M. Jackson Group Update – December 2022 – Vitamin D and Depression

Merry Christmas and Happy New Year!

A collection of postings on a range of issues is available on our website (www.mjacksongroup.ca).  This month’s post is again from Ken Pope’s listserv, where he kindly provides daily summaries of current articles in the field.

The article is as follows:
Pharmacological Research has scheduled a study for publication in a future issue: “Vitamin D protects against depression: Evidence from an umbrella meta-analysis on interventional and observational meta-analyses.” 
The authors are Vali Musazadeh et al.

Here’s how it opens:
Depression is a mental disorder that causes disabling effects of mood and anxiety disorders. Depression has also become a leading global cause of disease burden [1], [2]. Based on the evidence from the World Health Organization, more than 264 million people are affected by depression worldwide [3]. In the wake of the COVID-19 outbreak, a number of studies have demonstrated a rise in depression psychopathology and suicide tendencies across a variety of countries [4]. Depressive symptoms were the most common mental health condition during the COVID-19 pandemic, ranging from 14.6 to 48.3% across all populations, according to a systematic review [5]. People who suffer from depression may feel sad, anxious, hopeless, helpless, irritable, worthless, guilty, or ashamed [6]. There might also be decreased appetite or overeating, and inability to exercise, or even suicide among them [7]. Antidepressants, which have been used for many years to treat depression, have raised concerns about their effectiveness and tolerance [8], [9], [10]. Furthermore, the failure of depression to respond to a wide range of pharmaceutical treatments [11] indicates that other mechanisms are involved in the pathogenesis of depression, such as those affecting neuroendocrine, immunological, neurotrophic, and metabolic systems [12]. In spite of these challenges, complementary treatments for depression appears to be helpful.

Vitamin D is a unique neurosteroid hormone that may play a role in depression [13]. Vitamin D has numerous functions in the brain such as neuroimmunomodulation, regulation of neurotrophic factors, neuroprotection, neuroplasticity, and brain development [14]. Also, vitamin D receptors can be found on the neurons and glia in many parts of the brain, including the cingulate cortex and the hippocampus [15]. Vitamin D deficiency may have played a significant role in stress-related depression during the COVID-19 pandemic, according to a growing body of literature [16]. Vitamin D is thought to influence the serotoninergic system and contribute to the maintenance of circadian rhythms, both of which are associated with depressive symptoms [16], [17]. As a result, it is biologically plausible that vitamin D might play an important role in the treatment of depressive disorders [13].

Another excerpt:
In the current study, we included meta-analyses of randomized controlled trials (RCTs) and of observational studies (cohort and cross-sectional) that investigated the effect of vitamin D supplementation on depression symptoms considering the following criteria: reporting standardized mean difference (SMD), or odds ratio (OR) and their corresponding confidence intervals (CI) for vitamin D supplementation on depression symptoms. Other studies were excluded from this review, including original experimental studies, case reports, in vitro, ex-vivo, and in vivo investigations.

Here’s how the Discussion opens:
The current umbrella meta-analysis summarized 15 meta-analyses, which inluded 65 RCTs, and 31 observational (cohort and cross-sectional) studies. According to the results, vitamin D supplementation was efficient in alleviating symptoms of depression and an inverse association was observed between higher serum levels of vitamin D intake and overall depression. Based on sub-group analyses, vitamin D supplementation in studies using dosage of > 5,000 IU/day, and intervention duration of ≤20-weeks exhibited stronger effects in lowering symptoms of depression. Morever, the inverse association between lower serum vitamin D levels and depression was stronger among participants aged ≤50 years.

Recent studies have shown a significant association between vitamin D insufficiency or deficiency and depressive disorders [32]. Receptors of vitamin D and 1-alphahydroxylase enzymes, involved in the hydroxylation of 25-hydroxy vitamin D (25OHD) to the active form 1,25-dihydroxy vitamin D, are present on neurons and glia in multiple regions of the brain, including prefrontal cortex, substantia nigra, cingulate cortex and hippocampus and hypothalamus which have an important role in the pathophysiology of depression [13], [30], [34], [39]. Vitamin D is involved in the synthesis of neurotrophic factors and neurotransmitters (serotonin, dopamine, adrenalin, and noradrenaline) through VDRs in the adrenal cortex and due to its steroidal structure, modulates the hypothalamic-pituitary-adrenal axis and GABA‐A receptors activity [30], [34].

During depression, inflammatory markers increase [34]. Meanwhile, vitamin D displays antioxidant effects in the central nervous system, enhances nerve growth factors and the gene expression of antioxidant agents, down-regulates cytokines and inflammatory mediators such as nuclear factor-kB, which is linked to psychosocial stress and depression [32]. In general, vitamin D prevents the onset of depression by taking role in sixmain pathways: 1) Controlling the expression of calcium homeostasis genes; 3) Controlling serotonin synthesis via alleviating tryptophan hydroxylase 2 (TPH2) expression and repressing tryptophan hydroxylase1 (TPH1); 4) Controlling inflammation by reducing the expression of inflammatory cytokines; 5) Controlling the expression of mitochondrial proteins that preserve normal mitochondrial respiration; and 6) Preventing the hypermethylation of gene promotors such as Jumonji domain-containing protein 1 A and 3 (JMJD1A, JMJD3) and lysine-specific demethylase 1 and 2 (LSD1, LSD2). These genes have a significant role in the activation of GABAergic neurons [29], [42]. Fig. 5 exhibits the mechanism of action of vitamin D in preventing and lowering symptoms of depression.

Another excerpt:
Fig. 5. The mechanism of action of vitamin D in preventing and declining symptoms of depression.

Here’s how the article concludes:
The present umbrella of meta-analyses confirms the potential benefits of vitamin D supplementation in reducing symptoms of depression and an inverse relationship between higher serum levels of vitamin D and overall depression. Vitamin D supplementation in studies using dosage of >5,000 IU/day and intervention duration of ≤20-weeks exhibited better effects in lower symptoms of depression. Moreover, a greater risk of depression was shown among participants aged ≤ 50 with lower serum vitamin D levels.
REPRINTS & OTHER CORRESPONDENCE: Rania A. Mekary, School of Pharmacy, MCPHS University, 179 Longwood Avenue, Boston MA, 02115 rania.mekary@mcphs.edu
Ken Pope
Hector Y. Adames, Nayeli Y. Chavez-Dueñas, Melba J.T. Vasquez, & Ken Pope:Succeeding as a Therapist: How to Create a Thriving Practice in a Changing World (APA, September, 2022)
Ken Pope, Melba J.T. Vasquez, Nayeli Y. Chavez-Dueñas, & Hector Y. Adames:
Ethics in Psychotherapy & Counseling: A Practical Guide, 6th Edition (Wiley, 2021)

Ken Pope:
Five Steps to Strengthen Ethics in Organizations and Individuals: Effective Strategies Informed by Research and Histor
y   (Routledge, 2019)

Night of the ScorpionNissim Ezekiel 

I remember the night my mother
was stung by a scorpion. Ten hours
of steady rain had driven him
to crawl beneath a sack of rice.

Parting with his poison – flash
of diabolic tail in the dark room –
he risked the rain again.

The peasants came like swarms of flies
and buzzed the name of God a hundred times
to paralyse the Evil One.

With candles and with lanterns
throwing giant scorpion shadows
on the mud-baked walls
they searched for him: he was not found.
They clicked their tongues.
With every movement that the scorpion made his poison moved in Mother’s blood, they said.

May he sit still, they said
May the sins of your previous birth
be burned away tonight, they said.
May your suffering decrease
the misfortunes of your next birth, they said.
May the sum of all evil
balanced in this unreal world

against the sum of good
become diminished by your pain.
May the poison purify your flesh

of desire, and your spirit of ambition,
they said, and they sat around
on the floor with my mother in the centre,
the peace of understanding on each face.
More candles, more lanterns, more neighbours,
more insects, and the endless rain.
My mother twisted through and through,
groaning on a mat.
My father, sceptic, rationalist,
trying every curse and blessing,
powder, mixture, herb and hybrid.
He even poured a little paraffin
upon the bitten toe and put a match to it.
I watched the flame feeding on my mother.
I watched the holy man perform his rites to tame the poison with an incantation.
After twenty hours
it lost its sting.

My mother only said
Thank God the scorpion picked on me
And spared my children.


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