Are UHR patients who present with hallucinations alone at lower risk of transition to psychosis?

The aim of this study was to investigate whether Ultra High Risk for psychosis (UHR) patients who present with hallucinations alone at identification as UHR are at lower risk of transition to psychosis than UHR patients who present with symptoms other than hallucinations or hallucinations plus other symptoms.Our primary dataset was a retrospective "case-control" study of UHR patients (N=118). The second, independent dataset was a long-term longitudinal follow up study of UHR patients (N=416). We performed a survival analysis using Log-rank test and Cox regression to investigate the relationship between symptom variables and transition to a psychotic disorder.Hallucinations alone at baseline were not significantly associated with a reduced risk of transition to psychosis. In the case control study the presence of hallucinations when found in the absence of any thought disorder and visual hallucinations in the absence of substance misuse was associated with a reduced risk of transition to psychosis. In the longitudinal follow-up dataset perceptual disturbance found in the absence of a disorder of affect or emotion was associated with an increased risk of transition to psychosis

Morphology of the corpus callosum at different stages of schizophrenia: Cross-sectional study in first-episode and chronic illness (British Journal of Psychiatry 192 (429-434))

Morphology of the corpus callosum at different stages of schizophrenia: Cross-sectional study in first-episode and chronic illness (British Journal of Psychiatry 192 (429-434)

Markers of vulnerability to obsessive-compulsive disorder in an ultra-high risk sample of patients who developed psychosis

Aims: The study aims to identify markers of vulnerability to obsessive-compulsive disorder (OCD) in an ultra-high risk sample of patients who developed psychosis. Methods: Three hundred and eleven patients at ultra-high risk for psychosis were examined at baseline and after a mean of 7.4years follow-up. Patients who developed psychosis with OCD (PSY+OCD; n=13) and psychosis without OCD (PSY-OCD; n=45) were compared in terms of socio-demographic and clinical features. Results: PSY+OCD patients displayed greater severity of depression before and after conversion to PSY+OCD, and increased rates of depressive disorders before exhibiting PSY+OCD. However, they only displayed greater severity of anxiety and increased rates of non-OCD anxiety disorders after psychosis. Further, PSY+OCD patients were more likely to report a positive family history for anxiety disorders than PSY-OCD. Conclusion: Although depression and a family history of anxiety disorder may act as vulnerability markers for OCD in psychosis, the resulting anxiety may be a correlate or a consequence of PSY+OCD. © 2012 Blackwell Publishing Asia Pty Ltd

Cognitive deficits in youth with familial and clinical high risk to psychosis: A systematic review and meta-analysis

Objective: It is likely that cognitive deficits are vulnerability markers for developing schizophrenia, as these deficits are already well-established findings in first-episode psychosis. Studies at-risk adolescents and young adults are likely to provide information about cognitive deficits that predate the onset of the illness. Method: We conducted meta-analyses of studies comparing familial-high risk (FHR) or ultra-high risk (UHR; n = 2113) and healthy controls (n = 1748) in youth studies in which the mean age was between 15 and 29. Results: Compared with controls, high risk subjects were impaired in each domain in both UHR (d = 0.34-0.71) and FHR (d = 0.24-0.81). Heterogeneity of effect sizes across studies was modest, increasing confidence to the findings of the current meta-analysis (I2 = 0-0.18%). In both risk paradigms, co-occurrence of genetic risk with attenuated symptoms was associated with more severe cognitive dysfunction. In UHR, later transition to psychosis was associated with more severe cognitive deficits in all domains (d = 0.31-0.49) except sustained attention. However, cognitive impairment has a limited capacity to predict the outcome of high-risk patients. Conclusion: Cognitive deficits are already evident in adolescents and young adults who have familial or clinical risk for psychosis. Longitudinal developmental studies are important to reveal timing and trajectory of emergence of such deficits. © 2014 John Wiley & Sons A/S

Sulcogyral pattern and sulcal count of the orbitofrontal cortex in individuals at ultra high risk for psychosis

Three types of orbitofrontal cortex (OFC) sulcogyral patterns have been identified in the general population. The distribution of these three types has been found to be altered in individuals at genetic risk of psychosis, and in patients with first episode psychosis (FEP) and chronic schizophrenia. This study aims at establishing whether altered OFC sulcogyral patterns were present in a large cohort of individuals at ultra high risk (UHR) for psychosis. OFC pattern type was classified and the number of posterior and intermediate sulci present on the surface of the OFC was counted. OFC sulcogyral type and the number of sulci were compared between controls (n=58) and UHR participants who transitioned (n=49) versus those who did not transition (n=77) to psychosis. Finally, the relationship between sulcogyral type and number of sulci with intellectual quotient (IQ), symptom severity and social functioning of UHR individuals was explored. In line with other studies conducted in chronic schizophrenia and FEP, UHR individuals who later transitioned to psychosis showed a reduced incidence of the Type I OFC on the right hemisphere compared to controls (χ2=19.847, p<0.001). These highly consistent results point towards the protective effect of possessing a Type I OFC in the right hemisphere. Furthermore, OFC sulcus counts revealed that controls presented with a higher number of posterior (right hemisphere; χ2=11.658, p=0.003) and intermediate sulci (left: χ2=6.643, p=0.036; right: χ2=11.726, p=0.020) when compared to UHR individuals. However, no associations between OFC types or sulcus count and IQ, symptoms and functioning were observed. © 2014 Elsevier B.V

Sexual trauma increases the risk of developing psychosis in an ultra high-risk "prodromal" population

Studies indicate a high prevalence of childhood trauma in patient cohorts with established psychotic disorder and in those at risk of developing psychosis. A causal link between childhood trauma and development of psychosis has been proposed. We aimed to examine the association between experience of childhood trauma and the development of a psychotic disorder in a large "Ultra High Risk" (UHR) for psychosis cohort. The data were collected as part of a longitudinal cohort study of all UHR patients recruited to research studies at the Personal Assessment and Clinical Evaluation clinic between 1993 and 2006. Baseline data were collected at recruitment to these studies. The participants completed a comprehensive follow-up assessment battery (mean time to follow-up 7.5 years, range 2.4-14.9 years), which included the Childhood Trauma Questionnaire (CTQ), a self-report questionnaire that assesses experience of childhood trauma. The outcome of interest was transition to a psychotic disorder during the follow-up period. Data were available on 233 individuals. Total CTQ trauma score was not associated with transition to psychosis. Of the individual trauma types, only sexual abuse was associated with transition to psychosis (P =. 02). The association remained when adjusting for potential confounding factors. Those with high sexual abuse scores were estimated to have a transition risk 2-4 times that of those with low scores. The findings suggest that sexual trauma may be an important contributing factor in development of psychosis for some individuals. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved

Phenylthiocarbamide (PTC) perception in ultra-high risk for psychosis participants who develop schizophrenia: Testing the evidence for an endophenotypic marker

Reports suggesting that schizophrenia participants are more likely to be phenylthiocarbamide (PTC) non-tasters when compared to controls have recently been controversial. If supported, a genetic-based phenotypic variation in PTC taster status is implicated, suggesting a greater illness risk for those participants with recessive alleles for the TAS2R38 receptor. Should PTC insensitivity be a schizophrenia endophenotype, then it would be expected in follow-up of ultra high-risk for psychosis participants who later develop schizophrenia (UHR-S). UHR-S was hypothesised to show reduced PTC sensitivity compared to those who were previously at risk, but did not transition (UHR-NP). PTC perception was assessed in 219 UHR participants at long-term follow-up, of whom 53 had transitioned to psychosis (UHR-P) during the follow-up period. Fifteen of the 219 participants were diagnosed with schizophrenia. Seventy-eight had a family history of psychotic disorder. No differences in PTC taster status were found in UHR participants based upon transition to psychosis status, schizophrenia diagnosis, or family history of schizophrenia. This report indicates that schizophrenia development among UHR participants is not associated with PTC tasting deficits and fails to support previous findings that inability to detect the bitter taste of PTC is a schizophrenia endophenotype. © 2012 Elsevier Ireland Ltd

Volumetric abnormalities predating the onset of schizophrenia and affective psychoses: An MRI study in subjects at ultrahigh risk of psychosis

It remains unclear whether brain structural abnormalities observed before the onset of psychosis are specific to schizophrenia or are common to all psychotic disorders. This study aimed to measure regional gray matter volume prior to the onset of schizophreniform and of affective psychoses. We investigated 102 subjects at ultrahigh risk (UHR) of developing psychosis recruited from the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia. Twenty-eight of these subjects developed psychosis subsequent to scanning: 19 schizophrenia, 7 affective psychoses, and 2 other psychoses. We examined regional gray matter volume using 1.5 mm thick, coronal, 1.5 Tesla magnetic resonance imaging and voxel-based morphometry methods of image analysis. Subjects were scanned at presentation and were followed up clinically for a minimum of 12 months, to detect later transition to psychosis. We found that both groups of subjects who subsequently developed psychosis (schizophrenia and affective psychosis) showed reductions in the frontal cortex relative to UHR subjects who did not develop psychosis. The subgroup that subsequently developed schizophrenia also showed smaller volumes in the parietal cortex and, at trend level, in the temporal cortex, whereas those who developed an affective psychosis had significantly smaller subgenual cingulate volumes. These preliminary findings suggest that volumetric abnormalities in UHR individuals developing schizophrenia vs affective psychoses comprise a combination of features that predate both disorders and others that may be specific to the nature of the subsequent disorder. © 2012 The Author

Altered depth of the olfactory sulcus in ultra high-risk individuals and patients with psychotic disorders

A shallow olfactory sulcus has been reported in schizophrenia, possibly reflecting abnormal forebrain development during early gestation. However, it remains unclear whether this anomaly exists prior to the onset of psychosis and/or differs according to illness stage. In the current study, magnetic resonance imaging was used to investigate the length and depth of the olfactory sulcus in 135 ultra high-risk (UHR) individuals [of whom 52 later developed psychosis (UHR-P) and 83 did not (UHR-NP)], 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, and 87 healthy controls. While there was no group difference in the length of the sulcus, UHR-P subjects had significantly shallower olfactory sulcus at baseline as compared with UHR-NP and control subjects. The depth of this sulcus became increasingly more superficial as one moved from UHR-P subjects to FEP patients to chronic schizophrenia patients. Finally, the depth of the olfactory sulcus in the UHR-P subjects was negatively correlated with the severity of negative symptoms. These findings suggest that the altered depth of the olfactory sulcus, which exists before psychosis onset, could be predictive of transition to psychosis, but also suggest ongoing changes of the sulcus morphology during the course of the illness. © 2014 Elsevier B.V

Structural abnormalities in the cuneus associated with Herpes Simplex Virus (type 1) infection in people at ultra high risk of developing psychosis

It has been suggested that some cases of schizophrenia may be caused by an interaction between physiological risk factors and exposure to certain neurotropic infectious agents such as Herpes Simplex Virus type 1 (HSV1). This study investigated whether HSV1 exposure was associated with structural brain abnormalities in individuals who, because of genetic or other factors, were deemed at ultra high risk (UHR) of developing psychosis. Twenty-five UHR individuals with a history of HSV1 exposure (HSV1. +), 33 UHR participants without a history of HSV1 exposure (HSV1. -) and 19 healthy controls participated in the study. All participants underwent a T1-weighted structural MRI scan, and HSV1 exposure was determined based on the presence of IgG class antibodies in the blood serum. Voxel based morphometry revealed that the HSV1. + participants exhibited volumetric gray matter reductions in the cuneus, relative to both the HSV1. - and healthy control participants (p. <. 0.05, small volume corrected for familywise error). The results of the study suggest that a history of HSV1 infection is associated with volumetric gray matter reductions in individuals at ultra-high risk for developing psychosis, and are consistent with previous studies that have identified structural gray matter abnormalities in HSV1-infected patients with established schizophrenia. © 2011 Elsevier B.V