Cannabis May Produce More Brain Changes in Teens with Bipolar Disorder than in Healthy Teens

October 31, 2019 · Posted in Risk Factors · Comment 

smoking

At the 2019 meeting of the International Society for Bipolar Disorders, researcher Benjamin Goldstein of Sunnybrook Research Institute in Toronto reported that adolescents with bipolar disorder who smoked marijuana had greater deficits in certain brain areas than did adolescents who did not have bipolar disorder. The areas affected included the dorsal lateral and rostral middle frontal cortex, and middle cortex. Goldstein concluded, “Adolescents with [bipolar disorder] may be particularly sensitive to the neurostructural effects of cannabis.”

Marijuana in general causes adverse changes in brain structure and cognition and vulnerability to paranoia and psychosis. Heavy use in adolescence is associated with an increased incidence of the onset of bipolar disorder and schizophrenia. The Goldstein data suggest several possible causal mechanisms. Those with bipolar disorder may already have brain abnormalities that are exacerbated by marijuana use. Alternatively, marijuana and bipolar disorder together may impact brain structure more than either factor alone would.

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.

Comorbid Psychiatric Disorders Impair Response to Psychosocial Treatment in Adolescents with Bipolar Disorder

October 21, 2019 · Posted in Comorbidities · Comment 

teenagers

At the 2019 meeting of the International Society for Bipolar Disorders, researcher Marc J. Weintraub and colleagues followed 145 adolescents with bipolar disorder over a period of two years. The adolescents with comorbid disorders (compared to those with bipolar disorder alone) fared more poorly in response to psychosocial treatment.

Weintraub and colleagues found that the adolescents who had anxiety disorders in addition to their bipolar disorder spent more weeks depressed, had more severe symptoms of (hypo)mania, and had more family conflict over the course of the study than those adolescents who had bipolar disorder alone.

Participants who had attention deficit hyperactivity disorder (ADHD) in addition to their bipolar disorder had more weeks with (hypo)manic symptoms, had more severe (hypo)manic symptoms, and greater family conflict than those with bipolar disorder alone.

Those participants with comorbid oppositional defiant disorder (ODD) or conflict disorder in addition to their bipolar disorder had more depressive symptoms and family conflict throughout the study.

Editor’s Note: How to better approach treatment in these diagnostically complex young people is an urgent unmet need, as most research excludes participants with more than one psychiatric disorder. Clinicians treating young people with bipolar disorder and comorbidities such as anxiety disorder, ADHD, and ODD must generally rely on inferences from children with these illnesses, using their own intuition about best treatment approaches rather than having evidence from systematic studies about how best to treat these children. It appears that both psychosocial and pharmacological treatments must be tailored to these more complicated presentations.

Lithium Reverses Thinning of the Cortex That Occurs in Bipolar Disorder

October 9, 2019 · Posted in Brain Imaging · Comment 

gray matter

In a 2018 article in the journal Molecular Psychiatry, researcher Derrek P. Hibar reported findings from the largest study to date of cortical gray matter thickness. Researchers in the ENIGMA Bipolar Disorder Working Group, which comprises 28 international research groups, contributed brain magnetic resonance imaging (MRI) from 1837 adults with bipolar disorder and 2582 healthy control participants.

Hibar and colleagues in the working group found that in adults with bipolar disorder, cortical gray matter was thinner in the frontal, temporal, and parietal regions of both brain hemispheres. They also found that bipolar disorder had the strongest effect on three regions in the left hemisphere: the pars opercularis, the fusiform gyrus, and the rostral middle frontal cortex.

Those who had had bipolar disorder longer (after accounting for age at the time of the MRI) had less cortical thickness in the frontal, medial parietal, and occipital regions.

A history of psychosis was associated with reduced surface area.

The researchers reported the effects of various drug treatment types on cortical thickness and surface area. In adults and adolescents, lithium was associated with improvements in cortical thickness, and the researchers hypothesized that lithium’s protective effect on gray matter was responsible for this finding. Antipsychotics were associated with decreased cortical thickness.

In people taking anticonvulsant treatments, the thinnest parts of the cortex were the areas responsibly for visual processing. Visual deficits are sometimes reported in people taking anticonvulsive treatments.

Mounting Evidence of Mitochondrial Dysfunction in Bipolar Disorder

July 16, 2019 · Posted in Risk Factors · Comment 
mitochondrion

mitochondrion

At the 2019 meeting of the International Society for Bipolar Disorders, researchers Ana Andreazza, Olivia Dean and colleagues reviewed substantial data that implicate mitochondrial dysfunction in the mood and energy fluctuations that make up bipolar disorder. Most of the neurobiological alterations known to occur in bipolar disorder have a relationship to mitochondria, which produce energy within cells. These alterations include abnormalities in glutamate, gene expression, apoptosis (cell death), oxidative stress, low ATP (a molecule that stores energy), altered ion pumps, increased intracellular calcium, and insufficient glutathionine (an antioxidant made up of three amino acids).

Coenzyme Q10 is a mitochrondrial enhancer of Complex I, an enzyme that is key to the first step in mitochondrial energy production. A 2018 controlled study by Maryam Mehrpooya and colleagues published in the Journal of Clinical Psychopharmacology found that 200mg/day of CoQ10 was more effective than placebo at reducing symptoms of bipolar depression when added to patients’ stable treatment regimens that included mood stabilizers and antidepressants. The effect size was large (0.87), and it took eight weeks for the benefit over placebo to appear. Response rate to CoQ10 was 72% compared to 12% to placebo.

Editor’s Note: Some formulations of CoQ10 do not cross the blood-brain barrier easily, so only a very small percentage of the CoQ10 gets into the brain. Thus, consumers should be careful about the type of product they purchase. The one made by Takeda Pharmaceutical Company is likely to be effective.

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

Nimodipine Decreases Frontal and Parietal Cortical Activity During Working Memory in Healthy Subjects

January 30, 2019 · Posted in Genetics, Potential Treatments · Comment 

brain

At a recent scientific meeting, researcher Kristin Bigos and colleagues described the effects of nimodipine, a treatment for brain hemorrhage, on the brain during working memory tasks. Nimodipine is a dihydropyridine L-type calcium channel blocker. Calcium channel blockers prevent calcium from entering cells in the heart and blood vessel walls, and they are often used to treat high blood pressure.

Nimodipine acts on the CACNA1C calcium influx gene. Certain genetic variations in this gene (particularly the rs1006737 A allele) have been linked to vulnerability to bipolar disorder, schizophrenia, depression, and autism. Carriers of the risk allele also have higher CACNA1C mRNA expression in the dorsolateral prefrontal cortex and exhibit more activity in the frontal and parietal regions of the brain during working memory tasks, suggesting inefficient brain processing in these regions. Bigos and colleagues found that 60mg/day of nimodipine decreased frontal and parietal cortical activity by 39.1% and 42.8%, respectively, during a working memory task, suggesting that nimodipine improved the efficiency of memory processing. Nimodipine’s positive effects were greater in those participants who had the CACNA1C risk allele.

Editor’s Note:  Using a placebo-controlled off-on-off-on study design (meaning patients took placebo for a period, then nimodipine, then placebo again and nimodipine again), this editor (Robert M. Post), Peggy J. Pazzaglia and colleagues found that nimodipine had positive effects in both mania and depression in patients with bipolar disorder (described in the 2008 book Treatment of Bipolar Disorder: A Casebook for Clinicians and Patients by Robert M. Post and Gabriele S. Leverich). In a large randomized study of patients with bipolar disorder presented by Haroon R. Chaudhry at the 2010 meeting of the Society of Biological Psychiatry, lithium was associated with about a 50% response rate while the combination of lithium and nimodipine was associated with a 73% response rate.

It remains to be seen whether people with bipolar disorder who have the CACNA1C risk gene would respond better to nimodipine than those without the risk gene, and whether it would improve working memory more in the subgroup with the risk gene.

Inflammation Linked to Poor Sleep Quality and Worse Executive Functioning

January 18, 2019 · Posted in Risk Factors · Comment 

man drooling while sleeping

At a recent scientific meeting, researcher Ellen E. Lee and colleagues reported that compared to healthy volunteers, people with bipolar disorder or schizophrenia had elevated levels of inflammatory markers, which were associated with poor sleep. 

According to self-reports, people in the schizophrenia and bipolar disorder group had worse sleep quality than the control group. Those with schizophrenia or bipolar disorder also had significantly higher levels of the inflammatory markers CRP, IL-6, and TNF alpha compared to the healthy volunteers. Among people with bipolar disorder, executive functioning and sleep quality had a strong inverse association to levels of IL-6, such that lower sleep quality and worse executive functioning were associated with higher levels of IL-6. These findings suggest that sleep disturbance and inflammation may have negative consequences for cognitive functioning.

White Matter Abnormalities in Obesity

January 16, 2019 · Posted in Brain Imaging, Neurobiology · Comment 

obese man

Researcher Ramiro Reckziegel and colleagues reported at a recent scientific meeting that white matter is abnormal in obese adults with bipolar disorder. In a 2018 article in the journal Schizophrenia Bulletin, Reckziegel reported that body mass index (BMI) was associated with reduced fractional anisotropy, a measure of brain fiber integrity, in the cingulate gyrus in patients with bipolar disorder. This finding implies that obesity may play a role in white matter microstructure damage in the limbic system.

White Matter Abnormalities Linked to Irritability in Both Bipolar Disorder and DMDD

January 14, 2019 · Posted in Brain Imaging, Neurobiology · Comment 

white matterAt a 2018 scientific meeting, researcher Julia Linke of the National Institute of Mental Health reported that there were white matter tract abnormalities in young people who had irritability associated with either bipolar disorder or disruptive mood dysregulation disorder (DMDD). Thus, while these two disorders differ in terms of diagnosis, presentation, and family history, they seem to have this neurobiological abnormality in common.

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