Context:In focusing on potentially localizable cognitive impairments, the schizophrenia meta-analytic literature has overlooked the largest single impairment: on digit symbol coding tasks.Objective: To compare the magnitude of the schizophrenia impairment on coding tasks with impairments on other traditional neuropsychological instruments.Data Sources: MEDLINE and PsycINFO electronic databases and reference lists from identified articles.Study Selection: English-language studies from 1990 to present, comparing performance of patients with schizophrenia and healthy controls on coding tasks and cognitive measures representing at least 2 other cognitive domains. Of 182 studies identified, 40 met all criteria for inclusion in the meta-analysis.Data Extraction: Means, standard deviations, and sample sizes were extracted for digit symbol coding and 36 other cognitive variables. In addition, we recorded potential clinical moderator variables, including chronicity/ severity, medication status, age, and education, and potential study design moderators, including coding task variant, matching, and study publication date.Data Synthesis: Main analyses synthesized data from 37 studies comprising 1961 patients with schizophrenia and 1444 comparison subjects. Combination of mean effect sizes across studies by means of a random effects model yielded a weighted mean effect for digit symbol coding of g = −1.57 (95% confidence interval, −1.66 to −1.48). This effect compared with a grand mean effect of g=−0.98 and was significantly larger than effects for widely used measures of episodic memory, executive functioning, and working memory. Moderator variable analyses indicated that clinical and study design differences between studies had little effect on the coding task effect.Comparison with previous meta-analyses suggested that current results were representative of the broader literature. Subsidiary analysis of data from relatives of patients with schizophrenia also suggested prominent coding task impairments in this group. Conclusion:The 5-minute digit symbol coding task, reliable and easy to administer, taps an information processing inefficiency that is a central feature of the cognitive deficit in schizophrenia and deserves systematic investigation. Psychiatry. 2007;64:532-542 W ITH EVIDENCE FROM hundreds of studies, cognitive impairment is now widely recognized as a critical and reliable feature of schizophrenia. Meta-analytic methods have been useful in distilling this enormous literature. In the first major synthesis, Heinrichs and Zakzanis 1 found evidence of significant impairment across the full range of traditional neuropsychological tests, with some evidence of disproportionate impairment in the area of verbal memory. Other meta-analyses have focused more specifically on episodic memory, 2,3 executive functioning, 4 the Wisconsin Card Sorting Test,5,6 working memory, 7 and verbal fluency. 8 , 9 These meta-analyseshighlighting domains and measures associated with prefrontal and temporal brain regions-reflect the do...

Sensory physiology has been shown to influence female mate choice, yet little is known about the mechanisms within the brain that regulate this critical behaviour. Here we examine preference behaviour of 58 female swordtails, Xiphophorus nigrensis, in four different social environments (attractive and unattractive males, females only, non-attractive males only and asocial conditions) followed by neural gene expression profiling. We used a brain-specific cDNA microarray to identify patterns of genomic response and candidate genes, followed by quantitative PCR (qPCR) examination of gene expression with variation in behaviour. Our microarray results revealed patterns of genomic response differing more between classes of social stimuli than between presence versus absence of stimuli. We identified suites of genes showing diametrically opposed patterns of expression: genes that are turned 'on' while females interact with attractive males are turned 'off' when interacting with other females, and vice versa. Our qPCR results identified significant predictive relationships between five candidate genes and specific mate choice behaviours (preference and receptivity) across females exposed to males, with no significant patterns identified in female or asocial conditions or with overall locomotor activity. The identification of stimulus-and behaviour-specific responses opens an exciting window into the molecular pathways associated with social behaviour and mechanisms that underlie sexual selection.

Sex determination in vertebrates, the process of forming an ovary or testis from a bipotential gonad, can be initiated by genetic or environmental factors. Elements of the downstream molecular pathways underlying these different sex-determining mechanisms have been evolutionarily conserved. We find the first evidence that Sox9 expression is preferentially organized in the testis early in the temperature-sensitive period in a species with temperature-dependent sex determination (Trachemys scripta). This pattern occurs before sexually dimorphic Mis expression and in a temporal hierarchy that is similar to mammals. Furthermore, we extend previous findings that Dmrt1 expression at early stages of sex determination has a dimorphic pattern consistent with a possible upstream role in determining the fate of the bipotential gonad.

The developmental processes underlying gonadal differentiation are conserved across vertebrates, but the triggers initiating these trajectories are extremely variable. The red-eared slider turtle (Trachemys scripta elegans) exhibits temperature-dependent sex determination (TSD), a system where incubation temperature during a temperature-sensitive period of development determines offspring sex. However, gonadal sex is sensitive to both temperature and hormones during this period – particularly estrogen. We present a model for temperature-based differences in aromatase expression as a critical step in ovarian determination. Localized estrogen production facilitates ovarian development while inhibiting male-specific gene expression. At male-producing temperatures aromatase is not upregulated, thereby allowing testis development.

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Genes that mediate mate preferences potentially play a key role in promoting and maintaining biological diversity. In this study, we compare mate preference behavior in two related poeciliid fishes with contrasting behavioral phenotypes and relate these behavioral differences to gene profiles in the brain. Results reveal that one poeciliid fish, the Northern swordtail, exhibits robust mate preference as compared to the Western mosquitofish, which utilizes a coercive mating system. Female swordtails display no significant difference in association time between male-and female-exposure trials, whereas female mosquitofish spend significantly less time associating with males relative to females. Furthermore, the preference strength for large males is significantly lower in female mosquitofish relative to swordtails. We then examine expression of three candidate genes previously shown to be associated with mate preference behavior in female swordtails and linked to neural plasticity in other vertebrates: neuroserpin (NS), neuroligin-3 (NLG-3) and N-methyl-D-aspartate receptor (NMDA-R). Whole brain gene expression patterns reveal that two genes (NS and NLG-3) are positively associated with mate preference behavior in female swordtails, a pattern opposing that of the mosquitofish. In mosquitofish females, these genes are downregulated when females express biases toward males yet are elevated in association with total motor activity patterns under asocial conditions, suggesting that the presence of males in mosquitofish species may inhibit expression of these genes. Both gene expression and female behavioral responses to males exhibit opposing patterns between these species, suggesting that this genetic pathway may potentially act as a substrate for the evolution of mate preference behavior.

Sensory and social inputs interact with underlying gene suites to coordinate social behavior. Here we use a naturally complex system in sexual selection studies, the swordtail, to explore how genes associated with mate preference, receptivity, and social affiliation interact in the female brain under specific social conditions. We focused on 11 genes associated with mate preference in this species (neuroserpin, neuroligin-3, NMDA receptor, tPA, stathmin-2, β-1 adrenergic receptor) or with female sociosexual behaviors in other taxa (vasotocin, isotocin, brain aromatase, α-1 adrenergic receptor, tyrosine hydroxylase). We exposed females to four social conditions, including pairings of differing mate choice complexity (large males, large/small males, small males), and a social control (two females). Female mate preference differed significantly by context. Multiple discriminant analysis (MDA) of behaviors revealed a primary axis (explaining 50.2% between-group variance) highlighting differences between groups eliciting high preference behaviors (LL, LS) vs. other contexts, and a secondary axis capturing general measures distinguishing a non-favored group (SS) from other groups. Gene expression MDA revealed a major axis (68.4% between-group variance) that distinguished amongst differential male pairings and was driven by suites of “preference and receptivity genes”; whereas a second axis, distinguishing high affiliation groups (large males, females) from low (small males), was characterized by traditional affiliative-associated genes (isotocin, vasotocin). We found context-specific correlations between behavior and gene MDA, suggesting gene suites covary with behaviors in a socially relevant context. Distinct associations between “affiliative” and “preference” axes suggest mate preference may be mediated by distinct clusters from those of social affiliation. Our results highlight the need to incorporate natural complexity of mating systems into behavioral genomics.

Female mate choice behavior is a critical component of sexual selection, yet identifying the neural basis of this behavior is largely unresolved. Previous studies have implicated sensory processing and hypothalamic brain regions during female mate choice and there is a conserved network of brain regions (Social Behavior Network, SBN) that underlies sexual behaviors. However, we are only beginning to understand the role this network has in pre-copulatory female mate choice. Using in situ hybridization, we identify brain regions associated with mate preference in female Xiphophorus nigrensis, a swordtail species with a female choice mating system. We measure gene expression in 10 brain regions (linked to sexual behavior, reward, sensory integration or other processes) and find significant correlations between female preference behavior and gene expression in two telencephalic areas associated with reward, learning and multi-sensory processing (medial and lateral zones of the dorsal telencephalon) as well as an SBN region traditionally associated with sexual response (preoptic area). Network analysis shows that these brain regions may also be important in mate preference and that correlated patterns of neuroserpin expression between regions co-vary with differential compositions of the mate choice environment. Our results expand the emerging network for female preference from one that focused on sensory processing and midbrain sexual response centers to a more complex coordination involving forebrain areas that integrate primary sensory processing and reward.