Fish Oil Monotherapy on Depression in Adolescents at High Risk for Bipolar I Disorder: Ambiguity Persists

omega-3 fatty acids
Fish oil supplements

Researcher Robert K. McNamara and colleagues reported in the Journal of Child and Adolescent Psychopharmacology in a 2020 article that 12 weeks of treatment with omega-3 fatty acids in the form of fish oil did not reduce depression symptoms in adolescents at risk for bipolar disorder when compared to placebo. The primary outcome measured was the results of the Childhood Depression Rating Scale-Revised (CDRS-R).

Fish oil did perform better than placebo on two parts of the rating scale: symptom severity and symptom improvement, especially in weeks 11 and 12 of the study. Omega-3 fatty acids increased creatine and choline in the anterior cingulate, and also increased polyunsaturated fatty acids in red blood cells. The treatment was safe and well-tolerated.

A total of 42 patients between the ages of 9 and 21 who had been diagnosed with depression and had at least one parent with bipolar I disorder received either placebo or 3 fish oil capsules per day. Each capsule contained 450?mg EPA, 40?mg docosapentaenoic acid (DPA), and 260?mg DHA for a total daily dose of 2130?mg EPA + DHA.

Editor’s Note: Ambiguity persists about whether omega-3 fatty acids can improve unipolar or bipolar depression, attention-deficit hyperactivity disorder (ADHD), or prevent the progression of schizophrenia symptoms to the full syndrome. Given the lack of side effects, and the documented effects on red blood cells and brain choline, clinical use of these compounds could be considered in some circumstances.

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

April 7, 2020 · Posted in Diagnosis, Potential Treatments · Comment 

teen girl on beach

At 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.

Early Recognition and Treatment Needed

Researcher Boris Birmaher, the discussant of the symposium, described a sample of 100 children between the ages of 2 and 5; half had a parent with bipolar disorder, and these were compared to community controls. Those children who had a parent with bipolar disorder had a high incidence of attention-deficit hyperactivity disorder (ADHD) and ODD, and their conversion to a diagnosis of bipolar disorder was predicted by early age of onset of bipolar disorder in the parent (again) and by the presence of family conflict.

Birmaher emphasized that a delay before children and adolescents with bipolar disorder received their first treatment for the illness had terrible effects—more suicide attempts, completed suicides, substance abuse, and school failure. Birmaher urged early recognition of bipolar disorder and adequate treatment in order to delay onset of the disorder and to render its course more benign.

Childhood-Onset Bipolar Disorder Incidence

Researcher Anna Van Meter and colleagues showed that the incidence of bipolar disorder in children is about 2% worldwide. Researcher Kathleen Merikangas and colleagues report that 80% of adolescents with a bipolar spectrum disorder are not receiving any kind of treatment. Researcher Ben Goldstein indicated that about 50% of those with a full diagnosis of bipolar disorder receive treatment in Canada (where such treatment is cost-free).

Delayed Treatment Leads to Compounding Challenges

Since longer intervals without treatment predict poorer outcomes in bipolar disorder and schizophrenia, and early onset bipolar disorder has been linked to longer delays before first treatment, a significant number of children, particularly in the US, are at risk for disastrous outcomes. Earlier recognition and treatment is imperative, especially since even bipolar disorder not otherwise specified (BP-NOS) can be severe, impairing, associated with multiple simultaneous comorbid diagnoses, and has a familial (genetic) basis.

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.

Family Focused Therapy Effective in Youth at Risk for Bipolar Disorder Who Have Early Symptoms

March 27, 2020 · Posted in Current Treatments · Comment 

familyResearcher David Miklowitz developed Family Focused Therapy (FFT), in which families of young people at risk for bipolar disorder take part in therapy, learning about the illness and practicing strategies for communication and coping.

At a symposium at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, Miklowitz reported findings from recent studies of youth who were at high risk for bipolar disorder because of a family history of the illness and the presence of early symptoms such as depression or cyclothymia or bipolar not otherwise specified (BP-NOS). Family focused therapy reduced symptoms. It also slowed onset of a first episode of mania and slowed the conversion to a diagnosis of bipolar I or bipolar II. These results converge with a total of 10 other positive studies of family focused therapy in different populations in children and adults. FFT or its equivalent should be made available to all symptomatic children who are at risk for bipolar disorder because of a family history of the disorder.

Potential Problems when Youth at Risk for Bipolar Disorder Take SSRIs

March 24, 2020 · Posted in Current Treatments · Comment 

boy with pillsAt a symposium at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Manpreet Singh reported that in youth at high risk for bipolar disorder, 53% had an adverse event while taking a selective serotonin reuptake inhibitor antidepressant (SSRI), and 26% had a new onset of suicidality while taking an SSRI. These adverse events were associated with reduced size and increased activation of the amygdala, the brain region responsible for emotion processing. Singh concluded that dysfunction in the prefrontal-limbic network may predict adverse events in children at risk for bipolar disorder when they are given SSRI antidepressants. She urged caution in the use of antidepressants in this population. Researcher Joseph Biederman echoed this caution later in the meeting.

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 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.

Psychiatric Risks in Offspring of Parents with Bipolar/Unipolar Disorders

October 25, 2019 · Posted in Risk Factors · Comment 

familyAt the 2019 meeting of the International Society for Bipolar Disorders, researcher Martin Preisig and colleagues from Lausanne, Switzerland reported on a longitudinal study of mood disorders in offspring of parents with bipolar disorder, unipolar depression, or no history of psychiatric illness. The study included 446 children (with an average age of 10.1 years at the beginning of the study), who participated for an average of 11.9 years.

Preisig and colleagues determined symptoms and other factors that preceded psychiatric illness. They found that bipolar disorder in the offspring was preceded by sub-threshold hypomania, major depression, and conduct disorder. Bipolar disorder in the offspring was also predicted by parental early-onset bipolar disorder.

Major depression was preceded by separation anxiety disorder, and witnessing violence or being a victim of sexual abuse.

Preisig and colleagues concluded that not only did bipolar disorder and major depressive disorder have different familial origins, they also had different antecedents and risk factors.

Preventing Illness in the Offspring of a Parent with Bipolar Disorder

April 18, 2019 · Posted in Potential Treatments · Comment 

family with boy

A 2018 article by researcher Robert Freedman and colleagues in the American Journal of Psychiatry reported that prenatal nutritional supplements can reduce mental illness in at-risk offspring. The article made a good case for supplementation with folate, phosphatidylcholine, and vitamins A and D.

Here we describe some additional ways to minimize risk of mental illness in children who are at risk for bipolar disorder or other mental illnesses.

Some efforts at prevention can begin even before a child is conceived. Avoiding smoking or drinking alcohol and maintaining a nutritious diet to prevent inflammation and excessive weight gain before conception could reduce adverse epigenetic effects on the offspring. Epigenetics refers to environmental influences on gene transcription. The impact of life experiences such as a mother or father’s substance use is not registered in their child’s DNA sequence, but can influence the structure of the child’s DNA or its packaging.
Maternal good health and wellbeing during pregnancy has also been shown to improve neonatal health and functioning.

Once a child is born, they can be encouraged in healthy habits, including a nutritious diet, good sleeping habits, regular vigorous exercise, and mindfulness/meditation training (which pediatric psychiatrist James Hudziak has suggested should be universal).

For a child who is beginning to develop mood or behavioral symptoms, more intensive intervention may be prudent. Research supports the effectiveness of family interventions such as family-focused therapy (FFT) for youth with depression, cyclothymia, or bipolar disorder not otherwise specified (BP-NOS) and a family history of bipolar disorder. Researcher David J. Miklowitz described the effects of this intervention in a 2013 article in the Journal of the American Academy of Child and Adolescent Psychiatry.

Depression in children 3 to 6 years of age is as common as depression in older children (with rates around 1–2%), and robust improvements have been observed when families engage in parent child interaction therapy (PCIT) with a focus on emotional development. In PCIT, parents are coached while interacting with their children and encouraged to establish warm interactions while setting appropriate limits. In a study by Joan L. Luby and colleagues published in the American Journal of Psychiatry in 2018, using PCIT modified to include an emotional development component improved depression and associated symptoms in children aged 3 to 11, and it also improved mothers’ mood and behavior. Read more

Family History of Lithium Response A Potent Predictor of Lithium Effectiveness

February 11, 2019 · Posted in Current Treatments · Comment 

family

Researcher Martin Alda and colleagues reported at a 2018 scientific meeting that a family history of good response to lithium is highly predictive of response to lithium in a current bipolar patient. A good prospective response to lithium was seen in 68.6% of patients with a family member who responded well to lithium. Only 22% of those without a family member with a positive lithium response responded well to lithium.

Editor’s Note: Other predictors of a good response to lithium include: a family history of mood disorder, classical euphoric mania with clear-cut well intervals between episodes, lack of a simultaneous anxiety or substance abuse disorder, starting lithium early rather than late in the course of illness after many episodes or rapid cycling has occurred, and a sequential pattern of episodes of mania followed by depression, and then an interval of wellness (i.e. M-D-I rather than D-M-I). Even in those without these characteristics, lithium has many benefits including neuroprotection, reduction of suicide risk, and improved medical health (perhaps through its ability to increase the length of telomeres which are bits of DNA at the end of each chromosome). Longer telomeres are protective, while people with shorter ones may be vulnerable to some medical and psychiatric illnesses.

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