Association and linkage disequilibrium between a functional polymorphism of the dopamine-2 receptor gene and schizophrenia in a genetically homogeneous Portuguese population

A functional polymorphism in the promoter region of the DRD2 gene has been found to be associated with schizophrenia in Japanese(1,2) and Swedish populations.(3) We attempted to replicate these findings in a genetically homogeneous Portuguese population using a family-based study design. Analysis of 78 trios revealed evidence for association between the -141 C Ins allele and schizophrenia using the haplotype relative risk (HRR) method (chi(2) = 9.30, P = 0.0023). Further examination of this sample using an alternative family-based association analysis method, the transmission disequilibrium test (TDT), of 33 informative matings from the Portuguese trios provided evidence for an allelic association and linkage disequilibrium between the insertion allele and schizophrenia (chi(2) = 8.76, P = 0.0031). These consistent results using two alternative family-based association analysis methods replicate the findings of previous reports, and thus further implicate a potential role for the dopamine-2 receptor in the genetic etiology of schizophrenia.     

Association of a functional polymorphism of the serotonin transporter gene with anxiety-related temperament and behavior problems in children: a longitudinal study from infancy to the mid-teens

A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been associated with anxiety-related personality traits in adults. Initial studies showed that the short allele was associated with higher neuroticism, anxiety and harm avoidance. However, most attempts to replicate these findings have been negative. Because the association of candidate polymorphisms with behavioral traits may vary with stage of development, we investigated the association using participants in a longitudinal study of childhood temperament. DNA was available for 660 children who had been assessed for temperament from 4-8 months to 15-16 years, and for behaviour problems from 3-4 years to 15-16 years. No significant associations were found at most ages. However, at ages 13-14 years and 15-16 years, the long/long genotype was associated with higher anxiety. These findings do not support an association of the short allele with anxiety-related traits in early life.     

Hearing impairment and psychosis: a replication in a cohort of young adults

Previous work has demonstrated an association between hearing impairment and psychosis. In the current study, this association was studied in a cohort of young people. In addition, it was studied to what degree duration of hearing problems (i.e. onset earlier in life) impacted on risk. Data were derived from the Greek National Perinatal Survey, a prospective birth cohort study of 11,048 neonates at baseline, 6594 seven-year olds at T1 and 3500 nineteen-year olds at T2. A significant association was found at age 19 years between the presence of hearing impairment and the presence of self-reported positive psychotic-like experiences (beta = 0.18, S.E. = 0.02, p < 0.000). In addition, this association was conditional on the duration of hearing problems, in that the association at age 19 years was stronger if hearing impairment had already been reported at age 7 years (test for interaction: p = 0.022). These results replicate previous findings of an association between hearing impairment and psychosis, extend it to the age range of late adolescence, and suggest that longer duration is associated with stronger risk.     

Occipital hypoperfusion in a patient with psychogenic visual disturbance

A patient with bilateral diminished visual acuity and blurred vision was given the diagnosis of psychogenic visual disturbance after extensive psychiatric and ophthalmological examinations. Single photon emission computed tomography with Tc-99m-ethylcysteinate dimer demonstrated remarkably reduced regional cerebral blood flow (rCBF) in the bilateral occipital lobes. More specifically, rCBF was reduced in the visual association areas, but not in the primary visual areas. These findings suggest that functional suppression of the visual association area is associated with the development of psychogenic visual disturbance.     

Association study between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia: a meta-analysis

Positional, functional and association studies have strongly implicated the dystrobrevin binding protein 1 gene (DTNBP1) as a promising novel candidate gene for schizophrenia. Since the first association study was reported, there have been many attempts to replicate it. However the results have been mixed and these subsequent studies have produced negative as well as positive results. To reconcile these conflicting findings and to give a comprehensive picture of the relationship of DTNBP1 and schizophrenia, the current meta-analysis combined all published association studies involving nine polymorphisms up to May 2006. The results (12 studies including 3429 cases, 3376 controls and 721 trios) showed that there were five single nucleotide polymorphisms (SNPs) with p values < 0.05, however, sensitivity analyses showed that only one SNP was consistent across all nine studies (four of the five SNPs became non-significant after removal of one study), indicating that one study may cause the association findings for each of these four SNPs. In conclusion, there is only a weak association of one SNP in DTNBP1 with schizophrenia, which is not significant after multiple testing.     

Instability in self-esteem and paranoia in a general population sample

Background Research on the association between paranoia and self-esteem has yielded inconsistent findings. Some studies have indicated an association between paranoia and low self-esteem, while other studies have shown an association with high self-esteem. A plausible explanation for these inconsistencies is that self-esteem is unstable in paranoid individuals. Method The association between instability in self-esteem and paranoia was assessed in a general population risk set of 4636 individuals using logistic regression analysis. Results Self-esteem instability was significantly associated with the presence of paranoid symptoms (OR 1.27 95% CI 1.12–1.45) and not with other positive psychotic symptoms (OR 1.09 95% CI 0.96–1.23), adjusted for a range of a priori selected confounders. Conclusion The finding of a specific association between unstable self-esteem and paranoia is in line with a recent psychological model suggesting that paranoid beliefs arise partly as a consequence of dysfunctional efforts to regulate self-esteem.     

Neurolymphomatosis: a clinicopathologic syndrome re-emerges.

We describe a patient with sensorimotor peripheral neuropathy and cranial neuropathy due to autopsy-proven neurolymphomatosis defined by infiltration of peripheral nerves by tumor cells and review the findings in 39 previously reported patients. The cause of the neuropathy is not known. The association with immune-deficient states suggests virally mediated pathogenesis, possibly a retrovirus.     

Hypomelanosis of Ito: association with a chromosomal abnormality

We report the clinical and neuroradiologic findings and the association of a chromosome abnormality, t(2,8), with a case of hypomelanosis of Ito (incontinentia pigmenti achromians). Chromosome anomalies have not been previously recognized in this genetically determined, neurocutaneous disorder.     

Association between indicators of perinatal asphyxia and adverse outcome in the term infant: a methodological review

There are conflicting opinions about the significance of 5 perinatal findings felt to be indicators of asphyxia (meconium staining of the amniotic fluid, abnormal fetal heart rate patterns, acidotic fetal scalp blood gases, low Apgar scores, and acidotic cord blood gases). A review of the literature was undertaken to determine the strength of association of each of these findings with adverse outcomes. Although all studies contained methodological problems, these indicators were found to have strong associations with one or more adverse outcomes such as perinatal death, low Apgar scores or cerebral palsy. The strength of the association (relative risk) was found to vary inversely with the prevalence of the outcome.     

Diencephalic amnesia: a reappraisal.

The anatomical basis of memory disorder related to lesions of the diencephalon is a controversial matter. A study of a patient who developed severe amnesia in association with bilateral metastatic tumour invasion of the medial and posterior thalamus is reported. The findings in this case have led to further discussion of this unsettled issue.     

Association study of suicidal behavior and affective disorders with a genetic polymorphism in ABCG1, a positional candidate on chromosome 21q22.3

The gene that codes for the ABC transporter ABCG1 is located in a chromosomal susceptibility region (21q22.3) for affective disorders. Genetic variations in ABCG1 have been associated with affective disorders in Japanese males. In this study, we investigated the distribution of a G2457A polymorphism in patients with affective disorders, suicide attempters with various psychiatric diagnoses and healthy subjects. We initially found a trend towards a modest association with affective disorders in males (p = 0.046 for allele frequencies and p = 0.046 for AA versus GG). We conducted a replication study with independent patients and controls. There was no association with affective disorders, either in the replication or in the combined group. Furthermore, we found no association with suicidal behavior. These findings do not support the hypothesis that ABCG1 is a susceptibility gene for affective disorders or suicidal behavior.     

Acquired stuttering in a patient with Wernicke’s aphasia

We report a patient with aphasia caused by cerebral infarction in the left temporal, parietal and occipital lobes that was complicated by acquired stuttering (AS), which is an unusual association. Our findings indicated that Wernicke's area might be involved in the development of AS.     

Ectodermal dysplasia and brain cystic changes: confirmation of a novel neurocutaneous syndrome

Ectodermal dysplasia is a rare congenital disorder characterized by dry, brittle hair, dental malformations, and skin abnormalities. It is thought to be the result of embryonic ectodermal dysgenesis, affecting tissues and structures that are widely separated but with common developmental origins. Recently, this disorder has been associated with a unique neuroimaging appearance, consisting of widely dilated perivascular spaces. This association has been proposed as a novel neurocutaneous syndrome, identified in one report as "cerebrum polycystica vera." We report a similar patient with dilated perivascular spaces associated with dermatologic manifestations consistent with ectodermal dysplasia. This patient was otherwise normal, without neurocognitive deficit. Additional neuroimaging findings included widespread white-matter high signal intensity on T2-weighted magnetic resonance imaging, as well as normal findings on magnetic resonance spectroscopy. This case confirms the association of ectodermal dysplasia and brain cystic changes and appears to expand the phenotypic manifestations that may be seen in such patients.     

Motor neuron disease and malignancies: results of a population-based study

Summary Eight cases of malignancies with concurrent motor neuron disease (MND), derived from an unselected population representing all cases of MND diagnosed during a 15-year period in two Italian provinces, were studied to verify the existence of paraneoplastic forms of the disease. No statistically significant association between the two diseases was found. Therefore, from our findings the occurrence of a neoplasm in a patient affected by MND can be considered a chance association.This work was partly supported by CSI — Piemonte (Consorzio per il Sistema Informativo)     

Spurious genetic associations.

BACKGROUND: Genetic association studies are widely used in biomedical research and yet only a minority of positive findings stand the test of replication. I explored the capacity of association studies to produce false positive findings and the impact of various definitions of replication. METHODS: Genetically realistic simulation data of a typical genotyping/analytic approach for 10 single nucleotide polymorphisms (SNPs) in COMT, a commonly studied candidate gene. RESULTS: Candidate gene studies like those simulated here are highly likely to produce one or more false positive findings at alpha < or = .05, the pattern of findings can often be "compelling" or "intriguing," and false positive findings propagate and confuse the literature unless the definition of replication is precise. CONCLUSIONS: Findings from single association studies constitute "tentative knowledge" and must be interpreted with exceptional caution. For the association method to function as intended, every statistical comparison must be tracked and reported, and integrated replication is essential. Precise replication (the same SNPs, phenotype, and direction of association) is required in the interpretation of multiple association studies.     

Obsessive-compulsive disorder and immunology: a review

Interest in the possibility of an immune-mediated pathophysiology of obsessive-compulsive disorder and related disorders has increased. In the late 1980s, the National Institute of Mental Health reported an increase in obsessive-compulsive symptoms (OCS) in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCS but no chorea led to the coining of PANDAS (Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). This association has furthered interest in biological measures for immune and genetic susceptibility in non-PANDAS obsessive-compulsive disorder patients (OCD). Furthermore, some studies are trying to demonstrate alterations of immune parameters in OCD patients, with few positive results. In this narrative review, our objective was to describe the immunologic findings in OCD, PANDAS, and their association with SC.     

Terminal syringomyelia communicating with a spinal dermal sinus.

Terminal syringomyelia occurs in approximately 25% of patients with occult spinal dysraphism. Congenital spinal dermal sinus is an uncommon form of occult spinal dysraphism. This case report highlights the rare association of terminal syringomyelia communicating with a spinal dermal sinus, resulting in an unique clinical presentation. The clinical, radiological and surgical findings of this unusual case are reported.     

Volumes of association thalamic nuclei in schizophrenia: a postmortem study

The major association thalamic nuclei, the mediodorsal nucleus (MD) and the medial pulvinar nucleus (PUM) are regarded as important parts of the circuits among association cortical regions. Association cortical regions of the frontal, parietal and temporal lobes have been repeatedly implicated in the neuropathology of schizophrenia. Thus, the aim of the present postmortem study was to investigate the volumes of association thalamic nuclei in this disease. The volumes of the whole thalamus (THAL), MD and PUM were measured in each hemisphere of brains of 12 patients with schizophrenia and 13 age-matched and gender-matched normal control subjects without neuropsychiatric disorders. Patients with schizophrenia exhibited significant volume reductions in both the MD and the PUM, the reductions being more pronounced in the PUM. The volume of the PUM in the left (−19.7%, P=0.02) and right (−22.1%, P=0.01) hemispheres was significantly reduced in the schizophrenia group. The volume of the MD was reduced in both hemispheres in the schizophrenia group. However, the volume reduction was only significant in the left hemisphere (−9.3%, P=0.03). Patients with schizophrenia also exhibited a decreased volume of the THAL in the left (−16.4%, P=0.003) and right (−15.2%, P=0.006) hemispheres. There were no significant correlations between thalamic volumes and duration of illness or age of the patients.

In conclusion, the present data indicate volume reductions of association thalamic nuclei in schizophrenia. These anatomical findings are consistent with the view that schizophrenia may be associated with disturbances of association cortical networks. However, the findings of a substantial volume reduction of the THAL suggest that the volumes of additional thalamic nuclei may be also reduced in schizophrenia.     

Acquisition of American Sign Language by a noncommunicating autistic child

Experiments in the perception and language abilities of autistic children indicate that the children have auditory-visual association problems. These findings, combined with the findings that autistic communication is primarily gestural, led to the teaching of elements of American Sign Language to a 5-year-old nonverbal autistic boy. Results after 20 hours of training indicate that the child did acquire signs, that increasing signing led to increasing vocal speech, and that the child has rudimentary English syntax. The use of Ameslan signs spontaneously generalized to other situations and the training resulted in increased social interaction.     

Rhythmic movement disorder and cyclic alternating pattern during sleep: a video-polysomnographic study in a 9-year-old boy.

We report on polysomnographic findings in a 9-year-old boy affected by rhythmic movement disorder. The subject's rhythmic movements were found to be intimately linked to unstable nonrapid eye movement N-REM sleep, as shown by their close association with the A phases of the cyclic alternating pattern. We examine the complex interactions between arousal mechanisms and rhythmic movements occurring during sleep.