Valentina Baglioni

Tourette Syndrome and other tic disorders (TD) are common, highly heritable neurodevelopmental conditions with complex genetic architectures. We conducted a genome-wide association study of 13,247 TD cases and 536,217 European ancestry controls and identified six independent genome-wide significant loci, including a pleiotropic signal at 3p21 shared with attention-deficit/hyperactivity disorder, among other traits. Gene prioritization highlighted 20 genes, including PCDH9, HCN1, NCKIPSD, WDR6, DALRD3, and CELSR3. Integrative analyses provide genetic support for the role of cortico-striato-thalamo-cortical circuits in TD pathophysiology and further localize TD genetic risk to specific cell types, including dopamine D1- and D2-receptor-positive medium spiny neurons, cortical pyramidal neurons, and oligodendrocyte-lineage cells. We further demonstrate extensive genetic correlations with neurodevelopmental and psychiatric traits, but not with neurological disorders. These findings advance our understanding of the genetic basis of TD, pinpointing specific genes and cell types that drive pathophysiology and providing a foundation for future mechanistic studies.

Background Autoimmune encephalitis (AE) comprises a rare and heterogeneous group of immune-mediated disorders affecting the central nervous system, frequently characterized by both psychiatric and neurological symptoms. In pediatric populations, acute psychiatric manifestations, such as agitation, mood instability, and psychosis, may precede neurological signs, often complicating early diagnosis due to their overlap with primary psychiatric disorders. This retrospective observational study aimed to characterize the early psychiatric presentations of pediatric AE through the analysis of clinical records concerning inpatient admissions to a tertiary Child and Adolescent Neuropsychiatry Unit. Materials and Methods We screened 1,577 inpatient admissions for cases presenting with acute-onset psychiatric symptoms (July 2022–July 2024). Of 58 patients, 6 (mean age: 10.3 ± 5.2 years; 4 males, 2 females) received a final diagnosis of definite or probable AE based on established pediatric guidelines, thus meeting our inclusion criteria. Results All patients presented with psychiatric symptoms, including externalizing behaviors (2/6), mood disturbances with psychotic features (4/6), and sleep disorders (4/6). All underwent comprehensive diagnostic evaluations, including cerebrospinal fluid (CSF) analysis, electroencephalography, and brain MRI. CSF biochemical abnormalities were detected in 5 out of 6 patients, while neuronal antibodies were identified in 4 out of 6 cases (two with anti-NMDAR and two with anti-GAD65 positivity, including one with both). Conclusions Our findings underscore the relevance of early psychiatric symptoms in pediatric AE and emphasize the importance of considering autoimmune etiologies in new-onset psychiatric presentations, particularly in the absence of prior psychiatric history.

Background: Inherited metabolic disorders (IEMs) can be represented in children and adolescents by psychiatric disorders. The early diagnosis of IEMs is crucial for clinical outcome and treatment. The aim of this review is to analyze the most recurrent and specific psychiatric features related to IEMs in pediatrics, based on the onset type and psychiatric phenotypes. Methods: Following the PRISMA Statement, a systematic literature review was performed using a predefined algorithm to find suitable publications in scientific databases of interest. After removing duplicates and screening titles and abstracts, suitable papers were analyzed and screened for inclusion and exclusion criteria. Finally, the data of interest were retrieved from the remaining articles. Results: The results of this study are reported by type of symptoms onset (acute and chronic) and by possible psychiatric features related to IEMs. Psychiatric phenomenology has been grouped into five main clinical manifestations: mood and anxiety disorders; schizophrenia-spectrum disorders; catatonia; eating disorders; and self-injurious behaviors. Conclusions: The inclusion of a variety of psychiatric manifestations in children and adolescents with different IEMs is a key strength of this study, which allowed us to explore the facets of seemingly different disorders in depth, avoiding possible misdiagnoses, with the related delay of early and appropriate treatments.

Psychological, social, and biological aspects contribute synergistically to the maintenance and chronicity of pain in primary headaches. An integrated intervention seems to be the most appropriate in the management of these conditions, taking advantage not only of pharmacological strategies, but also of different approaches according to the global assessment and patient necessities. In this perspective, non-pharmacological treatments are becoming increasingly used to overcome these issues also in paediatric migraine treatment. Particularly, nutraceuticals, non-invasive neuromodulation, and behavioural approaches are well tolerated and of potential interest. This paper aims to present the main approaches reported in the literature in the management of migraine in children and adolescents presenting an up-to-date review of the current literature. We therefore performed a narrative presentation for each of these three categories: nutraceuticals (riboflavin; magnesium; melatonin; vitamin D; coenzyme Q10; and polyunsaturated fatty acid); non-invasive neuromodulation (trigeminal nerve stimulator; non-invasive vagal nerve stimulation; transcranial magnetic stimulation; and remote electrical neuromodulation), and behavioural therapies (biofeedback; cognitive behavioural therapy; and mindfulness-based therapy). These approaches are increasingly seen as a valid treatment option in primary headache management also in paediatrics, avoiding medication overuse and drug treatment contraindications.

Background: Cognitive functions represent foundational factors for mental health and quality of life (QoL). In Tourette syndrome (TS), psychiatric comorbidities are common and have been inconsistently reported to affect the cognition and QoL of patients, while the role of tic disorder duration has not been yet explored. Methods: To examine how comorbidities and TS duration may influence cognition and QoL, N = 80 children with TS (6–16 years) were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Standardized questionnaires were used to assess the presence and severity of TS main comorbidities and QoL. Data were interpreted using linear correlations, regression, and mediation analysis. Results: Depression and attention-deficit/hyperactivity disorder (ADHD) symptoms accounted for poorer cognitive performance. Anxiety oppositely predicted better cognitive performance, while no significant role for obsessive compulsive disorder (OCD) was observed. Disease duration was associated with lower total IQ, verbal reasoning, and working memory abilities. Depression, anxiety, and TS duration also deeply influenced QoL measures. Conclusions: TS common comorbidities have a differential impact on the cognitive abilities of children and adolescents, which translates into a complex influence on their perceived QoL. A longer clinical history of tics was related to worse cognitive outcomes, which prompts further consideration of disease duration in both clinical and research settings involving children and adolescents.

In pediatric neurology, tension-type headache (TTH) represents a very common type of primary headache during the pediatric age. Despite the high prevalence of TTH, this diagnosis is often underestimated in childhood, with relevant difficulties in the differential diagnosis of TTH from secondary and primary headache manifestations. Even among primary headaches, a clinical overlap is not so infrequent in children: migraine attacks could present tension headache-like features while tension-type headaches may display migraine-like symptoms as well. Several variables play a role in the complex trajectory of headache evolution, such as hormonal changes during adolescence, triggers and genetic and epigenetic factors. The trajectories and outcomes of juvenile migraine and TTH, as well as the transition of one form to the other, have been investigated in several long-term prospective studies. Thus, the aim of this paper is to review the current literature on the differential diagnosis workout of TTH in pediatrics, the possible outcomes during the developmental age and the appropriate therapeutic strategies. Indeed, TTH represents a challenging diagnostic entity in pediatrics, both from a clinical and a therapeutic point of view, in which early diagnosis and appropriate treatment are recommended.