New ECS, Basic Science Mashup

Out on PubMed are these three articles:

Effects of repeated electroconvulsive shocks on dopamine supersensitivity psychosis model rats.

Kimura M, Oda Y, Oishi K, Yoshino K, Kimura H, Niitsu T, Kanahara N, Shirayama Y, Hashimoto K, Iyo M.Schizophr Res. 2021 Jan 8;228:1-6. doi: 10.1016/j.schres.2020.11.062. Online ahead of print.PMID: 33429150

The abstract is copied below:

While the long-term administration of antipsychotics is known to cause dopamine supersensitivity psychosis (DSP), recent studies revealed that DSP helps form the foundation of treatment resistance. Electroconvulsive shock (ES) is one of the more effective treatments for treatment-resistant schizophrenia. The objective of this study was to examine whether repeated ES can release rats from dopamine supersensitivity states such as striatal dopamine D2 receptor (DRD2) up-regulation and voluntary hyperlocomotion following chronic administration of haloperidol (HAL). HAL (0.75 mg/kg/day) was administered for 14 days via mini-pumps implanted in rats, and DRD2 density and voluntary locomotion were measured one day after drug cessation to confirm the development of dopamine supersensitivity. The rats with or without dopamine supersensitivity received repeated ES or sham treatments, and then DRD2 density was assessed and a voluntary locomotion test was performed. Chronic treatment with HAL led to the up-regulation of striatal DRD2 and hyperlocomotion in the rats one day after drug cessation. We thus confirmed that these rats experienced a dopamine supersensitivity state. Moreover, after repeated ES, locomotor activity and DRD2 density in the DSP model rats fell to the control level, while an ES sham operation had no effect on the dopamine supersensitivity state. The present study suggests that repeated ES could release DSP model rats from dopamine supersensitivity states. ES may be helpful for patients with DSP.

Keywords: Antipsychotic; Dopamine D2 receptor (DRD2); Dopamine supersensitivity psychosis (DSP); Electroconvulsive shock (ES); Locomotion; Schizophrenia.

Electroconvulsive seizures lead to lipolytic-induced gene expression changes in mediobasal hypothalamus and decreased white adipose tissue mass.

Takefusa M, Kubo Y, Ohno M, Segi-Nishida E.Neuropsychopharmacol Rep. 2021 Jan 10. doi: 10.1002/npr2.12156. Online ahead of print.PMID: 33426813

The abstract is copied below:

Aims: Electroconvulsive seizure (ECS) therapy is highly effective in the treatment of several psychiatric disorders, including depression. Past studies have shown that the rodent model of ECS reveals the activation of multiple brain regions including the hypothalamus, suggesting that this method of brain stimulation broadly regulates central neuronal function, which results in peripheral function. The ventromedial nucleus of the hypothalamus (VMH) plays an important role in feeding and energy homeostasis. Our previous study showed that ECS increases the expression of anorexigenic factors in the VMH and has an anorexigenic effect in a mouse model. Since the VMH is also suggested to play a critical role in the peripheral lipid metabolism of white adipose tissue (WAT), we hypothesized that ECS alters lipid metabolism via activation of the VMH.

Methods and results: Here, we demonstrate that repeated ECS suppresses the fat mass of epididymal WAT and significantly increases the expression levels of lipolytic and brown adipose tissue markers such as Adrb3, Hsl/Lipe, and Ppargc1a. In the VMH, ECS increased the expression of multiple genes, notably Bdnf, Adcyap1, and Crhr2, which are not only anorexigenic factors but are also modulators of lipid metabolism. Furthermore, gold-thioglucose-induced hypothalamic lesions affecting the VMH abolished the effect of ECS on the WAT, indicating that hypothalamus activation is required for the phenotypic changes seen in the epididymal WAT.

Conclusion: Our data demonstrates a new effect of ECS on the lipid metabolism of WAT via induction of hypothalamic activity involving the VMH.

The two-cell model of glucose metabolism: a hypothesis of schizophrenia.

Roosterman D, Cottrell GS.Mol Psychiatry. 2021 Jan 5. doi: 10.1038/s41380-020-00980-4. Online ahead of print.PMID: 33402704 Review.

The abstract is copied below:

Schizophrenia is a chronic and severe mental disorder that affects over 20 million people worldwide. Common symptoms include distortions in thinking, perception, emotions, language, and self awareness. Different hypotheses have been proposed to explain the development of schizophrenia, however, there are no unifying features between the proposed hypotheses. Schizophrenic patients have perturbed levels of glucose in their cerebrospinal fluid, indicating a disturbance in glucose metabolism. We have explored the possibility that disturbances in glucose metabolism can be a general mechanism for predisposition and manifestation of the disease. We discuss glucose metabolism as a network of signaling pathways. Glucose and glucose metabolites can have diverse actions as signaling molecules, such as regulation of transcription factors, hormone and cytokine secretion and activation of neuronal cells, such as microglia. The presented model challenges well-established concepts in enzyme kinetics and glucose metabolism. We have developed a 'two-cell' model of glucose metabolism, which can explain the effects of electroconvulsive therapy and the beneficial and side effects of olanzapine treatment. Arrangement of glycolytic enzymes into metabolic signaling complexes within the 'two hit' hypothesis, allows schizophrenia to be formulated in two steps. The 'first hit' is the dysregulation of the glucose signaling pathway. This dysregulation of glucose metabolism primes the central nervous system for a pathological response to a 'second hit' via the astrocytic glycogenolysis signaling pathway.

For today's blog post I have broken the rule of only one new citation/post. The reason is that the above trilogy are so boring, dry, and difficult to read, that I thought we should dispense with them all together and quickly. 

To summarize: 1) ECT has effects on the dopamine system 2) ECS has effects on lipids and 3) ECS may have effects on glucose metabolism.

If any of these topics grabs you, please read the article in full and report back, if there is any "there" there.

I would note the mixed up nomenclature, calling ECT in humans "electroconvulsive shock (ES)", or "electroconvulsive seizure (ECS)." 

Seriously though, one thing to note is the ongoing basic science interest in the mechanism of action of ECS (in animal models) and its translation (sometimes fanciful) to the clinical treatment in humans, ECT.