Vitamin D and behavioral disorders in older adults: results from the CLIP study.

OBJECTIVES: Vitamin D is involved in brain health and function. Our objective was to determine whether vitamin D deficiency was associated with behavioral disorders in geriatric patients. DESIGN: The observational cross-sectional CLIP (Cognition and LIPophilic vitamins) study. The report followed the STROBE statement. SETTING: Geriatric acute care unit in a tertiary university hospital in France for 3 months at the end of winter and beginning of spring. PARTICIPANTS: 272 patients ≥65 years consecutively hospitalized or seen in consultation. MEASUREMENTS: Participants were separated into two groups according to vitamin D deficiency (i.e., serum 25-hydroxyvitamin D ≤25 nmol/L). Behavior was assessed using the reduced version of the Neuropsychiatric Inventory Scale (NPI-R) score and subscores. Age, sex, BMI, education level, comorbidities, MMSE and GDS scores, use psychoactive drugs and vitamin D supplements, and serum concentrations of calcium, parathyroid hormone, TSH and estimated glomerular filtration rate (eGFR) were used as potential confounders. RESULTS: Participants with vitamin D deficiency (n = 78) had similar NPI-R score (17.4 ± 20.3 versus 17.2 ± 16.1, p = 0.92) but higher (i.e., worse) subscore of agitation and aggressiveness (2.0 ± 3.3 versus 1.2 ± 2.4, p = 0.02) and higher (i.e., worse) subscore of disinhibition (0.99 ± 2.98 versus 0.38 ± 1.42, p = 0.02) than those without vitamin D deficiency (n = 194). In multiple linear regressions, vitamin D deficiency was inversely associated with the subscore of agitation and aggressiveness (ß = 1.37, p = 0.005) and with the subscore of disinhibition (ß = 0.96, p = 0.008). CONCLUSION: Vitamin D deficiency was associated with more severe subscores of agitation and aggressiveness and of disinhibition among older adults. This provides a scientific basis to test the efficacy of vitamin D supplementation on behavioral disorders in older patients with vitamin D deficiency.

Independent inhibitory control mechanisms for aggressive motivation and action.

Social behaviors often consist of a motivational phase followed by action. Here we show that neurons in the ventromedial hypothalamus ventrolateral area (VMHvl) of mice encode the temporal sequence of aggressive motivation to action. The VMHvl receives local inhibitory input (VMHvl shell) and long-range input from the medial preoptic area (MPO) with functional coupling to neurons with specific temporal profiles. Encoding models reveal that during aggression, VMHvl shellvgat+ activity peaks at the start of an attack, whereas activity from the MPO-VMHvlvgat+ input peaks at specific interaction endpoints. Activation of the MPO-VMHvlvgat+ input promotes and prolongs a low motivation state, whereas activation of VMHvl shellvgat+ results in action-related deficits, acutely terminating attack. Moreover, stimulation of MPO-VMHvlvgat+ input is positively valenced and anxiolytic. Together, these data demonstrate how distinct inhibitory inputs to the hypothalamus can independently gate the motivational and action phases of aggression through a single locus of control.

A dedicated hypothalamic oxytocin circuit controls aversive social learning.

To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTR cells minimally respond to aggressor cues. During defeat, aVMHvlOXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity.

Coptisine inhibits aggressive and proliferative actions of fibroblast like synoviocytes and exerts a therapeutic potential for rheumatoid arthritis.

OBJECTIVE: Coptisine, a natural bioactive small molecular compound extracted from traditional Chinese herb Coptis chinensis, has been shown to exhibit anti-tumor effect. However, its contribution to autoimmune diseases such as rheumatoid arthritis (RA) is unknown. Here, we evaluate the effect of coptisine in controlling fibroblast-like synoviocytes (FLS)-mediated synovial proliferation and aggression in RA and further explore its underlying mechanism(s). METHODS: FLS were separated from synovial tissues obtained from patients with RA. Protein expression was measured by Western blot or immunohistochemistry. Gene expression was detected by quantitative RT-PCR. The EdU incorporation was used to measure cell proliferation. Migration and invasion were determined by Boyden chamber assay. RNA sequencing analysis was used to seek for the target of coptisine. The in vivo effect of coptisine was evaluated in collagen-induced arthritis (CIA) model. RESULTS: Treatment with coptisine reduced the proliferation, migration, and invasion, but not apoptosis of RA FLS. Mechanistically, we identified PSAT1, an enzyme that catalyzes serine/one-carbon/glycine biosynthesis, as a novel targeting gene of coptisine in RA FLS. PSAT1 expression was increased in FLS and synovial tissues from patients with RA compared to healthy control subjects. Coptisine treatment or PSAT1 knockdown reduced the TNF-α-induced phosphorylation of p38, ERK1/2, and JNK MAPK pathway. Interestingly, coptisine administration improved the severity of arthritis and reduced synovial PSAT1 expression in mice with CIA. CONCLUSIONS: Our data demonstrate that coptisine treatment suppresses aggressive and proliferative actions of RA FLS by targeting PSAT1 and sequential inhibition of phosphorylated p38, ERK1/2, and JNK MAPK pathway. Our findings suggest that coptisine might control FLS-mediated rheumatoid synovial proliferation and aggression, and be a novel potential agent for RA treatment.

Interactive effects of mindfulness and negative urgency on intimate partner aggression perpetration.

Intimate partner aggression (IPA) is a costly and incompletely understood phenomenon. Negative urgency, the tendency to act impulsively in response to negative affect, is predictive of IPA perpetration. Mindfulness, by virtue of its emphasis on nonreactivity to negative affect, is an opposing force to urgent tendencies that may mitigate the negative urgency-IPA link. Yet, no research to date investigates the interactive effects of negative urgency and mindfulness on IPA perpetration. Two studies were conducted that measured and manipulated multiple facets of mindfulness alongside measures of negative urgency and tendencies of IPA perpetration (combined N = 508 undergraduate students in monogamous intimate relationships). Counter to our preregistered predictions, we found that negative urgency's association with greater IPA perpetration increased at higher levels of mindfulness. These findings suggest that mindfulness may not be a protective factor against IPA perpetration for individuals higher in negative urgency, but rather may serve as a risk factor.

Characterization of social hierarchy formation and maintenance in same-sex, group-housed male and female C57BL/6 J mice.

Social hierarchies are a prevalent feature of all animal groups, and an individual's rank within the group can significantly affect their overall health, typically at the greatest expense of the lowest-ranked individuals, or omegas. These subjects have been shown to exhibit various stress-related phenotypes, such as increased hypothalamic-pituitary axis activity and increased amygdalar corticotropin-releasing factor levels compared to higher-ranked subjects. However, these findings have been primarily characterized in males and in models requiring exhibition of severe aggression. The goals of the current study, therefore, were to characterize the formation and maintenance of social hierarchies using the tube test and palatable liquid competition in same-sex groups of male and female C57BL/6 J mice. We also aimed to examine the effects of tube test-determined social rank on plasma and hypothalamic oxytocin and vasopressin levels, peptides with established roles in social behaviors and the stress response. Lastly, we assessed the effects of environmental enrichment and length of testing on the measures outlined above. Overall, we demonstrated that males and females develop social hierarchies and that these hierarchies can be determined using the tube test. While we were unable to establish a consistent connection between peptide levels and social rank, we observed transient changes in these peptides reflecting complex interactions between social rank, sex, environment, and length of testing. We also found that many male and female omegas began to exhibit passive coping behavior after repeated tube test losses, demonstrating the potential of this assay to serve as a model of chronic, mild psychosocial stress.

Male-specific vasotocin expression in the medaka tuberal hypothalamus: Androgen dependence and probable role in aggression.

Terrestrial vertebrates have a population of androgen-dependent vasotocin (VT)-expressing neurons in the extended amygdala that are more abundant in males and mediate male-typical social behaviors, including aggression. Teleosts lack these neurons but instead have novel male-specific VT-expressing neurons in the tuberal hypothalamus. Here we found in medaka that vt expression in these neurons is dependent on post-pubertal gonadal androgens and that androgens can act on these neurons to directly stimulate vt transcription via the androgen receptor subtype Ara. Furthermore, administration of exogenous VT induced aggression in females and alterations in the androgen milieu led to correlated changes in the levels of tuberal hypothalamic vt expression and aggression in both sexes. However, genetic ablation of vt failed to prevent androgen-induced aggression in females. Collectively, our results demonstrate a marked androgen dependence of male-specific vt expression in the teleost tuberal hypothalamus, although its relevance to male-typical aggression needs to be further validated.

Longitudinal association of mindfulness with aggression and non-suicidal self-injury in adolescence: The mediating role of shame-proneness.

The aim of the current study was to investigate the longitudinal association of facets of mindfulness with aggression and non-suicidal self-injury (NSSI) among adolescents and to explore whether shame-proneness can mediate the longitudinal association. The present longitudinal study investigated the associations between mindfulness, aggression, and NSSI in a sample of 706 Chinese adolescents (M = 15.33; SD = 1.34; 50.20% girls). Five facet mindfulness questionnaire was completed at baseline and middle school students' shame scale was completed at 6-month follow-up. The Chinese version of Buss-Perry aggression questionnaire and adolescents' self-harm scale were completed at both baseline and 6-month follow-up. Shame-proneness significantly mediated the longitudinal association between (a) describing and aggression (-0.107, 95% CI: [-0.151 to -0.067]), and NSSI (-0.041, 95% CI: [-0.069 to -0.019]). (b) Acting with awareness and aggression (-0.094, 95% CI: [-0.139 to -0.061]), and NSSI (-0.036, 95% CI: [-0.062 to -0.016]). (c) Nonjudging and aggression (-0.062, 95% CI: [-0.107 to -0.024]) and NSSI (-0.024, 95% CI: [-0.047 to -0.008]). Describing, acting with awareness, and nonjudging were predictive factors of aggression and self-injury in adolescents, and shame-proneness played a crucial role in the negative longitudinal association between them. Findings from the current study may offer some implications in the domains of clinical practice and education to improve mental health and further ameliorate the misbehavior among adolescents.

An Integrative Review on Psychiatric Intensive Care.

Psychiatric intensive care units (PICUs) provide care and treatment when psychiatric symptoms and behaviors exceed general inpatient resources. This integrative review aimed to synthesize PICU research published over the past 5 years. A comprehensive search in MEDLINE, PsycINFO, PubMed and Scopus identified 47 recent articles on PICU care delivery, populations, environments, and models. Research continues describing patient demographics, and high rates of challenging behaviors, self-harm, and aggression continue being reported. Research on relatives was minimal. Patients describe restrictive practices incongruent with recovery philosophies, including controlling approaches and sensory deprivation. Some initiatives promote greater patient autonomy and responsibility in shaping recovery, yet full emancipatory integration remains limited within PICU environments. Multidisciplinary collaboration is needed to holistically advance patient-centered, equitable, and integrative PICU care. This review reveals the complex tensions between clinical risk management and emancipatory values in contemporary PICU settings. Ongoing reporting of controlling practices counters the recovery movement progressing in wider mental healthcare contexts. However, care innovations centered on patient empowerment and humane environments provide hope for continued evolution toward more liberation-focused PICU approaches that uphold both patient and provider perspectives.

Hypothalamic control of innate social behaviors.

Sexual, parental, and aggressive behaviors are central to the reproductive success of individuals and species survival and thus are supported by hardwired neural circuits. The reproductive behavior control column (RBCC), which comprises the medial preoptic nucleus (MPN), the ventrolateral part of the ventromedial hypothalamus (VMHvl), and the ventral premammillary nucleus (PMv), is essential for all social behaviors. The RBCC integrates diverse hormonal and metabolic cues and adjusts an animal's physical activity, hence the chance of social encounters. The RBCC further engages the mesolimbic dopamine system to maintain social interest and reinforces cues and actions that are time-locked with social behaviors. We propose that the RBCC and brainstem form a dual-control system for generating moment-to-moment social actions. This Review summarizes recent progress regarding the identities of RBCC cells and their pathways that drive different aspects of social behaviors.

Inside the mindful moment: The effects of brief mindfulness practice on large-scale network organization and intimate partner aggression.

Mindfulness can produce neuroplastic changes that support adaptive cognitive and emotional functioning. Recently interest in single-exercise mindfulness instruction has grown considerably because of the advent of mobile health technology. Accordingly, the current study sought to extend neural models of mindfulness by investigating transient states of mindfulness during single-dose exposure to focused attention meditation. Specifically, we examined the ability of a brief mindfulness induction to attenuate intimate partner aggression via adaptive changes to intrinsic functional brain networks. We employed a dual-regression approach to examine a large-scale functional network organization in 50 intimate partner dyads (total n = 100) while they received either mindfulness (n = 50) or relaxation (n = 50) instruction. Mindfulness instruction reduced coherence within the Default Mode Network and increased functional connectivity within the Frontoparietal Control and Salience Networks. Additionally, mindfulness decoupled primary visual and attention-linked networks. Yet, this induction was unable to elicit changes in subsequent intimate partner aggression, and such aggression was broadly unassociated with any of our network indices. These findings suggest that minimal doses of focused attention-based mindfulness can promote transient changes in large-scale brain networks that have uncertain implications for aggressive behavior.

Tension as a key factor in skin responses to pollution.

Being the more apparent organ exposed to the outdoor stressors, the effect of pollution on the skin has been widely studied in the last few decades. Although UV light is known as the most aggressive stressor to which our cutaneous tissue is daily exposed, other components of the tropospheric pollution have also shown to affect skin health and functionality. Among them, ozone has been proven to be one of the most toxic due to its high reactivity with the epidermal lipids. Studying the cutaneous effect of pollution in a laboratory setting presents challenges, therefore it becomes critical to employ appropriate and tailored models that aim to answer specific questions. Several skin models are available nowadays: in vitro models (2D cell lines and 3D cutaneous tissues), ex vivo skin explants and in vivo approaches (animals and humans). Although in the last 20 years researchers developed skin models that closely resemble human skin (3D cutaneous tissues), ex vivo skin explants still remain one of the best models to study cutaneous responses. Unfortunately, one important cutaneous property that is not present in the traditional ex vivo human skin explants is the physiological tension, which has been shown to be a cardinal player in skin structure, homeostasis, functional properties and responses to external stimuli. For this reason, in this study, to confirm and further comprehend the harmful mechanism of ozone exposure on the integumentary system, we have performed experiments using the state of art in cutaneous models: the innovative TenSkin™ model in which ex vivo human skin explants are cultured under physiologically relevant tension during the whole experimental procedure. Specifically, we were interested in corroborating previous findings showing that ozone exposure modulates the expression of cutaneous antimicrobial peptides (AMPs). The present work demonstrates that cutaneous exposure to ozone induces AMPs gene and protein levels (CAMP/LL-37, hBD2, hBD3) and that the presence of tension can further modulate their expression. In addition, different responses between tension and non-tension cultured skin were also observed during the evaluation of OxInflammatory markers [cyclooxygenase-2 (COX2), aryl hydrocarbon receptor (AhR), matrix-metallo-proteinase 9 (MMP9) and 4-hydroxy-nonenal (4HNE)]. This current study supports our previous findings confirming the ability of pollution to induce the cutaneous expression of AMPs via redox signaling and corroborates the principle that skin explants are a good and reliable model to study skin responses even though it underlines the need to holistically consider the role of skin tension before extrapolating the data to real life.

Guidelines and treatment for illicit drug related presentations in emergency departments: A scoping review.

OBJECTIVE: This review aimed to identify current pharmacological and non-pharmacological treatment employed in emergency departments (EDs) for the management of patients presenting with illicit drug-related presentations (IDP) and compare current treatments with recommendations provided in guidelines. METHOD: The review consists of English peer-reviewed journal articles and grey literature published in electronic databases: Ovid MEDLINE, PubMed, Embase Classic+Embase, Ovid Emcare and APA PsycInfo between 2015 and 2022. RESULTS: Twelve studies were identified from the search, with agitation and aggression being the most common presentations, and cannabis being the most prevalent illicit drug. Ventilatory support and restraints were the most reported non-pharmacological interventions while benzodiazepines and antipsychotics were the most commonly prescribed pharmacological agents. Non-coercive de-escalation strategies were recommended in all guidelines, with verbal de-escalation being the initial approach before other interventions, such as medications and restraints. However, de-escalation strategies were not reported in any studies. CONCLUSIONS: Pharmacological interventions for patients with IDP and related symptoms were in accordance with guidelines. Use of restraints was identified in included studies with notable lack of reporting of de-escalation strategies which may have been deemed insignificant and not reported. Future research could investigate the appropriateness of restrictive interventions as well as the employment of non-restrictive de-escalation strategies.

Loss of TRPC2 function in mice alters sex differences in brain regions regulating social behaviors.

The transient receptor potential cation channel 2 (TRPC2) conveys pheromonal information from the vomeronasal organ (VNO) to the brain. Both male and female mice lacking this gene show altered sex-typical behavior as adults. We asked whether TRPC2, highly expressed in the VNO, normally participates in the development of VNO-recipient brain regions controlling mounting and aggression, two behaviors affected by TRPC2 loss. We now report significant effects of TRPC2 loss in both the posterodorsal aspect of the medial amygdala (MePD) and ventromedial nucleus of the hypothalamus (VMH) of male and female mice. In the MePD, a sex difference in neuron number was eliminated by the TRPC2 knockout (KO), but the effect was complex, with fewer neurons in the right MePD of females, and fewer neurons in the left MePD of males. In contrast, MePD astrocytes were unaffected by the KO. In the ventrolateral (vl) aspect of the VMH, KO females were like wildtype (WT) females, but TRPC2 loss had a dramatic effect in males, with fewer neurons than WT males and a smaller VMHvl overall. We also discovered a glial sex difference in VMHvl of WTs, with females having more astrocytes than males. Interestingly, TRPC2 loss increased astrocyte number in males in this region. We conclude that TRPC2 normally participates in the sexual differentiation of the mouse MePD and VMHvl. These changes in two key VNO-recipient regions may underlie the effects of the TRPC2 KO on behavior.

Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice.

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.

The impact of mindfulness interventions for staff on the care, treatment, and experiences of people with intellectual disabilities: A systematic review.

BACKGROUND: Mindfulness interventions have been shown to ameliorate stress in support staff working with people with intellectual disabilities. This review aimed to explore what impact mindfulness interventions for staff have on their care and support behaviours, and on the experiences of people with intellectual disabilities receiving support. METHOD: A systematic search of PsycINFO, Web of Science, ASSIA, and PubMed identified nine studies meeting the inclusion criteria. Outcomes were collated and a quality assessment tool was used to inform the critical analysis of the studies. RESULTS: Despite identified methodological issues, positive results were consistently reported. These included reduced use of restrictive practices by staff, increased positive interactions between staff and people with intellectual disabilities, and reduced aggression displayed by people with intellectual disabilities. CONCLUSIONS: Further research in this area is required; however, this review supports the benefits of mindfulness on staff behaviour and the quality of life of people with intellectual disabilities.

Complementary and Integrative Treatments of Aggressiveness/Emotion Dysregulation: Associated with Disruptive Disorders and Disruptive Mood Dysregulation Disorder.

Youth with emotional dysregulation (ED) and irritability/aggression, common in disruptive disorders (frequently comorbid with attention-deficit/hyperactivity disorder), are underserved by conventional treatments. Anger dysregulation is usually the core feature of ED. Complementary and integrative Medicine (CIM) treatments for youth with disruptive disorders and ED are reviewed. Broad-spectrum micronutrient supplementation has a medium effect and is supported by two double-blind randomized controlled trials using similar formulations. Other CIM treatments supported by controlled data but needing further research, include omega-3 fatty acid supplementation, music therapy, martial arts, restricting exposure to media violence, decreasing sleep deprivation, and increased exposure to green-blue spaces.

Aggression: The dark side of mirror neurons sheds light on their functions.

Mirror neurons have been found mainly in neocortical structures of primates and rodents; however, their functions are still debated. A new study has discovered mirror neurons for aggressive behaviors in the ventromedial hypothalamus of mice, an evolutionarily ancient structure, highlighting a new function key for survival.

A hypothalamic pathway that suppresses aggression toward superior opponents.

Aggression is costly and requires tight regulation. Here we identify the projection from estrogen receptor alpha-expressing cells in the caudal part of the medial preoptic area (cMPOAEsr1) to the ventrolateral part of the ventromedial hypothalamus (VMHvl) as an essential pathway for modulating aggression in male mice. cMPOAEsr1 cells increase activity mainly during male-male interaction, which differs from the female-biased response pattern of rostral MPOAEsr1 (rMPOAEsr1) cells. Notably, cMPOAEsr1 cell responses to male opponents correlated with the opponents' fighting capability, which mice could estimate based on physical traits or learn through physical combats. Inactivating the cMPOAEsr1-VMHvl pathway increased aggression, whereas activating the pathway suppressed natural intermale aggression. Thus, cMPOAEsr1 is a key population for encoding opponents' fighting capability-information that could be used to prevent animals from engaging in disadvantageous conflicts with superior opponents by suppressing the activity of VMHvl cells essential for attack behaviors.

Deep brain stimulation may be a viable option for resistant to treatment aggression in children with intellectual disability.

INTRODUCTION: Deep brain stimulation (DBS) is a surgical technique used to manage aggression in patients who do not improve despite the use of appropriate drug treatment. OBJECTIVE: The objective of this study is to assess the impact of DBS on aggressive behavior refractory to the pharmacological and behavioral treatment of patients with Intellectual Disabilities (ID). METHODS: A follow-up was conducted on a cohort of 12 patients with severe ID, undergoing DBS in posteromedial hypothalamic nuclei; evaluated with the Overt Aggression Scale (OAS), before the intervention, at 6, 12, and 18 months of medical follow-up. RESULTS: After the surgical procedure, there was a significant reduction in the aggressiveness of patients in the follow-up medical evaluation at 6 months (t = 10.14; p < 0.01), 12 months (t = 14.06; p < 0.01), and 18 months (t = 15.34; p < 0.01), respect to the initial measurement; with a very large effect size (6 months: d = 2.71; 12 months: d = 3.75; 18 months: d = 4.10). From 12 months onward, emotional control stabilized and is sustained at 18 months (t = 1.24; p > 0.05). CONCLUSION: DBS in posteromedial hypothalamic nuclei may be an effective treatment for the management of aggression in patients with ID refractory to pharmacological treatment.