Biological Markers in Psychiatry and Its Relation with Translational Approaches: Brief Historical Review

Gargiulo, Ángel José Martín; Gargiulo, Mercedes María Lucrecia; Gargiulo, Augusto Pascual Ítalo; Mesones, Gonzalo; Martin, Gustavo; Gargiulo, A.; Mesones-Arroyo, Humberto Luis; Gargiulo, Pascual Ángel

doi:10.1007/978-3-319-17103-6_23

Cited by 5 publications

(5 citation statements)

References 160 publications

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“…However, other studies performed in important group of patients and delimitating subgroups with low urinary phenylethylamine excretion led to clear therapeutic results [6,8]. These evidences clearly point DPA as a therapeutic resource, in combination with other classical antidepressants or even alone [6,8], as it has been extensively reviewed [10]. Present findings give additional support to the evidences observed previously in our country [6] and corroborated in Germany [7].…”

Section: Discussionsupporting

confidence: 89%

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Comparative Effect between Antidepressants and D-phenylalanine, a Phenethylamine Precursor, in an Animal Model of Depression

Moreno Adaro,

Berríos Bravo,

Guevara

et al. 2023

Arch. Psychiatry Res.

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A relevant role has been attributed to phenethylamine in depressive disorders. It has been measured in human urine and rat brain in pathological conditions and after drug administration. Furthermore, a clinical correlation has been proposed between urinary elimination and depressive symptoms. Furthermore, its metabolic predecessor, D-phenylalanine, has been used as an antidepressant drug in the treatment of depressive disorders. The use of this amino acid has been realized alone, or in combination with classical antidepressants. In the present study, we tried to characterize its behavioural profile comparing it with imipramine and fluoxetine. Antidepressant drugs have been studied using diverse animal models. We used here the Porsolt test, or Forced Swimming Test (FST), measuring times of climbing, swimming and resting. When a comparison was performed between groups in climbing behaviour, significant differences were observed between imipramine treated group and saline controls (p < 0.05), and imipramine versus fluoxetine and D-phenylalanine (p < 0.01). When swimming was evaluated, clear differences between D-phenylalanine and the other groups were observed (p < 0.001). Additionally, a significant difference was also observed between imipramine and fluoxetine (p < 0.01). When resting was evaluated, high differences between D-phenylalanine versus all other groups were shown (p < 0.001). Observed behavioural profile was according to serotonergic antidepressant drugs effects. It is supported by the fact that swimming behaviours were increased, and a correlative decrease in resting was also present. We conclude that D-phenylalanine showed higher antidepressant potency than other classical antidepressants, at least at the doses used.

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Section: Discussionsupporting

confidence: 89%

“…Similar findings were obtained by Beckmann and Ludolph in Germany [8,9]. The use of this amino acid has been realized alone [8,10], or in combination with classical antidepressants [6]. In the present study, we tried to characterize its translational behavioural profile comparing it with imipramine and fluoxetine.…”

Section: Introductionsupporting

confidence: 73%

Comparative Effect between Antidepressants and D-phenylalanine, a Phenethylamine Precursor, in an Animal Model of Depression

Moreno Adaro,

Berríos Bravo,

Guevara

et al. 2023

Arch. Psychiatry Res.

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“…On the other hand, the diversity of possible locomotor combinations could explain why the individual reactions to one and the same antipsychotic treatment might vary from patient to patient and why these individual reactions are more predictable by objective evaluation of the patient's motor abnormalities . As we consider the schizotaxic LMPs as locomotor biomarkers for early detection of vulnerability to develop schizophrenia, such an approach links our findings with the classical neuroscience tradition of translational animal research in psychiatry . Since the locomotor behaviour is frequently used as an objectively measurable biomarker for testing novel experimental drugs in animal models of psychiatric disorders, the discovered subclinical locomotor abnormalities might be viewed as a translational human equivalent of these animal models .…”

Section: Translational Implications Of the Objective Locomotor Evaluamentioning

confidence: 90%

“…46,[68][69][70][71][72] As we consider the schizotaxic LMPs as locomotor biomarkers for early detection of vulnerability to develop schizophrenia, such an approach links our findings with the classical neuroscience tradition of translational animal research in psychiatry. 60,[72][73][74][75][76] Since the locomotor behaviour is frequently used as an objectively measurable biomarker for testing novel experimental drugs in animal models of psychiatric disorders, 72,73 the discovered subclinical locomotor abnormalities might be viewed as a translational human equivalent of these animal models. 72 It is well known that the experimentally induced hyperdopaminergia (eg, by dopamine agonists) in animal models of psychosis typically leads to objectively measurable hyperlocomotion, which is routinely used for objectively testing and measuring the effects of preclinical candidates for antipsychotic drugs.…”

Section: Clinical Implications Of the Translational Equilibriometrimentioning

confidence: 99%

Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications

Haralanov

Haralanova

Milushev

et al. 2018

Evaluation Clinical Practice

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Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20 years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the translational and clinical implications of the new approach and its future perspectives.

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“…The schneiderian's criteria have an influence even today [21]. In this conception, psychotic states must be ''explained'' by biological causes, and not merely ''understood'', in a traditional center European schedule (''erklaren'' vs. ''verstehen''), following the concepts of Jaspers, Schneider and, in the same way, Popper [21]. We are here studying efficient causes acting on the brain, explaining the consecutive behavioral disorders.…”

Section: Introductionmentioning

confidence: 99%

Glutamate and modeling of schizophrenia symptoms: Review of our Findings: 1990–2014

Gargiulo

2014

Pharmacological Reports

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In the early 90s, we studied the role of perception disturbances in schizophrenia in our first clinical approaches, using the Bender test in schizophrenic patients. Results were clear, showing a shape discrimination failure. Following this initial results, we reproduced nuclear symptoms of schizophrenia in animal models, showing that perceptual disturbances, acquisition disturbances, decrease in affective levels and working memory disturbances can be induced by specific N-methyl-D-aspartic acid (NMDA) glutamatergic blockade within the nucleus accumbens septi (NAS). We studied also another glutamatergic and dopaminergic drugs, finding that a decrease in glutamatergic transmission within NAS led to cognitive disturbances and affective flattening. An increase in glutamatergic transmission fully enhances cognition in the tasks used. Dopaminergic D-2 antagonists partially improved cognition. Our results link the proposed corticostriatal dysfunction with the thalamocortical disturbances underlying perceptual problems, but also influencing affective levels and cognitive variables. According to our translational findings, core schizophrenia symptoms may be translationally reproduced antagonizing NMDA receptors within NAS, and improved blocking the glutamate auto-receptor. Dopaminergic transmission appears to have a role in therapeutic but not in the early pathophysiology of schizophrenia.

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Biological Markers in Psychiatry and Its Relation with Translational Approaches: Brief Historical Review

Cited by 5 publications

References 160 publications

Comparative Effect between Antidepressants and D-phenylalanine, a Phenethylamine Precursor, in an Animal Model of Depression

Comparative Effect between Antidepressants and D-phenylalanine, a Phenethylamine Precursor, in an Animal Model of Depression

Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications

Glutamate and modeling of schizophrenia symptoms: Review of our Findings: 1990–2014

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