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.

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.”

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.

Hyperinsulinemia Associated Depression

Haider Sarwar writes in Clinical Medicine Insights (2022) that “Hyperinsulinemia promotes fat accumulation, causing obesity. Being an inflammatory state, obesity can induce further inflammation and is a risk factor for HPA (hypothalamic pituitary axis) dysregulation through hypercortisolism-related hyperglycemia….A disruption on SNS (sympathetic nervous system) activity increases insulin levels, and induces glycogenolysis in the liver and lipolysis in adipose tissue during hypoglycemia. Hyperglycemia-hyperinsulinemia exacerbates inflammation and increases the oxidative stress along with regulating the levels of norepinephrine in the brain sympathetic system. Increased inflammatory cytokines have also been shown to disrupt neurotransmitter metabolism and synaptic plasticity which play a role in the development of depression via inhibiting serotonin, dopamine, melatonin, and glutamate signaling. An increased level of plasma insulin over time in the absence of exercising causes …an increase in insulin resistance due to obesity and further culminates into depression….. Triple therapy with SSRI, bupropion, and cognitive behavioral therapy aids in improving glycemic control, lowering fasting blood glucose, decreasing the chances of relapse, as well as decreasing cortisol levels to improve cognition and the underlying depression.”

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.

Adolescent Delta-9-tetrahydrocannabinol  induces long-term neuronal  disturbances in dorsal vs. ventral hippocampus

December 6, 2022 · Posted in Neurobiology, Neurochemistry, Risk Factors · Comment 

De Felice et al reported in Neuropsychopharmacology (2022) how adolescent THC exposure in a rodent model can induce significant morphological disturbances and glutamatergic signaling abnormalities in the hippocampus.  The dorsal hippocampus is critical for cognitive and contextual processing, whereas the ventral region is critical for affective and emotional processing.  Adolescent THC exposure induces long-lasting memory deficits and anxiety like-behaviors concomitant with a wide range of differential molecular and neuronal abnormalities in dorsal vs. ventral hippocampal regions.

Editors Note:  While these data are in rodents, they provide insights into how THC use in adolescents exerts memory deficits and anxiety-like behavior in adulthood by dysregulation of glutamate signaling in the hippocampus.  These data converge with data in humans.  The bottom line is: use of marijuana in adolescence is not good for brain function, cognition, and behavior in adulthood.

PREVENT EPISODES, PROTECT YOUR BRAIN, BODY, AND SELF

December 1, 2022 · Posted in Course of Illness, Risk Factors · Comment 

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.

Participation in Sports May Mitigate Genetic Risk for ADHD in School-Aged Children

June 9, 2021 · Posted in Risk Factors · Comment 

At the 2021 meeting of the Society of Biological Psychiatry, researcher Keiko Kunitoki and colleagues reported that participation in sports decreased behavior abnormalities in 9- and 10-year-old children at genetic risk for attention deficit hyperactivity disorder (ADHD). Sports were associated with greater hippocampal volume, which was associated with fewer behavioral abnormalities. Kunitoki and colleagues concluded that “participation in team sports mitigated genomic risk for psychopathology at age 9–10 in part through increased hippocampal volume.”

Editor’s Note: These data are consistent with a program called the Vermont Family-Based Approach developed by researcher James Hudziak, who heads the Vermont Center for Children, Youth and Families at the University of Vermont. The program encourages families to practice different domains of wellness, such as music, mindfulness, exercise, and nutrition, among others. The idea is to support emotional and behavioral health, and to do so intensively in families where children show signs of mood and behavioral difficulties or are at risk for these difficulties.

Hudziak analyzed brain scans of 232 children aged 6 to 18 and reported that “practicing an instrument such as the piano or violin increased working memory, gray matter volume in the brain, and the ability to screen out irrelevant noise. Practicing mindfulness increased white matter volume and reduced anxiety and depression. Exercise also increased brain volume and neuropsychological abilities.”

In 2015, researcher Benjamin I. Goldstein reported that 20 minutes of vigorous exercise on a bike improved cognition and decreased hyperactivity in the medial prefrontal cortex in adolescents with and without bipolar disorder, and researcher Danella M. Hafeman reported that offspring of parents with bipolar disorder who exercised more had lower levels of anxiety.

To summarize, engaging in exercise, team sports, music, and meditation/mindfulness are beneficial for all children, and can be especially helpful for those at risk for depression or bipolar disorder. Children who are already symptomatic should additionally be offered something like family focused therapy (FFT), a multi-faceted approach developed by researcher David Miklowitz, in which families of young people at risk for bipolar disorder take part in therapy, learning together about the illness and practicing strategies for communication and coping.

Left Prefrontal Strokes Linked to Depression

man touching head

In a 2021 article in the journal Stroke, researcher Julian Klingbeil and colleagues reported that left, but not right, ventrolateral prefrontal stroke lesions were associated with increased risk of depression at six months post-stroke.

The study included 270 participants who had their first-ever stroke. Six months following their strokes, 19.6% of the participants had depression. Those who scored higher on a scale of depression and anxiety symptoms in the first month after their stroke were more likely to have depression six months after the stroke.

The researchers identified a cluster of locations for stroke lesions, mostly within the left ventrolateral prefrontal cortex, that they linked to depression symptoms six months post-stroke. Klingbeil and colleagues hope that recognizing lesions in this region as risk factors for depression will help with early diagnosis of depression among people who recently had a stroke.

Editor’s Note: Antidepressants have been shown to improve post-stroke recovery of neurological functional (and depression) that is caused by the cutoff of blood supply during a stroke (ischemia). Patients and their family members should talk with their neurologist about treatment of ischemic strokes with antidepressants, especially when the lesions occur on the left side of the brain.  

Insomnia Plays Critical Role in Bipolar Disorder

April 6, 2021 · Posted in Peer-Reviewed Published Data, Risk Factors · Comment 
man awake in bed

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.

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