Normal Behavioral Development Research Articles

Congenital absence of touch does not preclude normal cognitive and socioemotional development.

Attachment theory holds that development of normal affective and social behavior requires physical contact between infant and caregiver. The elevation of touch to paramount importance has gone unchallenged because, prior to the present study, no individual with a congenital lack of somatosensation has been reported, much less studied for psychosocial development. Here we describe Kim, who since birth, has been unable to perceive touch, temperature changes, or pain on the body surface. Despite her inability to sense physical contact, Kim has above-average intelligence. She functions normally in social situations with a variety of people, recognizing emotions in herself and others and demonstrating appropriate affect. Kim experiences anxiety that appears grounded in realistic fears and uncertainties particular to her somatic insensitivity, thus serving as adaptive vigilance in reaction to an abnormal sensorium. Her normal socioemotional development, evident from an early age, likely resulted from Kim being able to appreciate her parents' loving care through gaze, movement, and hearing. In sum, Kim upends the idea of touch as critical to developing a sense of self, secure attachment, and family bonds.

Synaptic pruning during adolescence shapes adult social behavior in both males and females.

Evolutionarily conserved, peer-directed social behaviors are essential to participate in many aspects of human society. These behaviors directly impact psychological, physiological, and behavioral maturation. Adolescence is an evolutionarily conserved period during which reward-related behaviors, including social behaviors, develop via developmental plasticity in the mesolimbic dopaminergic "reward" circuitry of the brain. The nucleus accumbens (NAc) is an intermediate reward relay center that develops during adolescence and mediates both social behaviors and dopaminergic signaling. In several developing brain regions, synaptic pruning mediated by microglia, the resident immune cells of the brain, is important for normal behavioral development. We previously demonstrated that during adolescence, in rats, microglial synaptic pruning shapes the development of NAc and social play behavior in males and females. In this report, we hypothesize that interrupting microglial pruning in NAc during adolescence will have persistent effects on male and female social behavior in adulthood. We found that inhibiting microglial pruning in the NAc during adolescence had different effects on social behavior in males and females. In males, inhibiting pruning increased familiar exploration and increased nonsocial contact. In females, inhibiting pruning did not change familiar exploration behavior but increased active social interaction. This leads us to infer that naturally occurring NAc pruning serves to reduce social behaviors toward a familiar conspecific in both males and females.

A perspective on ungulate management and welfare assessment across the traditional zoo to large landscape spectrum.

Wild ungulates are managed in human care in a range of settings from traditional zoos to large ranches. These varied settings present different portfolios of risks for good or poor welfare, which leads some to question whether a particular setting is "good for welfare" and have frustrated others interested in comparing the welfare of ungulates across these settings. Differing housing and management scenarios present different challenges and opportunities in terms of welfare but this commentary posits that good welfare is possible in all of these settings. In this commentary, we also consider natural behaviors that may, at face value, compromise welfare and discuss how taking a long view on welfare addresses concerns about these behaviors, in part using arguments related to normal behavioral development that likely improves welfare at other life stages. We also highlight the role of motivation in seemingly welfare-compromising behaviors. Finally, some indicators of welfare that we believe transcend management scenarios, and are thus able to be compared across scenarios, are suggested.

Follow-Up of Offspring Born to Parents With a Solid Organ Transplantation: A Systematic Review.

Pregnancy after solid organ transplantation (SOT) has potential risks for the offspring. Most existing research focused on short-term pregnancy outcomes. The aim of this systematic review was to evaluate available data concerning longer term outcomes (>1 year) of these children. A systematic literature search, following PRISMA guidelines, of PubMed and Embase was performed from the earliest date of inception through to 6th April 2022. Publications on all types of (combined) SOT were eligible for inclusion. In total, 53 articles were included. The majority assessed offspring after kidney (78% of offspring) or liver transplantation (17% of offspring). 33 studies included offspring aged >4 years and five offspring aged >18 years. One study was included on fathers with SOT. The majority of the 1,664 included children after maternal SOT had normal intellectual, psychomotor, and behavioral development. Although prematurity and low birth weight were commonly present, regular growth after 1 year of age was described. No studies reported opportunistic or chronic infections or abnormal response to vaccinations. In general, pregnancy after SOT appears to have reassuring longer term outcomes for the offspring. However, existing information is predominantly limited to studies with young children. Longer prospective studies with follow-up into adulthood of these children are warranted.

Effects of Social Housing on Dairy Calf Social Bonding.

Simple SummaryAlthough cows and calves are typically separated at birth in intensive dairy farming, socially housing dairy calves provides an opportunity for social bonding. When tested in our study, calves housed in pairs preferred to be near their pen-mate, but spent more time near other calves regardless of their familiarity, compared to individually housed calves. In contrast, individually housed calves showed no preference between a calf housed within visual contact and a calf housed elsewhere in the barn. Additionally, the behavior of individually housed calves was affected by the first calf approached during the social preference test.Social housing for dairy calves has a range of benefits for social development, yet there is limited understanding of how social bonds form early in life. We characterized effects of early life social contact on the development of social preference for calves varying in familiarity. A total of 40 calves were tested in a social preference test at 4 weeks of age to assess the formation of social bonds and preference for their peers. Within an open-field social preference test, focal calves were presented with two stimulus calves, one ‘more familiar’ and one ‘less familiar’. We found that pair-housed calves spent more time in close proximity with either stimulus calf and had a greater preference for their pen-mate, compared to another calf reared within visual contact. Individually housed calves exhibited no preference for calves reared within visual but not physical contact compared to calves that were completely unfamiliar. Of the calves that approached both stimulus calves, individually housed calves that approached the ‘less familiar’ calf first spent less time near the ‘more familiar’ calf, whereas behavior of pair-housed calves was not affected by the first calf approached. These results suggest that physical contact is necessary for the development of social bonds in young dairy calves, and early life social housing may support the development of normal social behavior in dairy cattle.

Disrupted Timing of MET Signaling Derails the Developmental Maturation of Cortical Circuits and Leads to Altered Behavior in Mice.

The molecular regulation of the temporal dynamics of circuit maturation is a key contributor to the emergence of normal structure-function relations. Developmental control of cortical MET receptor tyrosine kinase, expressed early postnatally in subpopulations of excitatory neurons, has a pronounced impact on the timing of glutamatergic synapse maturation and critical period plasticity. Here, we show that using a controllable overexpression (cto-Met) transgenic mouse, extending the duration of MET signaling after endogenous Met is switched off leads to altered molecular constitution of synaptic proteins, persistent activation of small GTPases Cdc42 and Rac1, and sustained inhibitory phosphorylation of cofilin. These molecular changes are accompanied by an increase in the density of immature dendritic spines, impaired cortical circuit maturation of prefrontal cortex layer 5 projection neurons, and altered laminar excitatory connectivity. Two photon in vivo imaging of dendritic spines reveals that cto-Met enhances de novo spine formation while inhibiting spine elimination. Extending MET signaling for two weeks in developing cortical circuits leads to pronounced repetitive activity and impaired social interactions in adult mice. Collectively, our data revealed that temporally controlled MET signaling as a critical mechanism for controlling cortical circuit development and emergence of normal behavior.

First Clinical Case report of a Libyan Girl with Kabuki Syndrome and Literature review

Kabuki syndrome is a rare autosomal disorder, diagnosed by presence of dysmorphic facies, mental retardation, short stature, skeletal and visceral abnormalities and cardiac anomalies. It is caused by a mutation in the KMT2D gene also known as MLL2 and in fewer cases due to mutations in the KDM6A gene. We report on the first description of a 2-year-old Libyan girl with Kabuki syndrome with typical facial features, skeletal abnormalities (fingertip foetal pads, brachydactyly, clinodactyly of the little finger, single simian crease, and abnormal lower limbs), cardiac anomalies, biliary atresia, single kidney and developmental dysplasia of the hips DDH. The patient also suffered from recurrent infections which has been noted in KS patients. The patient so far has shown normal neurological and behavioral development, but still has high liver enzymes

Thyroid hormone treatment alleviates the impairments of neurogenesis, mitochondrial biogenesis and memory performance induced by methamphetamine

Chronic use of methamphetamine (MA), a neurotoxic psychostimulant, leads to long-lasting cognitive dysfunctions in humans and animal models. Thyroid hormones (THs) have several physiological actions and are crucial for normal behavioral, intellectual and neurological development. Considering the importance of THs in the cognitive processes, the present study was designed to evaluate the therapeutic effects of THs on cognitive and neurological impairments induced by MA. Escalating doses of MA (1–10 mg/kg, IP) were injected twice daily for 10 consecutive days in rats and cognitive functions were evaluated using behavioral tests. The expression of factors involved in neurogenesis (NES and DCX), mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM), neuroinflammation (GFAP, Iba-1, and COX-2) as well as Reelin and NT-3 (synaptic plasticity and neurotrophic factor, respectively) was measured in the hippocampus of MA-treated animals. The effects of three different doses of T4 (20, 40 or 80 μg/kg; intraperitoneally) or T3 (20, 40 or 80 μg/rat; 2.5 μl/nostril; intranasal) treatment, once a day for one week after MA cessation, were assessed in MA-treated rats. After the last behavioral test, serum T4 and T3 levels were measured using radioimmunoassay. The results revealed that repeated escalating regimen of MA impaired cognitive functions concomitant with neurogenesis and synaptic plasticity impairments, mitochondrial dysfunction, and neuroinflammation. T4 or T3 treatment partially decreased the alterations induced by MA. These findings suggest that THs can be considered as potential candidates for the reduction of MA abuse related neurocognitive disturbances.

Treatment of Depressive Conditions in Pregnancy.

BACKGROUND:Mother’s mental state during pregnancy is of substantial importance for the mother, but also for the infant and his/her future growth and development. Depressive maternal disorders during pregnancy have a significant influence on the development of the baby during pregnancy as well as on the future development and mother-baby relation, the breastfeeding process and care for the baby.AIM:This study aimed to determine the influence of SSRI antidepressant therapy and psychosocial and therapeutic interventions on depression during pregnancy. It was also our aim to determine the relation between severity of depression and sociodemographic characteristics.METHODS:The study included 40 women, with diagnosis F32 and F33 according to ICD 10, that is, with severe depressive disorder within depressive episodes or recurrent depressive disorder. Patients were evaluated at the beginning of the treatment and 3 months after antidepressant treatment. They were followed-up for two years.RESULTS:The results obtained have shown that a larger number of mothers treated with antidepressant medications, had normal childbirth with the unremarkable condition of both, the mother and the newborn baby.CONCLUSION:A well-combined treatment of maternal depression during pregnancy reduces the risk of postpartum depression, which is by itself a prerequisite for normal emotional and behavioural development of the child.

Abstract # 1849 The role of immune system maturation in development of normal behavior in mice

Previous studies demonstrated differences in behavior and brain biochemistry between germ-free and conventional mice. We showed that mono-colonization with E. coli induces similar changes in behavior as with complex microbiota. BDNF and cFos expression in the amygdala and hippocampus regions were also changed after mono-colonization. Furthermore, using permanent colonizer E. coli JM83 and transient colonizer E. coli HA107 (mutant form of E. coli JM83) we demonstrated that changes in behavior persist despite mice reverting to germ-free status. Using mono-colonized SCID and MyD88-/- Ticam-/- mice we now show that signaling via the innate, and not adaptive immune pathway is crucial for this change in behavior. Analysis of colonic and brain tissues using NanoString technique has revealed that multiple innate immunity and neural system related genes are significantly altered after colonization, including networks previously linked to neuronal plasticity. To further investigate the role of Toll-like receptors, we gavaged germ-free mice with LPS and poly I:C for two weeks. Only mice given LPS displayed altered behavior suggesting that TLR-4 related pathways are crucial for the development of normal mouse behavior. In conclusion, bacterial colonization induces long lasting changes in behavior and brain chemistry, which are associated with alterations in multiple innate immunity and neural system related gene networks. Signalling via TLR-4 pathway appears to be crucial for gut-microbiota-brain axis communication and for the development of normal behavioral.

Potential biomarkers in personality disorders: current state and future research

This review article presents the most appropriate strategies for examining the phenotype for personality disorders. At present there are many neurobiological and molecular studies that suggest a genetic predisposition to different traits representative of expressed personality disorders. Nonetheless, it has not been possible to accurately and successfully replicate such results due to some difficulties regarding the sensitivity, specificity and validity of the clinical evaluation methods, and the size and type of the chosen population and experimental designs used for research. Unfortunately, diagnoses done in psychiatry and psychology have a classification system based on the prevalence and intensity of symptoms and do not take into account the etiology, neurobiology, epidemiology, genetics, and drug responses. On the other hand, explaining the phenomenology of personality disorderes and how genes work together to express this phenotype implies a revision of the chaos theory, addressing the connection between neurodevelopment, significantly stressful events during early childhood and epigenetic modifications in DNA related to stochastic events which may contribute to the development of normal or abnormal behavior

Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide.

Arginine:glycine aminotransferase (AGAT) (GATM) deficiency is an autosomal recessive inborn error of creative synthesis. We performed an international survey among physicians known to treat patients with AGAT deficiency, to assess clinical characteristics and long-term outcomes of this ultra-rare condition. 16 patients from 8 families of 8 different ethnic backgrounds were included. 1 patient was asymptomatic when diagnosed at age 3 weeks. 15 patients diagnosed between 16 months and 25 years of life had intellectual disability/developmental delay (IDD). 8 patients also had myopathy/proximal muscle weakness. Common biochemical denominators were low/undetectable guanidinoacetate (GAA) concentrations in urine and plasma, and low/undetectable cerebral creatine levels. 3 families had protein truncation/null mutations. The rest had missense and splice mutations. Treatment with creatine monohydrate (100-800 mg/kg/day) resulted in almost complete restoration of brain creatine levels and significant improvement of myopathy. The 2 patients treated since age 4 and 16 months had normal cognitive and behavioral development at age 10 and 11 years. Late treated patients had limited improvement of cognitive functions. AGAT deficiency is a treatable intellectual disability. Early diagnosis may prevent IDD and myopathy. Patients with unexplained IDD with and without myopathy should be assessed for AGAT deficiency by determination of urine/plasma GAA and cerebral creatine levels (via brain MRS), and by GATM gene sequencing.

The Short Questionnaire to Assess Health-Enhancing (SQUASH) Physical Activity in Adolescents: A Validation Using Doubly Labeled Water.

Accurate assessment of physical activity energy expenditure (PAEE) among adolescents is important for surveillance, evaluating interventions, and understanding the relation between energy balance and normal physiological and behavioral growth and development. The purpose of this study was to examine the validity of the Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH)13 for measuring PAEE among adolescents. The participants were seventeen adolescents (9 females; Mean age = 17.53; SD = 0.62). Energy expenditure was measured during a 9-day period with doubly labeled water (DLW). The SQUASH was self-administered on the morning of the 10th day and assessed commuting activities, leisure time activities, household activities, and activities at work and school over the previous 9 days. A Bland-Altman plot indicated that the SQUASH underestimated PAEE compared with DLW by a mean difference of 126 kcal·d-1 (95% limits of agreement: -1,207 to 1,459 kcal·d-1), representative of a 10% underestimation. The Spearman rank order correlation coefficient showed there was a significant association between the SQUASH and DLW (r = .50, P = .04), for estimating PAEE. When using a sample of highly active adolescents, the SQUASH is a valid self-report tool for measuring PAEE at the group and individual rank order level.

Differences in environmental enrichment generate contrasting behavioural syndromes in a basal spider lineage

Behavioural syndrome studies are commonly descriptive and often find a relationship between boldness, shyness and exploration. However, the mechanisms underlying behavioural syndromes are not well understood. In the present study, we examined the extent to which early experience acts as a modifier of behavioural tendencies in the basal tarantula, Brachypelma smithi. Juvenile individuals were housed for 2 years either in enriched controlled conditions, or in restricted (minimal) conditions. Behavioural assays were completed both in short-term and in long-term increments. We found both short-term and long-term differences in multiple contexts of behaviour between treatments. In addition, individuals in the enriched treatment developed correlations between several behavioural traits whereas individuals in the restricted treatment did not. This result suggests that early environment can induce behavioural syndromes in some populations, or conversely, that continual stress may break down normal behavioural development and thus prevent a behavioural syndrome from emerging. This study provides a cautionary tale for those studying behavioural syndromes in captivity, and because this is a basal spider species, it provides important insight into the evolution of spider behavioural syndromes.

Social isolation disrupts hippocampal neurogenesis in young non-human primates.

Social relationships are crucial for the development and maintenance of normal behavior in non-human primates. Animals that are raised in isolation develop abnormal patterns of behavior that persist even when they are later reunited with their parents. In rodents, social isolation is a stressful event and is associated with a decrease in hippocampal neurogenesis but considerably less is known about the effects of social isolation in non-human primates during the transition from adolescence to adulthood. To investigate how social isolation affects young marmosets, these were isolated from other members of the colony for 1 or 3 weeks and evaluated for alterations in their behavior and hippocampal cell proliferation. We found that anxiety-related behaviors like scent-marking and locomotor activity increased after social isolation when compared to baseline levels. In agreement, grooming—an indicative of attenuation of tension—was reduced among isolated marmosets. These results were consistent with increased cortisol levels after 1 and 3 weeks of isolation. After social isolation (1 or 3 weeks), reduced proliferation of neural cells in the subgranular zone of dentate granule cell layer was identified and a smaller proportion of BrdU-positive cells underwent neuronal fate (doublecortin labeling). Our data is consistent with the notion that social deprivation during the transition from adolescence to adulthood leads to stress and produces anxiety-like behaviors that in turn might affect neurogenesis and contribute to the deleterious consequences of prolonged stressful conditions.

Assisted reproduction and child neurodevelopmental outcomes: a systematic review

To systematically review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception. Systematic review. Not applicable. Children born after medically assisted reproduction vs. reference groups of spontaneously conceived children. Data were reviewed from worldwide published articles, without restrictions as to publication year or language. A total of 80 studies included between 31 and 2,446,044 children. Child neurodevelopmental outcomes categorized as cognitive, behavioral, emotional or psychomotor development, or diagnoses of mental disorders. For infants, studies on psychomotor development showed no deficits, but few investigated cognitive or behavioral development. Studies on toddlers generally reported normal cognitive, behavioral, socio-emotional, and psychomotor development. For children in middle childhood, development seems comparable in children born after assisted reproduction and controls, although fewer studies have been conducted with follow-up to this age. Very few studies have assessed neurodevelopmental outcomes among teens, and the results are inconclusive. Studies investigating the risk of diagnoses of mental disorders are generally large, with long follow-up, but the results are inconsistent. It may tentatively be concluded that the neurodevelopment of children born after fertility treatment is overall comparable to that in children born after spontaneous conception.

Epigenetics and its implications for Psychology

Epigenetics is changing the widely accepted linear conception of genome function by explaining how environmental and psychological factors regulate the activity of our genome without involving changes in the DNA sequence. Research has identified epigenetic mechanisms mediating between environmental and psychological factors that contribute to normal and abnormal behavioral development. the emerging field of epigenetics as related to psychology is reviewed. the relationship between genes and behavior is reconsidered in terms of epigenetic mechanisms acting after birth and not only prenatally, as traditionally held. Behavioral epigenetics shows that our behavior could have long-term effects on the regulation of the genome function. In addition, epigenetic mechanisms would be related to psychopathology, as in the case of schizophrenia. In the latter case, it would be especially relevant to consider epigenetic factors such as life adversities (trauma, disorganized attachment, etc.) as related to its clinical manifestations, rather than genetic factors. Moreover, epigenetics implies overcoming classical dualist dichotomies such as nature-nurture, genotype-phenotype or pathogenesis-pathoplasty. In general, it can be stated that behavior and environment will finally take on a leading role in human development through epigenetic mechanisms.

Investigating mechanisms underlying neurodevelopmental phenotypes of autistic and intellectual disability disorders: a perspective

Brain function and behavior undergo significant plasticity and refinement, particularly during specific critical and sensitive periods. In autistic and intellectual disability (ID) neurodevelopmental disorders (NDDs) and their corresponding genetic mouse models, impairments in many neuronal and behavioral phenotypes are temporally regulated and in some cases, transient. However, the links between neurobiological mechanisms governing typically normal brain and behavioral development (referred to also as “neurotypical” development) and timing of NDD impairments are not fully investigated. This perspective highlights temporal patterns of synaptic and neuronal impairment, with a restricted focus on autism and ID types of NDDs. Given the varying known genetic and environmental causes for NDDs, this perspective proposes two strategies for investigation: (1) a focus on neurobiological mechanisms underlying known critical periods in the (typically) normal-developing brain; (2) investigation of spatio-temporal expression profiles of genes implicated in monogenic syndromes throughout affected brain regions. This approach may help explain why many NDDs with differing genetic causes can result in overlapping phenotypes at similar developmental stages and better predict vulnerable periods within these disorders, with implications for both therapeutic rescue and ultimately, prevention.

Impacts of early intervention with fluoxetine following early neonatal immune activation on depression-like behaviors and body weight in mice

Several reports have suggested that early neonatal immune activation adversely influences the hypothalamic-pituitary-adrenal (HPA) axis development in humans and animal models. In addition, there have been several studies indicating that early intervention with fluoxetine (FLX) can alter HPA axis development and function, and prevent occurrence of behavioral abnormalities induced by common early-life insults. The present study aims to investigate the effects of early intervention with FLX following early neonatal immune activation on depression-like behaviors and body weight in mice. Neonatal mice in their postnatal days (PNDs) 3 and 5 received either lipopolysaccharide (LPS; 50 μg/kg, s.c.) or saline treatment, then male and female mice of both neonatal intervention groups received oral administration of FLX (5 and 10 mg/kg/day) or water via regular drinking bottles during the periadolescent period (PNDs 35-65). The results showed that neonatal LPS exposure elevated depression-like behaviors accompanied by increasing corticosterone levels in adulthood and decreasing body weight during neonatal and adolescent periods. Furthermore, the periadolescent FLX treatment inhibited the depression-like behaviors induced by neonatal infection in both sexes. This study obtained some experimental evidence indicating the potential adverse impacts of the FLX on normal behavioral development in male control animals. In conclusion, our findings suggest that an early pharmacological intervention with FLX may prevent emergence of depression-like behaviors induced by neonatal immune challenge without any detrimental effect on health in a sex- and dose-dependent manner in mice.

Childhood Trauma Experience and the Expression of Problematic Sexual Behavior in Children and Adolescents in State Custody

The present study is designed to identify which types of trauma experiences interact with later development of normal and abnormal sexual behavior in children and adolescents. More specifically, our goal is to determine which types of trauma exposure are related to issues of sexuality, sexually reactive behavior, sexually aggressive behavior, and the combination of both sexually reactive and sexually aggressive behavior. A sample of 5,976 children ages 5 to 18 who were wards of the State of Illinois were studied. All children were assessed with the Child and Adolescent Needs and Strengths (CANS) at entry into care. These data were used to understand the relationship between prior trauma experiences and the expression of problematic sexual behavior. Child sexual abuse was the most common form of maltreatment found in children and adolescents with problematic sexual behaviors. However, other types of trauma experiences, especially exposure to violence, were also related. Sexual abuse and multiple trauma experiences both appear to have an important possible etiological roles in the development of sexually problematic behaviors.