Associations between psychosis endophenotypes across brain functional, structural, and cognitive domains.

BACKGROUND: A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related. METHODS: This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes. RESULTS: The P300 amplitude and latency were not associated (regression coef. -0.06, 95% CI -0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10-0.28, p 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships. CONCLUSIONS: The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.

Effectiveness of endoscopic cricopharyngeal myotomy in adults with neurological disease: systematic review.

OBJECTIVE: To determine the effectiveness of endoscopic cricopharyngeal myotomy on upper oesophageal sphincter dysfunction in adults with upper oesophageal sphincter dysfunction and neurological disease. DATA SOURCES: Published and unpublished studies with a quasi-experimental design investigating endoscopic cricopharyngeal myotomy effects on upper oesophageal sphincter dysfunction in humans were considered eligible. Electronic databases, grey literature and reference lists of included studies were systematically searched. REVIEW METHODS: Data were extracted by two independent reviewers. Methodological quality was assessed independently using the PEDro scale and MINORS tool. RESULTS: Of 2938 records identified, 2 studies were eligible. Risk of bias assessment indicated areas of methodological concern in the literature. Statistical analysis was not possible because of the limited number of eligible studies. CONCLUSION: No determinations could be made regarding endoscopic cricopharyngeal myotomy effectiveness in the cohort of interest. Reliable and valid evidence on the following is required to support increasing clinical usage of endoscopic cricopharyngeal myotomy: optimal candidacy selection; standardised post-operative management protocol; complications; and endoscopic cricopharyngeal myotomy effects on aspiration of food and laryngeal penetration, mean upper oesophageal sphincter resting pressure and quality of life.

Failure to deactivate medial prefrontal cortex in people at high risk for psychosis.

Impaired working memory is a core feature of schizophrenia and is linked with altered engagement the lateral prefrontal cortex. Although altered PFC activation has been reported in people with increased risk of psychosis, at present it is not clear if this neurofunctional alteration differs between familial and clinical risk states and/or increases in line with the level of psychosis risk. We addressed this issue by using functional MRI and a working memory paradigm to study familial and clinical high-risk groups. We recruited 17 subjects at ultra-high-risk (UHR) for psychosis, 10 non-affected siblings of patients with schizophrenia (familial high risk [FHR]) and 15 healthy controls. Subjects were scanned while performing the N-back working memory task. There was a relationship between the level of task-related deactivation in the medial PFC and precuneus and the level of psychosis risk, with deactivation weakest in the UHR group, greatest in healthy controls, and at an intermediate level in the FHR group. In the high-risk groups, activation in the precuneus was associated with the level of negative symptoms. These data suggest that increased vulnerability to psychosis is associated with a failure to deactivate in the medial PFC and precuneus during a working memory task, and appears to be most evident in subjects at clinical, as opposed to familial high risk.

'Endoflip® evaluation of pharyngo-oesophageal segment tone and swallowing in a clinical population: a total laryngectomy case series'.

OBJECTIVES: To evaluate safety of positioning and distending the functional lumen imaging probe in the pharyngo-oesophageal segment in adults with known pharyngo-oesophageal segment dysfunction and to obtain preliminary measurements of pharyngo-oesophageal segment distensibility and opening during swallowing in a clinical group. METHODS: Prospective case series of ten adults post total laryngectomy (61-75 years) recruited from an outpatient ENT clinic. Functional lumen imaging probe was inserted trans-nasally, and the balloon was positioned in the pharyngo-oesophageal segment. Two 20-mL ramp distensions were completed, and subjects performed two dry and two 5-mL and 10-mL liquid swallows at a 12-mL balloon volume. Pharyngo-oesophageal segment distensibility was calculated from cross-sectional area (mm(2) ) and intraballoon pressure (mmHg) measures. During swallowing, extent (mm) and duration (secs) of pharyngo-oesophageal segment opening and intraballoon pressure drop (mmHg) were evaluated. RESULTS: Functional lumen imaging probe could be passed through the pharyngo-oesophageal segment in seven subjects, all of whom completed the protocol. During distensions, pharyngo-oesophageal segment cross-sectional area increased significantly (19.47-148.3 mm(2) , P < 0.001), and intraballoon pressure increased significantly (15- to 20-mL balloon volume, P = 0.005). Pharyngo-oesophageal segment diameter (5.1 mm) increased during dry (7.4 mm), 5-mL (7.3 mm) and 10-mL (7.7 mm) liquid swallows (P = 0.018). Pharyngo-oesophageal segment opening duration varied across dry (1 s), 5-mL (0.8 s) and 10-mL (1.6 s) liquid swallows. Resting intraballoon pressure (25.5 mmHg) did not alter significantly during swallowing (P = 0.656). CONCLUSION: Functional lumen imaging probe provides novel quantitative information regarding pharyngo-oesophageal segment distensibility and opening during swallowing in adults post total laryngectomy. No adverse events were observed in this first clinical study. Data were easy to acquire, and measures may direct candidacy for and establish effectiveness of interventions to alter pharyngo-oesophageal segment tone.

White matter microstructural abnormalities in families multiply affected with bipolar I disorder: a diffusion tensor tractography study.

BACKGROUND: White matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD. METHOD: Diffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract. RESULTS: We detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients. CONCLUSIONS: WM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.

A new evaluation of the upper esophageal sphincter using the functional lumen imaging probe: a preliminary report.

Objective and reliable evaluation of upper esophageal sphincter (UES) opening during swallowing based on videofluoroscopy and pharyngeal manometry challenges dysphagia clinicians. The functional lumen imaging probe (FLIP) is a portable tool based on impedance planimetry originally designed to measure esophogastric junction compliance. It is hypothesized that FLIP can evaluate UES distensibility, and can provide UES diameter and pressure measurements at rest, during swallowing, and during voluntary maneuvers. Eleven healthy adult subjects consented to FLIP evaluation. The probe was inserted transorally, and the balloon was positioned across the UES. Two 20-mL ramp distensions were completed. Changes in UES diameter and intraballoon pressure were measured during dry and 5-mL liquid swallows, and during voluntary swallow postures and maneuvers employed in clinical practice. The protocol was completed by 10 of 11 healthy subjects. Mean intraballoon pressure increased throughout 5-mL (5.8 mmHg; -4.5-18.6 mmHg), 10-mL (8.7 mmHg; 2.3-28.5 mmHg), 15-mL (17.3 mmHg; 9.5-34.8 mmHg), and 20-mL (31.2 mmHg; 16-46.3 mmHg) balloon volumes. Mean resting UES diameter (4.9 mm) increased during dry swallows (9.2 mm) and 5-mL liquid swallows (7.7 mm). Mean UES diameter increased during 5-mL liquid swallows with head turn to right (8.1 mm) and left (8.3 mm), chin tuck (8.4 mm), effortful swallow (8.5 mm), Mendelsohn maneuver (8.1 mm), and supraglottic swallow (7.8 mm). FLIP was safely inserted and distended in the UES, and provided useful quantitative data regarding UES distensibility and UES diameter changes during swallowing maneuvers. Further research is being conducted to explore the role of FLIP in UES evaluation.

New measures of upper esophageal sphincter distensibility and opening patterns during swallowing in healthy subjects using EndoFLIP®.

BACKGROUND: This paper aims to measure upper esophageal sphincter (UES) distensibility and extent and duration of UES opening during swallowing in healthy subjects using EndoFLIP(®). METHODS: Fourteen healthy subjects (20-50 years) were recruited. An EndoFLIP(®) probe was passed trans-orally and the probe balloon was positioned across the UES. Two 20-mL ramp distensions were completed and UES cross-sectional area (CSA) and intra-balloon pressure (IBP) were evaluated. At 12-mL balloon volume, subjects completed dry, 5- and 10-mL liquid swallows and extent (mm) and duration (s) of UES opening and minimum IBP (mmHg) were analyzed across swallows. KEY RESULTS: Thirteen subjects completed the study protocol. A significant change in UES CSA (P < .001) and IBP (P < .000) was observed during 20-mL distension. UES CSA increased up to 10-mL distension (P < .001), from which point IBP raised significantly (P = 0.004). There were significant changes in UES diameter (mm) (P < .000) and minimum IBP (mmHg) (P < .000) during swallowing events. Resting UES diameter (4.9 mm; IQR 0.02) and minimum IBP (18.8 mmHg; IQR 2.64) changed significantly during dry (9.6 mm; IQR 1.3: P < .001) (3.6 mmHg; IQR 4.1: P = 0.002); 5 mL (8.61 mm; IQR 2.7: P < .001) (4.8 mmHg; IQR 5.7: P < .001) and 10-mL swallows (8.3 mm; IQR 1.6: P < 0.001) (3 mmHg; 4.6: P < .001). Median duration of UES opening was 0.5 s across dry and liquid swallows (P = 0.91). Color contour plots of EndoFLIP(®) data capture novel information regarding pharyngo-esophageal events during swallowing. CONCLUSIONS & INFERENCES: Authors obtained three different types of quantitative data (CSA, IBP, and timing) regarding UES distensibility and UES opening patterns during swallowing in healthy adults using only one device (EndoFLIP(®)). This new measure of swallowing offers fresh information regarding UES dynamics which may ultimately improve patient care.

The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives.

We investigated the role of variation in putative psychosis genes coding for elements of the white matter system by examining the contribution of genotypic variation in three single-nucleotide polymorphisms (SNPs) neuregulin 1 (NRG1) SNP8NRG221533, myelin oligodendrocytes glycoprotein (MOG) rs2857766 and CNP (rs2070106) and one haplotype HAP(ICE) (deCODE) to white matter volume in patients with psychotic disorder and their unaffected relatives. Structural magnetic resonance imaging and blood samples for genotyping were collected on 189 participants including patients with schizophrenia (SZ) or bipolar I disorder (BDI), unaffected first-degree relatives of these patients and healthy volunteers. The association of genotypic variation with white matter volume was assessed using voxel-based morphometry in SPM5. The NRG1 SNP and the HAP(ICE) haplotype were associated with abnormal white matter volume in the BDI group in the fornix, cingulum and parahippocampal gyrus circuit. In SZ the NRG1 SNP risk allele was associated with lower white matter volume in the uncinate fasciculus (UF), right inferior longitudinal fasciculus and the anterior limb of the internal capsule. Healthy G-homozygotes of the MOG SNP had greater white matter volume in areas of the brainstem and cerebellum; this relationship was absent in those with a psychotic disorder and the unaffected relatives groups. The CNP SNP did not contribute to white matter volume variation in the diagnostic groups studied. Variation in the genes coding for structural and protective components of myelin are implicated in abnormal white matter volume in the emotion circuitry of the cingulum, fornix, parahippocampal gyrus and UF in psychotic disorders.

Neonatal ultrasound results following very preterm birth predict adolescent behavioral and cognitive outcome.

This study investigated the association between different neonatal ultrasonographic classifications and adolescent cognitive, educational, and behavioral outcomes following very preterm birth. Participants included a group of 120 adolescents who were born very preterm (<33 weeks of gestation), subdivided into three groups according to their neonatal cerebral ultrasound (US) classifications: (a) normal (N = 69), (b) periventricular hemorrhage (PVH, N = 37), and (c) PVH with ventricular dilatation (PVH + DIL, N = 14), and 50 controls. The cognitive functions assessed were full-scale IQ, phonological and semantic verbal fluency, and visual-motor integration. Educational outcomes included reading and spelling; behavioral outcomes were assessed with the Rutter Parents' Scale and the Premorbid Adjustment Scale (PAS). Adolescent outcome scores were compared among the four groups. A main effect for group was observed for full-scale IQ, Rutter Parents' Scale total scores, and PAS total scores, after controlling for gestational age, socioeconomic status and gender, with the PVH + DIL group showing the most impaired scores compared to the other groups. The current results demonstrate that routine neonatal ultrasound classifications are associated with later cognitive and behavioral outcome. Neonatal ultrasounds could aid in the identification of subgroups of children who are at increased risk of neurodevelopmental problems. These at risk subgroups could then be referred to appropriate early intervention services.

Do COMT, BDNF and NRG1 polymorphisms influence P50 sensory gating in psychosis?

BACKGROUND: Auditory P50 sensory gating deficits correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The well-supported role of catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF) and neuregulin 1 (NRG1) genes in neurodevelopment and cognition make a strong theoretical case for their influence on the P50 endophenotype. METHOD: The possible role of NRG1, COMT Val158Met and BDNF Val66Met gene polymorphisms on the P50 endophenotype was examined in a large sample consisting of psychotic patients, their unaffected relatives and unrelated healthy controls using linear regression analyses. RESULTS: Although P50 deficits were present in patients and their unaffected relatives, there was no evidence for an association between NRG1, COMT Val158Met or BDNF Val66Met genotypes and the P50 endophenotype. CONCLUSIONS: The evidence from our large study suggests that any such association between P50 indices and NRG1, COMT Val158Met or BDNF Val66Met genotypes, if present, must be very subtle.

No association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder.

The Disrupted-in-Schizophrenia-1 (DISC1) gene has been implicated in both schizophrenia and bipolar disorder by linkage and genetic association studies. Altered prefrontal cortical function is a pathophysiological feature of both disorders, and we have recently shown that variation in DISC1 modulates prefrontal activation in healthy volunteers. Our goal was to examine the influence of the DISC1 polymorphism Cys704Ser on prefrontal function in schizophrenia and bipolar disorder. From 2004 to 2008, patients with schizophrenia (N = 44), patients with bipolar disorder (N = 35) and healthy volunteers (N = 53) were studied using functional magnetic resonance imaging while performing a verbal fluency task. The effect of Cys704Ser on cortical activation was compared between groups as Cys704 carriers vs. Ser704 homozygotes. In contrast to the significant effect on prefrontal activation we had previously found in healthy subjects, no significant effect of Cys704Ser was detected in this or any other region in either the schizophrenia or bipolar groups. When controls were compared with patients with schizophrenia, there was a diagnosis by genotype interaction in the left middle/superior frontal gyrus [family-wise error (FWE) P = 0.002]. In this region, Ser704/ser704 controls activated more than Cys704 carriers, and there was a trend in the opposite direction in schizophrenia patients. In contrast to its effect in healthy subjects, variation in DISC1 Cys704Ser704 genotype was not associated with altered prefrontal activation in patients with schizophrenia or bipolar disorder. The absence of an effect in patients may reflect interactions of the effects of DISC1 genotype with the effects of other genes associated with these disorders, and/or with the effects of the disorders on brain function.

Expanding the range of ZNF804A variants conferring risk of psychosis.

A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).

Exaggerated neural response to emotional faces in patients with bipolar disorder and their first-degree relatives.

Neuroimaging studies have demonstrated abnormalities in patients with bipolar disorder, including overactivity in anterior limbic structures in response to fearful or happy facial expressions. We investigated whether such anomalies might constitute heritable deviations underlying bipolar disorder, by virtue of being detectable in unaffected relatives carrying genetic liability for illness. Twenty patients with bipolar I disorder, twenty of their unaffected 1st degree relatives and twenty healthy volunteers participated in functional magnetic resonance imaging experiments of facial emotion processing. In one of these experiments, the participants watched faces expressing fear of varying intensities (moderate and high), intermixed with the non-emotional faces, and in another experiment - faces expressing moderate or high degrees of happiness intermixed with non-emotional faces. Repeated measures 2x3x3 ANOVA with emotion (fear and happy), intensity (neutral, moderate, and high) as within-subjects variables and group (patients, relatives, and controls) as between-subjects variable produced two clusters of differential activation, located in medial prefrontal cortex and left putamen. Activity in medial prefrontal cortex was greater in patients and in relatives compared with healthy volunteers in response to both fearful and happy faces. Activity in left putamen in response to moderate fear was greater in patients and in relatives compared with controls. Patients (but not relatives) showed also a greater activation in response to high intensity happy faces, compared with controls. Region of Interest analysis of amygdala activation showed increased activity in left amygdala in both patients and relatives groups in response to intensively happy faces. Exaggerated medial prefrontal cortical and subcortical (putamen and amygdala) responses to emotional signals may represent heritable neurobiological abnormalities underlying bipolar disorder.

Foundation studies in education for therapy practice: curriculum updating.

OBJECTIVE: To describe the foundation studies element of the education for practice as a speech and language therapist in one Irish University, and how this element features in curriculum development and updating. BACKGROUND: This paper addresses the question of how best to introduce students to the ever-increasing depth and range of knowledge regarding communication disorders. This foundation is the basis upon which to build the knowledge, skills and attitudes that lead ultimately to generating prerequisites for clinician scientists to provide services for people with communication and swallowing disabilities. METHODS/RESULTS: Since its institution as a university course, the course curriculum in our department at Trinity College Dublin, Ireland, has been subjected to regular revision and updating to be in line with educational, professional and service requirements. In this paper, we select elements of our most recent revision of the curriculum, incorporating the redefinition of the desirable characteristics of our graduates. This paper presents an overview of curriculum development, and focuses on the initial part of the education that sets the foundation for acquiring the knowledge that we consider to be a relevant, solid basis for entering clinical work. CONCLUSIONS: The current foundation stage of the curriculum encompasses elements that reflect increasing knowledge, trends in education practices, and the seeds of life-long learning.

The corpus callosum and empathy in adults with a history of preterm birth.

Reduced posterior corpus callosum (CC) area has been consistently observed in children and adolescents born very preterm (VPT). CC structural differences are also observed in people diagnosed with empathy disorders. This study examined empathy in relation to CC size in VPT adults and controls. CC area was manually measured for 17 VPT adults and 9 controls. Participants completed the Interpersonal Reactivity Index (Davis, 1980) and the Empathy Quotient (Baron-Cohen & Wheelwright, 2004). VPT adults had reduced posterior CC area in contrast to controls, and a positive linear trend was observed between posterior CC size and gestational age. No between-group empathy differences were observed, although self-reported personal distress in response to social situations was higher in VPT adults, and negatively associated with anterior CC area. We conclude that VPT adults have a smaller posterior CC, which is associated with gestational age, and elevated social distress, which may be mediated by anterior CC size.

A functional MRI study of verbal fluency in adults with bipolar disorder and their unaffected relatives.

BACKGROUND: Individuals with a history of bipolar disorder demonstrate abnormalities of executive function, even during euthymia. The neural architecture underlying this and its relationship with genetic susceptibility for illness remain unclear. METHOD: We assessed 18 remitted individuals with bipolar disorder, 19 of their unaffected first degree relatives and 19 healthy controls using functional magnetic resonance imaging (fMRI) and a paced verbal fluency task with two levels of difficulty. RESULTS: Bipolar patients made significantly more errors in the easy level of the verbal fluency task than their relatives or controls. Analysis of variance of fMRI data demonstrated a significant main effect of group in a large cluster including retrosplenial cortex and adjacent precuneate cortex (x=7, y=-56, x=15). All three groups showed deactivation in these areas during task performance relative to a neutral or rest condition. Group differences comprised a lesser amount of deactivation in unaffected relatives compared with controls in the easy condition [F(2, 55)=3.42, p=0.04] and in unaffected relatives compared with bipolar patients in the hard condition [F(2, 55)=4.34, p=0.018]. Comparison with the control group indicated that both bipolar patients and their relatives showed similar deficits of deactivation in retrosplenial cortex and reduced activation of left prefrontal cortex. CONCLUSIONS: Bipolar disorder may be associated with an inherited abnormality of a neural network incorporating left prefrontal cortex and bilateral retrosplenial cortex.

Genetic modelling of childhood social development and personality in twins and siblings with schizophrenia.

BACKGROUND: Abnormalities in early social development and personality are present in patients with schizophrenia and their unaffected relatives. This study aimed to establish the degree to which these childhood and adolescent developmental abnormalities are genetically determined. METHOD: We used a combined twin and family study design (n=531) to assess childhood and adolescent social adjustment and schizotypal personality traits in 98 twin pairs (n=196) varying in their zygosity and concordance for schizophrenia and 156 sibling clusters (n=335) varying in their concordance for schizophrenia. RESULTS: Schizophrenia was significantly associated with childhood and adolescent deficits in social adjustment and personality, with additive genetic effects being the main source of these phenotypic correlations. CONCLUSIONS: Abnormalities of social adjustment and personality are present in children and adolescents who later develop schizophrenia, reflecting the influence of common genetic risk.

The effect of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis.

BACKGROUND: Morphometric endophenotypes which have been proposed for psychotic disorders include lateral ventricular enlargement and hippocampal volume reductions. Genetic epidemiological studies support an overlap between schizophrenia and bipolar disorder, and COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes have been implicated in the aetiology of both these disorders. This study examined associations between these candidate genes and morphometric endophenotypes for psychosis. METHOD: A total of 383 subjects (128 patients with psychosis, 194 of their unaffected relatives and 61 healthy controls) from the Maudsley Family Psychosis Study underwent structural magnetic resonance imaging and genotyping. The effect of candidate genes on brain morphometry was examined using linear regression models adjusting for clinical group, age, sex and correlations between members of the same family. RESULTS: The results showed no evidence of association between variation in COMT genotype and lateral ventricular, and left or right hippocampal volumes. Neither was there any effect of the BDNF, 5-HTTLPR, NRG1 and DTNBP1 genotypes on these regional brain volumes. CONCLUSIONS: Abnormal hippocampal and lateral ventricular volumes are among the most replicated endophenotypes for psychosis; however, the influences of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on these key brain regions must be very subtle if at all present.

Psychiatric disorder in young adults born very preterm: role of family history.

OBJECTIVE: To investigate whether young adults born very preterm (VPT) (<33 weeks) are at increased risk for psychiatric illness in adulthood and whether a family history of psychiatric disorder further increases this risk. METHODS: We assessed 169 VPT and 101 term born individuals using the Clinical Interview Schedule - Revised. RESULTS: Young adults born VPT had an increased risk for psychiatric disorder compared to controls (OR=3.1, 95% CI=1.1-8.6, p=0.03). Those born VPT who had a history of psychiatric disorder in a first-degree relative, had an increase in risk for psychiatric disorder compared to those born VPT without a family history (OR=5.2, 95% CI=1.8-14.9, p=0.002). CONCLUSION: Individuals born VPT are at increased risk of psychiatric illness in young adulthood compared to controls. In addition, a family history of psychiatric disorder in a first-degree relative may leave young adults born VPT particularly vulnerable to psychiatric illness.