Early Precursors of Mood Disorders in Young Children of Parents with Bipolar or Unipolar Disorder

July 24, 2020 · Posted in Course of Illness, Risk Factors · Comment 

At the 2020 meeting of the International Society for Bipolar Disorders, researcher Caroline Vandeleur presented findings from a 13-year study of children in Switzerland who have a parent with bipolar disorder or major depressive disorder. In contrast to findings from the US presented by Danella Hafeman, Vandeleur and colleagues found no evidence of psychopathology in 4 year-olds. They did find that in 7-year-olds, children of a parent with major depressive disorder were four times more likely to have a separation anxiety disorder. In an overall sample of 449 children with a mean age of 10 who were followed up for 13 years, major depression tended to be preceded by anxiety disorders. Participants who went on to be diagnosed with bipolar disorder had earlier symptoms of depression, subthreshold hypomania, conduct disorders, and drug abuse. These were especially common in those who had a parent with bipolar disorder.

Editor’s Note: These data indirectly confirm other observations in which children at high risk for mood disorders in the US showed earlier signs of psychopathology than those in other countries including the Netherlands and Canada.

Predicting Onset of Bipolar Disorder in Children at High Risk: Part I

April 3, 2020 · Posted in Diagnosis, Risk Factors · Comment 

teenage boy sitting on floor with arms on kneesAt the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, one symposium was devoted to new research on predicting onset of bipolar disorder in children who have a family history of the disorder. Below are some of the findings that were reported.

Symptom Progression

In offspring of parents with bipolar disorder, researcher Anne Cecilia Duffy found that symptoms in the children tended to progress in a typical sequence. Childhood sleep and anxiety disorders were first to appear, then depressive symptoms, then bipolar disorder.

Different Types of Illness May Respond Best to Different Medications

Duffy’s research also suggested links between illness features and a good response to specific medications. Those offspring who developed a psychotic spectrum disorder responded best to atypical antipsychotic medication. Those with classical episodic bipolar I disorder responded well to lithium, especially if there was a family history of lithium responsiveness. Those offspring with bipolar II (and anxiety and substance abuse) responded well to anticonvulsant medications.
If parents with bipolar disorder had experienced early onset of their illness, their children were more likely to receive a diagnosis of bipolar disorder.

The offspring of lithium-responsive parents tended to be gifted students, while those from lithium non-responders tended to be poorer students.

Comparing Risk Factors for Bipolar Disorder and Unipolar Depression

Researcher Martin Preisig and colleagues also showed that parental early onset of bipolar disorder (before age 21) was a risk factor for the offspring receiving a diagnosis of bipolar disorder. Parental oppositional defiant disorder (ODD) was also a risk factor for bipolar disorder in the offspring. The emergence of depression, conduct disorder, drug use, and sub-syndromal hypomanic symptoms also predicted the onset of mania during childhood.

Conversely, sexual abuse and witnessing violence were strong risk factors associated with a diagnosis of major (unipolar) depressive disorder. Being female and experiencing separation anxiety were also factors that predicted unipolar depression.

Predicting Conversion to Mania

Researcher Danella M. Hafeman reported that mood swings (referred to in the literature as “affective lability”), depression/anxiety, and having a parent who had an early onset of bipolar disorder were linked to later diagnoses of mania. Immediate risk factors that predicted an imminent onset of mania included affective lability, substance abuse, and the presence of sub-threshold manic symptoms.

Positive Effects of a Brief Session of Aerobic Exercise for Sedentary Children

March 31, 2020 · Posted in Current Treatments · Comment 

At a symposium at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Benjamin I. Goldstein reported that a single 20-minute session of aerobic exercise (achieving 70% of maximal heart rate) was associated with improvement in cognition and in abnormalities seen on brain imaging in young people. Goldstein urged clinicians to do motivational interviews with sedentary children in their care, emphasizing the positive cardiovascular and cognitive effects of exercise. He indicated this would be more effective than a focus only on weight loss, which is much more difficult to achieve.

Quetiapine Reduced Childhood Mania, Especially in Those with Thicker Frontal Temporal Regions

March 20, 2020 · Posted in Brain Imaging, Current Treatments · Comment 

white matterIn a symposium at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Melissa P. Delbello reported that six weeks of treatment with either lithium or quetiapine was effective in childhood mania, but quetiapine had a higher response rate of 71% versus 46% for lithium. Delbello found two types of structural changes on functional magnetic resonance imaging (fMRI). Some children had thicker frontal temporal regions, while others had thinning in these areas. The first group of patients had a 100% response to quetiapine, but only 53% of the second group responded to quetiapine.

In contrast, other researchers have found lithium superior to quetiapine. Vivian Kafantaris showed that patients who respond well to lithium show improvements in white matter abnormalities. Michael Berk and colleagues found that a year on lithium was superior to quetiapine on all measures including cognition and brain imaging in patients having their first episode of mania.

7-Year-Olds At Risk for Schizophrenia, But Not Bipolar Disorder, Show Specific Types of Cognitive Dysfunction

March 16, 2020 · Posted in Diagnosis · Comment 

young boy with question marks on a chalk boardA large Danish study investigated whether children at risk for schizophrenia and bipolar disorder would show signs of cognitive problems. The study by researcher Nicoline Hemager and colleagues was published in the journal JAMA Psychiatry in 2018.

The researchers identified 7-year-olds,197 who had family members with schizophrenia, 118 who had family members with bipolar disorder, and 199 control 7-year-olds with no family history of these illnesses. Those children at risk for schizophrenia had significantly more cognitive deficits and behavioral disorders than the controls, while those children at risk for bipolar disorder did not differ significantly from the controls. The deficits among the children at risk for schizophrenia were in the areas of processing speed and working memory, executive and visuospatial functions, and declarative memory and attention.

The researchers indicated that the neurocognitive profile seen in the children at risk for schizophrenia could help clinicians identify these children for early intervention.

Lithium Effective for Maintenance Treatment of Childhood-Onset Bipolar Disorder

March 10, 2020 · Posted in Current Treatments · Comment 

little girl with therapist

Evidence has been accumulating that lithium is effective in the treatment of young people with bipolar disorder. In a study by Robert Findling and colleagues published in the Journal of the American Academy of Child and Adolescent Psychiatry in 2018, participants aged 7–17 who responded well to lithium during a 24-week study were then randomized to receive either lithium continuation (17 participants) or placebo (14 participants) for 28 more weeks.

Those who continued lithium treatment were more likely to stay in the study. Participants who discontinued the study mostly reported that they did so due to re-emergence of their mood symptoms (mostly in the placebo group).

Lithium was well-tolerated and was not associated with any more weight gain than placebo. This study adds to the growing literature on the effectiveness and tolerability of lithium both acutely and in maintenance treatment in childhood bipolar disorder.

Lithium Better than Other Mood Stabilizers for Youth with Bipolar Disorder

March 6, 2020 · Posted in Current Treatments · Comment 

A new study by Danella M. Hafeman and colleagues finds that lithium is superior to other mood stabilizers in young people. The data in this case come from 340 youth aged 7–17 who participated in a study known as Course and Outcome of Bipolar Youth (COBY).

At each visit over an average of 10 years, participants reported medications taken, symptoms they had experienced, etc. during the preceding six-month period. During times that participants had taken lithium (compared to other mood stabilizers) they were older, on fewer antidepressants, and they were less likely to have an anxiety disorder.

Those participants who took lithium had half as many suicide attempts, fewer depressive symptoms, less psychosocial impairment, and less aggression than those who took other mood stabilizers.

The researchers concluded, “Findings are consistent with adult studies, showing that lithium is associated with decreased suicidality, less depression, and better psychosocial functioning. Given the paucity of evidence regarding lithium in children and adolescents, these findings have important clinical implications for the pharmacological management of youth with bipolar disorder.”

Editor’s Note: Lithium should especially be considered in those with a family history of mood disorders, and in particular in those with a family history of good response to lithium. Lithium is under-prescribed in both adults and children and should be given much higher consideration in light of the multiple benefits it provides in addition to mood stabilization. These include maintenance of memory, increases in longevity (perhaps based in its ability to increase the length of telomeres, the bits of protective material at the end of DNA strands that deteriorate with age and illness), and neuroprotection against loss of gray and white matter volume in the brain, which often occurs in mood disorders.

Prazosin Effective and Well-Tolerated for PTSD in Young People

March 2, 2020 · Posted in Potential Treatments · Comment 

young woman sleeping

In a poster session at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry (AACAP), three posters highlighted the efficacy and tolerability of prazosin, a drug typically used to treat high blood pressure, for the treatment of childhood-onset post-traumatic stress disorder (PTSD).

Researchers Samira Khan and Taniya Pradhan of West Virginia University reviewed cases in which 39 patients aged 8–19 received 1–5 mg of prazosin at bedtime. The mean dose was 1.72 mg. Sleep (including nightmares) improved in 92.3% of the youths, and mood improved in 33.3%. Sleep improved more in patients who received lower doses (1–2 mg) than those who received higher doses. About 70% of the patients whose data were included in the case series were also receiving psychotherapy while being treated with prazosin.

In another poster, researcher Vladimir Ferrafiat and colleagues from University Hospital of Rouen in France reported on a prospective study of 18 participants under age 15 with severe PTSD who were unresponsive to other medications. The participants were given 1 mg of prazosin at bedtime, which was increased to 3 mg in 20% of the participants. The youth were assessed weekly over a one-month period. Improvement was seen in all domains, including sleep, nightmares and daytime intrusive symptoms. Prazosin was well tolerated, with only one patient experiencing low blood pressure, which did not necessitate withdrawal from the study.

In the final poster, researcher Fatima Motiwala and colleagues reviewed the literature on the treatment of PTSD in children. Motiwala indicated that among the options, prazosin was widely used in her hospital, at doses starting at 1 mg given at bedtime and increasing to a mean of 4 mg at bedtime with excellent results and tolerability.

Editor’s Note: Although these were not double-blind controlled studies, the findings are noteworthy in that they provide consistent data on the effectiveness and tolerability of prazosin in low doses in children with PTSD, essentially mirroring controlled data in adults, where higher doses are typically required.

Lithium Reverses Some White Matter Abnormalities in Youth with Bipolar Disorder

July 23, 2019 · Posted in Brain Imaging, Current Treatments · Comment 

white matterMultiple groups of researchers have reported the presence of white matter tract abnormalities in patients with bipolar disorder. Some of these abnormalities correlate with the degree of cognitive dysfunction in these patients. These white matter tract abnormalities, which are measured with diffusion tensor imaging (DTI), are widespread and can appear as early as childhood in people with bipolar disorder. Researcher Vivian Kafantaris mentioned at the 2019 meeting of the International Society for Bipolar Disorders that lithium treatment in children and adolescents normalizes these alterations, as described in an article she and her colleagues published in the journal Bipolar Disorders in 2017.

Editor’s Note: This is another reason to consider the use of lithium in children with bipolar disorder. Lithium treatment may help normalize some of the earliest signs of neuropathology in the illness.

Lithium FDA-Approved for Bipolar Disorder in Children 7–17

July 19, 2019 · Posted in Current Treatments · Comment 

lithiumIn April 2019, the US Food and Drug Administration approved lithium for both the acute treatment of mania and for ongoing maintenance treatment of bipolar disorder in children and adolescents aged 7 to 17. Combined analysis of several studies indicates that lithium is effective and well-tolerated in both children and adolescents with bipolar disorder, both for acute treatment and to prevent bipolar episodes.

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