Age, puberty and attractiveness judgments in adolescents

Previous work has suggested that judgments of the attractiveness of some facial and vocal features change during adolescence. Here, over 70 Czech adolescents aged 12–14 made forced-choice attractivenessjudgments on adolescent faces manipulated in symmetry, averageness and femininity, and on adolescent opposite-sex voices manipulated in fundamental frequency (perceived as pitch), and completed questionnaires on pubertal development. Consistent with typical adult judgments, adolescents selected the symmetric, average and feminine male and female faces as more attractive significantly more often than the asymmetric, non-average and masculine faces respectively. Moreover, preferences for symmetric faces were positively associated with adolescents’ age and stage of pubertal development. Unexpectedly, voice pitch did not significantly influence adolescents’ attractivenessjudgments. Collectively, these findings present new evidence using refined methodology that adolescent development is related to variation in attractivenessjudgments

Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity

K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from Δ(9)-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation of novel, biologically active metabolites may be responsible for the distinct effects associated with K2 use. The present study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R).JWH-018, five potential monohydroxylated metabolites (M1-M5), and one carboxy metabolite (M6) were examined in mouse brain homogenates containing CB1Rs, first for CB1R affinity using a competition binding assay employing the cannabinoid receptor radioligand [(3)H]CP-55,940, and then for CB1R intrinsic efficacy using an [(35)S]GTPγS binding assay. JWH-018 and M1-M5 bound CB1Rs with high affinity, exhibiting K(i) values that were lower than or equivalent to Δ(9)-THC. These molecules also stimulated G-proteins with equal or greater efficacy relative to Δ(9)-THC, a CB1R partial agonist. Most importantly, JWH-018, M2, M3, and M5 produced full CB1R agonist levels of activation. CB1R-mediated activation was demonstrated by blockade with O-2050, a CB1R-selective neutral antagonist. Similar to Δ(9)-THC, JWH-018 and M1 produced a marked depression of locomotor activity and core body temperature in mice that were both blocked by the CB1R-preferring antagonist/inverse agonist AM251.Unlike metabolites of most drugs, the studied JWH-018 monohydroxylated compounds, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs. These observations, combined with higher CB1R affinity and activity relative to Δ(9)-THC, may contribute to the greater prevalence of adverse effects observed with JWH-018-containing products relative to cannabis

Convergent neural substrates of inattention in bipolar disorder patients and dopamine transporter‐deficient mice using the 5‐choice CPT

ObjectivesBipolar disorder (BD) is a debilitating psychiatric illness affecting 2%-5% of the population. Although mania is the cardinal feature of BD, inattention and related cognitive dysfunction are observed across all stages. Since cognitive dysfunction confers poor functional outcome in patients, understanding the relevant neural mechanisms remains key to developing novel-targeted therapeutics.MethodsThe 5-choice continuous performance test (5C-CPT) is a mouse and fMRI-compatible human attentional task, requiring responding to target stimuli while inhibiting responding to nontarget stimuli, as in clinical CPTs. This task was used to delineate systems-level neural deficits in BD contributing to inattentive performance in human subjects with BD as well as mouse models with either parietal cortex (PC) lesions or reduced dopamine transporter (DAT) expression.ResultsMania BD participants exhibited severe 5C-CPT impairment. Euthymic BD patients exhibited modestly impaired 5C-CPT. High impulsivity BD subjects exhibited reduced PC activation during target and nontarget responding compared with healthy participants. In mice, bilateral PC lesions impaired both target and nontarget responding. In the DAT knockdown mouse model of BD mania, knockdown mice exhibited severely impaired 5C-CPT performance versus wildtype littermates.ConclusionsThese data support the role of the PC in inattention in BD-specifically regarding identifying the appropriate response to target vs nontarget stimuli. Moreover, the findings indicate that severely reduced DAT function/hyperdopaminergia recreates the attentional deficits observed in BD mania patients. Determining the contribution of DAT in the PC to attention may provide a future target for treatment development

The Irish Affected Sib Pair Study of Alcohol Dependence: study methodology and validation of diagnosis by interview and family history.

Background: This article is the first report of the Irish Affected Sib Pair Study of Alcohol Dependence, whose goal is to detect the genomic location of susceptibility loci for alcohol dependence (AD). This article describes phenotypic characteristics of the probands, siblings, and parents included in the sample and examines agreement among different sources of diagnostic information, including the validity of family history (FH) assessment. Methods: Structured diagnostic interviews were conducted with 1414 individuals from 591 families ascertained in Ireland. AD was assessed among 1201 probands and affected siblings with use of the Semi-Structured Assessment for the Genetics of Alcoholism and among 213 parents with use of a modified version of the Structured Clinical Interview for DSM. Probands and siblings were also assessed for drinking history, comorbid disorders, and other clinical characteristics. FH reports based on FH-Research Diagnostic Criteria were obtained for 1113 of these individuals as well as for 3652 first-degree relatives who were not interviewed. Results: Sample characteristics confirm the severity of AD among the affected individuals. Agreement between FH ratings and diagnoses based on direct interviews was high for both parent-offspring and sibling-sibling comparisons (e.g., positive and negative predictive values > 80% for a range of cutoffs). Agreement among individuals about their family members was also high for a single item (1 month or more of drinking problems, tetrachoric r = 0.86-0.98), the total number of DSM-IV AD symptoms (polychoric r = 0.86-0.96), and classifications based on a range of cutoffs ([kappa] = 0.75-0.80). Use of multiple informants improved classification accuracy only slightly (6-10%). Conclusions: The authors successfully collected data for a large sample of affected sibling pairs for molecular genetic analysis of AD. Individuals with AD were able to provide accurate evaluations of alcoholism symptoms in their parents and adult siblings. A single screening item performed nearly as well as the full scale. Collecting information from multiple informants may not be cost effective for the gain in predictive accuracy. FH information collected from affected informants can be a valuable source of diagnostic information for family studies of alcoholism

Genomewide linkage study in the Irish affected sib pair study of alcohol dependence: evidence for a susceptibility region for symptoms of alcohol dependence on chromosome 4.

Alcoholism is a relatively common, chronic, disabling and often treatment-resistant disorder. Evidence from twin and adoption studies indicates a substantial genetic influence, with heritability estimates of 50-60%. We conducted a genome scan in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD). Most probands were ascertained through alcoholism treatment settings and were severely affected. Probands, affected siblings and parents were evaluated by structured interview. A 4 cM genome scan was conducted using 474 families of which most (96%) were comprised by affected sib pairs. Nonparametric and quantitative linkage analyses were conducted using DSM-IV alcohol dependence (AD) and number of DSM-IV AD symptoms (ADSX). Quantitative results indicate strong linkage for number of AD criteria to a broad region of chromosome 4, ranging from 4q22 to 4q32 (peak multipoint LOD=4.59, P=2.1 10-6, at D4S1611). Follow-up analyses suggest that the linkage may be due to variation in the symptoms of tolerance and out of control drinking. There was evidence of weak linkage (LODs of 1.0-2.0) to several other regions, including 1q44, 13q31, and 22q11 for AD along with 2q37, 9q21, 9q34 and 18p11 for ADSX. The location of the chromosome 4 peak is consistent with results from prior linkage studies and includes the alcohol dehydrogenase gene cluster. The results of this study suggest the importance of genetic variation in chromosome 4 in the etiology and severity of alcoholism in Caucasian populations

Sex differences in attraction to familiar and unfamiliar opposite-sex faces: men prefer novelty and women prefer familiarity

Familiarity is attractive in many types of stimuli and exposure generally increases feelings of liking. However, men desire a greater number of sexual partners than women, suggesting a preference for novelty. We examined sex differences in preferences for familiarity. In Study 1 (N = 83 women, 63 men), we exposed individuals to faces twice and found that faces were judged as more attractive on the second rating, reflecting attraction to familiar faces, with the exception that men’s ratings of female faces decreased on the second rating, demonstrating attraction to novelty. In Studies 2 (N = 42 women, 28 men) and 3 (N = 51 women, 25 men), exposure particularly decreased men’s ratings of women’s attractiveness for short-term relationships and their sexiness. In Study 4 (N = 64 women, 50 men), women’s attraction to faces was positively related to self-rated similarity to their current partner’s face, while the effect was significantly weaker for men. Potentially, men’s attraction to novelty may reflect an adaptation promoting the acquisition of a high number of sexual partners

The role of symmetry in attraction to average faces

Although many studies have demonstrated that average faces tend to be attractive, few studies have examined the extent to which symmetry contributes to the attractiveness of average faces. Such studies are potentially important, however, because average faces are highly symmetric and increasing the symmetry of face images increases their attractiveness. Here we demonstrate that increasing averageness of 2D face shape independently of symmetry is sufficient to increase attractiveness, indicating that preferences for symmetry cannot solely explain the attractiveness of average faces. Additionally, we show that averageness preferences are significantly weaker when the effects of symmetry are controlled for using computer graphic methods than when the effects of symmetry are not controlled for, suggesting that symmetry contributes to the attractiveness of average faces. Importantly, this latter finding was not explained by the greater perceived similarity between versions of faces that varied in averageness, but not symmetry, than between versions of faces that varied in both averageness and symmetry