Comparison of Social Abilities of Children with Fetal Alcohol Syndrome to Those of Children with Similar IQ Scores and Normal Controls

Children diagnosed with fetal alcohol syndrome (FAS) were assessed with items from the social skills domain of the Vineland Adaptive Behavior Scales (VABS) via interviews with their caregivers. Their scores were compared with scores from children in two control groups. The control groups included children matched for IQ to the FAS group (specifically on verbal IQ, henceforth, the VIQ group) and children with IQ scores in the average to above-average range (normal control group). Forty-five children (age range, 5 years 7 months to 12 years 11 months) were assessed ( n /group = 15). All groups differed with regard to social ability, as measured by the VABS (NC > VIQ > FAS), even when the effects of socioeconomic status were held constant. The three subdomains of the VABS social scale (interpersonal relationship skills, use of play and leisure time, and coping skills) were assessed, and results showed that the children with FAS were most impaired on the subdomain that assessed interpersonal relationship skills. An additional measure was constructed by obtaining an age-equivalent score for the VABS social scale and calculating a difference score by subtracting the child's chronological age from his/her age-equivalent score. There was a significant correlation between chronological age and difference scores for children in the FAS group but not for children in the two control groups. Specifically, in older children with FAS, there was an increased discrepancy between their ages and their age-equivalent scores, a discrepancy that was not present in children in the control groups. These results suggest that social deficits in children with FAS are beyond what can be explained by low IQ scores and indicate that there may be arrested, and not simply delayed, development of social abilities in children with FAS.     

Cardiac transplantation in patients over 50 years of age

Sixty-two patients underwent cardiac transplantation at the University of Arizona from March 1979 to March 1985. Thirteen patients (11 men and 2 women) were over 50 years of age at the time of transplantation and 49 were under the age of 50. The mean age (+/- SEM) of the patients over 50 was 53 +/- 1 years. Eight of these patients were treated with conventional immunosuppressive therapy (azathioprine, prednisone and rabbit antithymocyte globulin) and five, beginning in January 1983, were treated with cyclosporine, prednisone and rabbit antithymocyte globulin. Early mortality (0 to 90 days) was 16% in the group over 50 versus 18% for those under 50. The late mortality (greater than 90 days) was 36 and 33%, respectively. In both groups, rejection and infection were the principal causes of death. The incidence of infection was 1.9 +/- 0.5 episodes per patient in those patients over 50 and 1.9 +/- 0.4 in those under 50. The incidence of rejection was 1.3 episodes per patient-year in patients over 50 and 1.7 episodes per patient-year in those under 50. Actuarial survival at 1 year was 72 +/- 14% in the group over 50 and 66 +/- 7% in the group under 50 years of age. These data indicate that the results of cardiac transplantation for patients over 50 do not differ significantly from those for patients under 50. Therefore, it is concluded that a rigidly defined age criterion for cardiac transplant recipients is not acceptable. Each potential recipient must be evaluated in terms of individual risk and benefit from the procedure.     

Impaired B lymphopoiesis in old age: a role for inflammatory B cells?

Continued generation of new B cells within the bone marrow is required throughout life. However, in old age, B lymphopoiesis is inhibited at multiple developmental stages from hematopoietic stem cells through the late stages of new B cell generation. While changes in B cell precursor subsets, as well as alterations in the supporting bone marrow microenvironment, in old age have been known for the last 20 years, only more recently have insights into the cellular and molecular mechanisms responsible become clarified. Our recent discovery that B cells in aged mice are pro-inflammatory and can diminish B cell generation within the bone marrow suggests a potential mechanism of inappropriate “B cell feedback” which contributes to a bone marrow microenvironment unfavorable to B lymphopoiesis. We hypothesize that the consequences of a pro-inflammatory microenvironment in old age are (1) reduced B cell generation and (2) alteration in the “read-out” of the antibody repertoire. Both of these likely ensue from reduced expression of the surrogate light chain (λ5 + VpreB) and consequently reduced expression of the pre-B cell receptor (preBCR), critical to pre-B cell expansion and Vh selection. In old age, B cell development may progressively be diverted into a preBCR-compromised pathway. These abnormalities in B lymphopoiesis likely contribute to the poor humoral immunity seen in old age.

     

Age‐dependent differences in morphine‐induced taste aversions

Adolescence is a developmental period of particular importance given the host of neurobiological changes that occur during this stage of development. Drug use and abuse is said to be a function of the balance of its rewarding and aversive effects, and any age‐dependent differences in morphine's aversive effects could impact drug intake. The present experiments examined the ability of morphine sulfate (0, 3.2, 10, and 18 mg/kg) to induce taste aversions in adolescent and adult rats under high (20‐min fluid access each day; Experiment 1A/B) and low (50% of ad libitum access; Experiment 2A/B) deprivation conditions. In both studies, adolescent and adult rats were given a novel saccharin solution to drink and were subsequently injected with morphine. Independent of the deprivation condition, adults acquired stronger aversions than adolescents and did so at a faster rate. On a subsequent two‐bottle aversion test, all morphine‐injected subjects drank a significantly lower percentage of saccharin than vehicle‐injected controls with adults exhibiting stronger aversions than adolescents. These age‐dependent differences in morphine‐induced CTAs extend the findings with other drugs of abuse for which adolescents exhibit weaker aversions. The possible basis for and implications of these differences were discussed. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 415–428, 2013     

Activating memories of depression alters the experience of voluntary action

The sense of agency is a profoundly important human experience and is strongly linked to volitional action. The importance of this experience is underscored by the fact that many neurological and psychiatric disorders are partially characterized by an abnormal sense of agency (e.g., schizophrenia, anxiety disorders, depression). Healthy participants perceive the temporal interval between a voluntary action and its effect to be shorter than it actually is, and this illusion has been suggested as an implicit index of agency. Here, we investigated whether activating memories of depression alters perception of this action–effect interval, compared to activating memories of the previous day, or a baseline condition in which specific memories were not activated. Results showed that action–effect interval estimates were significantly longer after remembering a depressing episode than after remembering the previous day, or in the baseline condition. Thus, activating memories of depression alters the experience of voluntary actions and effects. We suggest that interval estimation measures could be useful in clinical settings, to implicitly assess the sense of agency in patients with disorders affecting their sense of control. In this way, obtaining action–effect interval estimates, pre-, during, and post-treatment, could aid in tracking treatment-induced changes in the sense of agency.     

To tell or not to tell – what to do about p.C282Y heterozygotes identified by HFE screening

Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild‐type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening.     

Trophoblast Immune Receptors in Maternal-Fetal Tolerance

During pregnancy, interactions between maternal immune cells and fetal trophoblast cells of the placenta would seemingly lead to disaster, as the trophoblast cells are semi-allogeneic and should trigger rejection by the maternal immune response. A fundamental immunologic question of pregnancy as posed by Sir Peter Medawar centers on how immunologic disaster is averted. It is becoming clear that many different mechanisms act during gestation to render the maternal immune system tolerant of the fetus. These include, among others, restricted major histocompatibility complex (MHC) protein expression, the presence of immunosuppressive B7 family members, immunomodulatory adhesion molecules, the expression of apoptosis-inducing proteins, and complement regulatory proteins. Understanding of maternal-fetal tolerance has clinically important implications for the fields of reproduction, autoimmunity and transplantation. Herein are discussed mechanisms by which trophoblast cells are protected from maternal immune cell attack. Specifically the role of trophoblast cell surface proteins at the maternal-fetal interface is considered.     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.