Cannabis use decreases prefrontal glutamate levels in early psychosis

Recent evidences have consistently reported lower glutamate (Glu) levels in various brain regions, including the medial prefrontal cortex (mPFC), in chronic schizophrenia but findings in the early (EP) or in the prodromal phase of the disorder are equivocal. Although regular cannabis use has been associated with an increased risk of subsequent psychosis and with a perturbed Glu signalling, to date, the critical question of whether or not Glu abnormalities exist in EP and are related to cannabis use remains unanswered. Magnetic resonance spectroscopy was used to measure [GlumPFC] of 35 EP subjects (18 of whom were regular cannabis users) and 33 healthy controls (HC). For correlative analysis, neuropsychological performances were scored by a comprehensive cognitive battery. [GlumPFC] was lower in EP users comparing to both HC and EP non-users (P = 0.001 and P = 0.01, respectively), while no differences were observed between HC and EP non-users. In EP users Glu declined with age (r = −0.46; P = 0.04) but this relationship was not observed in non-users. Among neuropsychological profiles, working memory was the only domain that differentiates patients depending on their cannabis use, with users having poorer performances. In summary, our research revealed that cannabis use in EP is associated with Glu decreased levels, which are normally not seen in the early phase of the disorder. This finding is in line with previous 1H-MRS studies in cannabis users without a psychotic disorder and sheds light for the role of cannabis use in the progression of the disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Brain glutamate in medication-free depressed patients: a proton MRS study at 7 Tesla

Psychological Medicine ◽

10.1017/s0033291717003373 ◽

2017 ◽

Vol 48 (10) ◽

pp. 1731-1737 ◽

Cited By ~ 10

Author(s):

Beata R. Godlewska ◽

Charles Masaki ◽

Ann L. Sharpley ◽

Philip J. Cowen ◽

Uzay E. Emir

Keyword(s):

Basal Ganglia ◽

Occipital Cortex ◽

Brain Regions ◽

Anterior Cingulate ◽

7 Tesla ◽

Resonance Spectroscopy ◽

Depressed Patients ◽

Water Signal ◽

Significant Difference

BackgroundThe possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5–3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine.MethodWe studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference.ResultsCompared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001).ConclusionsThe increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.

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The role of the corticotropin-releasing hormone and its receptors in the regulation of stress response

Vavilov Journal of Genetics and Breeding ◽

10.18699/vj21.025 ◽

2021 ◽

Vol 25 (2) ◽

pp. 216-223

Author(s):

E. V. Sukhareva

Keyword(s):

Stress Response ◽

Mental Disorders ◽

Brain Regions ◽

Hypothalamic Nucleus ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone ◽

Brain Functions ◽

Increased Risk ◽

Mediator Systems

Stress is an essential part of everyday life. The neuropeptide corticotropin-releasing hormone (CRH, also called CRF and corticoliberin) plays a key role in the integration of neuroendocrine, autonomic and behavioral responses to stress. The activation of the hypothalamic-pituitary-adrenal axis (HPA axis) by neurons of the paraventricular hypothalamic nucleus (PVN), the primary site of synthesis CRH, triggers stress reactions. In addition to the hypothalamus, CRH is widespread in extrahypothalamic brain structures, where it functions as a neuromodulator for coordination and interaction between the humoral and behavioral aspects of a stress response. The axons of neurons expressing CRH are directed to various structures of the brain, where the neuropeptide interacts with specific receptors (CRHR1, CRHR2) and can affect various mediator systems that work together to transmit signals to different brain regions to cause many reactions to stress. Moreover, the effect of stress on brain functions varies from behavioral adaptation to increased survival and increased risk of developing mental disorders. Disturbances of the CRH system regulation are directly related to such disorders: mental pathologies (depression, anxiety, addictions), deviations of neuroendocrinological functions, inflammation, as well as the onset and development of neurodegenerative diseases such as Alzheimer’s disease. In addition, the role of CRH as a regulator of the neurons structure in the areas of the developing and mature brain has been established. To date, studies have been conducted in which CRHR1 is a target for antidepressants, which are, in fact, antagonists of this receptor. In this regard, the study of the participation of the CRH system and its receptors in negative effects on hormone-dependent systems, as well as the possibility of preventing them, is a promising task of modern physiological genetics. In this review, attention will be paid to the role of CRH in the regulation of response to stress, as well as to the involvement of extrahypothalamic CRH in pathophysiology and the correction of mental disorders.

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Frequency and Intensity of Premonitory Urges to tic in Tourette Syndrome is associated with SMA GABA+ levels

10.31234/osf.io/j8uwc ◽

2021 ◽

Author(s):

Jason He ◽

Mark Mikkelsen ◽

David Huddleston ◽

Deana Crocetti ◽

Kim Cecil ◽

...

Keyword(s):

Tourette Syndrome ◽

Insular Cortex ◽

Brain Regions ◽

Resonance Spectroscopy ◽

Typically Developing ◽

Gabaergic Neurotransmission ◽

Primary Sensorimotor Cortex ◽

Tic Severity ◽

The Right

Background. Individuals with Tourette syndrome (TS) often report that they express tics as a means of alleviating the experience of unpleasant sensations. These sensations are perceived as an urge to act and are referred to as premonitory urges. Premonitory urges have been the focus of recent efforts to develop interventions to reduce tic expression in those with TS. Increasing evidence points to the role of both structural and functional alterations of prefrontal and limbic brain regions regarding the experience of premonitory urges to tic in TS. This study examined the contribution of brain GABA and glutamate levels of the right primary sensorimotor cortex (SM1), supplementary motor area (SMA), and insular cortex (insula) to tic and urge severity in children with TS.Methods. Edited magnetic resonance spectroscopy was used to assess GABA+ (GABA + macromolecules) and Glx (glutamate + glutamine) of the right SM1, SMA and insula in 68 children with TS (MAge = 10.59, SDAge = 1.33) and 41 typically developing controls (MAge = 10.26, SDAge = 2.21). We first compared GABA+ and Glx levels of these brain regions between groups. We then explored the association between regional GABA+ and Glx levels with urge and tic severity. Results. GABA+ and Glx of the right SM1, SMA and insula were comparable between the children with TS and typically developing controls. In children with TS, lower levels of SMA GABA+ was associated with more severe and more frequent premonitory urges. Neither GABA+ nor Glx levels were associated with tic severity. Conclusions. These results broadly support the role of GABAergic neurotransmission within the SMA in the experience of premonitory urges in children with TS.

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GABA—from Inhibition to Cognition: Emerging Concepts

The Neuroscientist ◽

10.1177/1073858417734530 ◽

2017 ◽

Vol 24 (5) ◽

pp. 501-515 ◽

Cited By ~ 18

Author(s):

T. Schmidt-Wilcke ◽

E. Fuchs ◽

K. Funke ◽

A. Vlachos ◽

F. Müller-Dahlhaus ◽

...

Keyword(s):

Cortical Neurons ◽

Brain Regions ◽

Mammalian Brain ◽

Resonance Spectroscopy ◽

Inhibitory Neurotransmitter ◽

Electrophysiological Properties ◽

Potential Strategy ◽

The One ◽

And Behavior

Neural functioning and plasticity can be studied on different levels of organization and complexity ranging from the molecular and synaptic level to neural circuitry of whole brain networks. Across neuroscience different methods are being applied to better understand the role of various neurotransmitter systems in the evolution of perception and cognition. GABA is the main inhibitory neurotransmitter in the adult mammalian brain and, depending on the brain region, up to 25% of the total number of cortical neurons are GABAergic interneurons. At the one end of the spectrum, GABAergic neurons have been accurately described with regard to cell morphological, molecular, and electrophysiological properties; at the other end researchers try to link GABA concentrations in specific brain regions to human behavior using magnetic resonance spectroscopy. One of the main challenges of modern neuroscience currently is to integrate knowledge from highly specialized subfields at distinct biological scales into a coherent picture that bridges the gap between molecules and behavior. In the current review, recent findings from different fields of GABA research are summarized delineating a potential strategy to develop a more holistic picture of the function and role of GABA.

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Cannabidiolɗs Role as a Potential Target in the Treatment for Schizophrenia

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1028 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S631-S631

Author(s):

A. Carvalho ◽

J. Felgueiras ◽

T. Abreu ◽

C. Freitas ◽

J. Silva

Keyword(s):

Endocannabinoid System ◽

Brain Regions ◽

Great Promise ◽

Novel Therapy ◽

Considerable Uncertainty ◽

Wide Range ◽

Competing Interest ◽

The Individual ◽

The Brain

ObjectivesSchizophrenia is a debilitating psychiatric disorder which places a significant emotional and economic strain on the individual and society-at-large. Unfortunately, currently available therapeutic strategies do not provide adequate relief and some patients are treatment-resistant. Therefore there is urgent need for the development of mechanistically different and less side effect prone antipsychotic compounds. Recently, the endocannabinoid system has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Modulation of this system by the main psychoactive component in cannabis, Δ9tetrahydrocannabinol (THC), induces acute psychotic effects and cognitive impairment. However, the non-psychotropic, plant-derived cannabinoid agent cannabidiol shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs.MethodsThe aim of this review is to analyse the involvement of the endocannabinoid system in schizophrenia and the potential role of cannabidiol in its treatment.Results and conclusionsThere is still considerable uncertainty about the mechanism of action of cannabidiol as well as the brain regions which are thought to mediate its putative antipsychotic effect. Further data is warrant before this novel therapy can be introduced into clinical practice.Disclosure of interestThe authors have not supplied their declaration of competing interest

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Region-specific changes in phospholipid metabolism in chronic, medicated schizophrenia

The British Journal of Psychiatry ◽

10.1192/bjp.180.1.39 ◽

2002 ◽

Vol 180 (1) ◽

pp. 39-44 ◽

Cited By ~ 39

Author(s):

J. Eric Jensen ◽

Yousef M. Al-Semaan ◽

Peter C. Williamson ◽

Richard W. J. Neufeld ◽

Ravi S. Menon ◽

...

Keyword(s):

Three Dimensional ◽

Chronic Schizophrenia ◽

Brain Regions ◽

Phospholipid Metabolism ◽

Anterior Cingulate ◽

Membrane Phospholipid ◽

Resonance Spectroscopy ◽

Significant Difference ◽

Prefrontal Region ◽

The Right

BackgroundMembrane phospholipid abnormalities in people with schizophrenia, measured with 31P magnetic resonance spectroscopy (31P-MRS), have been previously reported in brain regions involved in this disorder.AimsIn this 4.0 Tesla 31P-MRS study of people with schizophrenia, membrane phospholipid metabolism was examined in brain regions previously inaccessible due to their small volumes.MethodThree-dimensional chemical-shift imaging (3D–CSI) examined 15 cc volumes in 12 brain regions in 11 people with chronic schizophrenia and 11 healthy control volunteers.ResultsGlycerophosphoethanolamine was decreased in the anterior cingulate, right prefrontal cortex and left thalamus, but increased in the left hippocampus and cerebellum in those with schizophrenia. Phosphoethanolamine and glycerophosphocholine were decreased in the right prefrontal region and phosphocholine was decreased in the anterior cingulate. No significant difference in membrane phospholipid levels existed between groups in the parieto-occipital and posterior cingulate regions.ConclusionsAltered membrane phospholipid metabolism was demonstrated in all regions implicated in schizophrenia.

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Alpha-Synuclein as a Prominent Actor in the Inflammatory Synaptopathy of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22126517 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6517

Author(s):

Antonella Cardinale ◽

Valeria Calabrese ◽

Antonio de Iure ◽

Barbara Picconi

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Brain Regions ◽

Alpha Synuclein ◽

Snare Complex ◽

Synaptic Proteins ◽

Prodromal Phase ◽

Toxic Species ◽

The Central Nervous System

Parkinson’s disease (PD) is considered the most common disorder of synucleinopathy, which is characterised by intracellular inclusions of aggregated and misfolded α-synuclein (α-syn) protein in various brain regions, and the loss of dopaminergic neurons. During the early prodromal phase of PD, synaptic alterations happen before cell death, which is linked to the synaptic accumulation of toxic α-syn specifically in the presynaptic terminals, affecting neurotransmitter release. The oligomers and protofibrils of α-syn are the most toxic species, and their overexpression impairs the distribution and activation of synaptic proteins, such as the SNARE complex, preventing neurotransmitter exocytosis and neuronal synaptic communication. In the last few years, the role of the immune system in PD has been increasingly considered. Microglial and astrocyte activation, the gene expression of proinflammatory factors, and the infiltration of immune cells from the periphery to the central nervous system (CNS) represent the main features of the inflammatory response. One of the actors of these processes is α-syn accumulation. In light of this, here, we provide a systematic review of PD-related α-syn and inflammation inter-players.

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Use of cannabis components in the treatment of mental disorders

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.2036 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S552-S552

Author(s):

C. Tsopelas ◽

M. Dimitraka ◽

P. Ntounas ◽

A. Gatos-Gatopoulos ◽

D. Karadima ◽

...

Keyword(s):

Cognitive Impairment ◽

Mental Disorders ◽

Web Search ◽

Brain Activity ◽

Activity Patterns ◽

Cannabis Use ◽

Psychotic Symptoms ◽

Repeated Treatment ◽

Increased Risk ◽

Competing Interest

IntroductionThere is evidence that supports the increased risk of developing psychosis or psychotic like symptoms in vulnerable populations after use of cannabis. Cannabis’ main psychoactive component, Δ9-tetrahydrocannabinol (THC), induces acute psychotic effects and cognitive impairment. But there is also evidence to suggest that molecules in the cannabis plant could have an antipsychotic affect.AimsIn this review we are trying to explore the possibilities of cannabis use as a therapeutic agent in mental disorders.MethodsThorough research of the main databases, and web search engines for relevant studies, using appropriate keywords. We scrutinize them independently, before reaching consensus about appropriateness.ResultsIn animal models repeated treatment with cannabis constituent cannabidiol CBD or the atypical antipsychotic clozapine attenuates or reverses the schizophrenia-like behavioral disruption.In humans there are data that CBD counteracts psychotic symptoms and cognitive impairment associated with cannabis use. Also CBD may lower the risk for developing cannabis use associated psychosis. There are opposite effects of CBD and THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex.ConclusionsThe possible mechanism of action of GBD is not fully clarified, as it may involve anti-inflammatory or neuroprotective properties. These initial clinical studies with CBD treatment of psychotic symptoms argument the potential of CBD as an effective antipsychotic compound. Mechanisms responsible for these effects need to be further investigated.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Vitamin A: dietologist’s position

Medical alphabet ◽

10.33667/2078-5631-2020-21-49-57 ◽

2020 ◽

pp. 49-57

Author(s):

S. V. Orlova ◽

E. A. Nikitina ◽

L. I. Karushina ◽

Yu. A. Pigaryova ◽

O. E. Pronina

Keyword(s):

Immune Response ◽

Urinary Tract ◽

Gastrointestinal Tract ◽

Vitamin A ◽

Developed Countries ◽

Therapeutic Practice ◽

The Past ◽

Increased Risk ◽

Mucous Membranes

Vitamin A (retinol) is one of the key elements for regulating the immune response and controls the division and differentiation of epithelial cells of the mucous membranes of the bronchopulmonary system, gastrointestinal tract, urinary tract, eyes, etc. Its significance in the context of the COVID‑19 pandemic is difficult to overestimate. However, a number of studies conducted in the past have associated the additional intake of vitamin A with an increased risk of developing cancer, as a result of which vitamin A was practically excluded from therapeutic practice in developed countries. Our review highlights the role of vitamin A in maintaining human health and the latest data on its effect on the development mechanisms of somatic pathology.

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