Type of Trauma Affects Gene Transcription Effects in PTSD

January 22, 2018 · Posted in Neurobiology · Comment 

PTSDIn a 2017 article in the journal Neuropsychopharmacology, researcher Michael S. Breen and colleagues analyzed five separate studies of post-traumatic stress disorder (PTSD) and found that sex and type of trauma affected the immunological pathways that changed with PTSD. People with PTSD showed disruptions in gene expression in specific immunological pathways depending on what type of trauma they had experienced.

Men exposed to combat traumas showed downregulation in a pathway related to wound healing, while men who were exposed to interpersonal traumas had upregulation in a signaling pathway mediated by the inflammatory marker IL-12. Women exposed to interpersonal traumas showed upregulation of two pathways—one related to lipid metabolism and the other related to MAPK (or mitogen-activated protein kinase) activity.

The participants with PTSD also showed a lot of the same disruptions across all types of trauma, including disruptions that affected cytokine, innate immune, and type 1 interferon pathways.

These data show that immune dysregulation and inflammatory pathways play a role in the pathophysiology of PTSD.

Eye Movement Desensitization and Reprocessing Can Improve PTSD

January 18, 2018 · Posted in Current Treatments · Comment 

A 2014 meta-analysis of clinical trials showed that the therapeutic technique known as eye movement desensitization and reprocessing (EMDR) can reduce symptoms of post-traumatic stress disorder (PTSD). The meta-analysis also established that longer durations of EMDR treatment correlated with better outcomes.

The meta-analysis by Ying-Ren Chen and colleagues in the journal PLOS One evaluated 26 randomized controlled trials of EMDR in people with PTSD. Chen and colleagues found that EMDR reduced PTSD symptoms, depression, anxiety, and subjective distress.

EMDR is a psychotherapeutic technique intended to reduce the distress that a patient feels about a traumatic memory. The patient is encouraged to recall the traumatic event while focusing on an external stimulus. Typically this would mean using their eyes to track the therapist’s hand moving back and forth from left to right. This process can help patients reprocess the trauma and alleviate the stress that they feel upon recalling the traumatic memory.

Chen and colleagues found that EMDR sessions that lasted longer than one hour were more effective than those that lasted less than an hour. Another finding that was that groups led by therapists who were experienced in PTSD group therapy were more effective than groups led by therapists without that experience.

Other more recent research has established that traumatic memories can be reprocessed or even extinguished by making use of the memory reconsolidation window. Five minutes to one hour after a patient engages in active emotional recall of a traumatic memory, a window of time opens in which that memory is subject to reinterpretation and revision.

An experienced therapist can create a safe environment for a patient to recall traumatic events and find alternative ways of interpreting the experience—for example, by focusing on their strength in surviving the experience. This process resembles EMDR in many ways, but without the eye movements.

In a 2017 article in the journal Psychiatry Research, BNN Editor-in-Chief Robert M. Post and colleague Robert Kegan discuss the possibility of using the reconsolidation window to reprocess stressors that led to a depressive episode.

Proton Pump Inhibitors Linked to Gastric Cancer

January 16, 2018 · Posted in Current Treatments · Comment 

helicobacter pylori in the stomachProton pump inhibitors (PPIs), a type of medication used to reduce gastric acid, have been linked to gastric cancer in a new study by Ka Shing Cheung and colleagues. A 2017 article in Gut, the journal of the British Society of Gastroenterology, reports that receiving PPIs to treat stomach infections from the bacterium Helicobacter pylori increases the risk of later gastric cancer.

The study relied on a territory-wide health database in Hong Kong. Out of 63,397 subjects, 153 developed gastric cancer after being treated for Helicobacter pylori. PPI treatment was associated with a 2.4-fold increase in risk of gastric cancer, while treatment with histamine-2 receptor agonist drugs did not increase cancer risk.

Editor’s Note: PPIs are widely used in psychiatric patients. Care should be taken with their long-term use.

Diet Drinks May Worsen Glucose Control, Making Type 2 Diabetes More Likely

January 12, 2018 · Posted in Risk Factors · Comment 

Many people substitute diet drinks containing artificial sweeteners for sugary drinks in the hopes of reducing their diabetes risk. However, new research suggests that artificial sweeteners alter the gut’s response to glucose in a way that could actually worsen diabetes risk.

At the 2017 meeting of the European Association for the Study of Diabetes, researcher Richard Young described a small study in which he and his colleagues compared the effects of artificial sweeteners to those of placebo in healthy adults. Seventeen participants consumed an amount of artificial sweetener equivalent to what would be found in 1.2 to 1.5 liters of diet beverage per day for two weeks, while 16 participants received placebo.

Young and colleagues determined that glucose absorption and glycemic response increased in the participants who consumed the artificial sweetener. Those who consumed the sweetener absorbed 20% more glucose than those in the placebo group. While before the study the two groups had similar blood glucose levels, these rose by 24% in those who consumed the artificial sweetener.

Consuming artificial sweetener also seemed to affect the gut peptide GLP-1, which limits the rise in blood glucose after meals. The two groups had similar GLP-1 responses before the study, but after consuming artificial sweetener, participants showed a 34% reduction in GLP-1 response to glucose absorbed in the intestines.

Changes like these could increase the risk of type 2 diabetes. Young explained that artificial sweeteners may reduce the body’s ability to control blood sugar levels, leading to high glucose, and possibly predisposing those who consume artificial sweeteners to type 2 diabetes. Young and colleagues have previously found that switching from sugar to artificial sweeteners does not predict a lower risk of type 2 diabetes.

This study was the first of its kind in humans. Larger studies will help to clarify the effects of artificial sweeteners on glucose control.

Adipokines May Be the Link Between Mood Disorders and Obesity

January 10, 2018 · Posted in Comorbidities, Resources · Comment 

weightResearchers David J. Bond and Lakshmi Yatham think they may have identified why bipolar disorder and obesity occur so often together. In North America, more than 60% of people with bipolar disorder are overweight or obese, and obesity rates are 60% higher in people with bipolar disorder than in people without bipolar disorder.

Bond and Yatham hypothesized that adipokines might be responsible for both bipolar disorder and obesity. Adipokines are cell signaling proteins that regulate both mood and appetite. Abnormal levels of adipokines in blood could cause both mood episodes and weight gain.

The researchers measured blood levels of five adipokines (leptin, adiponectin, resistin, adipsin, and lipocalin-2) in 53 young people with bipolar disorder. They found three interesting links between adipokines, mood, weight, and medications, which they reported in the Journal of Clinical Psychiatry in 2017.

The first finding was that low levels of leptin and adiponectin (adipokines with antidepressant properties) predicted a greater risk of depressive relapse over a 12-month period. The second finding was that high levels of leptin and adipsin predicted greater weight gain over a 12-month period. The third finding was that treatment with second-generation antipsychotics, which often leads to weight gain and other metabolic side effects, was associated with higher levels of resistin, an adipokine linked to type 2 diabetes.

The findings about leptin were particularly interesting, because leptin’s appetite-regulating effects change with a person’s weight. In the study, low leptin predicted depression, while high leptin predicted weight gain. In people of normal weight, low leptin predicts weight gain, while in overweight or obese people, high leptin predicts weight gain. Bond and Yatham suggest that leptin’s mood-regulating effects may be more consistent, with low leptin increasing depression risk regardless of weight.

These findings may help researchers find ways of treating mood episodes that do not encourage weight gain.

Exercise in Childhood Decreases Depression Symptoms Two Years Later

January 8, 2018 · Posted in Risk Factors · Comment 

A 2017 study in the journal Pediatrics found that higher rates of moderate to vigorous physical activity at ages six and eight was linked to fewer symptoms of depression at age 10.

The study included 795 six-year-olds who were tracked for four years. Their physical activity was measured by accelerometry, the same type of technology found in smartphones and other consumer products that can track a person’s daily steps. Depression symptoms were assessed via interviews with the children and their parents.

While exercise seemed to reduce depression symptoms, sedentary behavior did not predict later depression.

Minimizing Cardiovascular Risk in Bipolar Disorder

January 5, 2018 · Posted in Comorbidities, Risk Factors · Comment 

heartAt the 2017 meeting of the American Association of Child and Adolescent Psychopharmacology, researcher Ben Goldstein gave an overview on cardiovascular risk and bipolar disorder. He noted a study by Nicole Kozloff and colleagues in the Journal of Affective Disorders in 2010 that indicated that onset of cardiovascular disorder occurred an average of 17 years earlier in those with BP I (at age 40-45 years) compared to controls (at age 55-60 years). Several risk factors made onset of cardiovascular disorder more likely, including diabetes, obesity, and the metabolic syndrome (which consists of any three of the five following symptoms: high cholesterol, triglycerides, blood sugar, blood pressure, and waist circumference).

Risk factors include pathophysiological and behavioral mechanisms and certain medications. Pathophysiological mechanisms include inflammation, oxidative stress, and autonomic and endothelial dysfunction.

Behavioral mechanisms include poor diet, exercise, sleep, and increases in tobacco and alcohol use.

Medications could also contribute, with the most to least problematic for weight gain including, among atypical antipsychotics: clozapine, olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, and lurasidone. Among mood stabilizers, worst to best for avoiding weight gain are: valproate, lithium, carbamazepine, oxcarbazepine, and lamotrigine.

Goldstein has data from retinal vascular photography (RVP), whereby blood vessels can be observed directly. As opposed to in adults, in youth large vessels are more problematic and arteriolar to venous ratio is abnormally higher in bipolar children compared to normal controls. This ratio is lower in bipolar adults, also reflecting increased cardiovascular risk.
Given the huge loss of life expectancy in bipolar disorder, primarily from cardiovascular disorders, Goldstein urges greater and earlier attention to reducing the pathophysiological, behavioral, and pharmacological mechanisms for poor health. These should be pursued in parallel with attempts at mood stabilization. Read more

An Inflammatory State Impedes Treatment for Bipolar Disorder

January 4, 2018 · Posted in Current Treatments · Comment 

A 2017 study by in the Journal of Clinical Psychiatry links inflammation to a poor antidepressant response in bipolar disorder. Many previous studies have found that elevated inflammatory markers are common in mood disorders, and that an inflammatory state seems to prevent response to certain therapies.

Researcher Francesco Benedetti and colleagues report that high levels of inflammatory cytokines (a type of small proteins) predicted a worse response to treatment with sleep deprivation and light therapy for bipolar depression. This treatment typically brings about a rapid antidepressant response.

Benedetti and colleagues measured 15 immune-regulating compounds in 37 patients who were experiencing an episode of bipolar depression and 24 healthy volunteers. Among those participants with bipolar disorder, 84% had a history of non-response to medication. Twenty-three of the 37 patients, or 62%, responded to the sleep deprivation/light therapy combination. Those who did not had higher levels of five cytokines: interleukin-8, monocyte chemoattractant protein-1, interferon-gamma, interleukin-6, and tumor necrosis factor-alpha.

Body mass index was correlated with cytokine levels and also reduced response to the treatment.

The finding supports a link between the immune system and mood disorders. Evaluating a patient’s level of inflammation may, in the future, allow doctors to predict the patient’s response to a given therapy. Patients with high levels of inflammation might benefit most from treatments that target their immune system.

A Calculator of Risk for Bipolar Disorder in Youth

January 3, 2018 · Posted in Risk Factors · Comment 

Daniella Hafeman of the University of Pittsburgh described a risk calculator for predicting an individual’s risk for bipolar disorder, which is available at www.pediatricbipolar.pitt.edu. Possible factors included in the risk calculation include a parent’s early age of onset of bipolar disorder, mood shifts early in life, a child’s anxiety or depression symptoms, later affective mood shifts, and new onset of subthreshold mania.

Editor’s Note: A “poor man’s” assessment of risk can also be of help to a family or clinician. There are four components. The first is genetic. Having one parent with bipolar disorder is a potent risk factor, and can be further magnified if the other parent also has a mood disorder. If three or more first degree relatives or three or more generations of first degree relatives have a mood disorder, this further increases risk four- to six-fold.

Perinatal vulnerability is another factor. Beyond these genetic vulnerabilities, a history of maternal toxoplasmosis or a viral infection during pregnancy, or the infant being noticeably underweight at birth can contribute to bipolar risk.

Childhood adversity also contributes to vulnerability to early onset of bipolar illness. A history of psychosocial stress in the child’s early years, such as abuse or abandonment, can be an added risk factor.

Prodromal or preliminary symptoms are also a risk factor. The development of an anxiety or depressive disorder, a disruptive behavioral disorder, or a bipolar not-otherwise-specified diagnosis (BP-NOS, used to describe manic symptoms of short duration) further increases risk. In studies by David Axelson and Boris Birmaher, 50% of children with an initial diagnosis of BP-NOS developed full-blown bipolar I or II illness upon several years of followup if there was a family history of bipolar disorder. About one-third converted to full bipolar disorder if there was no family history of bipolar disorder.

Thus, if a child has three or all four types of risk factors, their risk would be substantial. In this case, one might consider attempts at prevention. This could include a good diet rich in omega-3 fatty acids, regular exercise, joining a school sports team, developing good sleep habits, playing a musical instrument, and engaging in something akin to family focused therapy. Family focused therapy emphasizes psychoeducation, good communication skills, and problem solving. Attending to and treating parents’ symptoms and building a support system for both parents and the child can also help.

While these endeavors are not a guarantee to prevent the onset of more severe illness, they are all health-promoting in general and have few downsides.