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Article ; Online: Prevalence of co-occurring conditions in children and adults with autism spectrum disorder: A systematic review and meta-analysis.

Micai, Martina / Fatta, Laura Maria / Gila, Letizia / Caruso, Angela / Salvitti, Tommaso / Fulceri, Francesca / Ciaramella, Antonio / D'Amico, Roberto / Del Giovane, Cinzia / Bertelli, Marco / Romano, Giovanna / Schünemann, Holger Jens / Scattoni, Maria Luisa

Neuroscience and biobehavioral reviews

2023 Volume 155, Page(s) 105436

Abstract: This systematic review estimates the prevalence of co-occurring conditions (CCs) in children and adults with autism. A comprehensive search strategy consulting existing guidelines, diagnostic manuals, experts, carers, and autistic people was developed. ... ...

Abstract	This systematic review estimates the prevalence of co-occurring conditions (CCs) in children and adults with autism. A comprehensive search strategy consulting existing guidelines, diagnostic manuals, experts, carers, and autistic people was developed. PubMed and PsycInfo databases from inception to May 2022 were searched. PROSPERO registration: CRD42019132347. Two blind authors screened and extracted the data. Prevalence estimates for different CCs were summarized by using random effects models. Subgroup analyses were performed for age groups (children/adolescents vs adults) and study designs (population/registry-based vs clinical sample-based). Of 19,932 studies, 340 publications with about 590,000 participants were included and meta-analyzed to estimate the prevalence of 38-point prevalence, 27-lifetime, and 3 without distinction between point and lifetime prevalence. Point prevalence of developmental coordination disorder, sleep-wake problem, gastrointestinal problem, ADHD, anxiety disorder, overweight/obesity, feeding and eating disorder, elimination disorder, disruptive behavior, and somatic symptoms and related disorder were the most frequent CCs. Prevalence differed depending on the age group and study design. Knowing specific CCs linked to autism helps professional investigations and interventions for improved outcomes.
MeSH term(s)	Child ; Adolescent ; Adult ; Humans ; Autism Spectrum Disorder/epidemiology ; Prevalence ; Obesity ; Autistic Disorder ; Overweight
Language	English
Publishing date	2023-10-31
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2023.105436
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Article: Myeloid Dendritic Cells are Potential Players in Human Neurodegenerative Diseases.

Bossù, Paola / Spalletta, Gianfranco / Caltagirone, Carlo / Ciaramella, Antonio

Frontiers in immunology

2015 Volume 6, Page(s) 632

Abstract: Alzheimer's diseases (AD) and Parkinson's diseases (PD) are devastating neurodegenerative disturbances, wherein neuroinflammation is a chronic pathogenic process with high therapeutic potential. Major mediators of AD/PD neuroimmune processes are resident ...

Abstract	Alzheimer's diseases (AD) and Parkinson's diseases (PD) are devastating neurodegenerative disturbances, wherein neuroinflammation is a chronic pathogenic process with high therapeutic potential. Major mediators of AD/PD neuroimmune processes are resident immune cells, but immune cells derived from periphery may also participate and to some extent modify neuroinflammation. Specifically, blood borne myeloid cells emerge as crucial components of AD/PD progression and susceptibility. Among these, dendritic cells (DCs) are key immune orchestrators and players of brain immune surveillance; we candidate them as potential mediators of both AD and PD and as relevant cell model for unraveling myeloid cell role in neurodegeneration. Hence, we recapitulate and discuss emerging data suggesting that blood-derived DCs play a role in experimental and human neurodegenerative diseases. In humans, in particular, DCs are modified by in vitro culture with neurodegeneration-associated pathogenic factors and dysregulated in AD patients, while the levels of DC precursors are decreased in AD and PD patients' blood, possibly as an index of their recruitment to the brain. Overall, we emphasize the need to explore the impact of DCs on neurodegeneration to uncover peripheral immune mechanisms of pathogenic importance, recognize potential biomarkers, and improve therapeutic approaches for neurodegenerative diseases.
Language	English
Publishing date	2015
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2015.00632
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Article ; Online: Neurovascular Dysfunction in Alzheimer Disease: Assessment of Cerebral Vasoreactivity by Ultrasound Techniques and Evaluation of Circulating Progenitor Cells and Inflammatory Markers.

Cipollini, Virginia / Sette, Giuliano / Bossù, Paola / Ciaramella, Antonio / Salani, Francesca / De Carolis, Antonella / Troili, Fernanda / Orzi, Francesco / Giubilei, Franco

Alzheimer disease and associated disorders

2019 Volume 33, Issue 3, Page(s) 212–219

Abstract: Aims: The aims of this study were to assess vascular dysfunction in patients with Alzheimer disease (AD) by investigating cerebral vasomotor reactivity using transcranial Doppler ultrasound (TCD) and to evaluate any correlations between cerebral ... ...

Abstract	Aims: The aims of this study were to assess vascular dysfunction in patients with Alzheimer disease (AD) by investigating cerebral vasomotor reactivity using transcranial Doppler ultrasound (TCD) and to evaluate any correlations between cerebral vasoreactivity and endothelium dysfunction. Moreover, the frequency of circulating progenitor cells (CPCs) and the blood concentration of vascular/inflammatory markers were evaluated. Materials and methods: We recruited 35 AD subjects and 17 age-matched, sex-matched, and education-matched healthy control subjects. Cerebral vasomotor reactivity was assessed by means of the TCD-based breath-holding index test (BHI). The level of CPCs was evaluated by means of flow cytometry from venous blood samples, while blood vascular/inflammatory markers were measured by means of enzyme-linked immunosorbent assay. Results: Both cerebral assay blood flow velocity in the middle cerebral artery (MCAFV) and BHI values were significantly lower in AD subjects than in healthy controls (P<0.05). A positive trend was found between MCAFV and BHI values and Mini-Mental State Evaluation (MMSE) scores. Moreover, the hematopoietic progenitor cells' count was found to be lower in patients with AD than in controls (P<0.05). Finally, a significantly higher expression of the plasma chemokine CCL-2 was observed in AD patients than in healthy controls. Conclusions: Our results confirm that cerebral hemodynamic deterioration may be a critical marker of cognitive decline. Further studies are needed to investigate the role of circulating CPCs and chemokines as potential contributors to neurovascular dysfunction.
MeSH term(s)	Aged ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/physiopathology ; Biomarkers/blood ; Breath Holding ; Cerebrovascular Circulation ; Chemokine CCL2/blood ; Female ; Humans ; Male ; Mental Status and Dementia Tests ; Middle Cerebral Artery/diagnostic imaging ; Middle Cerebral Artery/physiopathology ; Stem Cells/immunology ; Ultrasonography, Doppler, Transcranial
Chemical Substances	Biomarkers ; Chemokine CCL2
Language	English
Publishing date	2019-08-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1002700-2
ISSN	1546-4156 ; 0893-0341
ISSN (online)	1546-4156
ISSN	0893-0341
DOI	10.1097/WAD.0000000000000331
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Zs.A 2569: Show issues

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Article ; Online: IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study.

Sacchinelli, Eleonora / Piras, Fabrizio / Orfei, Maria Donata / Banaj, Nerisa / Salani, Francesca / Ciaramella, Antonio / Caltagirone, Carlo / Spalletta, Gianfranco / Bossù, Paola

Neuroimmunomodulation

2018 Volume 25, Issue 3, Page(s) 129–137

Abstract: Objective: Interaction between the nervous and immune systems may influence emotions, ultimately affecting human health. Cytokines may play a role in developing emotional dysregulation as in alexithymia, a personality construct characterized by the ... ...

Abstract	Objective: Interaction between the nervous and immune systems may influence emotions, ultimately affecting human health. Cytokines may play a role in developing emotional dysregulation as in alexithymia, a personality construct characterized by the subclinical inability to identify and describe emotions, often associated with several psychiatric and psychosomatic disorders. The proinflammatory cytokine IL-18, with a recognized role in brain functions, may influence serotonin metabolism and appears to be associated with alexithymia. Healthy individuals carrying the long allele (L) of the serotonin transporter gene polymorphic region (5-HTTLPR), and thus having lower concentrations of serotonin in the synaptic cleft, show a greater tendency toward alexithymia, with some gender differences. To explore a potential physiological interaction between IL-18, serotonin neurotransmission, and alexithymia, we investigated whether IL-18 serum levels and 5-HTTLPR are linked to alexithymic traits in healthy subjects. Methods: We measured IL-18 serum levels in 115 Italian-Caucasian healthy subjects genotyped for 5-HTTLPR allele variants, divided by gender and assessed for alexithymia scores using the 20-item Toronto Alexithymia Scale. Results: IL-18 levels are significantly more elevated in individuals with the LL genotype (n = 25) than in carriers of the short allele (n = 90, p = 0.0073). Specifically, in LL males (n = 11), i.e., the group with the most relevant increase in IL-18, cytokine values positively correlated with difficulty identifying feelings, which is a component of alexithymia (r = 0.634, p = 0.036). Conclusions: These results indicate a possible novel interaction between IL-18 and the serotoninergic system to mediate emotional unawareness, suggesting putative biological predictors of emotional dysregulation, which in turn can act as a risk factor for a variety of medical conditions in susceptible subjects.
MeSH term(s)	Adolescent ; Adult ; Affective Symptoms/blood ; Affective Symptoms/diagnosis ; Affective Symptoms/genetics ; Aged ; Aged, 80 and over ; Awareness/physiology ; Biomarkers/blood ; Emotions/physiology ; Female ; Genetic Variation/physiology ; Heterozygote ; Humans ; Interleukin-18/blood ; Male ; Middle Aged ; Serotonin Plasma Membrane Transport Proteins/blood ; Serotonin Plasma Membrane Transport Proteins/genetics ; Young Adult
Chemical Substances	Biomarkers ; IL18 protein, human ; Interleukin-18 ; SLC6A4 protein, human ; Serotonin Plasma Membrane Transport Proteins
Language	English
Publishing date	2018-10-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1184368-8
ISSN	1423-0216 ; 1021-7401
ISSN (online)	1423-0216
ISSN	1021-7401
DOI	10.1159/000492030
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Article: Increased expression of Interleukin-18 receptor in blood cells of subjects with Mild Cognitive Impairment and Alzheimer’s disease

Salani, Francesca / Ciaramella, Antonio / Bizzoni, Federica / Assogna, Francesca / Caltagirone, Carlo / Spalletta, Gianfranco / Bossù, Paola

Cytokine. 2013 Feb., v. 61, no. 2

2013

Abstract: Inflammation has been proposed as a leading force in neurodegeneration and Interleukin (IL)-18 is a pro-inflammatory cytokine which is suggested to be implicated in Alzheimer’s disease (AD). However, the meaning of the IL-18 participation in this disease ...

Abstract	Inflammation has been proposed as a leading force in neurodegeneration and Interleukin (IL)-18 is a pro-inflammatory cytokine which is suggested to be implicated in Alzheimer’s disease (AD). However, the meaning of the IL-18 participation in this disease is still unclear. Since IL-18 activity is mediated by its heterodimeric receptor complex IL-18Rα/β, we evaluated the presence of both IL-18R chains on peripheral blood cells of AD patients, as well as in individuals with Mild Cognitive Impairment (MCI), at increased risk to develop AD. More specifically, we compared the levels of CD14⁺ monocytes and CD3⁺ T-lymphocytes bearing IL-18Rα and β chains in the two groups of patients with those in healthy control subjects, both before and after in vitro cell treatment with lipopolysaccharide (LPS). While no differences in the levels of monocytes and T-lymphocytes bearing IL-18Rα chain were found among the three groups, either in untreated and LPS-treated conditions, the IL-18Rβ chain expression appeared differently regulated in MCI and AD patients, as compared to controls. In particular, the amount of IL-18Rβ-bearing monocytes was similar among the three groups at unstimulated conditions, while after LPS treatment it was increased in MCI vs. controls. A significant increase of IL-18Rβ-bearing T-lymphocytes was also observed in MCI and AD vs. controls, both in untreated and LPS-stimulated conditions. Our findings indicate that the expression of IL-18R complex on blood cells is perturbed in AD and even more markedly in its preclinical state of MCI, confirming that an increased peripheral activity of IL-18 may be involved in the early phase of AD pathophysiology.
Keywords	T-lymphocytes ; central nervous system diseases ; inflammation ; interleukin-18 ; lipopolysaccharides ; monocytes ; pathophysiology ; patients ; risk
Language	English
Dates of publication	2013-02
Size	p. 360-363.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2012.11.001
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Myeloid dendritic cells are decreased in peripheral blood of Alzheimer's disease patients in association with disease progression and severity of depressive symptoms.

Ciaramella, Antonio / Salani, Francesca / Bizzoni, Federica / Orfei, Maria Donata / Caltagirone, Carlo / Spalletta, Gianfranco / Bossù, Paola

Journal of neuroinflammation

2016 Volume 13, Page(s) 18

Abstract: Background: Dendritic cells (DCs) are major orchestrators of immune responses and inflammation. They are migratory cells, which may play a role in Alzheimer's disease (AD), as suggested by prior in vitro studies. With the intent to investigate the ... ...

Abstract	Background: Dendritic cells (DCs) are major orchestrators of immune responses and inflammation. They are migratory cells, which may play a role in Alzheimer's disease (AD), as suggested by prior in vitro studies. With the intent to investigate the clinical relevance of DC modifications in vivo, the present study was aimed to evaluate the levels of blood DCs in AD patients, in relation to the progression of the disease, the severity of its symptoms, and the treatment with acetylcholinesterase inhibitors (AChEIs), a class of drugs used to improve cognitive functioning in people with dementia. Methods: The two main subpopulations of immature blood DCs, namely myeloid (mDCs) and plasmacytoid (pDCs) cells, were evaluated by flow cytometry analysis in 106 AD patients, in comparison with the same cells from 65 individuals with mild cognitive impairment (MCI) and 73 healthy control subjects (HC). The relationship between blood DC levels and symptom severity was also assessed in AD patients, and their blood DC frequency was considered both in the absence or presence of treatment with AChEIs. Results: A significant depletion in blood mDCs was observed in AD patients, as compared to HC and MCI subjects. At variance, pDC levels were comparable among the three groups of subjects. The mDC decrease was evident only after the emergence of AD clinical symptoms, as confirmed by the follow-up analysis of a subgroup of MCI subjects who exhibited a significant decline in mDCs after their conversion to AD. Notably, the mDC decline was inversely correlated in AD patients with the frequency and severity of depressive symptoms. Eventually, the mDC depletion was not observable in patients treated with AChEIs. Conclusions: Our results provide the first evidence that blood mDC levels are dysregulated in AD. This phenomenon appears mainly linked to AD progression, associated with stronger severity of AD-related symptoms, and influenced by AChEI treatment. Taken all together, these data suggest that blood mDCs may serve as a cell source to test disease-induced and treatment-related changes and support the innovative notion that DCs play a role in AD, as ultimate evidence of the immune system participation in disease progression.
MeSH term(s)	Aged ; Alzheimer Disease/complications ; Alzheimer Disease/pathology ; Cognitive Dysfunction/etiology ; Dendritic Cells/pathology ; Depression/etiology ; Disease Progression ; Female ; HLA-DR Antigens/metabolism ; Humans ; Italy ; Male ; Myeloid Cells/pathology ; Neuropsychological Tests ; Psychiatric Status Rating Scales
Chemical Substances	HLA-DR Antigens
Language	English
Publishing date	2016-01-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1742-2094
ISSN (online)	1742-2094
DOI	10.1186/s12974-016-0483-0
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Article ; Online: Increased expression of interleukin-18 receptor in blood cells of subjects with mild cognitive impairment and Alzheimer's disease.

Salani, Francesca / Ciaramella, Antonio / Bizzoni, Federica / Assogna, Francesca / Caltagirone, Carlo / Spalletta, Gianfranco / Bossù, Paola

Cytokine

2013 Volume 61, Issue 2, Page(s) 360–363

Abstract: Inflammation has been proposed as a leading force in neurodegeneration and Interleukin (IL)-18 is a pro-inflammatory cytokine which is suggested to be implicated in Alzheimer's disease (AD). However, the meaning of the IL-18 participation in this disease ...

Abstract	Inflammation has been proposed as a leading force in neurodegeneration and Interleukin (IL)-18 is a pro-inflammatory cytokine which is suggested to be implicated in Alzheimer's disease (AD). However, the meaning of the IL-18 participation in this disease is still unclear. Since IL-18 activity is mediated by its heterodimeric receptor complex IL-18Rα/β, we evaluated the presence of both IL-18R chains on peripheral blood cells of AD patients, as well as in individuals with Mild Cognitive Impairment (MCI), at increased risk to develop AD. More specifically, we compared the levels of CD14(+) monocytes and CD3(+) T-lymphocytes bearing IL-18Rα and β chains in the two groups of patients with those in healthy control subjects, both before and after in vitro cell treatment with lipopolysaccharide (LPS). While no differences in the levels of monocytes and T-lymphocytes bearing IL-18Rα chain were found among the three groups, either in untreated and LPS-treated conditions, the IL-18Rβ chain expression appeared differently regulated in MCI and AD patients, as compared to controls. In particular, the amount of IL-18Rβ-bearing monocytes was similar among the three groups at unstimulated conditions, while after LPS treatment it was increased in MCI vs. controls. A significant increase of IL-18Rβ-bearing T-lymphocytes was also observed in MCI and AD vs. controls, both in untreated and LPS-stimulated conditions. Our findings indicate that the expression of IL-18R complex on blood cells is perturbed in AD and even more markedly in its preclinical state of MCI, confirming that an increased peripheral activity of IL-18 may be involved in the early phase of AD pathophysiology.
MeSH term(s)	Aged ; Alzheimer Disease/blood ; Blood Cells/metabolism ; Case-Control Studies ; Cognitive Dysfunction/blood ; Female ; Humans ; Interleukin-18 Receptor alpha Subunit/blood ; Interleukin-18 Receptor beta Subunit/blood ; Male
Chemical Substances	IL18R1 protein, human ; Interleukin-18 Receptor alpha Subunit ; Interleukin-18 Receptor beta Subunit
Language	English
Publishing date	2013-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2012.11.001
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Article: Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment.

Bossù, Paola / Salani, Francesca / Ciaramella, Antonio / Sacchinelli, Eleonora / Mosca, Alessandra / Banaj, Nerisa / Assogna, Francesca / Orfei, Maria Donata / Caltagirone, Carlo / Gianni, Walter / Spalletta, Gianfranco

Frontiers in aging neuroscience

2018 Volume 10, Page(s) 285

Abstract: Alzheimer's disease (AD) is a fatal dementing neurodegenerative disease, currently lacking an efficacious disease-modifying therapy. In the last years, there has been some interest in the use of homotaurine as a potential therapeutic compound for AD, but ...

Abstract	Alzheimer's disease (AD) is a fatal dementing neurodegenerative disease, currently lacking an efficacious disease-modifying therapy. In the last years, there has been some interest in the use of homotaurine as a potential therapeutic compound for AD, but more work is still needed to prove its efficacy as disease modifier in dementia. Since inflammation is believed to play a key role in AD development, we sought to investigate here the
Language	English
Publishing date	2018-11-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2018.00285
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Article: IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study

Sacchinelli, Eleonora / Piras, Fabrizio / Orfei, Maria Donata / Banaj, Nerisa / Salani, Francesca / Ciaramella, Antonio / Caltagirone, Carlo / Spalletta, Gianfranco / Bossù, Paola

Neuroimmunomodulation

2018 Volume 25, Issue 3, Page(s) 129–137

Institution	Experimental Neuropsychobiology Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy Neuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA
Abstract	Objective: Interaction between the nervous and immune systems may influence emotions, ultimately affecting human health. Cytokines may play a role in developing emotional dysregulation as in alexithymia, a personality construct characterized by the subclinical inability to identify and describe emotions, often associated with several psychiatric and psychosomatic disorders. The proinflammatory cytokine IL-18, with a recognized role in brain functions, may influence serotonin metabolism and appears to be associated with alexithymia. Healthy individuals carrying the long allele (L) of the serotonin transporter gene polymorphic region (5-HTTLPR), and thus having lower concentrations of serotonin in the synaptic cleft, show a greater tendency toward alexithymia, with some gender differences. To explore a potential physiological interaction between IL-18, serotonin neurotransmission, and alexithymia, we investigated whether IL-18 serum levels and 5-HTTLPR are linked to alexithymic traits in healthy subjects. Methods: We measured IL-18 serum levels in 115 Italian-Caucasian healthy subjects genotyped for 5-HTTLPR allele variants, divided by gender and assessed for alexithymia scores using the 20-item Toronto Alexithymia Scale. Results: IL-18 levels are significantly more elevated in individuals with the LL genotype (n = 25) than in carriers of the short allele (n = 90, p = 0.0073). Specifically, in LL males (n = 11), i.e., the group with the most relevant increase in IL-18, cytokine values positively correlated with difficulty identifying feelings, which is a component of alexithymia (r = 0.634, p = 0.036). Conclusions: These results indicate a possible novel interaction between IL-18 and the serotoninergic system to mediate emotional unawareness, suggesting putative biological predictors of emotional dysregulation, which in turn can act as a risk factor for a variety of medical conditions in susceptible subjects.
Keywords	IL-18 ; Cytokines ; Alexithymia ; Emotional disturbances ; 5-HTTLPR genotype ; Serotonin ; Gender
Language	English
Publishing date	2018-10-16
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Original Paper
ZDB-ID	1184368-8
ISSN	1423-0216 ; 1021-7401
ISSN (online)	1423-0216
ISSN	1021-7401
DOI	10.1159/000492030
Database	Karger publisher's database

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Article: Hippocampal volume and depressive symptoms are linked to serum IL-18 in schizophrenia.

Bossù, Paola / Piras, Fabrizio / Palladino, Ilaria / Iorio, Mariangela / Salani, Francesca / Ciaramella, Antonio / Chiapponi, Chiara / Caltagirone, Carlo / Spalletta, Gianfranco

Neurology(R) neuroimmunology & neuroinflammation

2015 Volume 2, Issue 4, Page(s) e111

Abstract: Objective: Since schizophrenia (SCZ) is often accompanied by hippocampal abnormalities and dysregulation of cytokine production, this study aimed to investigate the impact of the cytokine interleukin (IL)-18, whose biological system appears to be ... ...

Abstract	Objective: Since schizophrenia (SCZ) is often accompanied by hippocampal abnormalities and dysregulation of cytokine production, this study aimed to investigate the impact of the cytokine interleukin (IL)-18, whose biological system appears to be perturbed in SCZ, on brain structure and clinical severity in patients with chronic SCZ. Methods: The serum levels of IL-18, including its free bioactive form (i.e., the cytokine fraction not bound to its specific endogenous inhibitor IL-18 binding protein), were evaluated in a case-control study involving 71 individuals with SCZ diagnosis and 29 healthy controls. All participants underwent brain MRI automatic evaluation for hippocampal volume estimation. The Positive and Negative Syndrome Scale (PANSS) was administered to measure severity of symptoms in patients with SCZ. Results: Lower amounts of free IL-18 were related to smaller hippocampal volume measures in patients with SCZ. Furthermore, in line with a possible neuroprotective effect of the cytokine, higher levels of free IL-18 corresponded to lower subscores of PANSS depression in patients with SCZ. Conclusions: These findings demonstrate that the levels of circulating bioactive IL-18 are related to both hippocampal volume and severity of psychopathologic symptoms in patients with SCZ, confirming the involvement of the cytokine in SCZ pathophysiology and suggesting hippocampal-dependent and neuroprotective functions of IL-18 in this clinical context.
Language	English
Publishing date	2015-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2767740-0
ISSN	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000000111
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