Teens with Bipolar Disorder at Increased Risk for Cardiovascular Disease

July 14, 2017 · Posted in Comorbidities, Risk Factors · Comment 

teen blood pressure checkA scientific statement from the American Heart Association reported in 2015 that youth with major depressive disorder and bipolar disorder are at moderate (Tier II level) increased risk for cardiovascular disorders. The combined prevalence of these illnesses in adolescents in the US is approximately 10%.

There are many factors that contribute to this risk, including inflammation, oxidative stress (when the body falls behind neutralizing harmful substances produced during metabolism), dysfunction in the autonomic nerve system, and problems with the endothelium (the inner lining of blood vessels). Lifestyle factors include adversity in early life, sleep disturbance, sedentary lifestyle, poor nutrition, and abuse of tobacco, alcohol, or other substances.

Taking some atypical antipsychotics as treatment for bipolar disorder also contributes to the risk of cardiovascular problems by increasing weight and/or lipid levels. Among the atypicals, ziprasidone (Geodon) and lurasidone (Latuda) come with the lowest likelihood of weight gain.

The statement by Benjamin I. Goldstein and colleagues that appeared in the Heart Association-affiliated journal Circulation suggested that therapeutic interventions should address some of these risk factors to help prevent cardiovascular problems and improve life expectancy for young people with depression or bipolar disorder. These could include a good diet, regular exercise, and treatments with good long-term tolerability that are aimed at preventing episodes.

The Role of Inflammatory Markers and BDNF

Inflammation worsens the risk of cardiovascular problems, while brain-derived neurotrophic factor (BDNF), which protects neurons and plays a role in learning and memory, may improve prospects for someone with depression or bipolar disorder.
A 2017 article by Jessica K. Hatch and colleagues including Goldstein in the Journal of Clinical Psychiatry suggests that inflammation and BDNF are mediators of cardiovascular risk in youth with bipolar disorder. The study looked at 40 adolescents with bipolar disorder and 20 healthy controls.

Those with bipolar disorder had greater waist circumference, body mass index, and pulse pressure than the controls. The youth with bipolar disorder also had higher levels of the inflammatory cytokine Il-6. Participants who had lower BDNF had greater thickness of the carotid vessel internal lining (intima media).

Hatch and colleagues point to the importance of prevention strategies in adolescents with these indicators of increased cardiovascular risk. These data complement the American Heart Association’s recognition of adolescent mood disorders as a large problem that deserves wider attention both in psychiatry and in the media.

Early Marijuana Use Linked To Abnormal Brain Function, Low IQ

May 10, 2017 · Posted in Risk Factors · Comment 

young marijuana usersA study of depression and marijuana use found that using marijuana before the age of 17 was linked to abnormal brain function and lower IQ. In a 2016 article in the journal Acta Psychiatrica Scandinavica, researcher Elizabeth Osuch and colleagues described a study that compared four categories of youth: frequent pot users with depression, frequent pot users without depression, those with depression who did not use pot, and healthy individuals who did not use pot. The researchers also compared those who began using pot after the age of 17 to those who began earlier.

The main findings were that brain function in the areas of reward processing and motor control differed across the four groups. Depression was linked to deficits in brain function. Marijuana use did not correct these deficits, and in some parts of the brain, worsened them.

Those who had used marijuana before the age of 17 had abnormalities in memory, visuo-spatial processing, self-referential activity, and reward processing. Those who had started using marijuana at younger ages also had lower IQ scores.

Early Cannabis Use and BDNF Gene Variant Increase Psychosis Risk

May 3, 2017 · Posted in Genetics, Risk Factors · Comment 

Teen smoking marijuanaNormal variations in genes can affect risk of mental illness. One gene that has been implicated in psychosis risk is known as BDNF. It controls production of brain-derived neurotrophic factor, a protein that protects neurons and is important for learning and memory. Another important gene is COMT, which controls production of the enzyme catechol-O-methyltransferase, which breaks down neurotransmitters such as dopamine in the brain.

Several forms of these genes appear in the population. These normal variations in genes are known as polymorphisms. Certain polymorphisms have been linked to disease risk. A study by Anna Mané and colleagues published in the Journal of Psychiatric Research in 2017 explored links between COMT and BDNF polymorphisms, cannabis use, and age at first episode of psychosis.

Mané and colleagues found that among 260 Caucasians being treated for a first episode of psychosis, the presence of a BDNF polymorphism known as val-66-met and a history of early cannabis use were associated with younger age at psychosis onset.

The val-66-met version of BDNF occurs in 25-35% of the population. It functions less efficiently than a version called val-66-val.

The researchers also found that males were more likely to have used cannabis at a young age.

Editor’s Note: In the general population, marijuana use doubles the risk of developing psychosis. Previous data had indicated that the risk was higher for those with a COMT polymorphism known as val-158-val that leads to more efficient metabolism of dopamine in the prefrontal cortex. The resulting deficits in dopamine increase vulnerability to psychosis compared to people with the val-158-met version of the COMT gene.

The new study by Mané and colleagues suggests that a common form of BDNF may be associated with an earlier onset of psychosis. Bottom line: Pot is dangerous for young users and can induce psychosis, particularly in people at genetic risk. Pot may be legal in many places, but heavy use in young people remains risky for mental health and cognitive functioning.

The company Genomind offers genetic testing for BDNF and COMT variants as part of a routine panel.

Only Fluoxetine is More Effective Than Placebo for Children and Adolescents with Depression

April 11, 2017 · Posted in Current Treatments · Comment 

Young Latina woman showing white medication tabletIn a meta-analysis published in 2016, researchers Andrea Cipriani, Xinyu Zhou, and colleagues reported that many antidepressants are not effective in children and adolescents. Fluoxetine alone was more effective than placebo. Other antidepressants also caused high study drop-out rates compared to placebo.

In an article published in the journal The Lancet, Cipriani, Zhou, and colleagues analyzed 34 randomized, controlled clinical trials of antidepressants in children and adolescents. These trials included a total of 5,260 participants and 14 different antidepressants.

The researchers determined that much of the evidence was of a low quality. Only fluoxetine was statistically significantly more effective than placebo. Fluoxetine was also more tolerable to patients than duloxetine or imipramine. Patients who received imipramine, venlafaxine, or duloxetine were more likely to drop out of studies due to adverse events compared to patients who received placebo.

The authors suggest that prescribing antidepressants to children or adolescents may not necessarily be beneficial, and that fluoxetine is probably the best option to consider.

Editor’s Note: It may be best to use caution when prescribing antidepressants to children or adolescents. First, these data that suggest that many antidepressants are ineffective in young people. In addition, depression in children and adolescents may be a sign of bipolar disorder, and antidepressant use may cause activation or switching into mania in vulnerable patients.

While there is a warning about using antidepressants in young people because of the risk of increased suicidal ideation, the actual suicide rate in young populations decreases when these patients take antidepressants and cognitive behavioral therapy. Psychotherapy should be a high priority. Other safe adjunctive approaches might include omega-3 fatty acids, N-acetylcysteine, vitamin D3, and folic acid. Evidence for the efficacy of rTMS in young people is also positive and growing.

Inflammation Predicts Poor Response to Fluoxetine in Kids

April 10, 2017 · Posted in Current Treatments · Comment 

Nurse taking blood sample from patient at the doctors office

Inflammation upsets the balance of neurotransmitters in the brain and can make antidepressants less effective. In new research by Maya Amitai and colleagues, children and adolescents were less likely to respond to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine if they had high levels of inflammation measured in the blood.

Amitai’s study included 41 patients between the ages of 9 and 18. They met criteria for a diagnosis of either major depression or an anxiety disorder. The participants were treated with the SSRI fluoxetine for eight weeks. Those with high levels of the inflammatory markers tumor necrosis factor (TNF) alpha, interleukin-6, and interleukin 1 beta were less likely to respond to the antidepressant treatment. The research was published in the Journal of Child and Adolescent Psychopharmacology in 2016.

Editor’s Note: These findings parallel those from studies of adults, suggesting that inflammation can predict poor response to antidepressants in all age groups.

Anxiety, Depression, Unstable Mood, and Low-Level Mania Best Predictors of Bipolar Disorder

May 4, 2016 · Posted in Diagnosis, Risk Factors · Comment 

kids at high risk for bipolar disorder

Researchers are looking for better ways of predicting whether children at risk for bipolar disorder will go on to develop the illness. A 2015 study by David Axelson and colleagues in the American Journal of Psychiatry reported that in the offspring of parents with bipolar disorder, diagnoses of sub-threshold mania, depression, and disruptive behavior disorders were associated with subsequent diagnosis of full-blown Bipolar I or Bipolar II disorders six to seven years later.

More recently, in an article by Danella M. Hafeman and colleagues in the American Journal of Psychiatry, the same group of investigators has examined how symptoms (rather than categorical diagnoses, as in the earlier study) predict the development of bipolar disorder. In children and adolescents at high risk for bipolar disorder (because they have a parent with the disorder) three types of symptoms were the best predictors of later bipolar disorder: anxiety/depression at the time participants entered the study, unstable mood or irritability both when entering the study and shortly before a bipolar diagnosis, and low-level manic symptoms observed shortly before diagnosis.

The earlier the age at which a parent was diagnosed with a mood disorder, the greater the risk that the offspring would also be diagnosed with bipolar disorder. Youth with all four risk factors (anxiety or depression, mood changes, low-level mania, and a parent who was diagnosed with a mood disorder at an early age) had a 49 percent chance of developing bipolar disorder, compared to a 2 percent chance among those without those risk factors.

Childhood onset of bipolar disorder and long delays until first treatment for depression or mania are both significant predictors of a poor outcome in adulthood compared to adult onsets and shorter delays to treatment. Read more

Inflammation Linked to Bipolar Illness in Young People

May 1, 2016 · Posted in Risk Factors · Comment 

inflammation linked to bipolar disorderThe Course and Outcome of Bipolar Youth study, or COBY, has been collecting information on young people with bipolar disorder and tracking their symptoms into adulthood since 2000. A 2015 study by Benjamin I. Golstein in the Journal of Clinical Psychiatry analyzed COBY data, identifying links between higher than average levels of inflammatory markers measured in the blood and participants’ histories of illness and familial risk factors.

High levels of the inflammatory marker hsCRP were associated with longer duration of illness, substance use disorder, and family history of suicide attempts or completed suicides. High levels of TNF-alpha were linked to suicide attempts, self-injury behaviors, and family history of substance use disorders. IL-6 was also linked to family history of substance use disorders.

There were also links between inflammatory markers and participants’ symptoms over the 6 months leading up to the blood tests. Levels of the inflammatory marker TNF-alpha were linked to the percentage of weeks patients had psychotic symptoms. Levels of IL-6 were associated with percentage of weeks with subthreshold mood symptoms and also with any suicide attempt. Levels of HsCRP were linked to maximum severity of depressive symptoms.

It is possible that targeting the elevated levels of inflammatory markers with anti-inflammatory treatments could improve patients’ response to treatments, but this topic requires further study.

Vitamin D3 Reduces Symptoms of Bipolar Spectrum Disorders

April 28, 2016 · Posted in Potential Treatments · Comment 

vitamin DVitamin D3 tends to be low in children and adolescents with mania, but supplements may help. In a small open study published in the Journal of Child and Adolescent Psychopharmacology in 2015, Elif M. Sikoglu and colleagues administered 2000 IU of vitamin D3 per day to youth aged 6–17 for eight weeks. Sixteen of the participants had bipolar spectrum disorders (including subthreshold symptoms) and were exhibiting symptoms of mania. Nineteen participants were typically developing youth.

At the beginning of the study, the youth with bipolar spectrum disorders had lower levels of the neurotransmitter GABA in the anterior cingulate cortex than did the typically developing youth. Following the eight weeks of vitamin D3 supplementation, mania and depression symptoms both decreased in the youth with bipolar spectrum disorders, and GABA in the anterior cingulate cortex increased in these participants.

Editor’s Note: GABA dysfunction has been implicated in the manic phase of bipolar disorder. While larger controlled studies of vitamin D supplementation are needed, given the high incidence of vitamin D deficiency in youth in the US, testing and treating these deficiencies is important, especially among kids with symptoms of bipolar illness.

Successful Double-Blind Placebo-Controlled Study of Lithium for Acute Mania in Kids 7–17

February 26, 2016 · Posted in Potential Treatments · Comment 

lithium for mania in kids

Lithium is the treatment of choice for adults with bipolar disorder, but has rarely been studied in children or adolescents. One of the first double-blind placebo-controlled trials of lithium for the treatment of mania in children and teens aged 7–17 showed that the drug produced greater improvement in mania than did placebo. Side effects included blurred vision, abdominal pain, diarrhea, nausea, vomiting, fatigue, thirst, increased thyroid-stimulating hormone, decreased appetite, dizziness, sedation, tremor, increased urination, and rash.

In the study by researcher Adelaide S. Robb and colleagues, which was presented at the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, doses began at 300mg twice a day, were based on each child’s weight, and were slowly increased.

At the same meeting, researcher Russell Scheffer presented data on 41 children who continued lithium treatment for 16 weeks with good results. The mean dose was 27.8 +/- 6.7 mg/kg per day.

Topiramate Added to Quetiapine Can Reduce Marijuana Craving in Young People

February 11, 2016 · Posted in Current Treatments · Comment 

marijuana craving

At the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Melissa P. DelBello reported that compared to placebo, the anticonvulsant topiramate reduced marijuana craving in young people aged 12–21 who were already taking the antipsychotic quetiapine. Functional magnetic resonance imaging (fMRI) revealed that topiramate altered the activation of brain regions common to both drug craving and mood dysregulation. Topiramate could be a good treatment to reduce marijuana abuse. The antioxidant n-acetylcysteine (NAC) is another option.

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