Cannabidiol (CBD) does not make cannabis safer
Amir Englund et al reported in Neuropsychopharmacology in A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios that CBD did not protect against the adverse effect of THC. These included impaired delayed verbal recall ( p?=?0.001) and induced positive psychotic symptoms on the PANSS ( p?=?2.41?×?10–5).
Editors Note: Not only does marijuana impair memory, it is a risk factor the onset of bipolar disorder and schizophrenia. When pot is used by a person with a unipolar or bipolar mood disorder, there are increases in depression and anxiety and an overall less favorable course of illness. If a person with a mood disorder uses heavy amounts of marijuana, they could consider buying N-acetylcysteine (NAC) 500mg and increasing the dose to 1,000mg twice a day within a week as this has been shown to decrease drug use compared to placebo in adolescents and young adults using and abusing pot. Most people who sell pot, are not well-informed about its dangers and just want to make money.
PREVENT EPISODES, PROTECT YOUR BRAIN, BODY, AND SELF
Kessing and Andersen 2017 wrote:”Overall, increasing number of affective episodes seemsto be associated with:(i) increasing risk of recurrence, (ii) increasing duration of episodes, (iii) increasing symptomatic severity of episodes,(iv) decreasing threshold for developing episodes, and (v) increasing risk of developing dementia.
Conclusion: Although the course of illness is heterogeneous, there is evidence for clinical progression of unipolar and bipolar disorder.”
These adverse outcomes emphasize the importance of early and sustained treatment to prevent the occurrence and accumulation of episodes.
ADHD Common in People with Mood Disorders
In a meta-analysis published in the journal Acta Psychiatrica Scandinavica in 2021, researcher Andrea Sandstrom and colleagues reported that people with mood disorders had a three times higher incidence of attention-deficit hyperactivity disorder (ADHD) than people without mood disorders. ADHD was also more likely to occur in people with bipolar disorder than in people with major depression. The comorbidity is most common in childhood, less so in adolescence, and lowest in adulthood.
Based on 92 studies including a total of 17,089 individuals, the prevalence of ADHD in people with bipolar disorder is 73% in childhood, 43% in adolescence, and 17% in adulthood. Data from 52 studies with 16,897 individuals indicated that prevalence of ADHD in major depressive disorder is 28% in childhood, 17% in adolescence, and 7% in adulthood.
Editor’s Note: A key implication of this research is that there is a huge overlap of bipolar disorder and ADHD in childhood, and that physicians need to specifically look for bipolar symptoms that are not common in ADHD to make a correct diagnosis. These include: brief or extended periods of mood elevation and decreased need for sleep in the youngest children; suicidal or homicidal thoughts and threats in slightly older children; hyper-sexual interests and actions; and hallucinations and delusions. When these are present, even when there are also clear-cut ADHD symptoms, a clinician must consider a diagnosis of bipolar disorder and treat the child with mood stabilizers prior to using stimulants or other traditional ADHD medications.
Conversely, physicians should be aware of the much lower incidence of ADHD in adolescents and adults with bipolar disorder. Here one should first make sure that the apparent ADHD symptoms of hyperactivity, inattention, poor concentration, etc. do not result from inadequately treated mania and depression, and if they do, treat these symptoms to remission prior to using traditional ADHD medications.
Study Examines Comorbidity of ADHD and Bipolar Disorder
In a 2021 review and meta-analysis in the journal Neuroscience and Biobehavioral Reviews, researcher Carmen Schiweck and colleagues described the comorbidity of attention-deficit hyperactivity disorder (ADHD) and bipolar disorder in adults. This was the first review and meta-analysis to quantify the comorbidity of the two fairly prevalent disorders. The meta-analysis included 71 studies with a combined total of 646,766 participants from 18 countries.
The review found that among people with ADHD, about 1 in 13 also have bipolar disorder, while among people with bipolar disorder, 1 in 6 have comorbid ADHD. The prevalence differed depending on the continent where patients lived and the diagnostic systems used there, with greater prevalence of both disorders in the US, where the Diagnostic and Statistical Manual of Mental Disorders is used, than in Europe, where the International Classification of Diseases is typically used. (Other parts of the world were less represented in the meta-analysis.) Schiweck and colleagues found that bipolar disorder had an onset about 4 years earlier in patients who had comorbid ADHD.
Insomnia Plays Critical Role in Bipolar Disorder
In a 2021 article in the Journal of Psychiatric Research, researcher Laura Palagini and colleagues reported that insomnia symptoms can affect the course of bipolar illness. In a helpful summary and interview in the Psychiatry & Behavioral Health Learning Network’s Psych Focus, she stated that:
“1) BD patients in a depressive phase with clinically significant insomnia met a greater severity not only of depressive symptoms and suicidal risk, but also of early life stressors and the cognitive part of hopelessness, compared with patients without insomnia
“2) insomnia symptoms could predict mood symptoms, suicidal ideation and plans, and the cognitive component of hopelessness
“3) insomnia symptoms might mediate the effect of early life stressors on mood symptoms, hopelessness, and suicidal ideation and behaviors.”
Palagini suggested that “Insomnia symptoms should be easily addressed in clinical practice with 1–2 questions. Insomnia treatment should be considered as a treatment to prevent …relapse and recurrence [of bipolar disorder] and to prevent suicide and the effect of early life stress on [bipolar disorder].”
Editor’s Note: Regular nightly rating of mood, functioning, hours of sleep, medications, life events, side effects, and other comorbid symptoms on the Monthly Mood Chart Personal Calendar (pdf) is an easy way for patients with bipolar disorder to carefully track their illness trajectory and the completeness of their response to medications.
A decrease in the hours of sleep should be used as a possible early warning sign of impending difficulties, or even a new episode. Patients should discuss with their physician the threshold of insomnia (such as the loss of 2 hours of sleep for two days in a row) that should trigger a call to the physician, and what interventions the patient might initiate for lesser amounts of sleep loss and/or changes in mood. Heading these off early may prevent the breakthrough of a full-blown manic or depressive episode.
Early Precursors of Mood Disorders in Young Children of Parents with Bipolar or Unipolar Disorder
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.
Danish Population-Based Study Identifies New Drug Candidates for Bipolar Disorder
At the 2020 meeting of the International Society for Bipolar Disorders, Lars Kessing of the Psychiatric Center Copenhagen described a study that examined incidence of bipolar disorder among a total of 1,605,365 participants who purchased one of six common medications over a ten-year-period, with the goal of identifying drugs that might be repurposed to prevent or treat bipolar illness. The drugs were non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen), low-dose aspirin, high-dose aspirin, statins, allopurinol, and angiotensin.
Because Denmark has population-based healthcare data, the researchers were able to identify participants who purchased these medications between 2005 and 2015, and could also assess these participants for two outcome measures: 1) whether they had received a diagnosis of mania or bipolar disorder as an inpatient or outpatient at a psychiatric hospital, and 2) a combined measure of whether they had received a diagnosis for mania or bipolar disorder in any setting or initiated lithium use. The data on these participants were compared to a random sample of 30% of the population of Demark.
Kessing and colleagues found that among those with steady use of low-dose aspirin, statins (used to lower blood cholesterol), and angiotensin agents (which can lower blood pressure), there was a significant decreased incidence of mania/bipolar disorder on both outcome measures.
In contrast, among those taking non-aspirin NSAIDs and high-dose aspirin, there was an increased incidence of bipolar disorder. (There were no statistically significant findings with regard to allopurinol, which is used to treat gout and kidney stones.)
The researchers concluded that population-based studies such as these can be used to identify drugs that may have secondary benefits, in this case low-dose aspirin, statins, and angiotensin agents, which have already been identified as potentially therapeutic in other research.
Cognitive Abnormalities in Patients Recently Diagnosed with Bipolar Disorder
At the 2020 meeting of the International Society for Bipolar Disorders, researcher Kamilla Miskowiak described a study in which she and her colleagues grouped 158 patients in remission from recently diagnosed bipolar disorder into groups based on their neurocognitive functioning and particularly their emotional processing, and also observed cognitive function in 52 first-degree relatives of those with bipolar disorder. These groups were compared to 110 healthy control participants.
Miskowiak and colleagues identified three clusters among the patients with bipolar disorder: 23% were globally impaired, 31% were selectively impaired, and 46% had normal cognition. Those who were globally impaired had problems recognizing facial expressions in social scenarios. Cognitive impairment has previously been documented in patients who have had a longer duration or more episodes of bipolar illness.
First-degree relatives of cognitively impaired patients had impaired recognition of facial expressions, but their cognition in non-emotional areas was normal. Miskowiak and colleagues concluded that the impaired affective cognition in relatives of patients with neurocognitive impairment was an indication of inherited risk for bipolar disorder.
Editor’s Note: Children with bipolar disorder also have this deficit in facial emotion recognition. That 23% of recently diagnosed patients with bipolar disorder were globally impaired indicates that some cognitive impairments can emerge early in the course of bipolar disorder. Researcher Lakshmi Yatham has previously found that cognition improves after a first episode of mania only if no further episodes occur in the one year following, indicating that episode prevention is crucial even after a patient’s first episode.
White Matter Disturbances in Bipolar Disorder
At the 2020 meeting of the International Society for Bipolar Disorders, researcher Clare Beasley described the cellular and molecular underpinnings of the white matter abnormalities typically seen in children and adults with bipolar disorder. Researchers consistently see white matter abnormalities in neuroimaging studies of bipolar disorder, but not much is understood about what creates these deficits.
Beasley and colleagues studied autopsy specimens and found that compared to controls, people with bipolar disorder had a number of abnormalities affecting glial cells, lipid composition, and axons.
The researchers found increased density of oligodendrocytes (glial cells that produce the myelin that wraps around axons, the long fibers of nerve cells where impulses travel out to other cells) and an associated protein called CNP in the prefrontal cortex. The myelin is what makes up white matter, while gray matter consists of cell bodies of neurons and glial cells.
People with bipolar disorder also had differently-shaped astrocytes, another type of glial cell that abuts synapses. The researchers found changes in lipid composition, including phospholipid and fatty acid levels, in the white matter of people with bipolar disorder. There were also problems with axons. Beasley and colleagues noted lower density of axon-associated proteins, which are involved in transport of substances along the axons in people with bipolar disorder.
The authors conclude that these data implicate specific disturbances in oligodendrocytes and axonal function associated with the white matter alterations usually seen in neuroimages of people with bipolar disorder.
Bipolar Disorder in Pregnancy and the Postpartum Period
At the 2020 meeting of the International Society for Bipolar Disorders, researcher Veerle Bergink reported several findings from a recent meta-analysis of articles on pregnancy and bipolar disorder. Bergink and colleagues found that pregnant women with bipolar disorder have a 37% risk of a postpartum relapse, more than twice the risk of postpartum mental disorders in the general population.
Using lithium as a treatment in the first trimester of pregnancy increased risk of congenital malformations in the fetus, but the risk was much smaller than previously thought and could be monitored by ultrasound.
Bergink and colleagues also reported that in a sample of 645 women with first-onset postpartum psychosis who received followup over a period of 7 to 25 years, 43% had no subsequent severe episodes outside of the postpartum period.
Another finding was that women with postpartum severe depression or mania had abnormalities in T cells, which are important in immune response.
