Familial clustering of psychiatric disorders and low IQ.

BACKGROUND: Although the ICD and DSM differentiate between different psychiatric disorders, these often share symptoms, risk factors, and treatments. This was a population-based, case-control, sibling study examining familial clustering of all psychiatric disorders and low IQ, using data from the Israel Draft-Board Registry on all Jewish adolescents assessed between 1998 and 2014. METHODS: We identified all cases with autism spectrum disorder (ASD, N = 2128), severe intellectual disability (ID, N = 9572), attention-deficit hyperactive disorder (ADHD) (N = 3272), psychotic (N = 7902), mood (N = 9704), anxiety (N = 10 606), personality (N = 24 816), or substance/alcohol abuse (N = 791) disorders, and low IQ (⩾2 SDs below the population mean, N = 31 186). Non-CNS control disorders were adolescents with Type-1 diabetes (N = 2427), hernia (N = 29 558) or hematological malignancies (N = 931). Each case was matched with 10 age-matched controls selected at random from the Draft-Board Registry, with replacement, and for each case and matched controls, we ascertained all full siblings. The main outcome measure was the relative recurrence risk (RRR) of the sibling of a case having the same (within-disorder RRR) or a different (across-disorder RRR) disorder. RESULTS: Within-disorder RRRs were increased for all diagnostic categories, ranging from 11.53 [95% confidence interval (CI): 9.23-14.40] for ASD to 2.93 (95% CI: 2.80-3.07) for personality disorders. The median across-disorder RRR between any pair of psychiatric disorders was 2.16 (95% CI: 1.45-2.43); the median RRR between low IQ and any psychiatric disorder was 1.37 (95% CI: 0.93-1.98). There was no consistent increase in across-disorder RRRs between the non-CNS disorders and psychiatric disorders and/or low IQ. CONCLUSION: These large population-based study findings suggest shared etiologies among most psychiatric disorders, and low IQ.

Understanding the association between advanced paternal age and schizophrenia and bipolar disorder.

BACKGROUND: Previous studies reported an association between advanced paternal age at birth and increased risk for schizophrenia and bipolar disorder. While some hypothesize that this association is caused by de-novo mutations in paternal spermatozoa, others cite factors associated with psycho-social characteristics of fathers who have children at a late age. This study aims to test these hypotheses. METHODS: A historical-prospective, population-based cohort study, performed by linking the Israeli Draft Board Registry and the Israeli National Psychiatric Hospitalization Registry (N = 916 439; 4488 with schizophrenia, 883 with bipolar disorder). Odds ratios (OR) and two-sided 95% confidence intervals (CI) were calculated by logistic regression models, using paternal age as predictor and risk for later hospitalizations for schizophrenia or bipolar disorder as outcome measure. Models were first fitted unadjusted, then adjusted for paternal age at birth of the first child. RESULTS: In the unadjusted model, offspring of fathers aged 45 and above at birth had increased risk of schizophrenia (OR = 1.71, 95% CI 1.49-1.99) and bipolar disorder (OR = 1.63, 95% CI 1.16-2.24). However, taking into account paternal age at birth of first child, advanced paternal age was no longer associated with increased risk of schizophrenia (OR = 0.60, 95% CI 0.48-0.79) or bipolar disorder (OR = 1.03, 95% CI 0.56-1.90). CONCLUSIONS: Controlling for paternal age at birth of the first offspring, advanced paternal age does not predict increased risk for schizophrenia or bipolar disorder. These data indicate that the association between advanced paternal age and having an offspring with schizophrenia and bipolar disorder is likely due to psychos-social factors, or common genetic variation associated with delayed initial fatherhood.

Slow update of internal representations impedes synchronization in autism.

Autism is a neurodevelopmental disorder characterized by impaired social skills, motor and perceptual atypicalities. These difficulties were explained within the Bayesian framework as either reflecting oversensitivity to prediction errors or - just the opposite - slow updating of such errors. To test these opposing theories, we administer paced finger-tapping, a synchronization task that requires use of recent sensory information for fast error-correction. We use computational modelling to disentangle the contributions of error-correction from that of noise in keeping temporal intervals, and in executing motor responses. To assess the specificity of tapping characteristics to autism, we compare performance to both neurotypical individuals and individuals with dyslexia. Only the autism group shows poor sensorimotor synchronization. Trial-by-trial modelling reveals typical noise levels in interval representations and motor responses. However, rate of error correction is reduced in autism, impeding synchronization ability. These results provide evidence for slow updating of internal representations in autism.

Perceptual bias reveals slow-updating in autism and fast-forgetting in dyslexia.

Individuals with autism and individuals with dyslexia both show reduced use of previous sensory information (stimuli statistics) in perceptual tasks, even though these are very different neurodevelopmental disorders. To better understand how past sensory information influences the perceptual experience in these disorders, we first investigated the trial-by-trial performance of neurotypical participants in a serial discrimination task. Neurotypical participants overweighted recent stimuli, revealing fast updating of internal sensory models, which is adaptive in changing environments. They also weighted the detailed stimuli distribution inferred by longer-term accumulation of stimuli statistics, which is adaptive in stable environments. Compared to neurotypical participants, individuals with dyslexia weighted earlier stimuli less heavily, whereas individuals with autism spectrum disorder weighted recent stimuli less heavily. Investigating the dynamics of perceptual inference reveals that individuals with dyslexia rely more on information about the immediate past, whereas perception in individuals with autism is dominated by longer-term statistics.

Risk of hospitalization for psychiatric disorders among siblings and parents of probands with psychotic or affective disorders: A population-based study.

Relatives of people diagnosed with psychotic and affective disorders have a higher risk of developing psychiatric disorders compared to the general population. This study examined the risk of hospitalization for psychiatric disorders among siblings and parents of patients affected with major psychiatric disorders. In this large population-based case-control study, 17,895 siblings and parents of 7671 hospitalized subjects with a diagnosis of narrowly defined schizophrenia (SZ), broadly defined SZ, schizoaffective disorder (SAD), bipolar disorder (BD) or unipolar depression (UD) were identified from the Israeli Psychiatric Hospitalization Registry and compared to 71,580 age and gender-matched controls from the Israeli Population Registry. Results indicated that siblings of people diagnosed with broadly defined SZ had a significantly higher risk of hospitalization for broadly (OR=11.06, 95% CI=7.93-15.41) and narrowly defined SZ (OR=10.59, 95% CI=6.8-16.33), SAD (OR=9.69, 95% CI=4.76-19.73), BD (OR=7.46, 95% CI=21.8-25.52), UD (OR=2.84, 95% CI=1.01-8.00), and other psychiatric disorders (OR=1.85, 95% CI=1.16-2.93), compared to controls. Siblings of patients with BD had a significantly higher risk of hospitalization for broadly defined SZ (OR=2.92, 95% CI=1.11-7.71) and for other psychiatric disorders (OR=6.67, 95% CI=2.17-20.50), compared to controls. Parents of probands with SZ were at significantly increased risk for all disorders examined, except for UD and ¨other psychiatric disorders¨, which was not significant in parents of probands with BD. This large, population-based study provides evidence for common genetic risk across different psychiatric disorders.

Dyslexics' faster decay of implicit memory for sounds and words is manifested in their shorter neural adaptation.

Dyslexia is a prevalent reading disability whose underlying mechanisms are still disputed. We studied the neural mechanisms underlying dyslexia using a simple frequency-discrimination task. Though participants were asked to compare the two tones in each trial, implicit memory of previous trials affected their responses. We hypothesized that implicit memory decays faster among dyslexics. We tested this by increasing the temporal intervals between consecutive trials, and by measuring the behavioral impact and ERP responses from the auditory cortex. Dyslexics showed a faster decay of implicit memory effects on both measures, with similar time constants. Finally, faster decay of implicit memory also characterized the impact of sound regularities in benefitting dyslexics' oral reading rate. Their benefit decreased faster as a function of the time interval from the previous reading of the same non-word. We propose that dyslexics' shorter neural adaptation paradoxically accounts for their longer reading times, since it reduces their temporal window of integration of past stimuli, resulting in noisier and less reliable predictions for both simple and complex stimuli. Less reliable predictions limit their acquisition of reading expertise.