Both Obesity and Bipolar Disorders in 2249 Individuals Show White Matter Microstructure Abnormalities
Lorielle Dietze of Dalhousie University “obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) values from 930 individuals with bipolar disorders (BD), and 1319 control individuals from 20 cohorts in the ENIGMA-BD Working Group.”
They “found that lower FA was associated with both BD and BMI, in five white matter tracts, including the corpus callosum and thalamic radiation. Nine ROIs were correlated with only BD, while higher BMI was uniquely correlated with lower FA in four white matter ROIs.”
They concluded: “For the first time we showed that both obesity and BD demonstrated lower FA in some of the same regions. The impact of obesity may be greater in some tracts in BD individuals.”
Greater Severity of Depression in Youth With Bipolar Disorder versus Unipolar Depression
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Aaron Silverman of the University of Toronto, CAMH found that “youth (age 13-21) with [Bipolar Disorders] compared to those with [unipolar] depression had significantly higher (more severe) ratings on depressed mood (p = .001), irritability (p = .037), anhedonia (p = .004), negative self-image (p < .001), hopelessness (p = .04), fatigue (p = .001), hypersomnia (p = .001), suicidal ideation (p = .04), and recurrent thoughts of death (p < .001).”
The Systematic Treatment Optimization Program for Early Mania
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
A. Rathseesh and L. Yatham reported on the importance of systematic vigorous treatment of a first manic episode. If more episodes occurred, losses in cognition did not fully recover. All patients remitted within 1 year of their first mania. Recurrence occurred in 58% by year 1 and 74% by year 4. Predictors of functional recovery included sustained euthymia, especially absence of depressive symptoms, good cognitive functioning, and maintaining a normal weight. More aggressive treatment to prevent relapses in years 1-4 after a first manic episode appears needed and how exactly to achieve this requires further study.
Disrupted Circadian Temperature Rhythm in Skin Temperature in Bipolar Mania
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Andrea Stautland of University of Bergen studied the nocturnal temperature of sleeping participants in mania and during remission between 3:00am and 6:00am (n=12). In mania, but not in remission there were “highly significant mean changes (lack of night time decreases) between baseline and 4:30am and 6:00am, with p=0.012 and p=0.037, respectively.”
Editors Note: This data is of interest in light of the new subtype of unspecified bipolar disorder called Temperature and Sleep Dysregulation Disorder (TSDD) characterized by profound behavioral dyscontrol, marked sleep disturbance, and temperature dysregulation (red face and ears, being too hot, going out in the cold underdressed). This extremely dysfunctional syndrome responds to high dose lithium; melatonin, clonidine, and other cooling techniques; and ascending and then repeated doses of intranasal ketamine (as described by Papolos et al 2013; 2018).
Early Antidepressant Use is Associated with Rapid Cycling Bipolar Disorder
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
A.C. Courtes and Jair Soares reported that “Antidepressants were prescribed as the first psychiatry medication in 74/114 (65%) of BD patients.” This and alcohol use disorder were independent predictors of rapid cycling.
Cannabis Use Disorder Increases Risk of Subsequent Unipolar Depression and Bipolar Disorder
Jefsen et al report in JAMA Psychiatry. that in “[6,651,765] individuals in Demark, cannabis use disorder was associated with an increased risk of (subsequent) both psychotic and nonpsychotic unipolar depression and bipolar disorder….Associations between CUD and subsequent affective disorders were estimated as hazard ratios (HRs) using Cox proportional hazards regression with time-varying information on CUD, adjusting for sex; alcohol use disorder; substance use disorder; having been born in Denmark; calendar year; parental educational level (highest attained); parental cannabis, alcohol, or substance use disorders; and parental affective disorders….Cannabis use was associated with an increased risk of bipolar disorder in men (HR, 2.96; ) and women (HR, 2.54; )”, and was highest for psychotic bipolar disorder (HR, 4.05; 95% CI, 3.52-4.65).
Editors Note: Marijuana is not a benign substance. “In all, 60,?696 individuals received a diagnosis of (cannabis use disorder) during follow-up, and 260,?746 (3.9%) developed an affective disorder.”
Obesity is associated with reduce cortical thickness in bipolar disorders
Sean R. McWhinney et al reported in Psychological Medicine (2023) that obesity was associated with reduced cortical thickness (but not surface area) in most areas of the brain in 2832 participants.
Editors Note: Patients and clinicians should try to prevent and reduce weight gain using the best tolerated medications from the outset and helping with weight loss by various measures. These can include the anticonvulsants topiramated and zonisamine, the combination of bupropion and naltrexone, and the use of new anti-diabetic drugs such as Jardiance and Farxiga that have weight loss (greater than with metformin) as a side effect. Prescribing a good diet and regular exercise is also indicated. Reducing obesity will likely make you live longer and maybe could even make you smarter.
Familial Aggregation of Major Depression Predicts Risk of Major Depression
Gronemann et al reported in JAMA Psychiatry: “In this cohort study of 2,903,430 individuals, maternal, paternal, full sibling, or half-sibling with MD were associated with 2-fold higher risks of MD in men and women….(E)xposure to family MD during childhood and adolescence was associated with increased risk. The risk increased with number of affected family members; (however) individuals exposed when 30 years or older had markedly lower risk.”
Editors Note: Even depression in grandparents adds further to the risk of depression. When there is high familial loading for depression and other psychiatric illnesses, one should be alert to the possible onset of depression in young individuals and treat them early and well accordingly.
Sleep Disturbances in Pediatric Bipolar NOS is the Same as in BP I
Gianni Faedda reported in Frontiers in Psychiatry (2012) that decreased need for sleep is as prominent in BP NOS children as in those with BP I. So it appears that with the exception of only brief periods of mania in BP NOS, these children have similar characteristics to those with full blown BP I. Thus in addition to the briefer periods of mania, one should be on the look out for all the symptoms of bipolar disorder that are not typical of ADHD, including brief or extended periods of euphoria, decreased need for sleep, more extreme degrees of irritability and poor frustration tolerance, hallucination, delusions, suicidal and homicidal ideation, more severe depression, and increases in sexual interest and actions. When these are present, the bipolar mood instability should be treated first and only then small doses of psychomotor stimulants can be used to treat what ever residual ADHD remains. The typical symptoms of ADHD are very of present and comorbid in childhood onset bipolar disorder and cannot be used to discriminate the two diagnoses. The children with BP NOS are as dysfunctional as those with BP I and take longer to stabilize, so pharmacological treatment may need to be intensive, multimodal, and supplemented by Family Focused Therapy (FFT) or a related family therapy. It is most often not conceptualized as such, but BP NOS as well as BP I should be considered as a medical emergency and handled by a sophisticated pediatrician and/or referred for psychiatric consultation and therapy. The longer bipolar disorder is not treated, the worse the outcome is in adulthood.
Two different subtypes of early onset unspecified bipolar disorder (USBD)
The first subtype is classical BP NOS (Not Otherwise Specified) having all the characteristics of full-blown bipolar disorder except for only having brief durations of mania and responding to conventional treatment. The second is what is now called Temperature and Sleep Dysregulation Disorder (TSDD) and was formerly described by D. Papolos as the Fear of Harm (FOH) syndrome, and requires a different treatment approach.
Clinicians should be alert to unique symptoms in children who might have TSDD as such a diagnosis would lead to a unconventional treatment paradigm. We emphasize the importance of specifically asking parents about evidence of over heating (red face and red ears) and high tolerance for cold (going outside markedly under-dressed) and the presence of fear of sleep and horrific nightmares, as these may lead one to consider the diagnosis of TSDD.
If these two novel aspects (temperature and sleep dysregulation) occur in the presentation of a highly fearful and behaviorally dysregulated child with bipolar-like symptoms, these may lead to the consideration of an unconventional treatment paradigm. It utilizes 1) high dose lithium; 2) clonidine and other practical approaches to achieve cooling and relieve over heating; and 3) ascending doses of intranasal ketamine (as described by Papolos et al 2013; 2018). This may be of considerable clinical importance as a large group of children with this unique presentation respond very poorly to conventional treatments for bipolar disorder and remain highly impaired and dysfunction throughout their childhood and adolescence.
If these children instead are treated with: lithium (to achieve blood levels of 1.0 meq/L or higher); clonidine (0.1- 0.3mg IR and 0.1mg ER at noon and HS) and other practical ways to achieve cooling; followed by ascending intranasal doses of ketamine (starting at 20mg and increasing toward 80-260mg/day, repeated every 2-3 days), marked improvement can be achieved. This occurs in conjunction with ketamine’s positive effects on fear and aggressive behaviors in association with its ability to reduce core body temperature.
We highlight this potential alternative treatment approach as long term positive effects have been achieved with it in open case series (Papolos et al 2013; 2018 ). The efficacy of this treatment approach has not been validated in controlled clinical trials, but we believe wider recognition of the two subtypes of USBD– BPNOS and TSDD,– will lead to more systematic research on treatment. Actively looking for the unique features of TSDD and pursuing its unconventional treatment may lead to long term positive effects in a child previously viewed as having an intractable psychiatric illness.
