Visual and auditory emotion recognition problems as familial cross-disorder phenomenon in ASD and ADHD

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are frequently comorbid disorders. Emotion recognition problems are considered an important familial deficit in ASD, but this is unknown in ADHD. Very few studies have directly compared emotion recognition performance of youth with ASD and/or ADHD and of their unaffected siblings across age to quantify the contribution of emotion recognition problems to the ADHD phenotype. We therefore devised a study of 64 ASD+ADHD participants, 89 ASD-only participants, 111 ADHD-only participants, 122 unaffected ASD(+ADHD) siblings, 69 unaffected ADHD-only siblings and 220 controls aged 7–18 years, who had completed two tasks assessing auditory and visual emotion recognition. Factor analysis was used to detect underlying dimensions of emotion recognition capacity. Linear mixed models were used to compare performance across groups and to assess age effects. The factor-analysis revealed four factors separating speed and accuracy regarding visual and auditory emotion recognition. ASD+ADHD, ASD-only, and ADHD-only participants all performed worse than controls. ASD+ADHD, ASD-only, and ADHD-only participants did not differ in the severity of their emotion recognition problems. Both unaffected sibling groups performed intermediate between patients and controls. For ASD+ADHD and ADHD-only participants, group differences were more marked in adolescence than childhood, whereas in ASD participants this was not observed. We conclude that emotion recognition problems are a familial deficit in ADHD to a similar extent as in ASD. Emotion recognition problems specifically - and social cognition problems more generally - should be assessed in clinical practice for ADHD.     

Event-related potentials to repeated speech in 9-month-old infants at risk for autism spectrum disorder

Background

Atypical neural responses to repeated auditory and linguistic stimuli have been reported both in individuals with autism spectrum disorder (ASD) and their first-degree relatives. Recent work suggests that the younger siblings of children with ASD have atypical event-related potentials (ERPs) to repeated tones at 9 months of age; however, the functional significance is unclear, and it is unknown whether this atypicality is also present in response to linguistic stimuli.

Methods

We analyzed ERPs to repetitive and deviant consonant-vowel stimuli at 9 months in 35 unaffected high-risk-for-autism (HRA) infant siblings of children with ASD and 45 low-risk control (LRC) infants. We examined a positive component, the P150, over frontal and central electrode sites and investigated the relationships between this component and later behavior.

Results

Over frontal electrodes, HRA infants had larger-amplitude ERPs to repetitions of the standard than LRC infants, whereas ERPs to the deviant did not differ between HRA and LRC infants. Furthermore, for HRA infants, the amplitude of ERPs to the standards was positively correlated with later language ability.

Conclusions

Our work suggests that atypical ERPs to repeated speech during infancy are a possible endophenotype of ASD but that this atypicality is associated with beneficial, rather than disordered, language development. Potential mechanisms driving these relationships and implications for development are discussed.     

A review of selected candidate endophenotypes for depression

Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria.     

Error rate on the antisaccade task: heritability and developmental change in performance among preadolescent and late-adolescent female twin youth

We examined heritability of error rate on the antisaccade task among female twin youths. This task appears to be sensitive to prefrontal functioning, providing a measure of individual differences in inhibitory control associated with genetic risk for schizophrenia. The sample consisted of 674 11-year-olds and 616 17-year-olds, comprising the two cohorts of female twins from the Minnesota Twin Family Study, a population-based investigation of substance abuse and related psychopathology. We used biometric model-fitting methods to determine the relative magnitude of genetic and environmental influences on performance. In both age cohorts, the best fitting model contained additive genes and nonshared environment. Despite substantial age-related differences in mean performance levels (effect size = .81), additive genes accounted for greater than half the variance in performance in both age cohorts. These results are consistent with the hypothesis that antisaccade error rate might serve as an endophenotype for behavior disorders reflecting frontal lobe dysfunction or problems with inhibitory control.     

The other allele: Exploring the long allele of the serotonin transporter gene as a potential risk factor for psychopathy: A review of the parallels in findings

Converging evidence suggests that the short allele of the serotonin transporter gene polymorphism increases risk for a variety of psychological disorders, including depression, anxiety, and alcoholism. Thus, the short allele is typically considered the “risk” allele, and findings related to the long allele are rarely discussed. However, upon closer examination, findings associated with the long allele of the serotonin transporter gene share striking similarities with findings from studies of psychopathy. Here, the parallels between findings associated with the long/long genotype and findings associated with psychopathic traits in the areas of neuropsychology, psychophysiology, hormones, and brain imaging are reviewed. It is suggested that the long/long genotype may be a potential risk factor for the development of psychopathic traits.     

Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study

INTRODUCTION: We assessed the usefulness of the P300 wave as endophenotype for schizophrenia by means of a meta-analysis of the literature as well as our own family study. METHOD: Meta-analysis: We conducted a systematic search for articles published between 1983 and 2003 that reported P300 measures in non-psychotic relatives of schizophrenic patients and in healthy controls. Meta-regression analyses were performed using a random effects procedure. The pooled standardized effect size (PSES) was calculated as the difference between the means of the two groups divided by the common standard deviation. Local study: We examined the P300 wave with a standard two-tone oddball paradigm in 30 patients with schizophrenia, 40 non-psychotic relatives, and 40 controls using linear mixed models. RESULTS: Meta-analysis: We pooled 472 relatives and 513 controls. The P300 amplitude was significantly reduced in relatives (PSES = 0.61; 95% CI: 0.30 to 0.91; P < 0.001). The P300 latency was significantly delayed in relatives (PSES of -0.50; 95% CI: -0.88 to -0.13; P = 0.009]. Local study: The patients showed a trend for amplitude reductions (P = 0.06) and significant latency delays (P < 0.01). The relatives displayed normal amplitude but had significant latency delays (P = 0.01). The P300 amplitude and especially the P300 latency are promising alternative phenotypes for genetic research into schizophrenia.     

Cognitive event-related potentials differentiate schizophrenia with obsessive-compulsive disorder (schizo-OCD) from OCD and schizophrenia without OC symptoms

Clinical and neurobiological evidence suggests that concurrent presentation of schizophrenia and obsessive–compulsive (schizo-OCD) symptoms represents a distinct clinical entity. Given that obsessive-compulsive disorder (OCD) and schizophrenia have been modeled as having different neurofunctional profiles, the overlap between them represents a heuristic challenge for cognitive and endophenotype research. Event-related potentials (ERPs) may be used to probe neurophysiological correlates of the cognitive, emotional and behavioral disturbances found in neuropsychiatric entities such as schizo-OCD. Here we measure ERPs during a discriminative response task (DRT) in patients presenting with the DSM-IV criteria for both schizophrenia and OCD. We also performed these measurements in patients with OCD without psychotic features, as well as in patients with schizophrenia without OC symptoms. Schizo-OCD patients showed a distinct ERP pattern, with abnormally increased target activation (akin to OCD patients, but unlike the pattern observed in schizophrenic patients) and reduced P300 amplitudes (akin to schizophrenic patients, but unlike OCD patients). Similar to the control subjects, schizo-OCD patients showed larger amplitudes in the non-target condition than in the target condition. These results suggest that schizo-OCD may not only be a distinct clinical entity from pure OCD and schizophrenia, but it may also be characterized by a distinguishable neurophysiologic pattern. Neurobiological underpinnings deserve further considerations and might drive to a definition of a distinctive endophenotype for schizo-OCD in the de-construction of the schizophrenia endophenotype.     

Antisaccade performance is related to genetic loading for schizophrenia

Disturbances of the oculomotor system are promising endophenotypes for schizophrenia. Increased error rates in the antisaccade task and prolonged antisaccade latencies have been found in patients with schizophrenia and their first degree relatives. We investigated oculomotor performance in 41 parents of schizophrenia patients and 22 controls with a prosaccade task and an antisaccade task. Parents were grouped into parents with a positive family history for schizophrenia (N = 9) and parents with a negative family history for schizophrenia (N = 32). An overlap-paradigm was applied; eye movements were recorded using infrared oculography. The combined group of parents made more antisaccade direction errors than controls (p = 0.005) and there was a linear increase in direction errors from controls via negative family history parents to positive family history parents (p = 0.008). Antisaccade latencies were prolonged in the combined parent group (p = 0.057) compared to controls and there was a linear increase in latency with genetic loading (p = 0.018). No group differences were found for prosaccade parameters. These results support the hypothesis that antisaccade impairment is associated with genetic loading for schizophrenia.     

Intra-individual variability in ADHD, autism spectrum disorders and Tourette's syndrome

The potential for response variability to serve as an endophenotype for attention deficit hyperactivity disorders (ADHD) rests, in part, upon the development of reliable and valid methods to decompose variability. This study investigated the specificity of intra-individual variability (IIV) in 53 children with ADHD by comparing them with 25 children with high functioning autism (HFA), 32 children with autism spectrum disorders (ASD), who also were comorbid for ADHD (ASD+ADHD), 21 children with Tourette's syndrome (TS), and 85 typically developing controls (TD). In order to decompose the variability of the reaction times, we applied three distinct techniques: ex-Gaussian modeling, intra-individual variability analysis, and spectral analysis. Our data revealed that children with HFA and children with ASD+ADHD exhibited substantial IIV compared with ADHD and TD children. We argue that: (1) all three methods lead to a single consistent conclusion; (2) careful documentation of the analytic steps used in spectral analysis is mandatory for comparison between studies; (3) the presence of comorbidities may constitute an important factor in the observed response variability in previous studies of ADHD.