Depression and Suicidal Thoughts Linked to Brain Inflammation

February 14, 2018 · Posted in Neurobiology · Comment 

depressed man

A 2017 article by Sophie E. Holmes and colleagues in the journal Biological Psychiatry reports that people with major unipolar depression, especially those with suicidal thoughts, have higher levels of the inflammatory marker translocator protein than do healthy individuals.

The participants with depression and suicidal thinking had high levels of translocator protein in the anterior cingulate cortex, which suggests that inflammation is affecting microglia.

Many studies have found links between different indicators of inflammation and mood disorders, leading researchers to speculate whether targeting the immune system could be an effective way to treat mood disorders. Patients with high levels of inflammation often fail to respond to typical treatments for depression.

Some previous research has found evidence of microglial activation in the brains of people who died from suicide.

The small study by Holmes and colleagues used positron-emission tomography, or PET scans, to observe evidence of translocator protein levels in the brain in 14 medication-free participants in a major depressive episode and 13 healthy volunteers. Those with depression, and particularly those with suicidal thoughts, showed more evidence of neuroinflammation.

Omega-3 Fatty Acids Improve Executive Function in Youth with Mood Disorders

January 29, 2018 · Posted in Current Treatments · Comment 

omega-3 fatty acids

A 2017 study by Anthony T. Vesco and colleagues in The Journal of Child Psychology and Psychiatry suggests that in youth with depression or bipolar not otherwise specified (BP-NOS), omega-3 fatty acid supplements improve executive functioning and behavior regulation compared to placebo.

Ninety-five participants aged 7–14 years received two capsules daily of either omega-3 fatty acids (1.87g total per day, mostly consisting of EPA) or placebo for 12 weeks. Those who received omega-3s showed improvement in executive functioning (which can include planning and decision-making), behavioral regulation, and metacognition, as rated by their parents.

Editor’s Note: Since omega-3 fatty acids have no known side effects, there is little reason not to try them in youth with depression or bipolar disorder.

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.

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.

Even Light Exercise Prevents Future Depressions

December 22, 2017 · Posted in Risk Factors · Comment 

walking

A 2017 article in The American Journal of Psychiatry suggests that regular leisure-time exercise of any intensity can protect against future depressions.

The study by Samuel B. Harvey and colleagues followed a group of 33,908 healthy adults for 11 years. The researchers found a link between regular leisure-time exercise and reduced incidence of future depression (but not anxiety). This link occurred regardless of the intensity of the exercise, and most of the effect occurred at low levels of exercise. Analysis suggested that 12% of future cases of depression could be prevented if all participants fit one hour of physical activity into their week.

A small part of the benefit came from the social and physical health benefits of exercise.
Harvey and colleagues suggested that from a public health perspective, increasing population levels of exercise modestly could lead to a substantial decrease in depressions.

Editor’s Note: Alongside maintenance treatment, in the form of antidepressants for unipolar depression or mood stabilizers and atypical antipsychotics for bipolar disorder, exercise could provide some benefits in preventing future depressions.

Probiotics May Improve Depression As Well As IBS

December 11, 2017 · Posted in Potential Treatments · Comment 

vitamin DA pilot study of people with irritable bowel syndrome (IBS) suggests that taking a probiotic nutritional supplement can improve depression as well as gastrointestinal upset.
In the 2017 study published in the journal Gastroenterology, researcher Maria Pinto Sanchez and colleagues at the Farncombe Family Digestive Health Research Institute found that when those with IBS took a probiotic, their co-occurring depression improved more than it did in people with IBS who took a placebo.

Senior author Premysl Bercik suggested the study confirms that the microbiota environment in the gut affects what goes on in the brain, opening new avenues for the treatment of psychiatric diseases.

The study included 44 adults with IBS who also had mild to moderate anxiety and depression. For 10 weeks, half received a daily dose of the probiotic Bifidobacterium longum NCC3001, while the others received placebo.

After 6 weeks, 64% of the probiotic group saw improvement in their depression, compared to 32% of the placebo group. Functional magnetic resonance imaging (fMRI) showed brain changes associated with the improvement in mood.

The researchers are planning larger trials of probiotics.

TDCS Better Than Placebo But Not as Good as Escitalopram at Improving Unipolar Depression

December 8, 2017 · Posted in Potential Treatments · Comment 

An article by André R. Brunoni and colleagues in the New England Journal of Medicine reports that transcranial direct current stimulation (tDCS) can treat unipolar depression more effectively than placebo, but not quite as effectively as the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram. TDCS consists of a constant, low direct current applied to the scalp via electrodes.

The study included 245 patients with moderate to severe depressive symptoms, many of whom also had anxiety disorders. To minimize the placebo effect, patients all participated in sessions wearing tDCS gear and received a daily pill. However, one group received real tDCS treatment but placebo pills, a second group received sham tDCS but real escitalopram pills, and the third group received both sham tDCS and placebo pills.

The real tDCS treatment consisted of 30-minute sessions of tDCS every day for 15 consecutive weekdays, then seven once-a-week treatments. The escitalopram dosage was 10 mg/day for three weeks, then 20 mg daily.

Ten weeks into treatment, those who received escitalopram showed the greatest improvement in depression. Those who received tDCS showed slightly less improvement, but still significantly more than those who received neither treatment. Cognitive performance either improved or stayed the same in all the groups.

In terms of side effects, those who received escitalopram were more likely to report sleepiness or severe constipation. Those who received tDCS reported more skin redness/tingling, itching, tinnitus, and nervousness. Two patients in the tDCS group had new-onset mania during treatment. There were no suicides, hospitalizations, or other serious side effects.

Botox for Depression

December 1, 2017 · Posted in Potential Treatments · Comment 

botox injectionSeveral recent clinical trials have suggested that Botox injections between the eyebrows may improve depression. The theory is that decreasing muscle tension could reduce feelings of depression, instead of depression causing muscle tension. In a phase 2 double blind multicenter trial of 258 women with depression, participants were randomized to receive 30 units of Botox, 50 units of Botox, or placebo. Those who received the 30-unit injections showed significantly greater improvement in depression at three weeks and nine weeks compared to those who received placebo. However, it was not superior to placebo at the primary endpoint of the study, six weeks, and the 50-unit dosage was not superior to placebo. Both doses were well tolerated.

Botox is derived from botulinum toxin, which can relax tense muscles. It is also being explored as a treatment for migraine headaches. The manufacturer, Allergan, expects to move forward with phase 3 trials of Botox for depression.

An Overview of Ketamine for Treatment-Resistant Depression

November 27, 2017 · Posted in Potential Treatments · Comment 

ketamineA 2017 series of articles by researcher Chittaranjan Andrade in the Journal of Clinical Psychiatry reviews the last 10 years of research on ketamine, the anesthetic drug that in smaller doses (0.5 mg/kg of body weight) can bring about rapid antidepressant effects. Ketamine is typically delivered intravenously (though it can also be delivered via inhaler, injected under the skin or into muscles, and least effectively by mouth). Ketamine can improve depression in less than an hour, but its effects usually fade within 3 to 5 days. Repeating infusions every few days can extend ketamine’s efficacy for weeks or months.

Andrade cited a 2016 meta-analysis of nine ketamine studies by T. Kishimoto and colleagues in the journal Psychological Research. The meta-analysis found that compared to placebo, ketamine improved depression beginning 40 minutes after IV administration. Its effects peaked at day 1 and were gone 10–12 days later. Remission rates were better than placebo starting after 80 minutes and lasting 3–5 days.

Several studies have found that ketamine also reduces suicidality.

Andrade reported that both effectiveness and side effects seem to be dose-dependent within a range from 0.1 mg/kg to 0.75 mg/kg.

Side effects of ketamine are typically mild and transient. A 2015 study by Le-Ben Wan and colleagues (also in the Journal of Clinical Psychiatry) that Andrade cited reported that in 205 sessions of ketamine administration, the most common side effects were drowsiness, dizziness, poor coordination, blurred vision, and feelings of strangeness or unreality. The feelings of unreality (dissociative effects) diminish with repeated infusions. Heart and blood pressure may also temporarily increase as a result of ketamine administration.

One study found that ketamine could speed up and add to the effects of the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram (Lexapro). A meta-analysis of 10 randomized controlled trials found that ketamine did not improve the effects of electroconvulsive therapy.

Ketamine has some history as a recreational club drug (sometimes known as ‘K’ or ‘special K’), and can be misused or abused.

While there have been many studies of ketamine’s antidepressant effects, Andrade concludes that none is of a standard to justify US Food and Drug Administration approval for the drug. It is hoped that larger, more rigorous trials will be completed in the next few years. However, ketamine is already being used widely to treat treatment-resistant unipolar and bipolar depression.

Vagus Nerve Stimulation Improves Depression When Other Treatments Fail

November 24, 2017 · Posted in Current Treatments · Comment 

VNSVagus nerve stimulation (VNS) has been approved by the US Food and Drug Administration as an adjunctive therapy for treatment-resistant unipolar and bipolar depression since 2005. The treatment consists of a pacemaker-like device implanted under the skin in the chest that delivers regular, mild electrical pulses to the brain via the left vagus nerve.

A 2017 study by Scott T. Aaronson and colleagues in the American Journal of Psychiatry reports that over a 5-year period, people with treatment-resistant depression who received VNS did better than those who received treatment as usual. The 795 participants at 61 US sites had either a depressive episode that had lasted for at least two years or had had three or more depressive episodes and had failed to respond to at least four treatments, including electroconvulsive therapy (ECT). Over five years, those who received VNS had higher response rates (67.6% versus 40.9%) and higher remission rates (43.3% versus 25.7%) compared to those who received treatment as usual.

While the study by Aaronson and colleagues was non-blind and non-randomized, it suggests that VNS could be helpful in the long-term management of treatment-resistant unipolar and bipolar depression.

Editor’s Note: VNS was FDA-approved for treatment-resistant seizures in patients aged 12 and older in 1997 and for children 4 years and older in 2017. It was also approved for cluster headaches in 2017. Insurance coverage and reimbursement for VNS is typically available for these neurological conditions, but not for the treatment of depression. This is an unfortunate example of the stigmatization of psychiatric illness—when an FDA-approved device can be kept from people in need of treatment.

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