Brain Imaging Predicts Psychotherapy Success in Patients with Social Anxiety Disorder

Posted on July 6, 2016 by JmaC

February 1, 2013 • Science Update

Treatment for social anxiety disorder or social phobia has entered the personalized medicine arena—brain imaging can provide neuromarkers to predict whether traditional options such as cognitive behavioral therapy will work for a particular patient, reported a National Institute of Mental Health (NIMH)-funded study that was published in the January 2013 issue of JAMA Psychiatry.

Background

Social anxiety disorder (SAD)— the fear of being judged by others and humiliated— is the third most prevalent psychiatric disorder in Americans, after depression and alcohol dependence, according to the National Comorbidity Survey, a U.S. poll on mental health. This fear can be so strong that it interferes with daily life activities like going to work or school. If left untreated, some sufferers use alcohol, food, or drugs to reduce the fear at social events, which often leads to other disorders such as alcoholism, eating disorders, and depression. The NIMH claims that 6.8 percent of U.S. adults and 5.5 percent of 13- to 15-year-olds, the age of onset for this chronic disorder, are annually afflicted.

Although psychotherapy and drugs, such as antidepressants and benzodiazepines, exist as treatments for SAD, current behavioral measures poorly predict which would work better for individual patients. “Half of social anxiety disorder patients have satisfactory response to treatment. There is little evidence about which patient would benefit from a particular form of treatment,” said John D. Gabrieli, Ph.D., lead author of the study. “Currently, there is no rational basis for prescribing one treatment over the other. Which treatment a patient gets depends on whom they see.”

Enter personalized medicine, the use of genetic or other biological markers to tailor treatments to those who would actually benefit from them, thus sparing the expense and side effects for those who would not. Brain imaging could identify neuromarkers or targeted areas of the brain that could one day optimize treatment for individual patients. Neuromarkers are being used in other areas of mental illness, for instance, to predict the onset of psychosis in schizophrenia and the likelihood of relapse in drug addiction.

In this study, Gabrieli, at the Massachusetts Institute of Technology in Cambridge, and his colleagues, used functional magnetic resonance imaging (fMRI) in 39 SAD patients before a 12-week course of cognitive behavioral therapy. The patients viewed angry versus neutral faces and scenes while undergoing fMRI examination (see first slide). Compared to neutral faces, angry faces convey disapproval and are likely to prompt excessive fear responses and negative connotations in SAD patients; cognitive behavioral therapy teaches these patients ways to downregulate their responses. The patients’ brain images were then compared to their scores on a conventional clinical measure, the Liebowitz Social Anxiety Scale (LSAS), a questionnaire which they took before and after therapy completion.

Results of the Study

SAD patients responded more to the images of faces and not scenes, which is characteristic for the social basis of this disorder. Patients whose brains reacted strongly to the facial images before treatment benefitted more from the therapy than those who reacted to these the least (see second slide). Specifically, changes in two occipitotemporal brain regions—areas involved in early processing of visual cues such as faces—correlated with positive cognitive behavioral therapy outcome. These neuromarkers predicted treatment outcome better than the currently used LSAS.

Significance

This study is the first of its kind to use neuroimaging to predict treatment response in SAD patients. Neuromarkers may become a practical clinical tool to guide the selection of optimal treatments for individual patients. Integration of neuromarkers with genetic, behavioral, and other biomarkers is likely to further refine the prediction.

What’s Next

A larger study comparing people with SAD with normal participants is needed to verify the results. fMRI studies using other facial expressions (disgust or fear) might be better predictors. Studies that look at other treatment options, such as drugs, are also needed to confirm which treatment is optimal.

social anxeity disorder - fMRI image examples

Researchers asked patients with social phobia to undergo functional magnetic resonance imaging (fMRI) while viewing images of neutral versus angry faces and scenes. The patients’ brains showed more activity when they viewed the faces.

Source: Gabrieli Lab, MIT

possible neuromarkers for social phobia

Patients with social phobia whose brains “lit” up the most, particularly in two regions towards the back of the brain that process what we see, responded the best to psychotherapy.

Source: Gabrieli Lab, MIT

Reference

Doehrmann O, Ghosh SS, Polli FE, Reynolds GO, Horn F, Keshavan A, Triantafyllou C, Saygin ZM, Whitfield-Gabrieli S, Hofmann SG, Pollack M, Gabrieli JD. Predicting Treatment Response in Social Anxiety Disorder from Functional Magnetic Resonance Imaging. JAMA Psychiatry. January 2013. 70(1):87–97.

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Pilot Study Will Test New Treatment to Reduce Self-Harm in Borderline Personality Disorder

Posted on July 6, 2016 by JmaC

NIMH recently funded Kim Gratz, Ph.D., University of Mississippi Medical Center, and colleagues to continue to test a new group therapy to help women with borderline personality disorder reduce self-harm behaviors and to improve functioning.

Borderline personality disorder is a serious mental illness noted by unstable moods, behavior and relationships, affecting around 1.4 percent of adults in the United States1 This disorder is also commonly associated with deliberate self-harm behaviors, such as cutting, burning, hitting, head banging, and other acts that injure oneself.

Unlike suicide attempts, self-harm behaviors do not arise from a desire to die, although some behaviors may be life-threatening.

“People with borderline personality disorder often carry out self-harm to regulate their emotions, relieve emotional distress, or distract themselves from internal pain,” explains Dr. Gratz. “Because self-harm works so well in the short-term to relieve emotional distress, it can be very difficult to stop.”

Studies have shown that dialectical behavioral therapy and mentalization-based treatment are effective for treating self-harm among people with borderline personality disorder. Dialectical behavior therapy teaches skills to manage emotions, tolerate distress, pay attention to what is happening in the here and now, and improve relationships. Mentalization-based treatment focuses on helping people to recognize that their own behaviors, and the behaviors of people around them, arise from internal, mental states such as thoughts, feelings, and desires. However, these treatments are difficult to implement in real-world treatment settings because they require specialized training, as well as multiple hours of treatment per week for an extended period of time (at least one year, and often longer). As a result, these treatments are not readily available to people living with borderline personality disorder in many communities.

To address this gap, Gratz and colleagues have developed a targeted, short-term, emotion regulation group therapy. This therapy focuses on teaching people healthy ways of managing their emotions (for example, by accepting their emotions) and is intended for people who are already receiving individual therapy in the community. Early tests suggest that this group therapy may be helpful as an add-on treatment.

In the first phase of their two-phase study, the researchers will use this acceptance-based emotion regulation group therapy to treat 24 women who have borderline personality disorder and engage in self-harm behaviors. The researchers will refine the treatment based on these initial findings. Then, during the second phase, 60 self-harming women with borderline personality disorder will be randomly assigned either to receive the group therapy immediately or to wait 14 weeks before receiving this add-on treatment. All participants will also continue in their own original course of treatment. Delaying the add-on treatment in the latter group will allow the researchers to study differences in outcomes that result from treatment.

The researchers expect to use the results of this pilot study to develop a larger-scale treatment outcome study.

Reference

1 Lenzenweger MF, Lane MC, Loranger AW, Kessler RC. DSM-IV personality disorders in the National Comorbidity Survey Replication . Biol Psychiatry. 2007 Sep 15;62(6):553-64.

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Coordinated Treatment Approach Improves Anxiety Symptoms

Posted on July 6, 2016 by JmaC

A coordinated, multi-component treatment approach was more effective in treating anxiety disorders than usual care found in primary care settings, according to an NIMH-funded study published May 19, 2010, in a special issue of the Journal of the American Medical Association devoted to mental health.

Background

Research has found that a collaborative care approach, in which one care manager coordinates a team of treatment providers, is effective in treating depression. However, research is limited on whether the same type of approach could work to treat anxiety disorders, which are commonly treated in primary care settings.

In response, Peter Roy-Byrne, M.D., of the University of Washington Seattle, and colleagues designed a flexible collaborative treatment model for anxiety disorders—Coordinated Anxiety Learning and Management (CALM)—and compared it to usual care. CALM included cognitive behavioral therapy (CBT) that was tailored to any one of four anxiety disorders—panic disorder, generalized anxiety disorder, social anxiety disorder or post traumatic stress disorder. It also included strategies to improve medication delivery and adherence. Of the 1,004 participants recruited from 17 primary care clinics in four U.S. cities, half were randomized to CALM and were allowed to choose whether they received CBT, medication, or both. The other participants were referred to usual care which could include medication, brief counseling with a physician, or referral to a mental health specialist. All participants were diagnosed with at least one of the four anxiety disorders addressed in the CBT program.

CALM participants received their initial treatment for 10 to 12 weeks. Those who still had symptoms after 12 weeks could receive additional CBT or medication, or both. They then received monthly follow-up phone calls to reinforce CBT skills or medication management advice for up to a year.

CALM relied on a computerized program to help train care managers in CBT techniques and ensure consistency of care. The computer program employed CBT principles common to all anxiety disorders, but included specific techniques designed to address the four anxiety disorders in the study, thus allowing for personalized treatment.

Care managers also encouraged participants to stay in treatment and monitored their reactions to medication, relaying any observations and suggestions for changes to the primary care provider. CALM tracked participants’ progress and outcomes through a web-based monitoring system as well.

Results of the Study

Participants in the CALM group showed significantly greater symptom improvement than those receiving usual care. After 12 months, about 63.6 percent receiving CALM had responded to treatment compared to 44.7 percent in usual care, and 51.5 percent receiving CALM had remitted compared to 33 percent in usual care.

CBT appeared to be the most popular treatment choice among those in the CALM group—57 percent chose CBT and medication combination treatment, and 34 percent chose CBT-only treatment, while 9 percent chose medication-only treatment. This preference is consistent with research that finds those with anxiety disorders tend to favor psychosocial treatment approaches over medication to treat their illness, said the researchers.

Significance

Because CALM included flexible treatment options, targeted multiple anxiety disorders, and was effective across a range of patients and clinics, it is broadly applicable in primary care settings. It could serve as a model for developing effective collaborative care of people with anxiety disorders as well as those with coexisting psychiatric disorders like depression, a situation commonly found in clinical settings.

What’s Next

Research is needed to determine how the strategy could best be implemented in primary care settings. In addition, a cost analysis of CALM is needed to determine whether it is a financially feasible option for payers and clinical settings.

Reference

Roy-Byrne P, Craske MG, Sullivan G, Rose RD, Edlund MJ, Lang AJ, Bystritsky A, Welch SS, Chavira DA, Golinelli D, Campbell-Sills, L, Sherbourne CD, Stein MB. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial.Journal of the American Medical Association. 19 May 2010. 303(19).

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A BRIGHT Technological Future for Mental Health Trials

Posted on July 6, 2016 by JmaC

The BRIGHTEN study

February 19, 2016 • Science Update

Playing games, watching movies, and paying bills through smartphones and tablets has become commonplace. Americans are used to doing almost everything through the technology in their pockets. Is mobile mental health research the next frontier in this smartphone revolution? Based on Dr. Patricia Areán’s  pioneering BRIGHTEN study, research via smartphone app is already a reality.

The BRIGHTEN study was remarkable because it used technology to both deliver treatment interventions and also to actually conduct the trial. In other words, the research team used technology to recruit, screen, enroll, treat, and assess participants.  BRIGHTEN was especially remarkable because the study showed that technology is an efficient way to pilot test promising new treatments.

Areán’s goal was to see if it was possible to do a randomized controlled trial (RCT) using nothing but mobile devices. An RCT is a study in which participants are randomly assigned to different therapies so that researchers can compare their effectiveness. Areán wanted to know if people would agree to participate in a mobile depression study, if a mobile study would be affordable, and if people would continue to use the mobile therapies.  Areán’s findings suggest that it is possible to recruit a large number of participants in a short amount of time. She also found that it was possible to conduct a study for minimal cost.  However, keeping participants interested in the study was more challenging.

Finding Participants

Areán and her team used three methods to recruit people for the BRIGHTEN depression study. They placed ads in city buses, newspapers, and on Craigslist across the country. They used ads on Facebook and Twitter, as well as GoogleAdwords, which pushed ads out to people using the Internet. The research team hoped to find 150 participants. They reached that goal in one week, which prompted the team to apply for an extension of the study.

A Model of the U.S.

Five months later, the team had more than 2,900 participants. The group was ethnically similar to the 2013 U.S. Census. In addition, participants represented people from 8 of the 15 most rural states. This diversity and the ability to reach underserved populations was a notable accomplishment for the BRIGHTEN study.

Participating

People responding to the BRIGHTEN ads were directed to the study’swebsite . Those who were interested could answer questions about their mobile devices, watch a consent video, and respond to questions that showed they understood the details of the study. After the consent process, visitors took a quiz to see if they were eligible for the study. Participants were randomly assigned to one of three depression treatments and then watched a video on how to download their treatment app. Each participant had a customized dashboard for monitoring study progress. Participants enrolled for 12 weeks and were asked to use the app daily, as well as complete monthly assessments. The apps provided a depression intervention and also collected data on participants’ social behavior (number of texts sent, places visited, etc.). Participants were compensated for being part of the study.

The Cost

Typical RCTs for treating depression involve participants working “face-to-face” with a therapist. These traditional, in-person RCTs can be very expensive and may take 3-5 years to recruit enough participants. Finding people who represent the population of the U.S. can be challenging and expensive. For example, it can be difficult to recruit people in rural New Mexico if the study is based on the East Coast. The BRIGHTEN study easily recruited people from all over the country in a very cost-effective way. As a result, the BRIGHTEN study cost less than most studies of the same size.

Staying the Course

Not all participants stayed with the study for the full 12 weeks: 66% completed four weeks, 50% completed 8 weeks, and 41% finished the 12-week assessment. Of course, not all research participants complete traditional psychotherapy trials that involve conventional, face-to-face therapy; however, dropout rates seem to be lower in trials that involve psychotherapy with some human contact.  In more traditional psychotherapy trials, dropout rates vary but appear to average around 20%.  In studies that involve computer-administered therapy for depression, dropout rates appear to be lower among psychotherapy conditions that include at least some human contact.

Results

The research team is still analyzing data to determine how well the apps treated depression and if one app was better than the others. However, early results show all three apps had a significant impact on mood and disability over time.

Next Steps

The BRIGHTEN study was not the first to use apps or mobile technology as part of a research project. However it did show that mobile technology is a successful way to recruit participants, reach a wide section of the population, and provide depression-oriented interventions. As more and more studies use app-based treatments as part of their research, finding ways to keep participants interested in using those interventions will be an important next step.

Learn more

Dr. Patricia Areán is professor in Psychiatry at University of Washington & co-director of the BRIGHTEN Center. Dr. Areán is a licensed clinical psychologist and mental health researcher. She runs several clinical trials, and has served on health committees, including the Institute of Medicine committee for setting standards for psychosocial interventions and the National Advisory Council to the National Institute of Mental Health.

Dr. Areán’s paper was published in the January issue of BMJ

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Studies Refine Understanding of Treatments for Bipolar Disorder

Posted on July 6, 2016 by JmaC

Two new studies provide additional details on best practices for treating people with bipolar disorder, a sometimes debilitating illness marked by severe mood swings between depression and mania. The two studies are part of the NIMH-funded Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Both were published in the September 2007 issue of the American Journal of Psychiatry.

Antidepressants provide no added benefit for people with mixed symptoms, and may worsen existing mania

Among STEP-BD participants who experienced manic symptoms while also in the midst of a depressive episode, those who received antidepressant medication along with a mood stabilizer recovered no faster than those who received a mood stabilizer plus placebo (sugar pill). The results, reported by Joseph Goldberg, M.D, of the Mount Sinai School of Medicine, and colleagues, are consistent with the March 2007 STEP-BD results that indicated a mood stabilizer alone appears to be just as effective as a mood stabilizer plus antidepressant for treating bipolar patients in a major depressive episode.

Moreover, Goldberg and colleagues found that at the three-month follow-up, manic symptoms were more severe among those who had received the antidepressant, compared to those who had received the placebo. Hence, the researchers caution that adjunctive antidepressant medication may actually exacerbate existing manic symptoms.

Intensive psychotherapies improve relationships and life skills

STEP-BD participants who received intensive psychotherapy in addition to medication reported better life satisfaction and better relationship skills than those who received only brief therapy and medication. However, patients in intensive psychotherapy fared no better in vocational skills.

David Miklowitz, PhD., of the University of Colorado, and colleagues evaluated participants’ improvements in relationship, life and work skills over a nine-month period of psychotherapy. Participants received one of three types of psychotherapy:

  • Family-focused therapy (FFT), which required the participation and input of participants’ family members and focused on enhancing family coping with the illness, communication, and problem-solving.
  • Cognitive behavioral therapy (CBT), which focused on helping the person understand distortions in thinking and activity, and learn new ways of coping with the illness.
  • Interpersonal and social rhythm therapy (IPSRT), which focused on helping the participant stabilize his or her daily routines and sleep/wake cycles, and solve key relationship problems.

All three therapies incorporated ways to overcome life challenges, such as finding a place to live, finding a satisfying job, or improving personal finances. They also taught participants strategies for managing mood states that interfere with enjoyment of activities.

Previous STEP-BD results reported in April 2007 revealed that those participants who received any of the three intensive psychotherapies recovered from depression faster and stayed well longer than those who received a brief, three-session educational program. In this follow-up study, the researchers found that although relationship skills improved and participants felt more satisfied with life overall, they reported little or no improvement in their work functioning.

Miklowitz and colleagues suggest that a different approach that targets specific vocational skills may be necessary. For example, certain vocational rehabilitation programs designed for people with schizophrenia may be adapted to the needs of people with bipolar disorder.

Colleen Labbe

 

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Mood Disorders Predict Later Substance Abuse Problems Mania symptoms and bipolar disorder II more likely to lead to substance abuse than depression

Posted on July 6, 2016 by JmaC

anuary 9, 2008 • Science Update

People with manic symptoms and bipolar disorder type II are at significant risk of later developing an alcohol abuse or dependence problem, a long-term study conducted in Switzerland confirms. The study was published in the January 2008 issue of the Archives of General Psychiatry.

Extensive research using retrospective reports has demonstrated a clear association between mood disorders and substance abuse. But few prospective long-term studies have been able to show evidence of this.

Kathleen Merikangas, Ph.D., of the NIMH Mood and Anxiety Disorders Program, collaborated with colleagues to follow 591 people (292 men and 299 women) over two decades, beginning in 1978 when the participants were 19 or 20 years old. The participants were interviewed six times between 1979 and 1999.

By 1993, almost 10 percent met criteria for major depression. Although bipolar disorder type I was very rare, 4 percent met criteria for bipolar disorder II—a milder form of the disorder. In addition, 24 percent had symptoms of mania but did not meet specific criteria for bipolar disorder.

By 1999, when participants were about 40 years old, 18 percent met criteria for alcohol abuse or dependence problems, while 8 percent met criteria for cannabis (marijuana) abuse and 3 percent met criteria for benzodiazepine abuse.

Merikangas and colleagues found that people who showed symptoms of mania, but who did not meet criteria for bipolar disorder, were at significantly greater risk for later developing an alcohol abuse or dependence problem. Those with bipolar disorder II were even more at risk of developing an alcohol problem or benzodiazepine abuse problem. Major depression was associated only with developing a benzodiazepine abuse problem among this population.

“The findings confirm the link between mood disorders and substance abuse or dependence problems,” said Dr. Merikangas. “They also suggest that earlier detection of bipolar symptoms could help to prevent consequent substance abuse problems.”

The study was known as the Zurich Cohort Study.

Reference

Merikangas, KR, Herrell R, Swendsen J, Rossler W, Ajdacic-Gross V, Angst J. Specificity of bipolar spectrum conditions in the comorbidity of mood and substance abuse disorders . Archives of General Psychiatry. 2008;65(1): 47-52.

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Faster-Acting Medications for Bipolar Disorder’s Manic Phase May Be Feasible

Posted on July 6, 2016 by JmaC

New Research Pinpoints Potential Molecular Target in Brain Cells

January 23, 2008 • Science Update

Scientists may be able to develop faster-acting medications for the manic phase of bipolar disorder, new research shows.

Current medications take several days to weeks to work, during which the extreme mood shifts of the disease may cause patients to engage in harmful behaviors, such as risky health behaviors or spending sprees. Bipolar disorder, also called manic-depressive illness, affects about 5.7 million Americans age 18 and older in any given year.

The faster medications would be aimed more directly at a molecular site on brain cells that current medications, such as lithium and valproate, reach through a slower, roundabout route. By targeting the site with a protein fragment they designed, NIMH scientists reduced manic-like behaviors and associated brain changes in rats. Jing Du, Ph.D., Husseini Manji, M.D., and colleagues published their results in the January 2 issue of The Journal of Neuroscience.

With further research, the molecular site could become a target for new medications for humans, or could point the way to other targets for new treatments, the scientists say. The site is an amino acid, serine 845 (S845), in the GluR1 subunit of the AMPA receptor. (See “About the Science.”).

The researchers also pinpointed a region of the brain that appears to be involved in mania: the CA1 region of the hippocampus, which feeds stored memories to the prefrontal cortex, the “active-thinking” part of the brain.

About the Science

The molecular site scientists targeted with the protein fragment they designed is a protein building block – the amino acid S845 – of a receptor on brain cells. More precisely, S845 is a building block in one of several subunits that come together to form the receptor, called AMPA. Receptors are proteins, on or in cells, that affect cell function when brain chemicals bind to them.

AMPA receptors play a crucial role in brain cells. They receive chemical signals from other cells, helping trigger electrical impulses through which the cells communicate. The AMPA receptors are part of a larger system in the brain, the glutamatergic system, which is thought to become over-active in mania. Scientists have evidence that current medications work by dampening this system.

Location, Location, Location

One of the subunits of the AMPA receptor, GluR1, plays a prominent role in this study. GluR1 subunits and other subunits have to be in the right place, at the right time, to join together to form AMPA receptors.

Under normal circumstances, the subunits that eventually will form the receptor can quickly change their locations in the cell, as needed, through chemical reactions. Current medications for mania also cause therapeutic changes in the locations of the subunits and the receptor. For example, they reduce excess levels of the GluR1 subunit on the cell surface.

But current medications take time to affect this process. Scientists suspect that this is because the molecular targets the medications initially act on must have trickle-down effects that eventually reach crucial targets – perhaps days or weeks later.

In a series of experiments, NIMH scientists showed thatthe S845 building block of the GluR1 subunit may be a crucial target. Targeting S845 alone brought about several positive changes in the locations of GluR1 and another important subunit of the AMPA system, GluR2, in rat-brain cells, and corrected behaviors in rats made manic with amphetamines.

Why S845?

The scientists took aim at S845 in the GluR1 subunit because they suspected that the roundabout route current medications take to relieve mania symptoms eventually leads there.

This site serves as an “on switch” for the GluR1 subunit. When a phosphate molecule binds with S845, the subunit goes into action, helping to form more AMPA receptors and to drive them to the surface of the cell, where their presence fosters electrical excitability among cells – which, in excess, is thought to contribute to mania. The protein fragment the researchers designed prevented phosphate molecules from binding with S845 in the GluR1 subunit.

Reference: Du J, Creson TK, Wu L-J, Ren M, Gray NA, Falke C, Wei Y, Wang Y, Blumenthal R, Machado-Vieira R, Yuan P, Chen G, Zhuo M, Manji HK. The Role of Hippocampal GluR1 and GluR2 Receptors in Manic-like Behavior. The Journal of Neuroscience, 2008 28: 68-79; doi:10.1523/JNEUROSCI.3080-07.2008. January 2008.

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Self Discipline Positive Affirmations

Posted on July 6, 2016 by JmaC
Present Tense Affirmations
I am disciplined
I am in complete control of myself
My willpower has the strength of steel
I am dedicated to achieving my goals
I relish the feeling of working through a difficult task
My mind is strong, capable, and disciplined
I have an unshakeable dedication to my goals
I am completely focused on succeeding
I succeed because I have self discipline
I set goals and I work persistently until they are accomplished

 

Future Tense Affirmations
I will become highly disciplined
My self control is growing stronger by the day
I am developing an intensely focused and dedicated mindset
I will always complete every project I start
I will achieve massive success because of my unbreakable willpower
With each passing day I gain more control over my impulses
I am finding it easier to push through difficult or boring projects
I will become someone who others see as a hard worker who always gets things done
I am becoming more focused and dedicated in all areas of my life
I am beginning to love the feeling of working hard and finishing what I start

 

Natural Affirmations
Self Discipline comes naturally to me
I can tap into my willpower whenever I need to
I find it easy to maintain focus and work through difficult projects
I’m the kind of person who just doesn’t stop until I reach my goal
Self control feels effortless and natural
My ability to control myself is one of my greatest strengths
People know they can depend on me because I always finish what I start
It’s easy for me to maintain a high level of focus and dedication
Having control over my impulses is easy
Making a plan, working hard, and seeing it through until the end is just what I do
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Tomorrow’s Antidepressants: Skip the Serotonin Boost?

Posted on July 6, 2016 by JmaC

Scientists Reverse Depression-Like Behaviors In Mice Without Raising Serotonin Levels

February 14, 2008 • Science Update

New research adds to evidence of potentially better molecular targets in the brain to treat depression and other mental disorders, according to NIMH-funded scientists.

The researchers suggest that imbalances in the activity of an enzyme called GSK3ß may be closer to the root cause of mental illnesses than are low serotonin levels. Serotonin, a brain chemical, is the ultimate target of several current medications that work by indirectly increasing it to relieve symptoms. In preliminary findings, the scientists suggest that GSK3ß might be a more fundamental – and thus, perhaps, better and faster – target for new medications.

In the new study, even when serotonin levels stayed low, the scientists were able to correct abnormal, mental-illness-like behaviors in mice by blocking GSK3ß. When activated, GSK3ß plays a crucial role inside brain cells by sending chemical signals that help regulate cell function – but this activity must occur at the right time and in the right amount for the brain to function properly.

To assess the effects of blocking GSK3ß, the scientists measured anxiety- and depression-like behaviors shown earlier to be linked to low serotonin levels in mice. For example, compared to normal mice, those with low serotonin gave up sooner when held back by their tails and were slower to come out of dark hiding places to explore their surroundings.

These abnormal behaviors were reversed when scientists blocked GSK3ß in mice with low levels of serotonin. The scientists blocked the enzyme with either genetic engineering or a chemical compound. Success with both approaches strengthens the case for GSK3ß’s involvement in mental illnesses – and its potential, with further research, as a new target for medications, the researchers say.

More About the Science

Serotonin is one of several neurotransmitters through which brain cells communicate with each other. Abnormalities in the serotonin system are known to occur in depression, bipolar disorder, anxiety disorder, autism, and schizophrenia, for example.

But increasingly abnormalities in the serotonin system appear to be just one part of chains of molecular events that underlie various mental disorders. Recent research reveals that components such as GSK3ß are involved in these chains of events.

In this study, scientists based their experiments on a gene that makes Tph2, another enzyme involved in serotonin production. A variation of that gene has been linked to depression in some people, and in this study, mice genetically engineered with an equivalent mutation in the Tph2 gene had an 80 percent drop in brain serotonin levels.

As serotonin levels dropped, the GSK3ß enzyme went into action, sending chemical signals into brain cells, and the mice developed abnormal behaviors. The scientists corrected the abnormal behaviors not by increasing serotonin levels, as current medications for many mental disorders do, but by blocking the GSK3ß enzyme, instead.

Taken together, the results offer evidence that both the GSK3ß enzyme and the Tph2 gene play a role in some mental disorders.

Reference

Beaulieu J-M, Zhang X, Rodriguiz RM, Sotnikova TD, Cools MJ, Wetsel WC, Gainetdinov RR, Caron MG. Role of GSK3ß in behavioral abnormalities induced by serotonin deficiency. Proceedings of the National Academy of Sciences, 105(4):1333-1338. January 29, 2008

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We Shall Over Come

Posted on July 5, 2016 by JmaC

It’s a beautiful day and I’m inside. Scared.

I don’t know how to get out of this repetition.

I don’t know how to get out on my own.

I drag myself down, down, down.

Catch me I scream in silence.

I want to get out but I don’t feel like myself.

A body, an image have imprisoned me.

I don’t know how to speak

I don’t know how to behave

I’m scared of the evil

But at times it makes me smile

Catch me I scream in silence.

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