46, XY disorder of sex development (46, XY DSD) is relatively rare and frequently missed in clinical practice, necessitating early standardized diagnosis and treatment. Androgen insensitivity syndrome (AIS), a major subtype, should be considered in phenotypic females with suggestive clinical clues.

A 29-year-old phenotypic female presented with primary amenorrhea and intermittent abdominal pain. Examination revealed normal breast development, sparse pubic hair, and female external genitalia. Pelvic ultrasonography and CT showed an absent uterus and ovaries, with bilateral inguinal masses.

The case met the 3 diagnostic criteria for 46, XY DSD: 46,XY karyotype, testicular tissue, and feminized external genitalia. A diagnosis clinically consistent with complete AIS was further supported by the characteristic phenotype - female appearance, normal breast development, sparse pubic hair, and absent Müllerian structures. Other etiologies of undervirilization, including 5α-reductase deficiency and 17β-hydroxysteroid dehydrogenase deficiency, were considered. Genetic confirmation was unavailable, limiting subtype certainty.

Following counseling, the patient underwent laparoscopic bilateral orchiectomy as prophylactic gonadectomy to reduce malignancy risk, together with inguinal hernia repair, followed by postoperative hormone replacement therapy. Postoperative histopathology confirmed testicular tissue with Leydig cell hyperplasia, absent spermatogenic cells, and no malignancy.

Abdominal pain resolved postoperatively, with improved psychological well-being and adaptation to the diagnosis under ongoing endocrine and psychological support.

46, XY DSD is underdiagnosed due to phenotypic variability, reliance on specialized tests, and social biases. AIS should be considered in the differential diagnosis of phenotypic females presenting with primary amenorrhea, developed secondary sexual characteristics, and an absent uterus on ultrasound. However, definitive subtyping requires AR gene sequencing, which was not available in this case. Early diagnosis requires careful assessment of newborn external genitalia, with specialist evaluation prompted by any atypical findings, and hormonal and genetic testing in adolescents with abnormal development. Multidisciplinary care - involving gynecologists, endocrinologists, surgeons, geneticists, and mental-health professionals - is essential for comprehensive management, including psychological support, hormone therapy, and timely prophylactic gonadectomy. Establishing specialized multidisciplinary centers for DSD is also recommended.

Prior evidence suggests that people from racial/ethnic minority (REM) groups experience greater psychological distress, especially if they are isolated from their cultural ingroup. This study examined associations between REM status and psychological symptoms measured before and after therapy, as well as interactions with neighbourhood-level REM density.

Electronic health records from 130,857 patients who accessed psychological interventions in primary care services in England were analyzed. Pre- and post-treatment depression (PHQ-9), anxiety (GAD-7) and functional impairment measures (WSAS) were linked to individual-level and neighbourhood-level demographic and socioeconomic data. Multilevel (mixed effect) models were used to examine associations between individual and neighbourhood socioeconomic variables with available measures of psychological distress.

Specific (rather than all) REM groups had higher indices of psychological distress, and there was little evidence of a moderating effect of neighbourhood ethnic density in the hypothesized direction. After controlling for socioeconomic variables, consistently higher indices of distress before and after therapy were evident for patients from White-other, Pakistani, Bangladeshi, and "Other" backgrounds.

Mental health inequalities are evident for people from specific REM groups.

The Research Domain Criteria (RDoC) domains of the negative valence system (NVS) and the cognitive system (CS) offer a framework for current research on aggression. In particular, the projects of the Transregio "Neuropsychobiology of Aggression" (Transregional Collaborative Research Center 379, TRR 379) are grouped according to these domains.

The present review article describes how these domains are conceptualized and what role they play in the investigation and understanding of aggressive behavior in mental disorders and its biological correlates within the framework of TRR 379.

This is a qualitative review that summarizes empirical findings based on exemplary studies and selected reviews and discusses recent developments. The focus is on work that explicitly links aggression to the NVS and/or CS and on work within TRR 379.

Using the NVS and the CS, the projects within TRR 379 are developing a wide range of innovative, experimental setups to investigate the various aspects of aggression in a transdiagnostic manner across large samples of individuals with mental disorders, in conjunction with established paradigms and questionnaires as well as a rich repertoire of neurophysiological measures. Based on the initial results, the interdisciplinary community of TRR 379 researchers engages in intensive and critical discussions on how the various aspects of the RDoC approach, as well as other transdiagnostic approaches such as "HiTOP" and "Computational Psychiatry," can be utilized both conceptually and methodologically for current and future projects. Early-career researchers are particularly active in this area.

Founder effects are important population genetic mechanisms that influence the distribution of inherited neurological diseases. To review the global distribution of founder mutations across the spectrum of inherited movement disorders, summarize the molecular mechanisms, and discuss their clinical implications for diagnosis, genetic counselling, and emerging precision therapies. A scoping review was conducted following PRISMA-ScR principles, searching PubMed/MEDLINE and secondary reference lists for studies reporting founder mutations, shared haplotypes, or population-specific mutation enrichment in inherited movement disorders; studies lacking genetic or epidemiological evidence for a founder effect were excluded. Seventy-one studies described 53 founder-mutation entries across 40 movement-disorder phenotypes and 48 genes or repeat-expansion loci (Table 1), most frequently spinocerebellar ataxias, dystonia, and NBIA syndromes. Shared haplotypes, mutation-age estimation, and genealogical evidence consistently supported a founder origin (e.g., TOR1A dystonia in Ashkenazi Jews, LRRK2/GBA1-associated Parkinson disease in Ashkenazi Jewish and North African populations, SCA2 in Cuba, SCA3 in the Azores and Brazil). These founder mutations enable ancestry-targeted diagnostic testing, inform genetic counselling and carrier screening in endogamous populations, and identify genetically homogeneous cohorts increasingly used for natural-history studies and precision therapeutic trials, including antisense and gene-silencing approaches. Founder effects, driven predominantly by endogamy, geographic isolation, and migration-associated bottlenecks, account for a disproportionate share of the mutational spectrum in spinocerebellar ataxias, dystonia, and NBIA syndromes. Ancestry-informed testing algorithms, targeted carrier screening, and enrolment of genetically homogeneous founder cohorts into precision therapeutic trials represent the most immediate translational applications of these findings.

Surrogacy includes traditional surrogacy, in which the carrier contributes her own oocyte, and gestational surro-gacy, in which the embryo is derived exclusively from the gametes of the intended parents or donors. In Brazil, only gestational surrogacy is legally recognized. It is governed by resolutions of the Federal Council of Medicine and the national health surveillance agency in the absence of spe-cific federal legislation, and it requires altruistic, unpaid participation and compliance with carrier eligibility crite-ria. This Position Statement, developed by the Strategic Committee on Gestational Surrogacy of the Brazilian As-sociation of Assisted Reproduction, addresses the clinical, bioethical, legal, and psychological dimensions of the prac-tice and is intended to guide specialists throughout Brazil. Clinical indications include uterine absence or anomalies, contraindications to pregnancy, medical conditions that may be aggravated by pregnancy, and biological inability to conceive or carry a pregnancy. No universally validated protocol for carrier selection exists; current requirements include a maximum age of 50 years, at least one previous live birth, and satisfactory physical and mental health. Peri-natal outcomes are comparable to those of conventional in vitro fertilization, although long-term data on cross-border arrangements remain scarce. The bioethical framework is based on autonomy, beneficence, non-maleficence, and justice. SBRA opposes simultaneous surrogacy arrange-ments because they are incompatible with the altruistic na-ture of the practice and supports gradual, age-appropriate disclosure of the child's gestational origin. Legal challenges include the absence of statutory regulation, cross-border reproductive tourism, and the child's right to know their origins. Continuous psychological support for all parties is mandatory and central to favorable long-term outcomes. Gestational surrogacy is a valid reproductive option for se-lected patients but requires rigorous oversight and must prioritize the best interests of the child within the Brazilian regulatory framework.

Fragile X syndrome is a monogenic disorder caused by the expansion of CGG trinucleotide repeats in the fragile X mental retardation 1 (FMR1) gene and is a major cause of inherited intellectual disability and reproductive impair-ment. Preimplantation genetic testing for monogenic disor-ders (PGT-M) has become an important strategy in assisted reproduction to prevent the transmission of FMR1-related disorders. This narrative review aimed to summarize cur-rent evidence on the molecular basis, technical approaches, clinical outcomes, and challenges associated with PGT-M for FMR1 CGG repeat expansions. A literature search was performed in the PubMed database, including English-lan-guage original studies, clinical investigations, and reviews. The reviewed studies demonstrate that advances in multi-plex PCR, linked-marker analysis, and next-generation se-quencing have significantly improved diagnostic accuracy, overcoming earlier limitations related to CGG repeat analy-sis, allele dropout, and mosaicism. Although women carry-ing FMR1 premutations frequently present with diminished ovarian reserve and reduced response to ovarian stimula-tion, pregnancy and live birth rates per embryo transfer are comparable to those of non-carriers when individual-ized stimulation protocols are applied. The combined ap-plication of PGT-M and Preimplantation Genetic Testing for Aneuploidy may be considered in selected clinical scenarios to optimize embryo selection, although indications should be individualized. In addition to its clinical benefits, PGT-M raises ethical, psychological, and economic considerations, emphasizing the importance of genetic counseling in re-productive decision-making. Overall, PGT-M represents a safe and effective tool in assisted reproduction for couples at risk of transmitting FMR1 related disorders, with grow-ing relevance in clinical practice and public health.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder frequently accompanied by epilepsy and TSC-associated neuropsychiatric disorders. Psychiatric-predominant seizure presentations may, however, delay recognition. This clinical challenge describes a 26-year-old woman with recurrent panic-like episodes characterized by dyspnea, choking sensations, palpitations, and derealization, followed by depressive symptoms. The episodes persisted despite treatment with selective serotonin reuptake inhibitors and benzodiazepines. Further examination revealed hypomelanotic macules, prompting neurologic and systemic evaluation. Brain imaging demonstrated findings consistent with cortical tubers and subependymal nodules, while video electroencephalography captured frequent focal seizures without impaired awareness arising from the left frontotemporal region. Positron emission tomography/computed tomography identified a corresponding frontal abnormality. Although genetic testing detected a nonclassical TSC1 variant, the TSC diagnosis was established on clinical grounds. Treatment with lacosamide eliminated detectable epileptiform activity and substantially reduced the frequency and severity of her panic-like episodes; depressive and anxiety symptoms also improved with combined lacosamide and duloxetine treatment. This case illustrates how focal seizures involving frontal, temporal, and limbic-autonomic networks may mimic primary panic disorder. Stereotyped, brief, recurrent, and treatment-refractory psychiatric episodes-particularly when accompanied by neurocutaneous findings-should prompt electroencephalography and brain imaging. The case also emphasizes that an uninformative or uncertain genetic result does not exclude clinically established TSC or alter recommended surveillance and multidisciplinary management.

Suicide is the second leading cause of death among youth, with growing evidence linking higher ambient temperatures to increased suicidality - a concerning trend as global temperatures rise. Sleep disruption is a theorized mechanism, though clinical evidence is lacking.

We performed a cross-sectional analysis of 5,590 pediatric patients (3-18 years) presenting to a psychiatric emergency department with and without suicidality (December 2018-March 2023). Seven-day averages of mean and minimum daily ambient temperatures and precipitation were obtained at home addresses from the PRISM Climate Group dataset. Logistic regression assessed insomnia as a moderator and mediator of the temperature-suicidality relationship, controlling for sociodemographic, diagnostic, and environmental variables. Negative controls included modeling suicidality using hypersomnia-temperature and insomnia-precipitation interactions.

Mean and minimum daily temperatures moderated the temperature-suicidality relationship only in those with insomnia (Mean Temperature: RR: 1.06 per 5°C [95% CI 1.01-1.06], p = 0.015; Minimum Temperature: RR: 1.06 per 5°C [95% CI 1.01-1.06], p = 0.010). Minimum temperature, a proxy for nighttime temperature, was associated with suicidality through insomnia in a mediation model (Indirect Pathway: OR: 1.05 [95% CI 1.00-1.11], p = 0.045), though mean temperature was not. No significant moderation occurred modeling suicidality with hypersomnia-temperature or insomnia-precipitation interactions.

This is the first clinical evidence that insomnia influences the heat-suicidality relationship in youth. Limitations include cross-sectional data that cannot establish temporal directionality of associations, heterogeneous suicidality outcomes, self-reported sleep data, and pandemic-era data collection. Larger mechanistic analyses of temperature, sleep, and suicidality are needed to understand climatic mental health impacts and develop interventions.

Acupuncture has shown clinical benefits in post-stroke rehabilitation, yet its central neural mechanisms remain incompletely understood. In particular, how cortical activation, inter-regional functional connectivity, and brain network topology are modulated during electroacupuncture stimulation has not been systematically characterised. This study aimed to investigate the central effects of verum electroacupuncture (VE) applied to the non-dominant hand in healthy adults. In a randomized, crossover design, functional near-infrared spectroscopy (fNIRS) data were collected from 24 participants during VE and sham electroacupuncture (SE) sessions. Cortical activation was assessed using a general linear model (GLM), functional connectivity (FC) was analysed using lagged cross-correlation, and brain network topology was examined using graph-theoretical metrics. No significant differences in cortical activation were observed between VE and SE. During the needles retention phase, VE significantly reduced functional connectivity between R-MPFC and right primary somatosensory cortex (R-PSC), and between middle MPFC and R-PSC. Graph-theoretical analysis revealed decreased clustering coefficient and increased small-worldness under VE. These findings suggest that VE may optimise brain networks through an connectivity-topology mechanism. Brain networks shifted from excessive localisation toward higher integration. This study establishes a baseline central response profile in healthy individuals and provides theoretical support for the application of electroacupuncture in post-stroke upper-limb rehabilitation. Trial registration: ITMCTR, TRN: ITMCTR2025000595, Registration date: 19 March 2025.

Epilepsy and sleep disorders are highly prevalent conditions that frequently coexist, exerting reciprocal adverse effects through shared neurobiological mechanisms.

We conducted a narrative review of the literature addressing the bidirectional relationship between epilepsy and sleep disorders, aiming to provide a comprehensive synthesis of its neurophysiological basis, clinical implications, and therapeutic consequences.

The epilepsy-sleep relationship is mediated by multiple neurobiological mechanisms, including thalamocortical network dynamics, circadian clock gene regulation, adenosinergic and orexinergic tone, synaptic homeostasis, and glymphatic clearance. A key pathophysiological concept underlying this relationship is that NREM sleep promotes interictal epileptiform discharges and seizure propagation through thalamocortical synchronization, whereas REM sleep exerts a protective effect. Epileptic activity disrupts both sleep macro- and microarchitecture, reducing total sleep time, sleep efficiency, and REM sleep, increasing wake after sleep onset, and destabilizing NREM microarchitecture as reflected by altered cyclic alternating pattern rates. Conversely, sleep disturbances lower the seizure threshold and contribute to disease progression: sleep deprivation is an independent seizure-precipitating factor, and comorbid obstructive sleep apnea further lowers the seizure threshold through intermittent hypoxia and arousal instability. Specific epileptic syndromes with a privileged sleep relationship are also reviewed, including sleep-related hypermotor epilepsy, epileptic encephalopathy with spike-wave activation in sleep, and self-limited childhood focal epilepsies. The differential diagnosis between NREM parasomnias and sleep-related epilepsies remains challenging; the diagnostic workup should always include a thorough clinical history characterizing the episodes, followed by video-polysomnography, which represents the gold standard. From a therapeutic standpoint, antiseizure medications exert heterogeneous effects on sleep architecture, and polytherapy is independently associated with worse sleep quality; targeting sleep disturbances therefore represents a modifiable strategy capable of improving seizure control, cognitive function, and quality of life.

A multidisciplinary approach integrating systematic screening for sleep disorders, optimization of antiseizure medication timing and selection, treatment of comorbid obstructive sleep apnea, and behavioral sleep interventions has the potential to meaningfully improve outcomes in patients with epilepsy. Wider implementation of these strategies in routine clinical practice is both a priority and an opportunity.