Changes in brain structure in remitted bipolar patients

Macoveanu et al reported in the Journal of Affective Disorders (2023) that compared to controls that remitted bipolar patients had “a decline in total white matter volume over time and they had a larger amygdala volume, both at baseline and at follow-up time. Patients further showed lower cognitive performance at both times of investigation with no significant change over time….Cognitive impairment and amygdala enlargement may represent stable markers of BD early in the course of illness, whereas subtle white matter decline may result from illness progression.”

Lumateperone for Bipolar I or Bipolar II Depression: Few Extrapyramidal and Motor Symptoms

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Tobie Escher of Intra-Cellular Therapies, Inc. reported on the excellent tolerability of lumateperone (42mg/day) in a “short-term population comprised 746 patients in pooled monotherapy trials (placebo, 374; lumateperone, 372) and 352 patients in the adjunctive study (adjunctive placebo, 175; adjunctive lumateperone, 177). Reported EPS [extrapyramidal symptom]-related TEAEs [treatment-emergent adverse events] were 1 patient (0.3%) with mild dyskinesia (lumateperone monotherapy), 1 (0.6%) with mild akathisia (adjunctive lumateperone), and 1 (0.3%) with severe akathisia (placebo monotherapy).”

Beneficial Cognitive Effects of Transcranial Infrared Laser Stimulation (TILS) in Bipolar Disorder

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Michael Gentry of The University of Texas At Austin reported on 30 individuals with remitted bipolar disorder (type I or type II). TILS was administered weekly to each participant over six consecutive weeks (1064 nm wavelength; bilaterally to the frontal poles; 10 minutes per weekly session)….. after six weeks of TILS administration, participants demonstrated decreased impulsivity on the Stop Signal Task and improved abilities to select correct responses on the Multitasking Test.

Intranasal Oxytocin for Internalizing Symptoms in Youth With Disruptive Behavior Disorders

Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego


E. Kendall reported that “Fifty-two youths with diagnoses of DBD [Disruptive Behavior Disorders] participated in [this] study, and twenty-five completed three weeks of treatment of intranasal OXT [oxytocin] and twenty-seven placebo (PBO)…. Youth who received OXT showed a significantly greater reduction of depression [ p=0.012] and anxiety [p=0.031] compared to the [placebo] group.”

They concluded that “Intranasal OXT can show efficacy in reducing internalizing symptoms in youth with DBD. This was accompanied by neural level changes implicated in emotion regulation (mPFC [medial prefrontal cortex] and ACC [anterior cingulate cortex]).”

Lumateperone Normalizes Pathological Levels of Acute Inflammation and Stimulates Important Pathways Involved in Mood Regulation

Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego

Sophie Dutheil of Intra-Cellular Therapies, Inc. reported that “In male and female C57BL/6 mice subjected to an acute stress or immune challenge, lumateperone reduced elevated levels of key proinflammatory cytokines. A number of key genes and pathways associated with the maintenance of tissue integrity and blood-brain barrier function were also altered by a single dose of lumateperone. Furthermore, we found that lumateperone administration conferred anxiolytic- and antianhedonic-like properties while enhancing the mTORC1 signaling pathway in the PFC.”

Probiotic as an adjunct to an antidepressant

Viktoriya L. Nikolova, et al reported in JAMA Psychiatry (2023) that the probiotic Bio-Kult Advanced; ADM Protexin was more effective than placebo as an adjunct to antidepressants for depression and anxiety.

Inflammatory marker CRP predicts worse course of adolescent bipolar disorder

March 1, 2023 · Posted in C – May become important in the future · Comment 

Sudhir Karthikeyan in Ben Goldstein’s lab in Toronto reported in  Brain Behav Immun (2022) that in 79 adolescents the inflammatory marker CRP (C-Reactive Protein) was higher and the anti-inflammatory cytokine Il-10 was lower during the most ill periods compared to normal volunteers. “Moreover, higher CRP levels (p = 0.009) at intake predicted greater time to recovery from the index symptomatic episode.”  They concluded that: “In the first repeated-measures study on this topic in adolescents with BD, we found evidence that CRP, an inexpensive and ubiquitous blood test, may be useful in predicting the prospective course of BD symptoms. “

Adiposity and Cognitive Function Are Bidirectionally Related

February 27, 2023 · Posted in C – May become important in the future, Risk Factors · Comment 

Sakib et al reported in JAMA New Open that ” In this cohort study that included 11,103 adolescents, executive function and episodic memory were bidirectionally associated with adiposity, and this association was statistically mediated through the morphology of the lateral prefrontal cortex. Obesity (BMI) was associated worse executive functioning, episodic memory, and task performance. Thus preserving cognition is another reason beyond physical health to follow a good diet, get exercise, and use medications for weight loss if obesity is a problem.”

Antihypertensives That Stimulate vs Inhibit Type 2 and 4 Angiotensin II Receptors Decrease Dementia 

Marcum et al in JAMA New Open (2023) found that in “57,773 Medicare beneficiaries, initiation of antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors was associated with a statistically significant 16% lower risk of incident dementia, over a median of 6.9 years of follow-up.”

“Angiotensin II receptor type 2 and 4–stimulating antihypertensive medications (hereafter, stimulating medications) included: Angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.
Angiotensin II receptor type 2 and 4–inhibiting antihypertensive medications (hereafter, inhibiting medications) included: angiotensin-converting enzyme (ACE) inhibitors, ?-blockers, and nondihydropyridine calcium channel blockers.”

Editors Note: If you have hypertension and are at risk for cognitive decline, know that your choice of effective antihypertensive drugs can lead to better cognitive outcomes. Drugs that stimulate the angiotensin II receptor type 2 and 4 help prevent dementia. These drugs include:
ARB type 1, dihydropyridine calcium channel blockers, and thiazide diuretics. (Good guys)

Those that inhibit Angiotensin II receptors types 2 and 4 do not prevent dementia. These drugs include:
ACE inhibitors, beta blockers, and non-dihydropyridine calcium channel blockers. (Bad guys)

Talk with your doc about drugs equally for blood pressure control but those that also have benefits for ultimate preservation of cognition.

6 Minutes of Intense Cycling Produces Major Increases in BDNF

Brain derived neurotrophic factor (BDNF) is necessary for new synapses and call survival.  A new study in J. Physiology (2023) reports that the increases in BDNF from short intense cycling exercise are much greater than from prolonged (90-minute) light cycling.  The authors think that this is cause by the increases in lactate produced which helps up regulate BDNF production. This could be good for fighting depression and Alzheimer’s disease, where BDNF levels are low. 

Bottom line:  If you don’t have much time, bust your buns.

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