Some Drugs for Hypertension Come with Greater Risk of Mood Disorders

July 26, 2017 · Posted in Current Treatments · Comment 

blood pressureDepression and bipolar disorder have been linked to atherosclerosis, the accumulation of fats, cholesterol, and plaques on the walls of the arteries. There is some evidence that drugs to treat hypertension may contribute to mood disorders. A large study published in the journal Hypertension in 2016 suggests that certain classes of anti-hypertensive drugs, calcium antagonists and beta blockers, may increase risk of mood disorders compared to other treatments for hypertension.

The study by researcher Angela H. Boal and colleagues used data from a hospital database to identify 144,066 patients between the ages of 40 and 80 who had taken anti-hypertensive drugs for more than 90 days. There was an independent linear connection between receiving a prescription for hypertenstion and being diagnosed with a mood disorder. Patients who took angiotensin-converting enzyme inhibitors or angiotensin receptor blocking drugs had the lowest rates of mood disorder admissions. Those taking calcium antagonists or beta blockers had an increased risk of a mood disorder, while those taking thiazide diuretics and those not taking anti-hypertensive drugs had no change in risk.

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.

Benefits of a Healthy Lifestyle

December 21, 2015 · Posted in Course of Illness, Risk Factors · Comment 

healthy lifestyleIn a talk at the 2015 meeting of the International Society for Bipolar Disorder, researcher Michael Berk suggested that a healthy lifestyle may improve mood disorder symptoms.

Diet is important. A study of more than 20,000 mothers revealed that those with unhealthy diets had children with more externalizing disorders, such as attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and mania. Diets high in fat and sugar were linked to depression. The Nurses’ Health Study, a long-term epidemiological study of 50,000 women, showed that people who exercised more were less likely to be depressed, while lower muscle mass was associated with greater depression. Exercise also has anti-inflammatory effects.

Avoiding smoking has benefits, too. A study by Pasco and colleagues showed that people who smoke are at increased risk for a new onset of a mood disorder. Smoking is associated with onset of a more severe mood disorder earlier in life, suicide attempts, alcohol and substance abuse, and decreased response to treatment. Fortunately, quitting smoking can reverse some of these risks.

A Symposium on High Risk Studies: Offspring of Parents with Bipolar Disorder

October 6, 2014 · Posted in Risk Factors · Comment 

family

In a symposium at the 2014 meeting of the International College of Neuropsychopharmacology, four researchers shared insights on children who are at higher risk for bipolar disorder because they have a parent with the disorder.

Researcher John Nurnberger has been studying 350 children of parents with bipolar disorder in the US and 141 control children of parents with no major psychiatric disorder, following the participants into adolescence. He found a major affective disorder in 23.4% of the children with parents who have bipolar disorder and 4.4% of the controls. Of the at-risk children, 8.5% had a bipolar diagnosis versus 0% of the controls.

Nurnberger found that disruptive behavior disorders preceded the onset of mood disorders, as did anxiety disorders. These diagnoses predicted the later onset of bipolar disorder in the at-risk children, but not in the controls. A mood disorder in early adolescence predicted a substance abuse disorder later in adolescence among those at risk.

In genome-wide association studies, the genes CACNA1C and ODZ4 are consistently associated with risk of bipolar disorder, but with a very small effect size. Therefore, Nurnberger used 33 different gene variants to generate a total risk score and found that this measure was modestly effective in identifying relative risk of developing bipolar disorder. He hopes that using this improved risk calculation along with family history and clinical variables will allow better prediction of the risk of bipolar onset in the near future.

Researcher Ann Duffy reported on her Canadian studies of children who have a parent with bipolar disorder and thus are at high risk for developing the disorder. In contrast to the studies of Nurnberger et al. and many others in American patients, she found almost no childhood onset of bipolar disorder before late adolescence or early adulthood. She found that anxiety disorders emerge first, followed by depression, and then only much later bipolar disorder. Bipolar disorder occurred with comorbid substance abuse disorders in only about 10-20% of cases in 1975, but substance abuse increased to 50% of bipolar cases in 2005. The incidence of comorbid substance disorder and the year at observation correlated strongly, indicating a trend toward increased substance abuse over the 30-year period.

Duffy found that having parents who were ill as opposed to recovered was associated with a more rapid onset of mood disorder in the offspring, usually in early adulthood. Duffy emphasized the need to intervene earlier in children of parents with bipolar disorder, but this is rarely done in clinical practice. Read more

Lithium Lowers Risk of Suicide

March 12, 2014 · Posted in Current Treatments · Comment 

man

Suicide is a serious risk for people with mood disorders. We have noted before that various studies of lithium show that the drug lowers suicide risk in people with mood disorders. A 2013 meta-analysis by Andrea Cipriani et al. in the journal BMJ confirms this finding. The review of 48 randomized controlled trials comparing lithium with placebo or other active drugs in the long-term treatment of mood disorders showed that lithium reduces the risk of suicide and death from any cause.

Lithium was more effective than placebo at reducing number of suicides and deaths from any cause, and more effective than carbamazepine and anticonvulsants in general at reducing deliberate self-harm. The authors wrote that lithium seems to reduce risk of suicide and death by more than 60% compared to placebo.

Lithium may reduce suicide risk by preventing relapse of mood disorders, but it may also have other mechanisms of action, such as decreasing aggression or impulsivity.

One thing to note about these findings is that the reduction in suicide risk also applies to those with unipolar depression, not just those with bipolar disorder. There is a case to be made that lithium treatment could be targeted specifically to reduce suicide risk.

Adversity May Increase Risk of Mood Disorders

October 29, 2013 · Posted in Risk Factors · Comment 

kid facing adversity

In adults with bipolar disorder, adversity in childhood has been associated with an earlier onset of bipolar disorder compared to those who did not experience some form of adversity such as verbal abuse, physical abuse, sexual abuse, loss of a parent, abandonment, or neglect. At the 2013 meeting of the Society of Biological Psychiatry, Nancy Low et al. reported that the number of these stressful life events a child experienced was associated with the number of their anxiety symptoms, psychiatric disorders, and lifetime substance abuse. Having experienced 3 or more adversities was associated with a 3.5-fold increased risk for developing a mood disorder and a 3-fold increase in anxiety disorders and alcohol or drug abuse.

While the study has not yet been published in a peer-reviewed journal, the abstract (#194) may be found in the meeting supplement, Volume 73, Number 9S of the journal Biological Psychiatry.

Editor’s Note: Low’s study is the first to report that childhood adversity is a risk factor for the onset of bipolar disorder in the general population.

Given the increasing evidence for the persistence of epigenetic marks on DNA and histones (which can’t change the sequence of genes but can change their structure) in those who have experienced such stressors in childhood, this could provide a mechanism for the long-term vulnerability of these children to the development of mood disorders and a variety of physical illnesses.

CRP in Blood Predicts Onset of New Episode in Childhood Mood Disorders

July 16, 2013 · Posted in Diagnosis, Risk Factors · Comment 
C-reactive protein

C-reactive protein

At the 2013 meeting of the International Society for Bipolar Disorders, researcher Barbara Gracious presented evidence that increased levels of high sensitivity c-reactive protein (hsCRP), a marker of inflammation, were associated with an increased risk for developing a full-blown mood episode in 71 youth (average age 13.8) participating in a study called Longitudinal Assessment of Manic Symptoms (LAMS-2).  The children were selected for the study because they had manic symptoms that were not severe enough to meet criteria for a diagnosis of bipolar I or II disorder. This research has not yet been published in a peer-reviewed journal, but the abstract can be found in first 2013 supplement of the journal Bipolar Disorders (page 67).

CRP levels are also known to predict cardiovascular disease and Type II diabetes.

Levels of 25-OH vitamin D, TNF?, and IL-6 did not predict a later mood disorder.

Editor’s Note: These data suggest the importance of assessing CRP and other markers in youth who are either prodromal (having early symptoms of a mood disorder) or at high risk because of a family history of a mood disorder.

The next step for clinical research would be to determine what treatment might decrease CRP and whether it would also prevent the development of mood episodes.

Harsh Physical Punishment is Associated with Mood and Other Disorders

April 11, 2013 · Posted in Risk Factors · Comment 

physical punishment

Physical punishment of children has long been a controversial subject. A 2012 article by Afifi et al. in the journal Pediatrics suggests that having experienced harsh physical punishment during childhood is associated with mood disorders, anxiety disorders, substance abuse and dependence, and personality disorders in adulthood.

In this study harsh physical punishment included pushing, grabbing, shoving, slapping, or hitting. Participants who had experienced more severe maltreatment in childhood (including physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect, and exposure to violence between intimate partners) were excluded from the study, and the results were adjusted for sociodemographic variables and family history of dysfunction, suggesting that physical punishment was the mediator of these effects.

Women with Bipolar Disorder at Higher Risk for Postpartum Depression

April 9, 2013 · Posted in Risk Factors · Comment 

postpartum depressionThe risk of having a depressive episode during pregnancy compared to afterward have not often been studied. A 2011 review article by Viguera et al. in the American Journal of Psychiatry compared rates of affective episodes among women with bipolar I and II disorders and recurrent major depressive disorder, both during pregnancy and the postpartum period. Risks were higher for women with bipolar disorder.

Among women with bipolar disorder, 23% experienced mood episodes during the pregnancy, while 52% had an episode in the months after giving birth. Among women with unipolar depression, 4.6% had a mood episode during pregnancy, while 30% did during the postpartum period, which is about double the risk seen in the general population. Depression was the most common type of morbidity the women experienced before and after giving birth.

Risk factors associated with mood episodes during pregnancy included (in descending order): younger age at illness onset, previous postpartum episodes, fewer years of illness, bipolar disorder, fewer children, and not being married. Risk factors associated with postpartum episodes included: younger age at illness onset, illness during pregnancy, bipolar disorder, fewer children, and more education.

Editor’s Note: The risk of postpartum depression increases from 15% in the general population, to 30% among women with unipolar disorder, to 50% in women with bipolar disorder. Special precautions should be taken to monitor and treat depression during and after pregnancy, in all women but particularly in those with a prior history of unipolar or bipolar disorder.

Obesity and Bipolar Disorder: News from the American Academy of Child and Adolescent Psychiatry

April 23, 2012 · Posted in Current Treatments, Risk Factors · Comment 

Overweight boyAt the annual meeting of the American Academy of Child and Adolescent Psychiatry in Toronto in October 2011, a symposium on the impact of obesity on the course of childhood onset bipolar illness was held.

Typical Treatment of Bipolar Disorder in Youth

David Axelson described the typical outcome of bipolar illness and the medications used during naturalistic treatment. The data came from the large collaborative Course and Outcome of Bipolar Illness among Youth (COBY) study, in which he and his colleagues followed 255 patients with bipolar I disorder (BP I), 30 patients with bipolar II (BP II), and 153 patients with bipolar not otherwise specified (BP NOS) for a mean of 5 years. He discussed only BP I children at the symposium.

The study initially followed 270 BP I children for a mean of 582 weeks. They ranged in age from 7 to 17 years (average 14.4 years). Ninety-three percent of the children were treated with one or more antimanic (AM) agents. These included atypical antipsychotics (AA) in 77%, valproate or carbamazepine in 44%, and lithium in 47%. Antidepressants (ADs) were used in 46% of the children, stimulants in 43%, and benzodiazepines in 21%. Sixty percent had been on two classes of antimanic medications concurrently at some point.

A univariate analysis showed that older children received smaller amounts of antipsychotics and more anticonvulsants and lithium. Variables associated with better response, that is, a rating of either much or very much improved on the Clinical Global Impressions scale for bipolar disorder (CGI-BP), included older age and treatment with atypical antipsychotics. Those who had comorbid attention deficit hyperactivity disorder (ADHD) or psychosis at baseline did more poorly.  Mean symptom scores were better when the children received any anti-manic treatment including an atypical or lithium, but worse when they received valproate or carbamazepine.

These data are similar to those from other prospective treatment outcome studies in childhood-onset bipolar I illness. Taken together they all suggest that the illness is difficult to treat and stabilize even when multiple medicines are used in combination.

Obesity and Mood Disorders in Youth

Another speaker, Ben Goldstein, indicated that in the scientific literature, obesity has been associated with a higher number of depressive episodes and longer length of depression, more recurrences of depression, more anxiety disorders, increased numbers of hospitalization, more suicide attempts, and worse functional outcomes. In the same group of patients discussed by Axelson above, 42% were overweight or obese, compared to a 34% incidence in the general population of children in this age range.

Factors associated with overweight included substance abuse, a history of physical abuse, prior hospitalization, and being on 2 or more medications. Those who were overweight or obese spent more time ill in a manic or depressive episode. Read more

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