Why Should I? Examining How Childhood Callous-Unemotional Traits Relate to Prosocial and Affiliative Behaviors and Motivations.

Childhood callous-unemotional (CU) traits are characterized by low empathy, limited prosocial behavior, and restricted social affiliation. However, few studies have investigated whether CU traits are associated with different subtypes of prosocial and affiliative behavior or the specific motivational difficulties underlying these behaviors. We addressed these questions using data from 135 young children (M = 5.48 years old; 58% female) who viewed depictions of adults or children in instrumental need, emotional need, or neutral situations. We assessed recognition, suggested initiation of, and motivation for prosocial or affiliative behavior in response to each depiction. We distinguished between subtypes of prosocial (instrumental and emotional) and affiliative (parallel, cooperative, associative) behavior, as well as self- versus other-orientated motivations. Parents reported on child CU traits and conduct problems. Overall, children accurately recognized prosocial and neutral situations, offered help, and expressed other-orientated motivations for prosocial behavior and social motivations for affiliative behavior. Higher CU traits were related to lower overall recognition accuracy, which was more pronounced for emotional need. Higher CU traits were also related to fewer offers of help and more denial of prosocial behavior, particularly for instrumental need. Finally, CU traits were related to lower probability of initiating affiliative behavior. CU traits were not differentially related to self- versus other-orientated motivations for prosocial or affiliative behavior. Findings demonstrate difficulties of children with CU traits in recognizing need and offering help. Interventions for CU traits could include modules that explicitly scaffold and shape prosociality and social affiliation.

"But not the music": psychopathic traits and difficulties recognising and resonating with the emotion in music.

Recognising and responding appropriately to emotions is critical to adaptive psychological functioning. Psychopathic traits (e.g. callous, manipulative, impulsive, antisocial) are related to differences in recognition and response when emotion is conveyed through facial expressions and language. Use of emotional music stimuli represents a promising approach to improve our understanding of the specific emotion processing difficulties underlying psychopathic traits because it decouples recognition of emotion from cues directly conveyed by other people (e.g. facial signals). In Experiment 1, participants listened to clips of emotional music and identified the emotional content (Sample 1, N = 196) or reported on their feelings elicited by the music (Sample 2, N = 197). Participants accurately recognised (t(195) = 32.78, p < .001, d = 4.69) and reported feelings consistent with (t(196) = 7.84, p < .001, d = 1.12) the emotion conveyed in the music. However, psychopathic traits were associated with reduced emotion recognition accuracy (F(1, 191) = 19.39, p < .001) and reduced likelihood of feeling the emotion (F(1, 193) = 35.45, p < .001), particularly for fearful music. In Experiment 2, we replicated findings for broad difficulties with emotion recognition (Sample 3, N = 179) and emotional resonance (Sample 4, N = 199) associated with psychopathic traits. Results offer new insight into emotion recognition and response difficulties that are associated with psychopathic traits.

Synthesis of (3alpha,7beta,17alpha)-7-methyl-19-norpregn-5(10)-en-20-yne-3,7,17-triol, a metabolite of ORG OD14, and its 7-epimer.

The syntheses of the 7beta-hydroxy metabolite of ORG OD14 (Livial((R))), (3alpha,7beta,17alpha)-7-methyl-19-norpregn-5(10)-en-20-yne-3,7,17-triol (35), and its 7-epimer, (3alpha,7alpha,17alpha)-7-methyl-19-norpregn-5(10)-en-20-yne-3,7,17-triol (11), are described.

Synthesis of (3alpha,7beta, 17alpha)-7-methyl-19-norpregn-5(10)-en-20-yne-3,7,17-triol, a metabolite of ORG OD14, and its 7-epimer.

The syntheses of the 7beta-hydroxy metabolite of ORG OD14 (Livial), (3alpha,7beta, 17alpha)-7-methyl-19-norpregn-5(10)-en-20-yne-3,7,17-t riol (35), and its 7-epimer, (3alpha,7alpha, 17alpha)-7-methyl-19-norpregn-5(10)-en-20-yne-3,7,17-t riol (11), are described.

Synthesis and in vitro muscarinic activities of a series of 3-(pyrazol-3-yl)-1-azabicyclo[2.2.2]octanes.

A series of 3-(pyrazol-3-yl)-1-azabicyclo[2.2.2]octane derivatives C (Fig. 1) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (OXO-M) and [3H]-pirenzepine (PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies measuring their potencies to inhibit the binding of OXO-M and PZ. Preferential inhibition of OXO-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs.

Synthesis, and in vitro and in vivo muscarinic pharmacological properties of a series of 1,6-dihydro-5-(4H)-pyrimidinone oximes.

A series of 1,6-dihydro-5-(4H)-pyrimidinone oxime derivatives I was synthesized (Scheme 1, Tables 1 and 2) and tested for muscarinic activity (Table 3) in receptor binding assays using [3H]-oxotremorine-M (Oxo-M) and [3H]-pirenzepine (Pz) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies that measured their potencies to inhibit the binding of Oxo-M and Pz. Preferential inhibition of Oxo-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. The series produced a wide range of active compounds with differing degrees of selectivity in M1, M2, and M3 functional models. Several compounds that have mixed agonist/antagonist profiles were able to reduce cholinergic-related cognitive impairments in models of mnemonic function. Substitutions (I, e.g. R2 or R3 = Me) at the 1,6-dihydro-5-(4H)pyrimidine ring disrupted binding and efficacy, whereas systematic variation of the oximes substituent R1 resulted in various degrees of potency and selectivity dependent on the nature of the substitution.

Synthesis and muscarinic activities of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives.

A series of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives (B) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (3H-OXO-M) and [3H]-pirenzepine (3H-PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies measuring their potencies to inhibit the binding of 3H-OXO-M and 3H-PZ. Preferential inhibition of 3H-OXO-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. All compounds with agonistic properties showed 3H-PZ/3H-OXO-M potency ratios in excess of 20. In contrast, for antagonists this ratio was found to be close to unity. Mono-halogenation resulted in compounds (4b and 4d) with M3 agonistic properties as shown by their atropine sensitive stimulant properties in the guinea pig ileum, but with very little or no M1 activity. Some minor in vivo effects were observed for both these compounds, with the iodinated compound 4d inducing salivation. Compound 4d also showed some positive mnemonic properties in rats where spatial short-term memory had been compromised by temporary cholinergic depletion. These data indicate that some M3 agonism may be desired in therapeutic agents aimed at the treatment of the cognitive deficits of Alzheimer's disease patients.

Synthesis and muscarinic M3 pharmacological activities of 1-azabicyclo[2.2.2]octan-3-one oxime derivatives.

A series of 1-azabicyclo[2.2.2]octan-3-one oximes and related 1-azabicyclo-[2.2.2]-octan-3-one hydroxylamines were synthesized and tested for muscarinic M3 activity. All compounds showed at least some muscarinic binding properties, however, only one member of the series demonstrated mucarinic M3 agonistic properties in vitro (contraction of guinea pig ileum) and in vivo (mydriasis, salivation). In addition, this compound partially reversed the cognitive deficit induced by central cholinergic depletion in two procedures testing memory in the rat, namely the delayed matching to position and swim maze tasks of spatial memory in the rat.

Mechanism of formation of mercapturic acids from aromatic aldehydes in vivo.

Male adult Wistar rats dosed i.p. with o-substituted benzaldehydes (o-F, o-Cl, and o-Br = V, VI, and VII) excreted mercapturic acids in urine. These acids were identified as N-acetyl-S-(ortho-substituted benzyl)cysteines (I, II, III). The total mercapturic acid excretion as % dose (2.0 mmol/kg, n = 4) was 1.2 +/- 0.4, 6.8 +/- 0.9, and 10.4 +/- 2.0 for V, VI, and VII. p-Cl-benzaldehyde administered in the same dose showed a non-significant urinary thioether excretion. The aim of the investigation was to prove in vivo a postulated metabolic pathway of substituted benzaldehydes via sulphate esters to mercapturic acids. After a single administration of the sodium salts of o- and p-Cl-benzylsulfuric acid a significant increase in mercapturic acid excretion of 21.2 +/- 1.8% and 14.5 +/- 1.2% of dose (2.0 mmol/kg, n = 4) was found. By pretreatment with pyrazole the mercapturic acid excretion increased after administration of o-Cl-benzyl alcohol (IX) whereas a significant decrease was found after administration of o-Cl-benzaldehyde (VI). After simultaneous administration of ethanol with IX and VI an increase in mercapturic acid excretion was observed. After previous administration of pentachlorophenol a significant decrease in urinary mercapturic acid excretion for IX and VI was found. These findings are in accordance with a metabolic pathway of substituted benzaldehydes via benzyl alcohols, subsequently sulphate esters to the corresponding benzylmercapturic acids.

Mercapturic acids as metabolites of aromatic aldehydes and alcohols.

After administration of substituted (CH3, OH, OCH3, F, CL, Br, NO2) benzaldehyde or benzyl alcohols in the rat an enhanced urinary thioether excretion was found in some cases. With p-substituted benzaldehyde only occasionally a slight increase could be shown, but with o-substituted aldehydes and alcohols thioether excretions amounted up to 13% of the dose. Mercapturic acids were isolated and identified by synthesis, mass-, and n.m.r.-spectrometry as the arylmethyl thioethers of N-acetylcysteine. Steric hindrance by o-substituents must be the main cause of a relative decrease in oxidation to the carboxylic acid and an increase of the importance of both the reduction of the aldehydes and the reaction of the alcohols, presumably to sulphuric acid esters, as intermediates for the alkylation of glutathione. Consequently, previous administration of pyrazole, an inhibitor of alcohol dehydrogenase, caused an even larger thioether excretion after injection of o-chlorobenzyl alcohol.