Editorial: Genetics of Brain Function and Cognition

There is overwhelming evidence for the existence of substantial genetic influences on individual differences in general and specific cognitive abilities, especially in adults. The actual localization and identification of genes underlying variation in cognitive abilities and intelligence has only just started, however. Successes are currently limited to neurological mutations with rather severe cognitive effects. The current approaches to trace genes responsible for variation in the normal ranges of cognitive ability consist of large scale linkage and association studies. These are hampered by the usual problems of low statistical power to detect quantitative trait loci (QTLs) of small effect. One strategy to boost the power of genomic searches is to employ endophenotypes of cognition derived from the booming field of cognitive neuroscienceThis special issue of Behavior Genetics reports on one of the first genome-wide association studies for general IQ. A second paper summarizes candidate genes for cognition, based on animal studies. A series of papers then introduces two additional levels of analysis in the black box between genes and cognitive ability: (1) behavioral measures of information-processing speed (inspection time, reaction time, rapid naming) and working memory capacity (performance on on single or dual tasks of verbal and spatio-visual working memory), and (2) electrophyiosological derived measures of brain function (e.g., event-related potentials). The obvious way to assess the reliability and validity of these endophenotypes and their usefulness in the search for cognitive ability genes is through the examination of their genetic architecture in twin family studies. Papers in this special issue show that much of the association between intelligence and speed-of-information processing/brain function is due to a common gene or set of genes, and thereby demonstrate the usefulness of considering these measures in gene-hunting studies for IQ.     

Is attention to detail a similarly strong candidate endophenotype for anorexia nervosa and bulimia nervosa?

Abstract

Objectives. To investigate whether attention to detail is a similarly strong candidate endophenotype of anorexia (AN) and bulimia nervosa (BN), and to explore the incidence and clinical correlates of attention to detail. Methods. A total of 266 women (including AN, BN, recovered AN, unaffected sisters of AN/BN & control women) undertook a thorough clinical assessment and were administered two neuropsychological measures of attention to detail (Group Embedded Figure Test; Rey-Osterrieth Complex Figure). Results. Superior attention to detail was found across all AN groups including recovered AN and unaffected AN sisters. Those with BN and their unaffected sisters showed a profile more consistent with poor global integration. The combined effect of superior attention to detail and poor global integration (“weak coherence”) was present in 42.3% of active cases and corresponded with a more severe illness, elevated obsessive-compulsive symptoms, and a higher likelihood of comorbid clinical anxiety and self-harm. Conclusions. Attention to detail is a stronger candidate endophenotype of AN compared to BN, where poor global integration may be more relevant. The unique contribution of both aspects of weak coherence (superior attention to detail/poor global integration) requires further exploration and understanding in both eating disorders. Integrating cognitive remediation of these traits into treatment for the subset of patients it is relevant for may improve outcome.     

Individual differences in male rat ejaculatory behaviour: searching for models to study ejaculation disorders

In addition to investigating sexual function in rats that display normal ejaculatory behaviour, studying rats that are either 'hyposexual' or 'hypersexual' may provide important insights into the aetiology of ejaculatory dysfunctions in men, such as premature and retarded ejaculation. To this end, rats were matched into groups of 'sluggish', 'normal' and 'rapid' ejaculators based on their ejaculation frequencies displayed in a series of weekly sexual behaviour tests. Selecting rats on this parameter revealed large and stable differences in other parameters of sexual behaviour as well, including ejaculation latency and mount frequency but not intromission frequency and mount latency, putative indices of sexual motivation. Neuroanatomically, Fos immunoreactivity as a measure of neuronal activation was increased in rapid ejaculators compared with sluggish ejaculators in ejaculation-related brain areas, presumably associated with the differences in ejaculatory behaviour. Although the total number of oxytocin neurones within subregions of the hypothalamus did not differ between groups, in the supraoptic nucleus of the hypothalamus more oxytocin neurones were activated in rapid ejaculators compared with the other groups. Apart from the differences observed in ejaculatory behaviour, groups did not differ with respect to their locomotor activity and approach-avoidance behaviour as measured in the elevated plus-maze. Finally, apomorphine-induced stereotypy was similar in sluggish and rapid ejaculators, suggesting no large differences in dopamine susceptibility. Altogether, the present results suggest stable differences in male rat ejaculatory behaviour. Further exploring the neurobiological mechanisms underlying these differences may be a promising approach to gain insights into the aetiology of sexual dysfunctions such as premature, retarded or an-ejaculation.     

Cognitive alterations in groups at risk for psychosis: neutral markers of genetic risk or indicators of social disability?

OBJECTIVE: To investigate whether cognitive alterations associated with vulnerability to psychosis, are associated with expression of psychopathology and functional outcome in groups at different levels of risk for psychotic illness. METHOD: Neurocognition, psychopathology and functional outcome were measured in subjects with variable risk for psychosis: i) 29 patients with psychotic disorder, ii) 46 subjects at familial risk, iii) 41 subjects at psychometric risk and iv) 54 control subjects. RESULTS: Dose-response relationships between cognitive dysfunction and increasing risk for psychosis were found. Cognitive alterations were predicted by negative symptoms in patients and by positive psychotic experiences in the familial risk group. In both at risk groups, cognitive speed was associated with functional outcome. CONCLUSION: Some cognitive impairments serve as neutral endophenotypic marker across the psychosis continuum. However, other cognitive alterations associated with transmission of psychosis may have a direct impact on the pathway from risk to psychopathology and alterations in functioning.     

Varieties of attention-deficit/hyperactivity disorder-related intra-individual variability.

Intra-individual variability in behavior and functioning is ubiquitous among children with attention-deficit/hyperactivity disorder (ADHD), but it has not been systematically examined or integrated within causal models. This article seeks to provide a conceptual, methodologic, and analytic framework as a foundation for future research. We first identify five key research questions and methodologic issues. For illustration, we examine the periodic structure of Eriksen Flanker task reaction time (RT) data obtained from 24 boys with ADHD and 18 age-matched comparison boys. Reaction time variability in ADHD differed quantitatively from control subjects, particularly at a modal frequency around .05 Hz (cycle length approximately 20 sec). These oscillations in RT were unaffected by double-blind placebo and were suppressed by double-blind methylphenidate. Together with converging lines of basic and clinical evidence, these secondary data analyses support the speculative hypothesis that the increased power of multisecond oscillations in ADHD RT data, and by inference, in attentional performance, represents a catecholaminergic deficit in the ability to appropriately modulate such oscillations in neuronal activity. These results highlight the importance of retaining time-series data and quantitatively examining intra-subject measures of variability as a putative endophenotype for ADHD.     

Lower TSH and higher T4 levels are associated with current depressive syndrome in young adults

OBJECTIVE: The relationship of individual thyroid function indices to depression in those without a history of prior thyroid dysfunction is uncertain. METHOD: We examined the relationship between thyroid-stimulating hormone (TSH) and thyroxine (T4) levels and current or lifetime history of depressive symptoms using information from 6869 participants, aged 17-39 years, in the Third National Health and Nutrition Examination Survey without history of thyroid-related illness. RESULTS: We found that lower TSH and higher T4 levels were associated with current depressive syndrome in men, but only higher T4 levels correlated with current depressive syndrome in women. Lifetime depressive syndrome was associated with neither TSH level nor T4 levels in men or women. CONCLUSION: These findings suggest that transient or 'state dependent' changes are associated with depression in those without a history of thyroid illness. Further studies to discern whether these depression-associated changes represent distinct endophenotypes of depression should be encouraged.     

Heritability of Selective Attention and Working Memory in Preschoolers

In this study aspects of selective attention and working memory were tested in a large sample of nearly 6-year old monozygotic and dizygotic twin pairs, using a computerized test battery (Amsterdam Neuropsychological tasks). In the selective attention task the presence of a foil signal (target signal at an irrelevant location) resulted in more false alarms than a non-target signal. In the working memory task an increase in memory load lead to an increase in response times and errors. We analyzed variations in absolute performance parameters (overall speed and accuracy) and relative performance parameters (increase in errors and/or reaction time). The results showed clear familial resemblances on performance. It proved difficult to ascribe these effects to shared genes or to shared environment. An exception was memory search rate, which was clearly heritable.     

The reality of “food porn”: Larger brain responses to food‐related cues than to erotic images predict cue‐induced eating

While some individuals can defy the lure of temptation, many others find appetizing food irresistible. The goal of this study was to investigate the neuropsychological mechanisms that increase individuals' vulnerability to cue‐induced eating. Using ERPs, a direct measure of brain activity, we showed that individuals with larger late positive potentials in response to food‐related cues than to erotic images are more susceptible to cue‐induced eating and, in the presence of a palatable food option, eat more than twice as much as individuals with the opposite brain reactivity profile. By highlighting the presence of individual brain reactivity profiles associated with susceptibility to cue‐induced eating, these findings contribute to the understanding of the neurobiological basis of vulnerability to obesity.