Untreated Episodes of Bipolar Disorder Worsen Over Time, But Prevention is Possible

September 18, 2017 · Posted in Course of Illness · Comment 

Pensive man

A 2017 literature review by researcher Lars V. Kessing and Per K. Andersen in the journal Acta Psychiatrica Scandinavica reports that the greater a patient’s number of previous episodes of bipolar disorder, the more likely that patient is to have a more difficult course of illness and poorer outcomes. The number of episodes was associated with more rapid recurrences, duration and severity of episodes, more automatic episodes (i.e. not triggered by stress), risk of dementia, treatment resistance, lack of recovery between episodes, and brain volume losses.

In an article in the journal Bipolar Disorders in 2016, BNN Editor-in-Chief Robert M. Post described the value of preventive treatment in reducing episodes and protecting the brain from the damage that accompanies them.

Given that episodes, stressors, and bouts of substance abuse can affect the way genes are transcribed via a phenomenon known as epigenetics, preventing these occurrences could lead to an easier course of illness and improved outcomes. Patients should provide their physicians with feedback about their response to prior medications and any side effects they experience over time so that their medication regime can be adjusted until it is maximally effective.

Patients with severe illness and multiple previous episodes may need a complex medication regimen that includes multiple types of medications that target different systems of neurotransmitters.

This philosophy of treatment is presented in several publications, including the 2008 book Treatment of Bipolar Illness: A Casebook for Clinicians and Patients by Post and Gabrielle Leverich, and more recently in the article “Treatment of Bipolar Depression: Evolving Recommendations” in the journal Psychiatric Clinics of North America. An open access article by Post, “New Perspectives on the Course and Treatment of Bipolar Disorders,” published in the journal Edizioni Minerva Medica S.p.A. in 2017, describes the need for early and sometimes complex combination therapy, including the non-intuitive idea that more medications (carefully prescribed) can actually produce fewer side effects than large doses of a single medication.

Another good resource for patients is a daily personal calendar that can be used to track ongoing symptoms, side effects, and response to medications. We offer several types of these calendars free here. My Mood Monitor, or What’s My M3, is a validated screening instrument that can detect depression, anxiety disorders, and mania in response to weekly self-reports. It is available online and as an app, and can be used to track illness course and response to treatment.

Short Telomeres Associated with Family Risk of Bipolar Disorder

September 13, 2017 · Posted in Genetics, Risk Factors · Comment 

telomeres

Telomeres are bits of genetic material at the end of each strand of DNA that protect chromosomes as they replicate. Short telomeres have been linked to aging and a variety of medical and psychiatric diseases. Stress and depressive episodes can shorten telomeres, while treatment with lithium can lengthen them.

Telomere length is a heritable trait, and a 2017 study by researcher Timothy R. Powell and colleagues suggests that shorter telomeres are a familial risk factor for bipolar disorder.

The study, published in the journal Neuropsychopharmacology, compared the telomere lengths of 63 people with bipolar disorder, 74 of their immediate relatives (49 of whom had no lifetime psychiatric illness, while the other 25 had a different mood disorder), and 80 unrelated people with no psychiatric illness. The well relatives of the people with bipolar disorder had shorter telomeres than the unrelated healthy volunteers.

Relatives (both well and not) and people with bipolar disorder who were not being treated with lithium both had shorter telomeres than people with bipolar disorder who were being treated with lithium.

Another finding was that longer telomeres were linked to greater volume of the left and right hippocampus, and improved verbal memory on a test of delayed recall. This study provides more evidence that taking lithium increases the volume of the hippocampus and has neuroprotective benefits for people with bipolar disorder.

Methylphenidate Does Not Cause Mania When Taken with a Mood Stabilizer

September 8, 2017 · Posted in Comorbidities, Current Treatments · Comment 

ADHDMethylphenidate is an effective treatment for attention-deficit hyperactivity disorder (ADHD). Ritalin may be the most commonly recognized trade name for methylphenidate, but it is also sold under the names Concerta, Daytrana, Methylin, and Aptensio. A 2016 article in the American Journal of Psychiatry reports that methylphenidate can safely be taken by people with bipolar disorder and comorbid ADHD as long as it is paired with mood-stabilizing treatment.

The study was based on data from a Swedish national registry. Researchers led by Alexander Viktorin identified 2,307 adults with bipolar disorder who began taking methylphenidate between 2006 and 2014. Of these, 1,103 were taking mood stabilizers including antipsychotic medications, lithium, or valproate, while 718 were not taking any mood stabilizing medications.

Among those who began taking methylphenidate without mood stabilizers, manic episodes increased over the next six months. In contrast, patients taking mood stabilizers had their risk of mania decrease after beginning treatment with methylphenidate.

Viktorin and colleagues suggest that 20% of patients with bipolar disorder may also have ADHD, so it is not surprising that 8% of patients with bipolar disorder in Sweden receive a methylphenidate prescription.

Mood-stabilizing drugs can worsen attention and concentration, so methylphenidate treatment can be helpful if it can be done without increasing manic episodes. However, Viktorin and colleagues suggest that due to the risk of increasing mania, anyone given a prescription for methylphenidate monotherapy should be carefully screened to rule out bipolar disorder.

The researchers confirmed that taking methylphenidate for ADHD while taking a mood stabilizer for bipolar disorder is a safe combination.

Safety of Atypical Antipsychotics in Pregnancy

August 31, 2017 · Posted in Current Treatments · Comment 

pregnant woman

A 2017 article in the Journal of Clinical Psychiatry systematically reviewed data on the risks related to schizophrenia, bipolar disorder, and treatment with atypical antipsychotic medication during pregnancy. The article by researcher Sarah Tosato and colleagues suggests that a mother’s illness may be more harmful to a fetus than treatment for that illness is.

The review analyzed 49 articles about illness-related and atypical antipsychotic–related risks in bipolar disorder and schizophrenia. Tosato and colleagues found that abrupt discontinuation of treatment led to a high risk of relapse in pregnant women with bipolar disorder or schizophrenia.

Schizophrenia was linked to a slight increase in obstetric complications for mothers, while both bipolar disorder and schizophrenia were linked to a slight increase in complications for newborns. Mothers ill with schizophrenia had the highest risk for serious complications, including stillbirth, neonatal or infant death, and intellectual disability in the child.

The researchers reported that untreated bipolar disorder and schizophrenia are risk factors for birth defects, but use of atypical antipsychotics is not. Children’s neurodevelopment also does not seem to be affected by mothers’ use of atypical antipsychotics during pregnancy.

The authors suggest that, given parents agree and understand any risks involved, the least harmful choice of action is to maintain treatment of women with bipolar disorder and schizophrenia during pregnancy at the safest minimum dosage to keep their illness at bay.

Birth Defects from Valproate Lower in Bipolar Disorder than in Epilepsy

August 30, 2017 · Posted in Current Treatments · Comment 

pregnancyThe anticonvulsant valproate increases the risk of serious birth defects in fetuses exposed to it. However, a 2017 report by ANSM, France’s agency for health and product safety, and its national insurance fund for employed workers shows that these risks are lower for women taking valproate for bipolar disorder than for women taking valproate for epilepsy.

In France, the risk of a major fetal malformation was 10.2 per 1000 women in the general population, about twice that (22.2 per 1000) in women taking valproate for bipolar disorder, and about 4 times higher (46.5 per 1000) in women taking valproate for epilepsy. The authors suggest that treatment for bipolar disorder may be more likely to be interrupted during pregnancy, and this could explain the different levels of risk by diagnosis.

Among the risks of defects in the fetuses of women being treated with valproate for epilepsy, the risk of a ventricular septal defect (a hole in the wall separating the lower heart chambers) was 11.2% compared to 2.7% in fetuses not exposed to valproate, while risk of an atrial septal defect (a hole in the wall separating the upper heart chambers) was 19.1% in the fetuses of those prescribed valproate for epilepsy compared to 1.9% in unexposed fetuses. Risk of hypospadias (placement of the urethra opening on the underside of the penis rather than its end) was 22.7% compared to 4.8% in the general population.

Risks of a major malformation were dose dependent in those with epilepsy (but interestingly, not in those with bipolar disorder), meaning the more valproate patients with epilepsy took, the higher their risk of a fetus with birth defects.

The only birth defects that were more common in the fetuses of women taking valproate for bipolar disorder than in fetuses not exposed to valproate were hypospadias (17.5% risk compared to 4.8% in the general population) and craniostenosis, a deformity of the skull (4.2% risk compared to 0.4% in the general population).

The relative safety of valproate in women being treated for bipolar disorder compared to those being treated for epilepsy is good news for some. However, fetal exposure to valproate has also been linked to deficits in cognitive development.

The risk of spina bifida, which causes lifetime paralysis, in a fetus may no longer be such a catastrophic  issue for women taking valproate for bipolar disorder (where the risk did not exceed that of the general population), as was once assumed based on data from women with epilepsy (where the risk is usually 2-4%, but was 8% in this French study). This may be of some comfort to women with bipolar disorder who require valproate treatment to remain stable and wish to become pregnant or in those who experience an unplanned pregnancy.

Dutch Study Links Low Vitamin D to Bipolar Disorder

August 15, 2017 · Posted in Risk Factors · Comment 

Vitamin D sources

A 2016 study in the Netherlands found that people with bipolar disorder are more likely to have vitamin D deficiency than the general population. Vitamin D deficiency has been linked to other psychiatric disorders including schizophrenia and unipolar depression. Poor diet and lack of exposure to sunlight can put someone at risk for vitamin D deficiency.

The study, led by Remco Boerman and published in the Journal of Clinical Psychopharmacology, included 118 adults with bipolar disorder, 149 with schizophrenia, and 53 with schizoaffective disorder. More than 30% of these participants had deficient levels of vitamin D. Only 15% had optimum levels of the vitamin. More than 22% of the participants with bipolar disorder were deficient in vitamin D, while close to 35% of those with schizophrenia and schizoaffective disorder were deficient.

Study participants had vitamin D levels that were 25% lower than those of the white Dutch population, and vitamin D deficiency was 4.7 times more common in those with psychiatric disorders than the general Dutch population.

The authors suggested screening people with bipolar disorder, schizophrenia, and schizoaffective disorder for low levels of vitamin D.

Bipolar Disorder and Diabetes Linked

July 19, 2017 · Posted in Risk Factors · Comment 

diabetes linked to bipolar disorderA systematic literature review in 2016 showed a definitive link between bipolar disorder and diabetes. Bipolar disorder almost doubles the risk of diabetes while diabetes more than triples the risk of bipolar disorder. The article by Ellen F. Charles and colleagues was published in the International Journal of Bipolar Disorders.

The review included seven large cohort studies. The studies, based on elderly populations only, examined bipolar disorder and diabetes rates. Charles and colleagues suggested that shared mechanisms could cause both illnesses. New disease models that explain the link between bipolar disorder and diabetes could lead to better treatments.

The review also reported that both bipolar disorder and diabetes were independently associated with risk of cognitive decline and dementia in these elderly individuals. People with diabetes had more brain atrophy on average than others who share their age and gender but did not have diabetes. People with bipolar disorder who also had diabetes and either insulin resistance or glucose intolerance had neurochemical changes in the prefrontal cortex that indicated poor neuronal health. In some cases, these patients also had reduced brain volume in the hippocampus and cortex.

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.

Continuing Marijuana Use After a First Episode of Psychosis Increases Risk of Relapse

May 5, 2017 · Posted in Risk Factors · Comment 

marijuanaA 2016 article in the journal JAMA Psychiatry reports that continuing to use cannabis after a first episode of psychosis increases risk of relapse. The study by Sagnik Bhattacharyya and colleagues employed longitudinal modeling to determine the role of cannabis use in psychotic relapse. The researchers followed 90 women and 130 men for two years after a first episode of psychosis, and found that the more marijuana they used, the more likely they were to have a relapse of psychosis.

Relapse rates were highest (59.1%) for participants who used pot continuously following their first episode of psychosis. Relapse rates were lower (36.0%) for those who used cannabis intermittently thereafter, and lowest (28.5%) among those who discontinued cannabis use after their first episode of psychosis.

A statistical test known as a cross-lagged analysis was used to establish that cannabis use affected later relapse, rather than relapse of psychosis leading to further cannabis use.

Another statistical strategy using fixed-effect models revealed that risk of psychotic relapse was 13% higher during times of cannabis use than during periods of no cannabis use.

These findings offer some hope that the likelihood of psychosis relapse can be reduced, since ongoing cannabis use is a risk factor that can be modified, unlike family history or genetics. Bhattacharyya and colleagues called for research into interventions that can help discourage cannabis use in people who have had a first episode of psychosis.

Editor’s Note: N-acetylcysteine, a nutritional supplement sold in health food stores, can reduce cannabis use compared to placebo in teen users.

More News About Genetic Risk for Bipolar Disorder

April 25, 2017 · Posted in Risk Factors · Comment 
DNA helix with one base pair highlighted

A change to just one base pair may increase the risk of early-onset bipolar disorder

In a 2017 article in the Journal of Clinical Psychiatry, researcher Paul E. Croarkin and colleagues describe findings from their study of genetic risk factors for early-onset bipolar disorder. The researchers focused on single nucleotide polymorphisms (SNPs), which are variations in a single base pair of a DNA sequence. SNPs are normal variations or copying errors that occur when DNA is replicated. Croarkin and colleagues tracked 8 SNPs that had been linked to bipolar disorder in previous studies. They examined 69 patients from a study of early-onset mania, 732 adult patients with bipolar disorder (including 192 with early-onset illness), and 776 healthy controls. The researchers compared patients with early-onset illness to controls, and also looked for connections between specific SNPs and early-onset illness.

The SNPs analyzed in the study map to three genes that have repeatedly been associated with the risk for bipolar disorder in other studies. These include CACNA1C (one of several genes that create calcium channels), ANK3, and ODZ4. Croarkin and colleagues determined that the presence of these SNPs, particularly the ones that involved the CACNA1C gene, were associated with early-onset bipolar disorder.

Editor’s Note: These findings may lead to better treatment for early-onset bipolar disorder. The CACNA1C calcium influx gene that has repeatedly been connected to bipolar illness can be blocked by the calcium channel blocker nimodipine. Nimodipine has lithium-like effects in mania and depression in adults. One case report by Pablo A. Davanzo in the Journal of Child and Adolescent Psychopharmacology described success using nimodipine and the thyroid medication levothyroxine to treat a 13-year-old boy with very rapid cycling bipolar disorder that had previously failed to respond to multiple medications.

Nimodipine deserves further study in children showing symptoms of bipolar disorder. The company Genomind provides testing for the CACNA1C gene. We hope it will soon be determined whether the presence of this SNP predicts a good response to nimodipine.

Being able to predict who will get bipolar disorder is a long way off. However, there are some clear risk factors. Young people from families that have had several generations of bipolar disorder or related disorders are at increased risk for bipolar disorder. This risk increases for children who experience adversity in childhood, such as abuse or neglect. The presence of early mild symptoms of mania, depression, or disruptive behavior further increase this risk.

For doctors, a patient’s clinical history of these three types of risk factors can help identify whether they are at increased risk of developing bipolar disorder. Patients with several risk factors should be observed closely and treated with psychotherapy or medication as needed.

Parents of children between the ages of 2 and 12 who have shown some signs of mood or behavioral symptoms are encouraged to join our Child Network. We provide a secure online platform where parents record their children’s symptoms of anxiety, depression, attention-deficit hyperactivity disorder (ADHD), oppositional behavior, and mania on a weekly basis. Symptoms are charted over time in a graphical depiction that can be shared with the child’s doctor. For more information, see page 11 of this issue. To join, visit our website bipolarnews.org and click on the tab for the Child Network.

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