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We’re back!
After a pandemic-related hiatus, we’re back, and we hope to bring you articles regularly. For print subscribers, we hope to send out a single large issue in the coming months.
Young Men at Highest Schizophrenia Risk From Cannabis Abuse
Roughly 15% of schizophrenia cases among young males may be preventable by avoiding cannabis use disorder (CUD). Not only does cannabis abuse markedly increase the risk of schizophrenia, its use has transgenerational effects such that offspring from a cannabis user are more prone to use opiates.
Editors Note: Youngsters need to know two things.
1. Any supposedly legitimate drug bought on line may look like the real thing, but it is all-too-often laced with fentanyl which can kill someone in 5 minutes. No street-bought drug is safe, no matter how real it looks.
2. Marijuana will not kill you, but can make you psychotic for the rest of your life. The widely circulated notion that pot is safe is just a conspiracy by the plant growers to make money and by politicians who are ignorant of the facts. Pot doubles the rate of paranoia in the general population and if you have a good functioning genetic (val158val) version of COMT, this works too well to deplete dopamine in the prefrontal cortex and further increases the risk of paranoia and psychosis.
The Cognitive Effects of Electroconvulsive Therapy in Community Settings
Harold Sackeims’ review in Neuropsychopharmacology, 32, 244-254 (2007) remains one of the best updates indicating that the cognitive effects of Electroconvulsive Therapy (ECT) are not always benign. They followed 347 patients from seven facilities in New York city and tested them after their last session of ECT and then again 6 months later. They reported that “Electrical waveform and electrode placement had marked cognitive effects. Sine wave stimulation resulted in pronounced slowing of reaction time, both immediately and 6 months following ECT. Bilateral (BL) ECT resulted in more severe and persisting retrograde amnesia than right unilateral ECT. Advancing age, lower premorbid intellectual function, and female gender were associated with greater cognitive deficits. Thus, adverse cognitive effects were detected 6 months following the acute treatment course. Cognitive outcomes varied across treatment facilities and differences in ECT technique largely accounted for these differences. Sine wave stimulation and BL electrode placement resulted in more severe and persistent deficits.”
Editors note: This is why it is important to recommend right unilateral ultra brief pulse (RUUBP) ECT both for acute and continuation treatment if necessary. Continuing RUUBP ECT rather than converting to bilateral ECT would appear to be preferable.
DRAMATIC PROPHYLACTIC RESPONSE TO NIMODIPINE: A Case Report
(This is an invited contribution by Robert Westhead.)
This 50 year old man had a lifetime of incapacitating rapid cycling (10 days up and 10 days down) bipolar I disorder, but then for the past 4 years has had a complete remission on nimodipine (60mg QID). He remains on lithium (800mg), and of his other long-term medications, he has titrated quetiapine down from 800mg to 50mg and has discontinued phenelzine.
He had previously failed to respond to combinations of:
· Lithium
· Anticonvulsant mood stabilizers (including divalproex sodium, lamotrigine, carbamazepine and pregablin)
· Atypical antipsychotics (including quetiapine, aripiprazole and lurasidone)
· Antidepressants (including SSRIs eg citalopram and sertraline, NSRIs eg venlaflaxine and mirtazapine, and a MAOI eg phenelzine)
· Thyroxine
· Propranolol
· Clonazepam
He wanted to highlight this dramatic response to nimodipine in combination with lithium as this dihydropyridine calcium channel blocker is not well known or frequently used for its prophylactic effectiveness.
He noted that as well as stopping the rapid cycling, the nimodipine has provided complete relief from comorbid social anxiety symptoms and remediated cognitive and memory impairment.
This response to nimodipine potentially also has pathophysiological implications. Nimodipine directly blocks the CACNA1C calcium influx gene that has repeatedly been associated with vulnerability to depression, bipolar disorder, and schizophrenia in gene wide association studies. This patient does not know whether he carries this gene variant, but assays for it are routinely available as performed by the company Genomind.
Thus, it remains an open question as to whether those who have the CACNA1C variant would be more responsive to nimodipine compared to those without the variant. Certainly, the efficacy of this agent in treatment of patients with bipolar disorder deserves further consideration and study.
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.
Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomized clinical trial
von Rotz et al reported in eClinical Medicine (the Lancet) that a single dose of psilocybin produced a huge AD (anti-depressant) effect compared to placebo. A dose of 0.215mg Kg (about 15mg for a 70kg person) had a rapid onset AD effect that persisted for at least 14 days. Music was played and in a living room like environment. Psychological support was provided on 3 visits pretreatment and on days 8 and 14 for a total of 14 hours
Inflammatory marker CRP predicts worse course of adolescent bipolar disorder
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
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.”
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.
Abuse Histories Decrease Rate of Remission to Antidepressant Treatment
Harkness et al reported in The Canadian Journal of Psychiatry (2023) “Greater severity of emotional maltreatment perpetrated by the mother was a significant and direct predictor of lower odds of week 16 remission (odds ratio [OR]=1.68, P =0.02). In contrast, the relations of paternal-perpetrated emotional maltreatment and physical maltreatment to week 16 remission were indirect, mediated through greater severity of anhedonia at week 8.”
Editors note: Response to ADs is less good in those with a history of abuse in childhood. Therefore psychotherapy should be added to medications in such situations to attempt to enhance responsiveness.
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.
