Faculty Bibliography

A common problem in statistical modelling is to distinguish between finite mixture distribution and a homogeneous non-mixture distribution. Finite mixture models are widely used in practice and often mixtures of normal densities are indistinguishable from homogenous non-normal densities. This paper illustrates what happens when the EM algorithm for normal mixtures is applied to a distribution that is a homogeneous non-mixture distribution. In particular, a population-based EM algorithm for finite mixtures is introduced and applied directly to density functions instead of sample data. The population-based EM algorithm is used to find finite mixture approximations to common homogeneous distributions. An example regarding the nature of a placebo response in drug treated depressed subjects is used to illustrate ideas

The authors prospectively followed patients with treatment-resistant obsessive-compulsive disorder (OCD). Between 1988 and 1995, 56 patients with a history of inadequate response to oral clomipramine received 14 infusions of intravenous clomipramine. The follow-up period ranged from 4 to 11 years after treatment. Of the 44 subjects interviewed at follow-up, 70.5% had current OCD and 29.5% had sub-threshold OCD. Almost half reported feeling much improved or very much improved compared to their state prior to treatment with intravenous clomipramine

Schizophrenia is a brain disorder with a complex etiology believed to have both genetic and environmental risk factors. Although the precise pathology of the disease and the mechanisms that cause the emergence of symptoms remain elusive, understanding the causes of schizophrenia and its risk factors have evolved considerably over the past decade. The discussion has shifted from the reductionist 'genes versus environment' debate to a more integrative approach, ie, the functions of susceptibility genes, epigenetics and paternal age, and toxic exposures throughout early development. This article discusses evidence for three major categories of risk factors, including genetic contributions, the role of paternal age and potential mechanisms by which it exerts its influence on risk, and new findings on the role of environmental exposures

There is a strong genetic component for schizophrenia risk, but it is unclear how the illness is maintained in the population given the significantly reduced fertility of those with the disorder. One possibility is that new mutations occur in schizophrenia vulnerability genes. If so, then those with schizophrenia may have older fathers, since advancing paternal age is the major source of new mutations in humans. We found that paternal age at conception is a robust risk factor for schizophrenia, explaining perhaps a quarter of all cases. The predisposing genetic events appear to occur stochastically in proportion to advancing paternal age, and the possible mechanisms include de novo point mutations or defective epigenetic regulation of paternal genes. The risk might also be related to paternal toxic exposures, nutritional deficiencies, suboptimal DNA repair enzymes or other factors that influence the fidelity of genetic information in the constantly replicating male germ line. We propose that de novo genetic alterations in the paternal germline cause an independent and common variant of schizophrenia and that abnormal methylation of paternally imprinted genes could be the mechanism. These findings suggest exciting new directions for research into the aetiology of schizophrenia.

ABSTRACT: BACKGROUND: It has been acknowledged that the frequency spectrum of measured electromagnetic (EM) brain signals shows a decrease in power with increasing frequency. This spectral behaviour may lead to difficulty in distinguishing event-related peaks from ongoing brain activity in the electro- and magnetoencephalographic (EEG and MEG) signal spectra. This can become an issue especially in the analysis of low frequency oscillations (LFOs) - below 0.5 Hz - which are currently being observed in signal recordings linked with specific pathologies such as epileptic seizures or attention deficit hyperactivity disorder (ADHD), in sleep studies, etc. METHODS: In this work we propose a simple method that can be used to compensate for this 1/f trend hence achieving spectral normalisation. This method involves filtering the raw measured EM signal through a differentiator prior to further data analysis. RESULTS: Applying the proposed method to various exemplary datasets including very low frequency EEG recordings, epileptic seizure recordings, MEG data and Evoked Response data showed that this compensating procedure provides a flat spectral base onto which event related peaks can be clearly observed. CONCLUSION: Findings suggest that the proposed filter is a useful tool for the analysis of physiological data especially in revealing very low frequency peaks which may otherwise be obscured by the 1/f spectral activity inherent in EEG/MEG recordings

Childhood-onset schizophrenia (COS) occurs in children before the age of 13, though it may remain undiagnosed for a much longer period. Children with COS suffer from aberrant social and cognitive development, before the onset of psychosis and display symptoms as motor development delay, language development delay and social withdrawal. Apart from environmental stress, genetic vulnerability factors also contribute to the increased risk of disease development. At present, clinicians and researchers are working on the identification of children and adolescents at risk for developing the disease and also at developing prophylactic and therapeutic techniques like pharmacotherapeutic and psychosocial treatments.

In recent years, there has been a growing interest in sleep problems associated with attention-deficit/hyperactivity disorder (ADHD). The etiology of these sleep problems is multifactorial. In this paper, we review the current literature on the treatment of the most common disorders or factors underlying sleep problems associated with ADHD. In particular, we focus on the management of sleep problems associated with ADHD medications, restless legs syndrome, excessive nocturnal motricity in sleep, sleep disordered breathing, sleep-onset insomnia and psychiatric comorbidities associated with ADHD. Given the paucity of randomized, controlled, double-blinded, placebo-controlled studies, it is hoped that this review will encourage further methodologically sound studies in order to be able to develop treatment guidelines.