Hypofunctional Dopamine Uptake and Antipsychotic Treatment-Resistant Schizophrenia

Amato, Davide; Kruyer, Anna; Samaha, Anne‐Noël; Heinz, Andreas

doi:10.3389/fpsyt.2019.00314

Cited by 39 publications

(27 citation statements)

References 257 publications

(355 reference statements)

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“…This complex may represent an interesting new pharmacological target in SCZ. The D2S receptor is involved whenever SCZ treatment resistance is discussed or phenomena of presynaptic D2 receptor supra-sensitivity induced by antipsychotics ( Amato et al., 2019 ).…”

Section: Section 2: Dr Alterations In Schizophreniamentioning

confidence: 99%

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Martel¹,

McArthur²

2020

Front. Pharmacol.

177

125

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Dopamine receptors are widely distributed within the brain where they play critical modulator roles on motor functions, motivation and drive, as well as cognition. The identification of five genes coding for different dopamine receptor subtypes, pharmacologically grouped as D1- (D1 and D5) or D2-like (D2S, D2L, D3, and D4) has allowed the demonstration of differential receptor function in specific neurocircuits. Recent observation on dopamine receptor signaling point at dopamine—glutamate-NMDA neurobiology as the most relevant in schizophrenia and for the development of new therapies. Progress in the chemistry of D1- and D2-like receptor ligands (agonists, antagonists, and partial agonists) has provided more selective compounds possibly able to target the dopamine receptors homo and heterodimers and address different schizophrenia symptoms. Moreover, an extensive evaluation of the functional effect of these agents on dopamine receptor coupling and intracellular signaling highlights important differences that could also result in highly differentiated clinical pharmacology. The review summarizes the recent advances in the field, addressing the relevance of emerging new targets in schizophrenia in particular in relation to the dopamine – glutamate NMDA systems interactions.

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Section: Section 2: Dr Alterations In Schizophreniamentioning

confidence: 99%

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Martel¹,

McArthur²

2020

Front. Pharmacol.

177

125

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“…Antipsychotic drugs (APDs) are widely used to treat psychosis in schizophrenia 1,2 and symptoms in other neuropsychiatric conditions 3 . Blocking dopamine signaling onto 60-80% of striatal D2 receptors (D2r) is thought to underlie their therapeutic efficacy 4,5 .…”

mentioning

confidence: 99%

Neuronal signature of an antipsychotic response

Parrilla-Carrero¹,

Kruyer²,

Chalhoub³

et al. 2020

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D2 receptor blockade has been cited as a principal mechanism of action of all antipsychotic medications, but is poorly predictive of symptom improvement or neurophysiological responses recorded using human brain imaging. A potential hurdle in interpreting such human imaging studies arises from the inability to distinguish activity within neuronal subcircuits. We used single cell resolution imaging to record activity in distinct populations of medium spiny neurons in vivo within the mouse ventral striatum, a structure associated with schizophrenia symptoms and antipsychotic therapeutic efficacy. While we expected the antipsychotic haloperidol to excite D2 receptor expressing neurons, we report a strong cellular depression mediated by the hypofunctional NMDA channel, which may be mediated in part by the action of haloperidol on the sigma1 receptor. Altogether, the impact of haloperidol on Ca2+ events in D2 receptor expressing neurons predicted psychomotor inhibition. Our results elucidate mechanisms by which antipsychotics act rapidly in the brain to impact psychomotor outputs.

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“…Among the CNS changes in schizophrenia that represent possible neural distortions, the theory of dopaminergic dysregulation is currently the most significant. 38 Tyrosine hydroxylase (TH) is a crucial enzyme in dopamine biosynthesis that acts as a significant signaling molecule in the CNS. Several transcription factors regulate the expression of the TH gene, the most important of which is the cAMP response element-binding protein (CREB).…”

Section: Discussionmentioning

confidence: 99%

Serum galectin-3 levels are decreased in schizophrenia

Kılıç

Işık

Demirdaş

et al. 2020

Braz. J. Psychiatry

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Objective: To determine whether changes in serum galectin-3 (gal-3) concentrations in schizophrenia patients have etiopathogenetic importance. Since very little research has assessed the connection between galectins and schizophrenia, we wanted to examine alterations in the inflammatory marker gal-3 in schizophrenia and investigate possible correlations between clinical symptomatology and serum concentrations. Methods: Forty-eight schizophrenia patients and 44 healthy controls were included in this study. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were administered to determine symptom severity. Venous blood samples were collected, and serum gal-3 levels were measured. Results: Mean serum gal-3 levels were significantly lower in schizophrenia patients, and there were no significant differences in age or sex with the control group. There was also a significant positive correlation between serum gal-3 concentrations and negative schizophrenia symptoms according to the SANS. Conclusion:The results indicate that gal-3 is decreased in schizophrenia patients, which could contribute to inflammation in the pathogenesis of schizophrenia.

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Hypofunctional Dopamine Uptake and Antipsychotic Treatment-Resistant Schizophrenia

Cited by 39 publications

References 257 publications

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Neuronal signature of an antipsychotic response

Serum galectin-3 levels are decreased in schizophrenia

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