Steroid Dexamethasone Facilitates Fear Extinction

October 12, 2017 · Posted in Potential Treatments · Comment 

startle responseA 2017 article by Vasiliki Michopoulos and colleagues in the journal Psychoendocrinology reports that the potent steroid dexamethasone reduced the fear-potentiated startle response in patients with post-traumatic stress disorder (PTSD) but not in healthy controls. Dexamethasone acts on glucocorticoid receptors to suppress the body’s secretion of cortisol.

In the study, participants both with and without PTSD were taught to associate a picture of a blue square or a purple triangle with an uncomfortable short blast of air to the larynx (voicebox) and a loud burst of broadband noise in the participants’ headphones.

Some participants were given a placebo the night before the study, while others received a 0.5 mg dose of dexamethasone. Those who received dexamethasone the night before the study acquired a startle response to the blue square or purple triangle as much as other participants.

People without PTSD were easily able to eliminate their fear of the visual symbol when it was no longer linked to the noise and the blast of air, regardless of whether they had taken dexamethasone. However, among those with PTSD, only those who received dexamethasone were able to eliminate this fear-potentiated startle response and properly discriminate between safe and unsafe signals. People with PTSD who received the placebo maintained the fearful response to the blue square or purple triangle and startled in response to safe symbols.

People with PTSD may have difficulty learning to inhibit their fearful responses to stimuli that are no longer dangerous. In this study, the patients with PTSD continued to startle even after repeated presentations of the visual symbol without any accompanying air blast, while the controls showed excellent extinction of the response. After dexamethasone, but not placebo, patients with PTSD were just as successful in extinguishing the fear potentiated startle response as the controls. The authors conclude that dexamethasone could help facilitate extinction-based interventions used in PTSD, such as exposure therapy delivered during cognitive behavioral therapy or virtual reality exposure therapy.

Antibiotic Doxycycline May Block PTSD Symptoms

October 10, 2017 · Posted in Potential Treatments · Comment 

doxycycline capsulesA 2017 proof-of-concept study suggests that the antibiotic doxycycline can block the formation of negative thoughts and fear memories, perhaps offering a new way to treat or prevent post-traumatic stress disorder (PTSD).

In the study by Dominik R. Bach in the journal Molecular Psychiatry, healthy adults who received doxycycline had a lower fear response to fearful stimuli compared to healthy adults who received a placebo. The 76 participants received either doxycycline or placebo and then were taught to associate a color with an electric shock. Later, they were exposed to the color accompanied by a loud sound (but no shock), and their startle response was measured by tracking eye blinks, an instinctive response to sudden threats. Bach and colleagues found that the fear response was 60% lower in those participants who received doxycycline, suggesting that the antibiotic disrupted the fear memory linking the color to a threat.

The theory is based on evidence that doxycycline can inhibit metalloproteinase enzymes, which are involved in memory formation.

While in the study doxycycline was delivered before the fearful event occurred, there is hope that the antibiotic could also do some good after the fact. There is growing evidence that actively recalling a traumatic event can open a ‘memory reconsolidation window’ during which emotions associated with that event are open to change. Bach and colleagues hope to follow up with studies involving this reconsolidation window.

Another line of research is exploring how pain medications may reduce the emotional power of traumatic memories, because intense pain strengthens memory consolidation.

Revising Traumatic Memories in the Reconsolidation Window

October 6, 2017 · Posted in Potential Treatments · Comment 

elderly womanWe have previously described in the BNN how therapies can take advantage of the memory reconsolidation window to reduce the power of traumatic memories. Five minutes to one hour following active emotional recall of a traumatic event, a ‘window’ opens during which therapies can revise or extinguish the traumatic memory. A 2017 article by our Editor-in-Chief Robert M. Post and Robert Kegan in the journal Psychiatric Research describes how the reconsolidation window could theoretically be used to prevent recurring depressive episodes.

The theory is based on the idea that depressive episodes initially stem from stressors, but eventually become ingrained in the brain’s habit memory system. Cognitive behavioral therapy during the memory reconsolidation window might be a good way to disrupt these habit memories.

The memory reconsolidation window has already been used successfully to reduce traumatic memories and even to reduce heroin and cocaine cravings in addiction. The idea in changing traumatic memories, in the words of researcher Göran Högberg in a 2011 article in the journal Psychology Research in Behavior Management, is to “change a reliving intruding memory into a more distant episodic memory.” Post and Kegan suggest that work in depression would have a similar goal, to rework the triggering experience and render the depressive experience “less harsh, severe, [and] self-defeating (guilt-inducing).”
In exploring this new therapeutic approach, Post and Kegan suggest that it might be best to begin with patients whose depressive episodes are triggered by stressors.

The patient would be encouraged to recall the memory of the particular stressor and any emotions related to it. Then they would be prompted to reframe the memory, either by recognizing adaptive aspects of their response, focusing on their youth at the time of the stressor in the case of childhood memories, addressing any guilt the patient may feel, or other techniques used in trauma therapy. Evoking positive feelings during this period via relaxation exercises would be another useful practice.

In addition to targeting stressors that precede depression, the stress of the depressive experience itself could be a target of reframing during the reconsolidation window.
Questions remain, such as whether to target early or more recent memories, and whether this technique would be as useful in reducing manic episodes. Patient characteristics might also affect the success of this type of therapeutic intervention.

Post and Kegan also address how the therapy might be used in different stages of illness, and how it might be combined with other therapies, such as medications or procedures such as repeated transcranial magnetic stimulation (rTMS).

Three Experts’ Different Approaches to Treating PTSD in Veterans

October 4, 2017 · Posted in Current Treatments, Potential Treatments · Comment 

PTSDIn the BNN we have previously described some experts’ preferred treatment algorithms for patients with treatment-resistant post-traumatic stress disorder (PTSD), which is often complicated by traumatic brain injury (TBI). In this article, we update and expand upon these expert views.

David Bakish has worked as Medical Director at the Ottawa Psychopharmacology Clinic and is a former professor of psychiatry at the University of Ottawa in Ottawa, Ontario. In addition, he works with the Canadian military seeing patients with PTSD, substance abuse, and traumatic brain injuries. He uses a symptom-driven approach to PTSD, including 6 to 7 targeted medications added in sequence.

Albert Sattin is a professor of psychiatry and biobehavioral sciences at UCLA, belongs to their Brain Research Institute, and is affiliated with both the Ronald Reagan UCLA Medical Center and the Veterans Affairs Greater Los Angeles Healthcare System. He prefers to treat PTSD with a three-part combination of the blood pressure–lowering drug prazosin, a selective serotonin reuptake inhibitor (SSRI) antidepressant, and the atypical antidepressant mirtazapine.

Murray Raskind pioneered placebo-controlled studies of prazosin for PTSD and served as director of the Veterans Affairs Puget Sound Health Care System Mental Health Service, in addition to serving in the Department of Psychiatry and Behavioral Sciences at the University of Washington School of Medicine. Raskind’s approach to PTSD includes prazosin, the tricyclic antidepressant amitriptyline, and if needed for sleep, the sedative zolpidem.

Only SSRIs are approved by the US Food and Drug Administration (FDA) for the treatment of PTSD, but these on their own are rarely sufficient to handle the insomnia and other symptoms that accompany PTSD. Exposure therapy, in which patients are gradually led to approach trauma-related memories, feelings, and situations they previously avoided, is the most recommended type of therapy, but it too is often insufficient to treat all the complexities of the illness. Read on for more on each doctor’s approach to treating PTSD. Read more

Deep TMS May Improve Treatment-Resistant Bipolar Depression

October 2, 2017 · Posted in Current Treatments · Comment 

deep tmsDeep transcranial magnetic stimulation (dTMS) is a non-invasive treatment that has been shown to be effective in unipolar depression. It consists of a helmet fitted to the head, which uses magnetic coils to create an electric field in a desired brain region.

A 2017 double-blind randomized study by Diego F. Taveres and colleagues in the journal Neuropsychopharmacology found that 20 sessions of dTMS targeting the left dorsolateral prefrontal cortex produced greater improvement in bipolar depression over 4 weeks of treatment than the same number of sham sessions in which participants wore a helmet that delivered similar sounds and scalp sensations without the electrical effects to the brain. The participants had treatment-resistant bipolar depression that was being treated with medication.

However, dTMS’ effects were not significantly different from those of the sham over four additional weeks of follow-up, nor were remission rates significantly different across the two groups. Out of 50 participants, seven dropped out of the study—two from the sham group, and five from the active dTMS group. But there were no occasions on which a participant switched into mania following treatment.

This study suggests that dTMS has the potential to more rapidly improve treatment-resistant bipolar depression as well as unipolar depression.

Brain Scans Differentiate Suicidal from Non-Suicidal Patients with Bipolar Disorder

September 29, 2017 · Posted in Brain Imaging · Comment 

brainPeople with bipolar disorder are at high risk for suicidal behavior beginning in adolescence and young adulthood. A 2017 study by Jennifer A. Y. Johnston and colleagues in the American Journal of Psychiatry uses several brain-scanning techniques to identify neurobiological features associated with suicidal behavior in people with bipolar disorder compared to people with bipolar disorder who have never attempted suicide. Clarifying which neural systems are involved in suicidal behavior may allow for better prevention efforts.

The study included 26 participants who had attempted suicide and 42 who had not. Johnston and colleagues used structural, diffusion tensor, and functional magnetic resonance imaging (MRI) techniques to identify differences in the brains of attempters and non-attempters.

Compared to those who had never attempted suicide, those who had exhibited reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum. They also had reduced white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions. In addition, attempters had reduced functional connectivity between the amygdala and the left ventral and right rostral prefrontal cortex. Better right rostral prefrontal connectivity was associated with less suicidal ideation, while better connectivity of the left ventral prefrontal area was linked to less lethal suicide attempts.

Chronic Fatigue Linked to Low Metabolism

September 27, 2017 · Posted in Theory · Comment 

fatigue

A 2016 article in the journal PNAS suggests that people with chronic fatigue syndrome, also known as myalgic encephalopathy, share a low metabolic profile.

In the study, researcher Robert K. Naviaux and colleagues measured 612 different metabolites in 63 metabolic pathways. They found abnormalities in 20 of these pathways in people with chronic fatigue. Eighty percent of the abnormal measurements were low.

The low metabolic profile resembled a stage of development some worm larvae go through when environmental conditions are harsh. The phase, called dauer, can be brought on by harsh temperatures, low food supply, or pheromones that indicate high population density. It resembles hibernation in some ways, including changes to mitochondrial function. Dauer allows larvae to live for 4 months rather than their normal lifespan of 3 weeks. They can resume normal development when conditions improve.

The authors suggest that chronic fatigue is a metabolic response to environmental stress, and hope to clarify the link between mitochondrial function and the illness.

Evidence-Based Psychotherapies for Young Children

September 25, 2017 · Posted in Current Treatments · Comment 

TherapyAs many as 7–10% of children under the age of 5 have mood or behavioral problems, and this risk is even higher when a parent has a mood disorder. However, many families are not able to access treatment for these children due to their location, a lack of providers, or insurance problems.

A 2016 article by Mary Margaret Gleason and colleagues in the journal Technical Report in Pediatrics summarizes psychotherapeutic treatments for children that are supported with rigorous evidence. Some of these include infant-parent psychotherapy, video feedback for positive parenting, attachment biobehavioral catch-up (or ABC, in which caregivers are taught to re-interpret the signals of children who previously experienced maltreatment, providing nurturing in response), parent-child interaction therapy, and programs that combine parenting support with illness prevention, such as the Incredible Years series (for behavioral difficulties), the New Forest Programme (for attention-deficit hyperactivity disorder or ADHD), and Helping the Noncompliant Child (for oppositional behavior).

Gleason and colleagues suggest that pediatricians should take the lead in assessing young children and recommending appropriate psychotherapeutic approaches.

One resource available to parents is our own Child Network. It consists of an online portal where parents can provide weekly ratings of their children’s symptoms. These can be provided to the child’s physician to facilitate diagnosis and to clinicians to more effectively evaluate the results of treatment. The data provided to the Child Network will in turn help us understand how children are being treated in the community. There a few initial forms to fill out, but the weekly rating process is quick and can provide a great picture of a child’s wellbeing over time, including evaluating the effectiveness of any treatments.

Offspring of Bipolar Parents Have More Psychiatric Illness

September 22, 2017 · Posted in Risk Factors · Comment 

family with boyA 2017 study from the Czech Republic found that children and adolescents with at least one parent with bipolar disorder had much higher lifetime rates of mood and anxiety disorders than their peers who did not have a parent with bipolar disorder. The offspring of bipolar parents also had lower quality of life, less social support, poorer self-perception, poorer relationships with their peers and parents, and more difficult home lives than those whose parents did not have bipolar disorder.

The study by Michal Goetz and colleagues in the Journal of Child and Adolescent Psychopharmacology reported that 86% of the children of bipolar parents would be diagnosed with a psychiatric disorder in their lifetime. Similarly, David Axelson and colleagues from the Pittsburgh Bipolar Offspring Study reported in the American Journal of Psychiatry in 2015 that 74.2% of children with a parent with bipolar disorder would receive a lifetime psychiatric diagnosis, and a 2006 study by Myrna M. Weissman in the American Journal of Psychiatry found that the offspring of a unipolar depressed parent were three times more likely to have a psychiatric illness than offspring of nondepressed parents over 20 years of follow-up. Another study by this editor (Robert M. Post) and colleagues in the Bipolar Collaborative Network published in the Journal of Affective Disorders in 2016 found that a third of children at high risk due to a parent’s bipolar diagnosis would go on to have a psychiatric illness.

The Goetz study included a total of 86 participants between the ages of 7 and 18. Half had a parent with bipolar disorder and half did not. One limitation of the study was its recruitment procedure. Parents with bipolar disorder who enrolled their children in the study may have done so out of concern for their offspring’s mental health, increasing illness rates in the group with bipolar parents. Researchers were also aware of parents’ diagnoses, which may have affected their ratings of the young people’s symptoms. Despite these limitations, the study and its predecessors still suggest that psychiatric illness in a parent puts children at very high risk for a psychiatric illness themselves and can affect their wellbeing in a variety of ways.

Goetz and colleagues suggest that there is a need for proactive and complex care of families with psychiatric illness. They suggest that good communication is needed between adult and youth psychiatric services, with physicians who treat adults with bipolar disorder inquiring about those patients’ children and referring them to specialized psychiatric services for youth.

Editor’s Note: I not only endorse the conclusions of Goetz and colleagues, but would further recommend that parents with a diagnosis of bipolar disorder or unipolar depression discuss their children’s mood and behavior with their own psychiatrists and the children’s primary care physicians.

Parents of children aged 2 to 12 may enroll in our own Child Network, a secure online portal where they can record weekly ratings of their children’s symptoms and share these with their physicians.

There are many effective psychotherapeutic interventions for children with anxiety and mood disorders that should be sought for a child with symptoms that impair his or her functioning. Two evidence-based treatments are Family Focused Therapy, which incorporates family members into treatment so that they better understand the illness and can be supportive of the affected child, and cognitive behavioral therapy, in which negative patterns of thoughts and behaviors are challenged and patients are taught more effective problem-solving skills. When childhood psychiatric illness is recognized and treated appropriately, the results are often excellent, and it is possible that heading off the illness early may even prevent the development of more severe illness later in the child’s life.

Generic Seroquel XR Approved

September 20, 2017 · Posted in Current Treatments · Comment 

Earlier this year, the US Food and Drug Administration approved a generic version of Seroquel XR tablets (Quetiapine Fumarate Extended-Release Tablets), which are used to treat both depression and mania in bipolar disorder, schizophrenia, and to augment the effects of antidepressants in unipolar depression. Also known as quetiapine, the generic tablets will be available in 50 mg, 150 mg, 200 mg, 300 mg, and 400 mg doses.

Seroquel XR is taken once per day several hours before bedtime in the acute treatment for bipolar depression (300 mg/day), mania or mixed episodes (300–600 mg/day) or their prevention (400 mg/day); or paired with antidepressants to treat unipolar depression (150–300 mg/day).

The generic tablets, which are expected to be more affordable than Seroquel XR, are produced by Pharmadax Inc.

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