Sara Palumbo

Background: Research in behavioral genetics has demonstrated that genetic factors significantly contribute to individual differences in behavior, while environmental exposures shape gene expression through epigenetic mechanisms. This interaction is also relevant to the development of antisocial behavior and psychopathic traits. One of the first evidence of gene–environment interaction was the association between low-activity variants of the MAOA gene, childhood maltreatment, and increased risk of antisocial behavior [¹]. Similarly, our research in incarcerated populations showed that adverse paternal parenting is associated with higher levels of psychopathy and the HTR1B rs13212041 TT genotype appears to modulate the individual susceptibility to negative experiences [²]. Single genetic variants, however, exert only modest effects and current evidence supports a polygenic model in which multiple genetic factors interact with environmental adversity to influence neurodevelopment and behavioral outcomes. Using a genome-wide/endophenotype informed analysis, for example, we identified novel gene–environment interactions as risk factors for psychopathy, involving three independent genetic loci in interaction with paternal maltreatment, which were previously associated with disruptive behavior, temperament, and neuroticism [³]. More recently, we also evaluated whether machine-learning models, integrating behavioral, environmental, and genetic variables, could be helpful to predict psychopathic traits. Methods: We compared logistic regression, random forest, support vector machine, XGBoost, and multilayer perceptron. Results: Support vector machine showed the highest accuracy for predicting Psychopathy Check List-Revised (PCL-R) Factor 2 (antisocial lifestyle). Feature-importance analyses identified impulsivity (BIS-11), empathy (IRI), childhood maltreatment (MOPS), and 12 SNPs as the most informative predictors. Notably, removing genetic variables or MOPS scores substantially reduced the model accuracy, indicating that both genetic and environmental information meaningfully contributed to prediction of antisocial behavior. Conclusions: These findings confirm that genetic influences are neither deterministic nor sufficient to explain criminal behavior but may contribute to interindividual differences in vulnerability, particularly through their interaction with environmental and psychosocial factors. In forensic psychiatry, the integration of genetic and environmental information into behavioral assessment may provide additional objective correlates that complement, rather than replace, traditional clinical and psychosocial evaluations. Such an integrated approach could potentially contribute to a more comprehensive understanding of individual vulnerability and behavioral trajectories. However, the use of genetic information in assessments of criminal responsibility should be approached with caution and proven expertise, given the complex, multifactorial nature of antisocial and criminal behavior.

Emotional dyscontrol in multiple sclerosis: an opinion article

Children with high Callous-Unemotional (CU) traits show deficits in recognizing and processing facial expressions. Alterations in emotion recognition have been linked to a higher synaptic concentration of monoaminergic neurotransmitters. The current study investigated the relationship between the MAOA-Low-activity alleles and the ability to recognize and process facial expressions in 97 male children (8–12 years old) diagnosed with disruptive behavior disorder. Participants completed a computerized emotion-recognition task while an eye-tracking system recorded the number (Fixation Count, FC) and length (Fixation Duration, FD) of fixations to the eye region of the emotional stimuli. Children with high CU traits exhibited lower scores in recognition of sadness and anger, and lower FC and FD for sadness and fear than children with low CU traits. Children carrying the MAOA-Low-activity alleles displayed lower FD for sadness, and FD and FC for fear than those carrying the MAOA-High-activity alleles. These genetic effects appeared even stronger in children with CU traits. Moderation analysis revealed that CU traits were associated with lower FC and FD for fear, and lower FD for sadness, probably due to the MAOA-Low-activity alleles. Our findings, although to be replicated, suggest MAOA-Low-activity alleles as potential genetic biomarkers to identify CU children in need of training focused on emotion processing.

Children with high Callous-Unemotional (CU) traits show deficits in recognizing and processing facial expressions. Alterations in emotion recognition have been linked to a higher synaptic concentration of monoaminergic neurotransmitters. The current study investigated the relationship between the MAOA-Low-activity alleles and the ability to recognize and process facial expressions in 97 male children (8-12 years old) diagnosed with disruptive behavior disorder. Participants completed a computerized emotion-recognition task while an eye-tracking system recorded the number (Fixation Count, FC) and length (Fixation Duration, FD) of fixations to the eye region of the emotional stimuli. Children with high CU traits exhibited lower scores in recognition of sadness and anger, and lower FC and FD for sadness and fear than children with low CU traits. Children carrying the MAOA-Low-activity alleles displayed lower FD for sadness, and FD and FC for fear than those carrying the MAOA-High-activity alleles. These genetic effects appeared even stronger in children with CU traits. Moderation analysis revealed that CU traits were associated with lower FC and FD for fear, and lower FD for sadness, probably due to the MAOA-Low-activity alleles. Our findings, although to be replicated, suggest MAOA-Low-activity alleles as potential genetic biomarkers to identify CU children in need of training focused on emotion processing.

Whether brain structure could reflect empathy and psychopathy in the same antisocial population is unknown. In White adult males from prison (N = 549, M_age = 34 ± 11 years), we measured empathy with the Perspective Taking (IRI-PT) and Empathic Concern (IRI-EC) subscales of the Interpersonal Reactivity Index, and psychopathic traits with the Psychopathy Checklist-Revised or Youth Version (PCL-R/YV). A subsample (N = 278, M_age = 36 ± 11 years) underwent MRI, from which we derived cortical thickness (CT) and surface area (SA). CT did not relate to IRI-PT or IRI-EC, while SA of the left inferior temporal gyrus (L ITG) related negatively to IRI-PT and positively to PCL-R and PCL-R item 8 (Callousness/Lack of Empathy). L-ITG SA predicted scores on IRI-PT – but not IRI-EC – in an out-of-sample test (R² = 0.030). Mapping onto the histological BigBrain gradient, higher scores on IRI-PT – but not IRI-EC – entailed a progressive SA reduction from Bin 1 (sensorimotor) to Bin 5 (limbic). Psychopaths (PCL-R/YV ≥ 30, N = 73/39) had: (1) reduced IRI-PT and IRI-EC scores (Cohen's Ds = -0.423, -0.564, respectively); (2) increased L-ITG SA (Cohen's D = 0.560); (3) increased global SA (Cohen's D = 0.480); and (4) reduced SA covariance between the left precentral and left isthmus-cingulate cortices. There were no group differences in global, modular, or nodal SA covariance, as indexed by canonical graph-theoretical metrics. We provide novel insights into the brain correlates of empathy and psychopathy in incarcerated males.

Endogenous ouabain (EO) is a steroid hormone secreted by the adrenal glands, usually associated with adverse cardiovascular effects. However, recent studies have highlighted its possible role in blood pressure control and in cardio-renal damage, and it seems to be involved in the adaptive response to hypoxia. The aim of this study is to detect the EO in human and animal models of hypoxia. We collected blood samples from seven competitive elite apnea divers, 11 noncompetitive elite apnea divers, and 26 healthy control subjects. Animal blood samples were collected from 16 common bottlenose dolphins (Tursiops truncatus), two phocids and two otariids kept under human care, and 11 wild loggerhead sea turtles (Caretta caretta) hosted in two rescue centers. We measured EO plasma concentrations with a Scintillation Proximity Assay. In elite apnea divers and healthy control subjects, EO plasma concentrations were positively correlated to weight (p < 0.05). Elite apnea divers showed statistically significant (p < 10-6) higher EO plasma concentrations compared to healthy subjects without any diving experience or experience in other sports activities involving breath-holding. In dolphins, EO plasma concentrations were positively correlated to age, total length, and weight (p < 0.05). In loggerhead sea turtles, EO plasma concentrations were negatively correlated to total length and weight (p < 0.05). In pinnipeds, correlation analysis was not performed due to the small number of animals. Herein, we demonstrate, for the first time, that different taxa, phylogenetically distant from each other and which perform apneas without reporting neurological damages, express EO. Our findings, although preliminary, are in line with the recently emerging hypothesis on a possible role of EO in the adaptive response to hypoxia and represent a helpful hint for future investigations aimed to identify novel molecules useful to treat very disabling pathological conditions such as idiopathic pulmonary arterial hypertension or obstructive sleep apnea.

The serine/threonine protein kinase v-AKT homologs (AKTs), are implicated in typical and atypical neurodevelopment. Akt isoforms Akt1, Akt2, and Akt3 have been extensively studied outside the brain where their actions have been found to be complementary, non-overlapping and often divergent. While the neurological functions of Akt1 and Akt3 isoforms have been investigated, the role for Akt2 remains underinvestigated. Neurobehavioral, electrophysiological, morphological and biochemical assessment of Akt2 heterozygous and knockout genetic deletion in mouse, reveals a novel role for Akt2 in axonal development, dendritic patterning and cell-intrinsic and neural circuit physiology of the hippocampus and prefrontal cortex. Akt2 loss-of-function increased anxiety-like phenotypes, impaired fear conditioned learning, social behaviors and discrimination memory. Reduced sensitivity to amphetamine was observed, supporting a role for Akt2 in regulating dopaminergic tone. Biochemical analyses revealed dysregulated brain mTOR and GSK3β signaling, consistent with observed learning and memory impairments. Rescue of cognitive impairments was achieved through pharmacological enhancement of PI3K/AKT signaling and PIK3CD inhibition. Together these data highlight a novel role for Akt2 in neurodevelopment, learning and memory and show that Akt2 is a critical and non-redundant regulator of mTOR activity in brain.