine can help in Depression – 2018

This is the article in Newsweek below:

Ketamine could offer a fast and effective treatment for people with depression, even those who have failed to respond to current therapy options. A new medical reviewpublished this month adds to the growing evidence that the drug could be used in a clinical setting.

The review, published in the Harvard Review of Psychiatry, analyzed 47 studies on ketamine as a treatment for depression. The paper outlined specific ways in which ketamine affected the brains of depression patients.

Ketamine is a drug that can relieve pain and cause feelings of relaxation. It is generally used as an anesthetic in medical setting, but it is also abused as a party drug. Recreational users typically seek a sensation described as being similar to an out-of-body experience. 

A New Drug for Depression

03_05_ketamineKetamine could double as a depression treatment.

Despite its popularity at parties, ketamine has been the subject of numerous clinical studies for its potential to treat depression. Data have been mounting in its favor, and now a team at Harvard Medical School has reviewed the evidence thus far. 

The authors found that many patients given ketamine displayed measurable positive changes in brain activity in areas associated with the ability to process and control emotions, Business Insider reported.

Those changes include activation of the subgenual anterior cingulate cortex—connected to both emotions and cognition—as observed by neuroimaging. The activation was directly associated with improvement of depression symptoms in as little as 24 hours after patients received a single intravenous subanesthetic ketamine dose.

The drug also enhanced how the brain responded to positive emotions, a change indicated by increased connectivity in the right-hemisphere caudate. That enhancement helped relieve symptoms of depression, possibly because of this region’s connection to the brain’s reward system. 

Related: Perfectionists Are More Likely to Be Depressed—But One Thing Might Help Them

Ketamine also appears to decrease the ability to self-monitor, the report noted. This decrease may cause “emotional blunting,” which could help increase reward processing—and, in turn, happiness.

How Does Ketamine Work? 

Although the review did not describe exactly how ketamine produces its antidepressant effect, the authors noted that the effect may be indirect. Past research found that ketamine affects several receptors in the brain, such as opioid receptors, adrenegic receptors and serotinin receptors. The review concluded that the side effects of ketamine’s effect on those receptors may be the root cause of its antidepressant response. However, more research is needed to confirm this. 

Related: Are Nice People More Likely to Be Depressed?

The recent review is the latest scientific publication to suggest that this commonly used (and abused) drug could be an extremely helpful depression treatment.

22308, Anxiety, Depression, ketamine, Ketamine for PTSD and Depression, Lyme Disease, PTSD

KETAMINE INFUSIONS |KETAMINE DEPRESSION | KETAMINE DOCTORS IN VIRGINIA | FAIRFAX KETAMINE | 703-844-0184 | KETAMINE AND DEPRESSION TREATMENT | 22308 |22305 | 22304 | 22191 |22192 |22193 | 20118 | 20104 | KETAMINE TREATMENT FOR DEPRESSION |CRPS |RSD |KETAMINE INFUSIONS FOR PAIN | SPRINGFIELD , VA KETAMINE | 22303 22307 22306 22309 22308 22311 22310 22312 22315 22003 20120 22015 22027 20121 22031 20124 22030 22033 22032 22035 22039 22041 22043 22042 22046 22044 22060 22066 20151 22079 20153 22101 22102 20171 20170 22124 22151 22150 22153 22152 20191 20190 22181 20192 22180 20194 22182

Leave a comment

NOVA Health Recovery  <<< Ketamine infusion center in Alexandria, Virginia 703-844-0184  – consider ketamine for addiction treatment

CAll 703-844-0184 for an immediate appointment!

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com

Ketamine center in Fairfax, Virginia    << Ketamine infusions

NOVA Health Recovery – KETAMINE SYSTEMS<< Link

703-844-0184 NOVA Health Recovery Ketamine Infusion Center – Beat depression and Anxiety. https://novahealthrecovery.com/

Each year, 13 to 14 million people in America suffer from major depression. Of those numbers who seek treatment, about 30-40% don’t get any better or recover through using the standard depression medications prescribed by healthcare professionals.

Untreated depression puts someone at a greater risk of alcohol and drug abuse, hospitalization and attempted suicide. However, there’s a growing body of research which shows there is a new reason to hope, and it’s the anesthesia drug ketamine.

Ketamine is a popular illicit party drug because it provides the user with hallucinogenic effects. The medication is used in only a handful of clinics around the United States, people who weren’t helped by standard psychiatric treatments are receiving a series of ketamine infusions to help ease the effects of their depression. Ketamine has also been used in emergency rooms to help curb suicidal thoughts, which means the drug is a potential lifesaver.

Ketamine is a fast-acting drug, the effects peak, often within hours, and healthcare providers who give it to a patient at a therapeutic dose say its side effects are brief and mild in most people. The drug hasn’t been studied for long-term safety and effectiveness and the Food and Drug Administration hasn’t approved it to treat depression.

Medical experts do not yet fully understand all the ways ketamine works, but it does work differently than antidepressants such as Zoloft, Prozac and Effexor. The way the drug works might explain why people who don’t respond to traditional treatment methods respond so well to ketamine.

It’s important to remember that no matter how successful ketamine may prove to be, one single treatment isn’t enough to cure depression. To successfully treat depression, a medical professional will need to address all aspects of a person’s disease from the biological, psychological to social and environmental angles.

A Brief History of Ketamine
Ketamine is an anesthetic that has been used on both humans and animals for over 52 years.  Unlike other anesthetics, it doesn’t depress patients’ breathing or circulatory systems and it is very fast-acting.

How Is Ketamine Used
Because of its effectiveness and safety when delivered appropriately, ketamine is being used more in the following ways: treating depression and other mood disorders and pain conditions including Complex Regional Pain Syndrome (CPRS/RSD).  Leading institutions such as Yale University, The National Institute of Mental Health, and  Massachusetts General Hospital have completed research that demonstrates the efficacy and safety of ketamine infusion treatments for these conditions.

The Visit
The medicine is given very slowly over 40 minutes.  Most people can expect to be with us for about 90 minutes.  You will leave treatment without side effects and you should not experience side effects between treatments.​

In As Little As One Treatment
Ketamine treatments may free you from depression, OCD, PTSD, anxiety, CRPS/RSD, fibromyalgia & other chronic pain conditions.

Ketamine Infusion for Depression, Bipolar Disorder or PTSD?

Ketamine could be the bridge for somebody who is suicidal because if they are given the drug and it’s effective for 3 days, the person could be hooked up with outpatient resources, other medications and psychotherapy.

Not all cases of suicidal thoughts are linked to depression, post-traumatic stress disorder, borderline personality disorder and alcohol and other substance abuse issues can also account for some suicides. Further research is needed to determine how ketamine can be utilized for treatment of depression and other psychiatric disorders.

Does Ketamine Infusion Work for Depression?

Social Anxiety and Ketamine:

Approximately one-third to one-half of all people with Social Anxiety Disorder (SAD) do not experience adequate clinical benefits from using the current treatment methods for SAD. These treatments include conventional approaches like selective serotonin reuptake inhibitors or SSRIs or cognitive behavioral therapy. Failing to relieve anxiety in patients with social anxiety disorder is a source of distress, substantial morbidity and it decreases the quality of a person’s life over the long term.

Feeling shy or uncomfortable in certain public situations isn’t an indication of a social anxiety disorder, particularly if these emotions are present in young children. A person’s comfort level in social situations will vary and depend on the individual’s personality and life experiences. Some people are naturally reserved and other people are outgoing, some are a mixture of both.  In contrast to everyday nervousness, social anxiety disorder includes distress, avoidance and unease that interferes with one’s daily life, routine, work, school and other activities.

There’s been new evidence from neuroimaging and pharmacological studies which support the importance of glutamate abnormalities in the pathogenesis of social anxiety disorder. In a previous clinical study, an elevate glutamate to creatinine ratio was found in the anterior cortex of social anxiety disorder patients when compared with healthy control subjects.

Ketamine is a potent agonist of the N-methyl-D-aspartate receptor is a major glutamate receptor in the brain. The drug is normally used as an anesthetic because of its dissociative properties. In a multitude of controlled clinical studies, ketamine has proven to be an effective treatment for reducing symptoms of depression and anxiety. Ketamine has produced a rapid antidepressant effect in unipolar and bipolar depression and the effects peak 1-3 days following infusion and is observed long after the drug has been metabolized and excreted by the body.

The results of several studies involving ketamine infusion show the medication may have significant anxiolytic effects. For patients with major depressive disorders or social anxiety disorder, the drug has shown strong and significant reductions in co-morbid anxiety symptoms. If you want to find out more information about how ketamine infusion may work for you, please contact us at 703-844-0184 – NOVA Health Recovery

 

PTSD TREATMENT:

Ketamine is a drug that was developed more than 50 years ago to be used as anesthesia during surgery, and it has also been used as an illicit street drug. Recently, ketamine has been found to be a valuable and extremely effective treatment for depression, anxiety, PTSD, OCD and certain pain disorders, like fibromyalgia.

Our Ketamine treatment center in Bowie MD offer infusions on an outpatient basis and following a consultation with medical staff it can be determined if the medication is appropriate and safe for a person. A patient using ketamine infusion therapy is monitored during the process by a clinical coordinator to ensure a smooth, supportive and successful treatment process.

Because the effects of a ketamine infusion are short-lived, patients will usually receive a series of infusions over a series of 2-3 weeks. Ketamine infusions for PTSD is an off-label use and it means the Food and Drug Administration has not approved the drug for this particular use. However, the drug’s safety and effectiveness have been demonstrated in multiple research studies and off-label prescribing is a common and necessary practice in the medical world.

Unlike most of the common antidepressant medications that may take weeks or months before a patient and doctor can even determine if it works, ketamine infusions yield positive results within hours or days. Many patients will know within the first few hours or days if ketamine is working for them or not. The most common experience when using ketamine infusions is no side effects between treatments, so it is a good option for those with treatment-resistant depression or those who have troublesome side effects from other medications commonly prescribed.

Ketamine Safety and Tolerability In Clinical Trials For Treatment-resistant Depression

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in DepressionA preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department

Ketamine for Depression: Where Do We Go from Here?

A Systematic Review of Ketamine for Complex Regional Pain Syndrome

The Promise of Ketamine For Treatment-resistant Depression: Current Evidence and Future Directions

Ketamine-Induced Optimism: New Hope for the Development of Rapid-Acting Antidepressants

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression

NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses

A review of ketamine in affective disorders:Current evidence of clinical efficacy,limitations of use and pre-clinical evidence on proposed mechanisms of action

Intravenous Ketamine for the Treatment of Mental Health Disorders: A Review of Clinical Effectiveness and Guidelines

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder​

Researchers find new ways of managing clinical and seasonal depression

Areas we Serve:

Maryland (MD):

Bethesda 20814 – Bethesda 20816 – Bethesda 20817 – Chevy Chase 20815 – Colesville 20904 – Cabin John 20815 – Glen Echo 20812 – Gaithersburg 20855 – Gaithersburg 20877- Gaithersburg 20878 – Gaithersburg 20879 – Garrett Park 20896 – Kensington 20895 – Montgomery Village 20886 – Olney 20830 – Olney 20832 – Potomac 20854 – Potomac 20859 – Rockville 20850 – Rockville 20852 – Rockville 20853 – Silver Spring 20903 – Silver Spring 20905 – Silver Spring 20906 – Silver Spring 20910 – Takoma Park 20912 – Wheaton 20902

 

Washington DC:

Crestwood 20011- North Capitol Hill 20002 – Cathedral Heights 20016 – American University Park 20016 – Columbia Heights 20010 – Mount Pleasant 20010 – Downtown 20036 – Dupont Circle 20009 – Logan Circle 20005- Adams Morgan 20009 – Chevy Chase 20015 – Georgetown 20007 – Cleveland Park 20008 – Foggy Bottom 20037 – Rock Creek Park – Woodley Park 20008 – Tenleytown 20016

 

Northern Virginia:

McLean 22101- McLean 22102 – McLean 22106 – Great Falls 22066 – Arlington 22201 – Arlington 22202 – Arlington 22203 – Arlington 22205 – Falls Church 22041 – Vienna 22181 – Alexandria 22314 – 22308 -22306 -22305 -22304  Fairfax – 20191 – Reston – 22009 – Springfield – 22152  22015  Lorton 22199

Fairfax, Va

2303 –  22307 – 22306 – 22309 – 22308 22311 – 22310 – 22312

22315 -22003 – 20120 – 22015 – 22027 20121 – 22031 –  20124

22030 – 22033 – 22032 – 22035 – 22039 22041 – 22043

22042 – 22046 – 22044 – 22060 – 22066 20151 – 22079 – 20153 – 22101

22102 – 20171 – 20170 – 22124 – 22151 22150 – 22153

22152 – 20191 – 20190 – 22181- 20192 22180 – 20194 –  22182

Woodbridge – 22191 – 22192 -22193 -22194 – 22195

Springfield – 22150 – 22151 -22152-22153-22154-22155 -22156 – 22157 -22158 -22159 -22160 – 22161

Front Royal 22630

Warren County 22610 22630 22642 22649

Fredericksburg Va 22401 22402 – 22403 – 22404 -22405 -22406 -22407 -22408 – 22412

Please call Sendi Hair Loss Center now at 703-574-0974 for quality Hair Restoration services in Alexandria, VA.

20105    Aldie      Loudoun County 20106  Amissville            Culpeper County 20107 Arcola   Loudoun County

20108    Manassas            Manassas City 20109       Sudley Springs   Prince William County

20109    Manassas            Prince William County 20110       Manassas            Manassas City

20111    Manassas            Prince William County 20111       Manassas Park  Prince William County

20112    Manassas            Prince William County 20113       Manassas Park  Manassas Park City

20115    Marshall               Fauquier County 20116  Marshall               Fauquier County

20117    Middleburg        Loudoun County 20118  Middleburg        Loudoun County

20119    Catlett  Fauquier County – 20120 Sully Station    Fairfax County

20120    Centreville          Fairfax County – 20121   Centreville          Fairfax County

20122    Centreville          Fairfax County – 20124   Clifton   Fairfax County

20128    Orlean  Fauquier County -20129                Paeonian Springs             Loudoun County

20130    Paris      Clarke County

20131    Philomont           Loudoun County 20132  Purcellville          Loudoun County

20134    Hillsboro              Loudoun County 20134  Purcellville          Loudoun County

20135    Bluemont            Clarke County 20136       Bristow Prince William County

20137    Broad Run           Fauquier County 20138  Calverton            Fauquier County

20139    Casanova             Fauquier County 20140  Rectortown        Fauquier County

20141    Round Hill            Loudoun County 20142  Round Hill            Loudoun County

20143    Catharpin            Prince William County

20144    Delaplane            Fauquier County20146   Ashburn               Loudoun County

20147    Ashburn               Loudoun County 20148  Brambleton        Loudoun County

20148    Ashburn               Loudoun County 20151  Chantilly               Fairfax County

20151    Fairfax  Fairfax County 20152      South Riding       Loudoun County

20152    Chantilly               Loudoun County 20152  Fairfax  Loudoun County

20153    Chantilly               Fairfax County 20153      Fairfax  Fairfax County

20155    Gainesville          Prince William County 20156       Gainesville          Prince William County

20158    Hamilton              Loudoun County 20159  Hamilton              Loudoun County

20160    Lincoln  Loudoun County 20160  Purcellville          Loudoun County

20163    Sterling Loudoun County 20164  Sterling Loudoun County

20165    Potomac Falls    Loudoun County 20165  Sterling Loudoun County

20166    Dulles    Loudoun County 20166  Sterling Loudoun County

20167    Sterling Loudoun County 20168  Haymarket          Prince William County

20169    Haymarket          Prince William County 20170       Herndon              Fairfax County

20171    Oak Hill Fairfax County 20171      Herndon              Fairfax County

20172    Herndon              Fairfax County 20175      Leesburg             Loudoun County

20176    Lansdowne         Loudoun County 20176  Leesburg             Loudoun County

20177    Leesburg             Loudoun County 20178  Leesburg             Loudoun County

20180    Lovettsville         Loudoun County 20181  Nokesville           Prince William County

20182    Nokesville           Prince William County 20184       Upperville           Fauquier County

20185    Upperville           Fauquier County 20186  Warrenton          Fauquier County

20187    New Baltimore  Fauquier County 20187  Vint Hill Farms   Fauquier County 20187  Warrenton          Fauquier County

20188    Vint Hill Farms   Fauquier County 20188  Warrenton          Fauquier County

20190    Reston  Fairfax County 20190      Herndon              Fairfax County

20191    Reston  Fairfax County 20191      Herndon              Fairfax County

20194    Reston  Fairfax County 20194      Herndon              Fairfax County

20195    Reston  Fairfax County 20195      Herndon              Fairfax County

20197    Waterford           Loudoun County 20198  The Plains            Fauquier County

Loudon County:

Loudoun County, VA – Standard ZIP Codes

20105 | 20117 | 20120 | 20129 | 20130 | 20132 | 20135 | 20141 | 20147 | 20148 | 20152 | 20158 | 20164 | 20165 | 20166 | 20175 | 20176 | 20180 | 20184 | 20189 | 20197 | 22066

Ashburn, VA – Standard ZIP Codes
20147 20148
Leesburg, VA – Standard ZIP Codes
20175 20176
Sterling, VA – Standard ZIP Codes
20164 20165 20166

Waterford, VA 20197

Dulles, VA – Standard ZIP Codes
20166 20189
Purcellville, VA – Standard ZIP Codes
20132
Chantilly, VA – Standard ZIP Codes
20151 20152

Mcclean, Va Zip codes: 22043, 22046, 22066,22101, 22102, 22207

 

Depression, ketamine, Uncategorized

KETAMINE | FAIRFAX | ALEXANDRIA | 703-844-0184| KETAMINE THERAPY | KETAMINE AS AN ANTI-DEPRESSANT – NIH -| Dr. Sendi | Ketamine Springfield, Va | Ketamine Loudon | Ketamine for depression | email@novahealthrecovery.com

Leave a comment

NOVA Health Recovery  <<< Ketamine infusion center in Alexandria, Virginia 703-844-0184  – consider ketamine for addiction treatment

CAll 703-844-0184 for an immediate appointment!

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com

Ketamine center in Fairfax, Virginia    << Ketamine infusions

NOVA Health Recovery – KETAMINE SYSTEMS<< Link

 

 

Here is an interesting piece regarding the rapid effects of Ketamine on reversing depression, in specific, making events more pleasurable through modulating the action of Glutamate in the brain.

This article was written by Dr. Zarate:

Ketamine and depression – NIH

Highlight: Ketamine: A New (and Faster) Path to Treating Depression

Two charts show the effect of ketamine or placebo on the Hamilton Depression Rating Scale.

Left: Change in the 21-item Hamilton Depression Rating Scale (HDRS) following ketamine or placebo treatment.
Right: Proportion of responders showing a 50 percent improvement on the HDRS following ketamine or placebo treatment.34

Source: Carlos Zarate, M.D., Experimental Therapeutics and Pathophysiology Branch, NIMH

The most commonly used antidepressants are largely variations on a theme; they increase the supply within synapses of a class of neurotransmitters believed to play a role in depression. While these drugs relieve depression for some, there is a weeks-long delay before they take effect, and some people with “treatment-resistant” depression do not respond at all.

The delay in effectiveness has suggested to scientists that the medication-induced changes in neurotransmitters are several steps away from processes more central to the root cause of depression. One possibility for a more proximal mechanism is glutamate, the primary excitatory, or activating, neurotransmitter in the brain. Preliminary studies suggested that inhibitors of glutamate could have antidepressant-like effects, and in a seminal clinical trial, the drug ketamine—which dampens glutamate signaling—lifted depression in as little as 2 hours in people with treatment-resistant depression.34

The discovery of rapidly acting antidepressants has transformed our expectations—we now look for treatments that will work in 6 hours rather than 6 weeks. But ketamine has some disadvantages; it has to be administered intravenously, the effects are transient, and it has side effects that require careful monitoring. However, results from clinical studies have confirmed the potential of the glutamate pathway as a target for the development of new antidepressants. Continuing research with ketamine has provided information on biomarkers that could be used to predict who will respond to treatment.35Clinical studies are also testing analogs of ketamine in an effort to develop glutamate inhibitors without ketamine’s side effects that can then be used in the clinic.36 Ketamine may also have potential for treating other mental illnesses; for example, a preliminary clinical trial reported that ketamine reduced the severity of symptoms in patients with PTSD. 37 Investigation of the role of glutamate signaling in other illnesses may provide the impetus to develop novel therapies based on this pathway.

One of the imperatives of clinical research going forward will be to demonstrate whether the ability of a compound to interact with a specific brain target is related to some measurable change in brain or behavioral activity that, in turn, can be associated with relief of symptoms. In a study of ketamine’s effects in patients in the depressive phase of bipolar disorder, ketamine restored pleasure-seeking behavior independent from and ahead of its other antidepressant effects. Within 40 minutes after a single infusion of ketamine, treatment-resistant depressed bipolar disorder patients experienced a reversal of a key symptom—loss of interest in pleasurable activities—which lasted up to 14 days.38 Brain scans traced the agent’s action to boosted activity in areas at the front and deep in the right hemisphere of the brain. This approach is consistent with the NIMH’s RDoC project, which calls for the study of functions—such as the ability to seek out and experience rewards—and their related brain systems that may identify subgroups of patients with common underlying dysfunctions that cut across traditional diagnostic categories.

The ketamine story shows that in some instances, a strong and repeatable clinical outcome stemming from a hypothesis about a specific molecular target (e.g., a glutamate receptor) can open up new arenas for basic research to explain the mechanisms of treatment response; basic studies can, in turn, provide data leading to improved treatments directed at that mechanism. A continuing focus on specific mechanisms will not only provide information on the potential of test compounds as depression medications, but will also help us understand which targets in the brain are worth aiming at in the quest for new therapies.

PET scan data superimposed on anatomical MRI

PET scans revealed that ketamine rapidly restored bipolar depressed patients’ ability to anticipate pleasurable experiences by boosting activity in the dorsal anterior cingulate cortex (yellow) and related circuitry. Picture shows PET scan data superimposed on anatomical MRI.38

References

1 Analysis based on: US Burden of Disease Collaborators. (2013). The state of US health, 1990–2010: Burden of diseases, injuries, and risk factors.JAMA, 310(6), 591–608. (PubMed ID: 23842577)

2 Walker E. R., McGee R. E., & Druss B. G. (2015). Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis.JAMA Psychiatry, 72(4), 334-341. (PubMed ID: 25671328)

3 Centers for Disease Control and Prevention (CDC). (2013). Web-based Injury Statistics Query and Reporting System(WISQARSTM). Atlanta, GA: National Center for Injury Prevention and Control, CDC.

4 Insel, T. R. (2008). Assessing the economic cost of serious mental illness.American Journal of Psychiatry, 165(6), 663–665. (PubMed ID: 18519528)

5 Soni, A. (2009). The five most costly conditions, 1996 and 2006: Estimates for the US civilian noninstitutionalized population (Statistical Brief# 248). Rockville, MD: Agency for Healthcare Research and Quality.

6 Murray, F. E. (2012). Evaluating the role of science philanthropy in American research universities (Working Paper No. 18146). Cambridge, MA: National Bureau of Economic Research.

7 Terry, S. F. & Terry, P. F. (2011). Power to the people: Participant ownership of clinical trial data. Science Translational Medicine, 3(69), 69cm3. (PubMed ID: 21307299)

8 Calculated from: McGrath, J., Saha, S., Chant, D., & Welham, J. (2008). Schizophrenia: A concise overview of incidence, prevalence, and mortality. Epidemiologic Reviews, 30(1), 67–76. (PubMed ID: 18480098)

9 Addington, J., Heinssen, R. K., Robinson, D. G., Schooler, N. R., Marcy, P., Brunette, M. F., … & Kane, J. M. (2015). Duration of untreated psychosis in community treatment settings in the United States. Psychiatric Services: A Journal of the American Psychiatry Association. [Epub ahead of print] (PubMed ID: 25588418)

10 Marshall, M., Lewis, S., Lockwood, A., Drake, R., Jones, P., & Croudace, T. (2005). Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: A systematic review. Archives of General Psychiatry, 62(9), 975–983. (PubMed ID: 16143729)

11 Clementz, B., Sweeney, J., Hamm J., Ivleva, E., Ethridge, L., Pearlson, G., … & Tamminga C. (2016). Identification of distinct psychosis biotypes using brain-based biomarkers.American Journal of Psychiatry. (PubMed ID: 26651391)

12 Hakamata, Y., Lissek, S., Bar-Haim, Y., Britton, J. C., Fox, N. A., Leibenluft, E., … & Pine, D. S. (2010). Attention bias modification treatment: A meta-analysis toward the establishment of novel treatment for anxiety.Biological Psychiatry, 68(11), 982–990. (PubMed ID: 20887977)

13 Britton, J. C., Bar‐Haim, Y., Carver, F. W., Holroyd, T., Norcross, M. A., Detloff, A., … & Pine, D. S. (2012). Isolating neural components of threat bias in pediatric anxiety.Journal of Child Psychology and Psychiatry, 53(6), 678–686. (PubMed ID: 22136196)

14 Lent, R., Azevedo, F. A., Andrade‐Moraes, C. H., & Pinto, A. V. (2012). How many neurons do you have? Some dogmas of quantitative neuroscience under revision. European Journal of Neuroscience, 35(1), 1–9. (PubMed ID: 22151227)

15 Zhang, Y., Pak, C., Han, Y., Ahlenius, H., Zhang, Z., Chanda, S., … & Südhof, T. C. (2013). Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron, 78(5), 785–798. (PubMed ID: 23764284)

16 Krey, J. F., Paşca, S. P., Shcheglovitov, A., Yazawa, M., Schwemberger, R., Rasmusson, R., & Dolmetsch, R. E. (2013). Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. Nature Neuroscience, 16(2), 201–209. (PubMed ID: 23313911)

17 Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium. (2011). Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43(10), 969–976. (PubMed ID: 21926974)

18 Schizophrenia Working Group of the Psychiatric Genomics Consortium. (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421–427. (PubMed ID: 25056061)

19 Nishimasu, H., Ran, F.A., Hsu, P. D., Konermann, S., Shehata, S. I., Dohmae, N., … & Nureki, O. (2014). Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell, 156(5), 935–949. (PubMed ID: 24529477)

20 Chung, K., Wallace, J., Kim, S. Y., Kalyanasundaram, S., Andalman, A. S., Davidson, T. J., … & Deisseroth, K. (2013). Structural and molecular interrogation of intact biological systems. Nature, 497(7449), 332–337. (PubMed ID: 23575631)

21 Colantuoni, C., Lipska, B. K., Ye, T., Hyde, T. M., Tao, R., Leek, J. T., … & Kleinman, J. E. (2011). Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature, 478(7370), 519–523. (PubMed ID: 22031444)

22 Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., … & Šestan, N. (2011). Spatio-temporal transcriptome of the human brain. Nature, 478(7370), 483–489. (PubMed ID: 22031440)

23 Li, G., Wang, L., Shi, F., Lyall, A. E., Lin, W., Gilmore, J. H., & Shen, D. (2014). Mapping longitudinal development of local cortical gyrification in infants from birth to 2 years of age. The Journal of Neuroscience, 34(12), 4228–4238. (PubMed ID: 24647943)

24 Hill, J., Inder, T., Neil, J., Dierker, D., Harwell, J., & Van Essen, D. (2010). Similar patterns of cortical expansion during human development and evolution. Proceedings of the National Academy of Sciences, 107(29), 13135–13140. (PubMed ID: 20624964)

25 Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., … & Jones, A.R. (2012). An anatomically comprehensive atlas of the adult human brain transcriptome. Nature,489(7416), 391–399. (PubMed ID: 22996553)

26 Miller, J. A., Ding, S. L., Sunkin, S. M., Smith, K. A., Ng, L., Szafer, A., … & Lein, E.S. (2014). Transcriptional landscape of the prenatal human brain. Nature, 508(7495), 199–206. (PubMed ID: 24695229)

27 Willsey, A. J., Sanders, S. J., Li, M., Dong, S., Tebbenkamp, A. T., Muhle, R. A., … & State, M. W. (2013). Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell, 155(5), 997–1007. (PubMed ID: 24267886)

28 Gulsuner, S., Walsh, T., Watts, A. C., Lee, M. K., Thornton, A. M., Casadei, S., … & McClellan, J. M. (2013). Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell, 154(3), 518–529. (PubMed ID: 23911319)

29 Whiteford, H. A., Degenhardt, L., Rehm, J., Baxter, A. J., Ferrari, A. J., Erskine, H. E., … & Vos, T. (2013). Global burden of disease attributable to mental and substance use disorders: Findings from the Global Burden of Disease Study 2010. Lancet, 382(9904), 1575–1586. (PubMed ID: 23993280)

30 Insel, T. R. (2012). Next-generation treatments for mental disorders. Science Translational Medicine, 4(155), 155ps19. (PubMed ID: 23052292)

31 Hyman, S. E. (2012). Revolution stalled. Science Translational Medicine, 4(155), 155cm11. (PubMed ID: 23052291)

32 Biomarkers Definitions Working Group (2001). Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clinical Pharmacology and Therapeutics, 69(3), 89–95. (PubMed ID: 11240971)

33 McGrath, C. L., Kelley, M. E., Holtzheimer, P. E., Dunlop, B. W., Craighead, W. E., Franco, A. R., … & Mayberg, H. S. (2013). Toward a neuroimaging treatment selection biomarker for major depressive disorder. JAMA Psychiatry, 70(8), 821–829. (PubMed ID: 23760393)

34 Zarate Jr, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., … & Manji, H. K. (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of General Psychiatry, 63(8), 856–864. (PubMed ID: 16894061)

35 Cornwell, B. R., Salvadore, G., Furey, M., Marquardt, C. A., Brutsche, N. E., Grillon, C., & Zarate Jr, C. A. (2012). Synaptic potentiation is critical for rapid antidepressant response to ketamine in treatment-resistant major depression. Biological Psychiatry, 72(7), 555–561. (PubMed ID: 22521148)

36 Zarate Jr, C. A., Mathews, D., Ibrahim, L., Chaves, J. F., Marquardt, C., Ukoh, I., … & Luckenbaugh, D. A. (2013). A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression. Biological Psychiatry,74(4), 257–264. (PubMed ID: 23206319)

37 Feder, A., Parides, M. K., Murrough, J. W., Perez, A. M., Morgan, J. E., Saxena, S., … & Charney, D. S. (2014). Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: A randomized clinical trial. JAMA Psychiatry, 71(6), 681-688. (PubMed ID: 24740528)

38 Lally N., Nugent A. C., Luckenbaugh D. A., Ameli R., Roiser J. P., & Zarate C. A. (2014). Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression.Translational Psychiatry. [E-pub ahead of print] (PubMed ID: 25313512)

39 Smith, M., Saunders, R., Stuckhardt, L., & McGinnis, J. M. (Eds.). (2013). Best care at lower cost: The path to continuously learning health care in America. Washington, DC: National Academies Press. (PubMed ID: 24901184)

40 Chambers, D.A., Glasgow, R.E., & Stange, K.C. (2013). The dynamic sustainability framework: Addressing the paradox of sustainment amid ongoing change.Implementation Science, 8(1), 117. (PubMed ID: 24088228)

41 Ben-Zeev, D., Schueller, S. M., Begale, M., Duffecy, J., Kane, J. M., & Mohr, D. C. (2015). Strategies for mHealth research: Lessons from 3 mobile intervention studies. Administration and Policy in Mental Health and Mental Health Services Research, 42(2), 157-167. (PubMed ID: 24824311)

42 Mohr, D. C., Burns, M. N., Schueller, S. M., Clarke, G., & Klinkman, M. (2013). Behavioral intervention technologies: Evidence review and recommendations for future research in mental health. General Hospital Psychiatry,35(4), 332–338. (PubMed ID: 23664503)

43 Aitken, M., & Gauntlett, C. (2013). Patient apps for improved healthcare from novelty to mainstream.Parsippany, NJ: IMS Institute for Healthcare Informatics.

https://www.nimh.nih.gov/about/strategic-planning-reports/highlights/index.shtml

I also threw in a reprint of the article from NIH regarding strategic principle #2 to find biomarkers of mental health disorders:

Highlight: GPS for the Brain? BrainSpan Atlas Offers Clues to Mental Illnesses

Image from BrainSpan Atlas shows the location and expression level of the gene TGIF1 in a brain from 21 weeks postconception.

The recently created BrainSpan Atlas of the Developing Human Brain incorporates gene activity or expression (left) along with anatomical reference atlases (right) and neuroimaging data (not shown) of the mid-gestational human brain. In this figure, the location and expression level of the gene TGIF1 is shown in a brain from 21 weeks postconception.

Source: Allen Institute for Brain Science

Technologies have come a long way in mapping the trajectory of mental illnesses. Early efforts provided information on anatomical changes that occur over the course of development. In a step that has been hailed as providing a “GPS for the brain,” the BrainSpan Atlas of the Developing Brain, a partnership among the Allen Institute for Brain Science, Yale University, the University of Southern California, and NIMH—has created a comprehensive 3-D brain blueprint.25 The Atlas details not only the anatomy of the brain’s underlying structures, but also exactly where and when particular genes are turned on and off during mid-pregnancy—a time during fetal brain development when slight variations can have significant long-term consequences, including heightened risk for autism or schizophrenia.26 Knowledge of the location and time when a particular gene is turned on can help us understand how genes are disrupted in mental illnesses, providing important clues to future treatment targets and early interventions. The Atlas resources are freely available to the public on the Allen Brain Atlas data portal. Already, the BrainSpan Atlas has been used to identify genetic networks relevant to autism and schizophrenia.27,28 In both of these studies, the fetal pattern of gene expression revealed relationships that could not be detected by studying gene expression in the adult brain. As most mental illnesses are neurodevelopmental, mapping where and when genes are expressed in the brain provides a fundamental atlas for charting risk.

Brain Atlas NIH