Diagnostic Task Specific Activations in Functional MRI and Aberrant Connectivity of Insula with Middle Frontal Gyrus Can Inform the Differential Diagnosis of Psychosis

Stoyanov, Drozdstoy; Aryutova, Katrin; Kandilarova, Sevdalina; Paunova, Rositsa; Arabadzhiev, Zlatoslav; Todeva-Radneva, Anna; Kostianev, Stefan; Borgwardt, Stefan

doi:10.3390/diagnostics11010095

Cited by 37 publications

(34 citation statements)

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“…Interestingly, the combined impact of leaky gut, immune activation and natural IgM biomarkers was more important than that of neurotoxicity indices, although the MITOTOX index comprising the neurotoxic cytokines/chemokines and TRYCATs coupled with LPS and the oxidative stress damage was strongly associated with the physiosomatic symptoms. Previously, we have discussed that the symptomatome, G-CoDe, Qol-phenome, and the BCPS-worsening index are significantly associated with indices of increased neurotoxicity as indicated by increased levels of neurotoxic cytokines including IL-6, TNF-α, CCL11, MIP-1, increased levels of neurotoxic TRYCATs, including PA, XA, and 3HK, and signs of oxidative/chlorinative stress as indicated by increased LOOH, MDA, and AOPP levels (Maes et al, 2020a;2021b).…”

Section: Biomarker Correlates: Focus On Immune Activation and Neurotoxicitymentioning

confidence: 99%

“…CCL11 was not included in this index to allow for the additional effects of this . chemokine; and d) the MITOTOX index was computed as zTNF-α + zIL-6 + zCCL11 + zTRYCAT ratio + zLOOH + zMDA + zAOPP + zIgA LPS (Maes et al, 2020a;2021b).…”

Section: Assaysmentioning

confidence: 99%

“…Moreover, it is important to note that the plasma levels of Hp, which is an acute phase protein (APP), are significantly increased in schizophrenia in conjunction with other acute phase proteins and complement factors, including C3C (Maes et al, 1997). As such, part of the immune-inflammatory and oxidative stress responses in schizophrenia (Maes et al, 1997;2021b) may be explained by an increased Hp-2 gene frequency, increased zonulin levels and accompanying leaky gut (Maes et al, 2001;2019a).…”

Section: Biomarker Correlates: Focus On Leaky Gutmentioning

confidence: 99%

“…CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) which lead to aberrations in neuroplasticity and connectivity especially in the salience network (anterior insula and anterior cingulate cortex), amygdala, the prefronto-striato-thalamic, prefrontoparietal, prefronto-temporal, and dorsolateral prefrontal cortex Orellana and Slachevsky, 2013;Maes et al, 2020a;2021b;Stoyanov and Maes, 2021;Stoyanov et al, 2021).…”

Section: Mechanistic Explanationsmentioning

confidence: 99%

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In schizophrenia, chronic fatigue syndrome- and fibromyalgia-like symptoms are driven by breakdown of the paracellular pathway with increased zonulin and immune activation-associated neurotoxicity

Maes

Andres

Vojdani

et al. 2021

Preprint

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Background: A meaningful part of schizophrenia patients suffer from physiosomatic symptoms (formerly named psychosomatic) which are reminiscent of chronic fatigue syndrome and fibromyalgia (FF) and are associated with signs of immune activation and increased levels of tryptophan catabolites (TRYCATs). Aims: To examine whether FF symptoms in schizophrenia are associated with breakdown of the paracellular pathway, zonulin, lowered natural IgM responses to oxidative specific epitopes (OSEs); and whether FF symptoms belong to the behavioral-cognitive-physical-psychosocial-(BCPS)-worsening index consisting of indices of a general cognitive decline (G-CoDe), symptomatome of schizophrenia, and quality of life (QoL)-phenomenome. Methods: FF symptoms were assessed using the Fibromyalgia and Chronic Fatigue Rating scale in 80 schizophrenia patients and 40 healthy controls and serum cytokines/chemokines, IgA levels to TRYCATs, IgM to OSEs, zonulin and transcellular/paracellular (TRANS/PARA) molecules were assayed using ELISA methods. Results: A large part (42.3%) of the variance in the total FF score was explained by the regression on the PARA/TRANS ratio, pro-inflammatory cytokines, IgM to zonulin, IgA to TRYCATs (all positively) and IgM to OSEs (inversely). There were highly significant correlations between the total FF score and G-CoDe, symtopmatome, QoL phenomenome and BCPS-worsening score. FF symptoms belong to a common core shared by G-CoDe, symtopmatome, and QoL phenomenome. Discussion: The physio-somatic symptoms of schizophrenia are driven by various pathways including increased zonulin, breakdown of the paracellular tight-junctions pathway, immune activation with induction of the TRYCAT pathway, and consequent neurotoxicity. It is concluded that FF symptoms are part of the phenome of schizophrenia and BCPS-worsening as well.

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Section: Biomarker Correlates: Focus On Immune Activation and Neurotoxicitymentioning

confidence: 99%

Section: Assaysmentioning

confidence: 99%

Section: Biomarker Correlates: Focus On Leaky Gutmentioning

confidence: 99%

Section: Mechanistic Explanationsmentioning

confidence: 99%

See 2 more Smart Citations

In schizophrenia, chronic fatigue syndrome- and fibromyalgia-like symptoms are driven by breakdown of the paracellular pathway with increased zonulin and immune activation-associated neurotoxicity

Maes

Andres

Vojdani

et al. 2021

Preprint

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Section: Translational Approachmentioning

confidence: 99%

Implications from translational cross-validation of clinical assessment tools for diagnosis and treatment in psychiatry

Aryutova

Paunova

Kandilarova

et al. 2021

WJP

Self Cite

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Traditional therapeutic methods in psychiatry, such as psychopharmacology and psychotherapy help many people suffering from mental disorders, but in the long-term prove to be effective in a relatively small proportion of those affected. Therapeutically, resistant forms of mental disorders such as schizophrenia, major depressive disorder, and bipolar disorder lead to persistent distress and dysfunction in personal, social, and professional aspects. In an effort to address these problems, the translational approach in neuroscience has initiated the inclusion of novel or modified unconventional diagnostic and therapeutic techniques with promising results. For instance, neuroimaging data sets from multiple modalities provide insight into the nature of pathophysiological mechanisms such as disruptions of connectivity, integration, and segregation of neural networks, focusing on the treatment of mental disorders through instrumental biomedical methods such as electro-convulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS). These methodologies have yielded promising results that have yet to be understood and improved to enhance the prognosis of the severe and persistent psychotic and affective disorders. The current review is focused on the translational approach in the management of schizophrenia and mood disorders, as well as the adaptation of new transdisciplinary diagnostic tools such as neuroimaging with concurrently administered psychopathological questionnaires and integration of the results into the therapeutic framework using various advanced instrumental biomedical tools such as ECT, TMS, tDCS and DBS.

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Case series of patients with early psychosis presenting hypoperfusion in angular gyrus and self‐disturbance: Implication for the sense of agency and schizophrenia

Yoshikawa,

Obata,

Kakiuchi

et al. 2024

Neuropsychopharm Rep

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BackgroundSelf‐disturbance has been considered as a core symptomatology of schizophrenia and its emergence from the prodromal phase makes it a crucial target for early detection and intervention in schizophrenia. Currently, the clinical assessment of self‐disturbance relies on the self‐report of patients, and clinicians have no diagnostic tools in clinical practice. Identifying the neural substrate of self‐disturbance would be of great clinical value by shedding light on the core dimension of schizophrenia.Case PresentationWe first introduce an adolescent patient who initially presented self‐disturbance, and clinically detectable hypoperfusion in angular gyrus (AG) was observed when early psychosis was suspected. Interestingly, the hypoperfusion in AG may correspond to improvement and exacerbation of self‐disturbance. This clinical observation led us to pursue the relationship between the decreased blood flow in the AG and self‐disturbance. Among 15 cases with suspected early psychosis in which single photon emission computed tomography was performed to exclude organic factors, we found additional 5 cases, including one prodromal patient, showing hypoperfusion in the AG and self‐disturbance with significant correlation (r = 0.79, p = 0.00025).DiscussionThe self‐disturbance has been interpreted as a reflection of disturbance of the “Sense of Agency”, the ability to attribute their action and/or thoughts to themselves. AG has been shown to play a pivotal role in the sense of agency. These cases suggest that the hypoperfusion in AG associated with the disruption in the sense of agency would be an early clinical sign of schizophrenia. Further longitudinal studies are needed to test this hypothesis.

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Diagnostic Task Specific Activations in Functional MRI and Aberrant Connectivity of Insula with Middle Frontal Gyrus Can Inform the Differential Diagnosis of Psychosis

Cited by 37 publications

References 57 publications

In schizophrenia, chronic fatigue syndrome- and fibromyalgia-like symptoms are driven by breakdown of the paracellular pathway with increased zonulin and immune activation-associated neurotoxicity

In schizophrenia, chronic fatigue syndrome- and fibromyalgia-like symptoms are driven by breakdown of the paracellular pathway with increased zonulin and immune activation-associated neurotoxicity

Implications from translational cross-validation of clinical assessment tools for diagnosis and treatment in psychiatry

Case series of patients with early psychosis presenting hypoperfusion in angular gyrus and self‐disturbance: Implication for the sense of agency and schizophrenia

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