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Article ; Online: The role of neuroactive steroids in tic disorders.

Branca, Caterina / Bortolato, Marco

2024 Volume 160, Page(s) 105637

Abstract: Tics are sudden, repetitive movements or vocalizations. Tic disorders, such as Tourette syndrome (TS), are contributed by the interplay of genetic risk factors and environmental variables, leading to abnormalities in the functioning of the cortico- ... ...

Abstract	Tics are sudden, repetitive movements or vocalizations. Tic disorders, such as Tourette syndrome (TS), are contributed by the interplay of genetic risk factors and environmental variables, leading to abnormalities in the functioning of the cortico-striatal-thalamo-cortical (CSTC) circuitry. Various neurotransmitter systems, such as gamma-aminobutyric acid (GABA) and dopamine, are implicated in the pathophysiology of these disorders. Building on the evidence that tic disorders are predominant in males and exacerbated by stress, emerging research is focusing on the involvement of neuroactive steroids, including dehydroepiandrosterone sulfate (DHEAS) and allopregnanolone, in the ontogeny of tics and other phenotypes associated with TS. Emerging evidence indicates that DHEAS levels are significantly elevated in the plasma of TS-affected boys, and the clinical onset of this disorder coincides with the period of adrenarche, the developmental stage characterized by a surge in DHEAS synthesis. On the other hand, allopregnanolone has garnered particular attention for its potential to mediate the adverse effects of acute stress on the exacerbation of tic severity and frequency. Notably, both neurosteroids act as key modulators of GABA-A receptors, suggesting a pivotal role of these targets in the pathophysiology of various clinical manifestations of tic disorders. This review explores the potential mechanisms by which these and other neuroactive steroids may influence tic disorders and discusses the emerging therapeutic strategies that target neuroactive steroids for the management of tic disorders.
MeSH term(s)	Male ; Humans ; Tics ; Neurosteroids ; Pregnanolone/pharmacology ; Tic Disorders ; Tourette Syndrome
Chemical Substances	Neurosteroids ; Pregnanolone (BXO86P3XXW)
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2024.105637
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Article ; Online: Psychological resilience and hyperthymia: Is there a link?

Scheggi, Simona / Bortolato, Marco

Journal of affective disorders

2023 Volume 338, Page(s) 187–188

MeSH term(s)	Humans ; Resilience, Psychological ; Personality
Language	English
Publishing date	2023-06-09
Publishing country	Netherlands
Document type	Letter
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2023.06.021
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Article: Editorial: Behavioral Addictions, Risk-Taking, and Impulsive Choice.

Bortolato, Marco / Madden, Gregory J

Frontiers in behavioral neuroscience

2022 Volume 16, Page(s) 924030

Language	English
Publishing date	2022-05-09
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2022.924030
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Article ; Online: Endocannabinoid-dependent decrease of GABAergic transmission on dopaminergic neurons is associated with susceptibility to cocaine stimulant effects in pre-adolescent male MAOA hypomorphic mice exposed to early life stress.

Serra, Valeria / Aroni, Sonia / Bortolato, Marco / Frau, Roberto / Melis, Miriam

Neuropharmacology

2023 Volume 233, Page(s) 109548

Abstract: Vulnerability to cocaine use disorder depends upon a combination of genetic and environmental risk factors. While early life adversity is a critical environmental vulnerability factor for drug misuse, allelic variants of the monoamine oxidase A (MAOA) ... ...

Abstract	Vulnerability to cocaine use disorder depends upon a combination of genetic and environmental risk factors. While early life adversity is a critical environmental vulnerability factor for drug misuse, allelic variants of the monoamine oxidase A (MAOA) gene have been shown to moderate its influence on the risk of drug-related problems. However, data on the interactions between MAOA variants and early life stress (ES) with respect to predisposition to cocaine abuse are limited. Here, we show that a mouse model capturing the interaction of genetic (low-activity alleles of the Maoa gene; MAOA
MeSH term(s)	Animals ; Male ; Mice ; Central Nervous System Agents/pharmacology ; Cocaine/pharmacology ; Cocaine-Related Disorders/metabolism ; Dopaminergic Neurons ; Endocannabinoids/metabolism ; Monoamine Oxidase/genetics ; Monoamine Oxidase/metabolism ; Ventral Tegmental Area ; Stress, Physiological
Chemical Substances	Central Nervous System Agents ; Cocaine (I5Y540LHVR) ; Endocannabinoids ; Monoamine Oxidase (EC 1.4.3.4)
Language	English
Publishing date	2023-04-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2023.109548
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Article ; Online: A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals.

Piras, Ignazio S / Braccagni, Giulia / Huentelman, Matthew J / Bortolato, Marco

CNS neuroscience & therapeutics

2023 Volume 29, Issue 11, Page(s) 3173–3182

Abstract: Aims: Antisocial personality disorder (ASPD) and conduct disorder (CD) are characterized by a persistent pattern of violations of societal norms and others' rights. Ample evidence shows that the pathophysiology of these disorders is contributed by ... ...

Abstract	Aims: Antisocial personality disorder (ASPD) and conduct disorder (CD) are characterized by a persistent pattern of violations of societal norms and others' rights. Ample evidence shows that the pathophysiology of these disorders is contributed by orbitofrontal cortex (OFC) alterations, yet the underlying molecular mechanisms remain elusive. To address this knowledge gap, we performed the first-ever RNA sequencing study of postmortem OFC samples from subjects with a lifetime diagnosis of ASPD and/or CD. Methods: The transcriptomic profiles of OFC samples from subjects with ASPD and/or CD were compared to those of unaffected age-matched controls (n = 9/group). Results: The OFC of ASPD/CD-affected subjects displayed significant differences in the expression of 328 genes. Further gene-ontology analyses revealed an extensive downregulation of excitatory neuron transcripts and upregulation of astrocyte transcripts. These alterations were paralleled by significant modifications in synaptic regulation and glutamatergic neurotransmission pathways. Conclusion: These preliminary findings suggest that ASPD and CD feature a complex array of functional deficits in the pyramidal neurons and astrocytes of the OFC. In turn, these aberrances may contribute to the reduced OFC connectivity observed in antisocial subjects. Future analyses on larger cohorts are needed to validate these results.
MeSH term(s)	Humans ; Transcriptome ; Antisocial Personality Disorder/genetics ; Antisocial Personality Disorder/diagnosis ; Conduct Disorder ; Prefrontal Cortex
Chemical Substances	4-aminospiroperidol (114442-96-5)
Language	English
Publishing date	2023-06-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2423461-8
ISSN	1755-5949 ; 1755-5930
ISSN (online)	1755-5949
ISSN	1755-5930
DOI	10.1111/cns.14283
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Article ; Online: The steroidogenic inhibitor finasteride reverses pramipexole-induced alterations in probability discounting.

Floris, Gabriele / Scheggi, Simona / Pes, Romina / Bortolato, Marco

Brain research bulletin

2022 Volume 181, Page(s) 157–166

Abstract: Pramipexole is a potent agonist of ... ...

Abstract	Pramipexole is a potent agonist of D
MeSH term(s)	5-alpha Reductase Inhibitors/pharmacology ; Animals ; Behavior, Animal/drug effects ; Choice Behavior/drug effects ; Disease Models, Animal ; Dopamine Agonists/pharmacology ; Finasteride/pharmacology ; Impulsive Behavior/drug effects ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Pramipexole/pharmacology ; Probability Learning ; Rats ; Receptors, Dopamine D3/agonists ; Receptors, Dopamine D3/drug effects ; Receptors, Dopamine D3/metabolism
Chemical Substances	5-alpha Reductase Inhibitors ; Dopamine Agonists ; Drd3 protein, rat ; Receptors, Dopamine D3 ; Finasteride (57GNO57U7G) ; Pramipexole (83619PEU5T)
Language	English
Publishing date	2022-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2022.01.020
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Article ; Online: The mediating role of impulsivity in the associations between child maltreatment types and past month substance use.

Brown, Shaquanna / Fite, Paula J / Bortolato, Marco

Child abuse & neglect

2022 Volume 128, Page(s) 105591

Abstract: Background: Child maltreatment has emerged as an important risk factor for substance use. However, despite evidence consistently demonstrating that substance use peaks during emerging adulthood, less is known about the specificity of maltreatment ... ...

Abstract	Background: Child maltreatment has emerged as an important risk factor for substance use. However, despite evidence consistently demonstrating that substance use peaks during emerging adulthood, less is known about the specificity of maltreatment effects on substance use during this critical developmental period. Further, the factors that might play a role in these associations are not well understood. Objective: The current study examined the associations between child maltreatment types (i.e., physical abuse, physical neglect, sexual abuse, emotional abuse, and emotional neglect) and past month marijuana, alcohol, and tobacco use among emerging adults, and tested whether impulsivity accounted for these associations. Methods: Participants were 500 emerging adults ranging in age between 18 and 25 years old (M = 18.96, SD = 1.22, 49.6% male) recruited from a large, public university in the Midwest United States. Results: Tests of indirect effects suggested that impulsivity accounted for associations between emotional abuse and past month marijuana, alcohol, and tobacco use. Conclusions: Current findings provide support for impulsivity as a mechanism linking childhood emotional abuse to substance use among emerging adults, highlighting the need for targeted screening and intervention.
MeSH term(s)	Adolescent ; Adult ; Adult Survivors of Child Abuse/psychology ; Child ; Child Abuse/psychology ; Female ; Humans ; Impulsive Behavior ; Male ; Physical Abuse ; Substance-Related Disorders/epidemiology ; Substance-Related Disorders/psychology ; Young Adult
Language	English
Publishing date	2022-03-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	799143-5
ISSN	1873-7757 ; 0145-2134
ISSN (online)	1873-7757
ISSN	0145-2134
DOI	10.1016/j.chiabu.2022.105591
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Article ; Online: Elevated levels of serotonin 5-HT

Braccagni, Giulia / Scheggi, Simona / Bortolato, Marco

European archives of psychiatry and clinical neuroscience

2022 Volume 273, Issue 2, Page(s) 411–425

Abstract: Antisocial behavior (ASB) is characterized by frequent violations of the rights and properties of others, as well as aggressive conduct. While ample evidence points to a critical role of serotonin in the emotional modulation of social responses, the ... ...

Abstract	Antisocial behavior (ASB) is characterized by frequent violations of the rights and properties of others, as well as aggressive conduct. While ample evidence points to a critical role of serotonin in the emotional modulation of social responses, the implication of this neurotransmitter in ASB is unclear. Here, we performed the first-ever postmortem analysis of serotonergic markers in the orbitofrontal cortex (OFC) of male subjects with ASB (n = 9). We focused on this brain region, given its well-recognized role in social response and ASB pathophysiology. Given that all individuals also had a substance use disorder (SUD) diagnosis, two age-matched control groups were used: SUD only and unaffected controls. Tissues were processed for immunoblotting analyses on eight key serotonergic targets: tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of brain serotonin synthesis; serotonin transporter (SERT), the primary carrier for serotonin uptake; monoamine oxidase A (MAOA), the primary enzyme for serotonin catabolism; and five serotonin receptors previously shown to influence social behavior: 5-HT
MeSH term(s)	Adult ; Humans ; Male ; Middle Aged ; Young Adult ; Antisocial Personality Disorder/complications ; Antisocial Personality Disorder/enzymology ; Antisocial Personality Disorder/metabolism ; Autopsy ; Monoamine Oxidase/metabolism ; Prefrontal Cortex/enzymology ; Prefrontal Cortex/metabolism ; Receptor, Serotonin, 5-HT2A/metabolism ; Substance-Related Disorders/complications ; Substance-Related Disorders/enzymology ; Substance-Related Disorders/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism ; Aggression ; Case-Control Studies
Chemical Substances	Monoamine Oxidase (EC 1.4.3.4) ; monoamine oxidase A, human (EC 1.4.3.4.) ; Receptor, Serotonin, 5-HT2A ; TPH2 protein, human (EC 1.14.16.4) ; Serotonin Plasma Membrane Transport Proteins
Language	English
Publishing date	2022-09-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1045583-8
ISSN	1433-8491 ; 0175-758X ; 0940-1334
ISSN (online)	1433-8491
ISSN	0175-758X ; 0940-1334
DOI	10.1007/s00406-022-01480-y
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Article ; Online: The role of monoamine oxidase A in the neurobiology of aggressive, antisocial, and violent behavior: A tale of mice and men.

Kolla, Nathan J / Bortolato, Marco

Progress in neurobiology

2020 Volume 194, Page(s) 101875

Abstract: Over the past two decades, research has revealed that genetic factors shape the propensity for aggressive, antisocial, and violent behavior. The best-documented gene implicated in aggression is MAOA (Monoamine oxidase A), which encodes the key enzyme for ...

Abstract	Over the past two decades, research has revealed that genetic factors shape the propensity for aggressive, antisocial, and violent behavior. The best-documented gene implicated in aggression is MAOA (Monoamine oxidase A), which encodes the key enzyme for the degradation of serotonin and catecholamines. Congenital MAOA deficiency, as well as low-activity MAOA variants, has been associated with a higher risk for antisocial behavior (ASB) and violence, particularly in males with a history of child maltreatment. Indeed, the interplay between low MAOA genetic variants and early-life adversity is the best-documented gene × environment (G × E) interaction in the pathophysiology of aggression and ASB. Additional evidence indicates that low MAOA activity in the brain is strongly associated with a higher propensity for aggression; furthermore, MAOA inhibition may be one of the primary mechanisms whereby prenatal smoke exposure increases the risk of ASB. Complementary to these lines of evidence, mouse models of Maoa deficiency and G × E interactions exhibit striking similarities with clinical phenotypes, proving to be valuable tools to investigate the neurobiological mechanisms underlying antisocial and aggressive behavior. Here, we provide a comprehensive overview of the current state of the knowledge on the involvement of MAOA in aggression, as defined by preclinical and clinical evidence. In particular, we show how the convergence of human and animal research is proving helpful to our understanding of how MAOA influences antisocial and violent behavior and how it may assist in the development of preventative and therapeutic strategies for aggressive manifestations.
MeSH term(s)	Aggression/physiology ; Animals ; Antisocial Personality Disorder/etiology ; Antisocial Personality Disorder/genetics ; Antisocial Personality Disorder/metabolism ; Antisocial Personality Disorder/physiopathology ; Behavior, Animal/physiology ; Gene-Environment Interaction ; Humans ; Monoamine Oxidase/deficiency ; Monoamine Oxidase/physiology ; Social Behavior ; Violence
Chemical Substances	Monoamine Oxidase (EC 1.4.3.4)
Language	English
Publishing date	2020-06-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	185535-9
ISSN	1873-5118 ; 0301-0082
ISSN (online)	1873-5118
ISSN	0301-0082
DOI	10.1016/j.pneurobio.2020.101875
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Article ; Online: What drugs modify the risk of iatrogenic impulse-control disorders in Parkinson's disease? A preliminary pharmacoepidemiologic study.

Jeon, Nakyung / Bortolato, Marco

PloS one

2020 Volume 15, Issue 1, Page(s) e0227128

Abstract: Introduction: Parkinson's disease (PD) patients treated with pramipexole (PPX) and ropinirole (ROP) exhibit a higher risk of developing impulse control disorders (ICDs), including gambling disorder, compulsive shopping, and hypersexuality. The ... ...

Abstract	Introduction: Parkinson's disease (PD) patients treated with pramipexole (PPX) and ropinirole (ROP) exhibit a higher risk of developing impulse control disorders (ICDs), including gambling disorder, compulsive shopping, and hypersexuality. The management of ICDs in PD is challenging, due to the limited availability of effective therapeutic alternatives or counteractive strategies. Here, we used a pharmacoepidemiological approach to verify whether the risk for PPX/ROP-associated ICDs in PD patients was reduced by drugs that have been posited to exert therapeutic effects on idiopathic ICDs-including atypical antipsychotics (AAs), selective serotonin reuptake inhibitors (SSRIs), and glutamatergic modulators (GMs). Methods: To quantify the strength of the associations between PPX/ROP and other medications with respect to ICD risk, odds ratios (ORs) were calculated by multivariable logistic regression, adjusting for age, gender, marital status race, psychiatric comorbidities, and use of cabergoline and levodopa. Results: A total of 935 patients were included in the analysis. Use of GMs, SSRIs, and AAs was not associated with a decreased ICD risk in PD patients treated with PPX/ROP; conversely, ICD risk was significantly increased in patients treated with either GMs (Adjusted Odds Ratio, ORa: 14.00 [3.58-54.44]) or SSRIs (ORa: 3.67 [1.07-12.59]). Results were inconclusive for AAs, as available data were insufficient to compute a reliable ORa. Conclusions: These results suggest that some of the key pharmacological strategies used to treat idiopathic ICD may not be effective for ICDs associated with PPX and ROP in PD patients. Future studies with larger cohorts are needed to confirm, validate, and extend these findings.
MeSH term(s)	Aged ; Antiparkinson Agents/adverse effects ; Antiparkinson Agents/therapeutic use ; Antipsychotic Agents/therapeutic use ; Disruptive, Impulse Control, and Conduct Disorders/drug therapy ; Disruptive, Impulse Control, and Conduct Disorders/epidemiology ; Disruptive, Impulse Control, and Conduct Disorders/etiology ; Disruptive, Impulse Control, and Conduct Disorders/prevention & control ; Female ; Humans ; Iatrogenic Disease/epidemiology ; Iatrogenic Disease/prevention & control ; Indoles/adverse effects ; Indoles/therapeutic use ; Male ; Middle Aged ; Parkinson Disease/drug therapy ; Pramipexole/adverse effects ; Pramipexole/therapeutic use ; Selective Serotonin Reuptake Inhibitors/therapeutic use
Chemical Substances	Antiparkinson Agents ; Antipsychotic Agents ; Indoles ; Serotonin Uptake Inhibitors ; ropinirole (030PYR8953) ; Pramipexole (83619PEU5T)
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0227128
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