Autism clinical trials: biological and medical issues in patient selection and treatment response

Biomedical measures are critical in the initial patient-screening and -selection phases of a clinical trial in autism and related disorders. These measures can also play an important role in the assessment and characterization of response and can provide an opportunity to study underlying etiologic and pathophysiologic processes. Thus, biomedical measures, including clinical laboratory analyses, metabolic screening, and chromosomal analysis, are used to screen for potential safety-related problems, to decrease biological and genetic heterogeneity, and to define subgroups. Neurobiological measures can be examined as possible predictors, modifiers or surrogates of therapeutic response, and adverse effects. Neurobiological research measures can also be used to study mechanisms and extent of drug action and to perform baseline and longitudinal investigations of possible pathophysiologic alterations. The potential utility and desirability of specific measures are considered and the general approach to choosing measures for incorporation is discussed.     

Body piercing,tattooing, self-esteem,and body investment in adolescent girls

Postmodern perspectives of body piercing and tattooing interpret these as signifiers of the self and attempts to attain mastery and control over the body in an age of increasing alienation. In this exploratory study, 79 adolescent females, ages 15 to 18 (M = 16.08, SD = 1.36), completed the Coopersmith Self-Esteem Inventory (SEI; Coopersmith, 1981), the Beck Depression Inventory (BDI; Beck, 1978), the Body Investment Scale (BIS; Orbach & Mikulincer, 1998), and the State-Trait Anger Expression Inventory (STAXI-2; Spielberger, 1996). Analyses revealed that body piercings and tattoos were significantly correlated with trait anger (Angry Reaction subscale scores). A multiple regression analysis indicated that three of the dependent variables (Trait Anger-Reaction, BDI, and Feeling subscale of the BIS) were predictors of the total number of body piercings and tattoos.     

Additive impact of childhood emotional,physical, and sexual abuse on suicide attempts among low-income African American women

This study examines the association between exposures to multiple forms of childhood abuse (emotional, physical, sexual) and adult suicidal behavior in a sample of low-income, African American women. We hypothesized a linear relation between childhood abuse and risk for making a suicide attempt, such that the more forms of childhood abuse to which a woman was exposed, the greater her risk would be to make a suicide attempt. Logistic regression analyses revealed that, compared to women who did not report any experiences of childhood abuse, women who experienced one, two, or three forms of abuse were 1.83, 2.29, or 7.75 times more likely to attempt suicide, respectively (all statistically significant). Furthermore, compared to women who reported one or two types of abuse, women who reported all three types of abuse were statistically more likely to attempt suicide. These findings have implications for clinicians working with African American women who report either childhood abuse or exhibit suicidal behavior.     

Alterations in the thickness of motor cortical subregions after motor-skill learning and exercise

Behavioral manipulations such as housing in an enriched environment have been shown to increase brain weight and visual cortical thickness. The present study was designed to test whether skill learning or repetitive movements can alter the thickness of the motor cortex. One group of 6-mo-old Long-Evans female rats learned motor skills on an obstacle course that increased in difficulty over training and required balance and coordination. A second group ran voluntarily in exercise wheels attached to their home cage but had little opportunity for skill learning. The third group was handled daily but received no opportunity for learning or exercise. Each condition lasted 26–29 d. The skill-learning and exercise conditions had greater heart weight, and the exercise condition had greater adrenal gland weights than controls. The thickness of the motor cortex was measured in four coronal planes between −2.33 mm to −0.3 mm from bregma. Regions of interest that corresponded to published maps of forelimb and hind-limb representations were analyzed together. Rats in the skill-learning condition had significantly thicker medial cortical areas in the two anterior planes (−0.8 and −0.3 mm from bregma). These regions correspond to previously mapped hind-limb representations. The exercise group had greater thickness of the medial region at −0.8 mm from bregma. Cortical thickness in all conditions varied significantly along the medial to lateral axis. For both treatments, the effects were restricted to medial and anterior regions of interest rather than posterior or lateral regions of interest. The results indicate that robust exercise, in addition to skill learning, is capable of altering the thickness of the motor cortex, but that the effects are restricted rather than distributed within the regions studied.     

Ethnic differences in clinical presentation of depression in adult women

This study examined ethnic differences in self-report and interviewer-rated depressive symptoms and estimated the contributions of sociodemographic and psychosocial factors in predicting severity of depression. One hundred twenty-five clinically depressed African American (n = 46), Caucasian (n = 36), and Latina (n = 43) women were recruited. After controlling for differences in socioeconomic status, African American women reported more symptoms of distress and Latinas were rated as significantly more depressed than the other groups. However, these ethnic differences were not moderated by either education or employment. Finally, hierarchical regression analysis indicated that severity of depression was predicted by low education, being single, being Latina, high perceived stress, and feelings of hopelessness. Additional research is needed to validate these results and to investigate their clinical significance.     

Analysis of multivariate frequency data by graphical models and generalizations of the multidimensional row-column association model

Models used to analyze cross-classifications of counts from psychological experiments must represent associations between multiple discrete variables and take into account attributes of stimuli, experimental conditions, or characteristics of subjects. The models must also lend themselves to psychological interpretations about underlying structures mediating the relationship between stimuli and responses. To meet these needs, the author extends the graphical latent variable models for nominal and/or ordinal data proposed by C. J. Anderson and J. K. Vermunt (2000) to situations in which dependencies between observed variables are not fully accounted for by the latent variables. The graphical models provide a unified framework for studying multivariate associations that include log-linear models and log-multiplicative association models as special cases.     

Low body temperature,time dilation,and long-trace conditioned flavor aversion in rats

Conditioned flavor aversion was examined in Wistar-derived albino rats that were immersed in cold water for 0, 2.5, 5, or 10 min immediately following 10-min exposure to a.1% saccharin solution and given an intraperitoneal (i.p.) injection of 0.15 M lithium chloride (LiCl) either 90, 135, 180, or 225 min later. Cold water immersion for 2.5, 5, and 10 min led to body temperature decreases of approximately 4.5, 7, and 10 degrees C, respectively. Rats whose body temperatures were not reduced (0 min immersion) showed no saccharin aversion when the LiCl was delayed 90 min. Rats whose body temperatures were reduced 4.5, 7, and 10 degrees C displayed conditioned aversions at LiCl delays up to 135, 180, and 225 min, respectively. These results were interpreted in terms of a cold-induced slowing of a biochemical clock that may uniquely govern specific timing processes involved in associative learning over long delays, such as long-trace conditioned flavor aversion, learned safety, and certain types of learning that involve an extensive time lapse (e.g., extinction of fear).     

LANGUAGE ABILITIES OF CHILDREN WHO STUTTER: A PRELIMINARY STUDY

The purpose of this study was to examine differences between children who do (CWS) and children who do not stutter (CWNS) on standardized tests of receptive/expressive language and receptive vocabulary. Subjects were 16 boys and 4 girls who stutter (mean age = 46.80 months) and 16 boys and 4 girls who do not stutter (mean age = 47.55 months). Each child was audio recorded during a loosely structured, 30-minute conversation with an adult. This conversational interaction was subsequently assessed to provide information pertinent to the child's frequency and type of speech disfluency. After completion of the adult-child conversational interaction, each child was administered and responded to standardized tests of syntactic, semantic, and phonological abilities and development. Results indicated that the difference between measures of receptive/expressive language and receptive vocabulary is significantly greater for CWS than CWNS; however, this difference between receptive/expressive language and receptive vocabulary scores was not significantly correlated with the overall stuttering frequency of CWS. Findings were taken to suggest that the semantic development of CWS may lag behind their syntactic development, a possible imbalance among components of the speech-language systems of CWS that may contribute to the difficulties they have establishing normal speech fluency. Research supported by an NIH grant (DC00523) to Vanderbilt University.