A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis

Background

We evaluated whether (1) a diagnosis of obsessive-compulsive disorder (OCD) at baseline, or (2) the persistence, remission or emergence of de novo OCD at follow-up, were associated with the development of different psychotic disorders in a cohort of individuals at ultra-high risk (UHR) for psychosis.

Methods

Patients were assessed for OCD at baseline and after a mean of 7.4 years follow-up and classified into: (i) Non-OCD group - patients without OCD both at baseline and follow-up (n = 269; 86.2%), (ii) Incident OCD group - patients without OCD at baseline but with OCD at follow-up (n = 17; 5.4%), (iii) Remitting OCD group - patients with OCD at baseline but without OCD at follow-up (n = 20; 6.4%), (iv) Persistent OCD group - patients with OCD both at baseline and at follow-up (n = 6; 1.9%). Rates of different DSM-IV psychotic disorders at follow-up were compared across these groups.

Results

Patients who displayed remitting OCD were not related to the development of any DSM-IV psychotic disorder. A diagnosis of incident OCD was associated with greater rates of psychotic disorders at follow-up, particularly mood disorders with psychotic features and psychotic disorders not otherwise specified (PDNOS), and greater baseline severity of general psychopathology, alogia, and avolition-apathy. Two of the six patients (40%) with persistent OCD developed schizophrenia, while only 12.5%, 5.0%, and 9.7% of incident, remitting, and non-OCD groups, respectively, exhibited the same condition at follow-up. Rates of antipsychotic use in the previous two years were not significantly different between the groups.

Conclusions

Our findings suggest that, in a cohort of individuals at UHR for psychosis, remission of OCD does not increase the risk of psychosis, while de novo OCD was associated with development of mood disorders with psychotic features and PDNOS.     

Impairment of olfactory identification ability in individuals at ultra-high risk for psychosis who later develop schizophrenia

OBJECTIVE: Previous investigation has revealed stable olfactory identification deficits in neuroleptic-naive patients experiencing a first episode of psychosis, but it is unknown if these deficits predate illness onset. METHOD: The olfactory identification ability of 81 patients at ultra-high risk for psychosis was examined in relation to that of 31 healthy comparison subjects. Twenty-two of the ultra-high-risk patients (27.2%) later became psychotic, and 12 of these were diagnosed with a schizophrenia spectrum disorder. RESULTS: There was a significant impairment in olfactory identification ability in the ultra-high-risk group that later developed a schizophrenia spectrum disorder but not in any other group. CONCLUSIONS: These findings suggest that impairment of olfactory identification is a premorbid marker of transition to schizophrenia, but it is not predictive of psychotic illness more generally.     

Increased PLA2 activity in individuals at ultra-high risk for psychosis

European Archives of Psychiatry and Clinical Neuroscience - Phospholipase A2 is the main enzyme in the metabolism of membrane phospholipids. It comprises a family of enzymes divided into iPLA2,...     

Antibodies to infectious agents in individuals at ultra-high risk for psychosis.

BACKGROUND: While there is evidence that some cases of schizophrenia may be associated with microbial infections, the role of microbial agents has not been investigated in people with emerging psychosis. METHODS: Participants were 105 help seeking ultra-high risk individuals. Psychiatric measures included the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms. Serum IgG antibodies against human herpesviruses and Toxoplasma gondii were determined using immunoassay methods. Multiple linear regression with adjustment for age and sex was applied to test associations between serum antibodies and psychiatric measures. RESULTS: Higher levels of serum IgG antibodies against Toxoplasma gondii in Toxoplasma-positive individuals were significantly associated with more severe positive psychotic symptoms. No significant association was observed between antibody levels and psychiatric measures in individuals positive for human herpesviruses. CONCLUSIONS: In some individuals infection with Toxoplasma gondii may be an environmental factor contributing to the manifestation of positive psychotic symptoms.     

Fine motor function and neuropsychological deficits in individuals at risk for schizophrenia

Deficits in fine motor function and neuropsychological performance have been described as risk factors for schizophrenia. In the Basel FEPSY study (Früherkennung von Psychosen; English: Early Detection of Psychosis) individuals at risk for psychosis were identified in a screening procedure (Riecher–Rössler et al. 2005). As a part of the multilevel assessment, 40 individuals at risk for psychosis and 42 healthy controls matched for age, sex and handedness were investigated with a fine motor function test battery and a neuropsychological test battery. Individuals at risk showed lower performances in all subtests of the fine motor function tests, predominantly in dexterity and velocity (wrist/fingers and arm/hand). In the neuropsychological test battery, individuals at risk performed less well compared to healthy controls regarding sustained attention, working memory and perseveration. The combined evaluation of the two test batteries (neuropsychological and fine motor function) separates the two groups into individuals at risk and healthy controls better than each test battery alone. A multilevel approach might therefore be a valuable contribution to detecting beginning schizophrenia.     

Stress and protective factors in individuals at ultra-high risk for psychosis, first episode psychosis and healthy controls

Stress-vulnerability models of schizophrenia regard psychosocial stress as an important factor in the onset and aggravation of psychotic symptoms, but such research in the early phases of psychosis is limited. Protective factors against the effects of stress might be the key to understanding some inconclusive findings and to the development of optimal psychosocial interventions. The present study compared self-reported levels of stress, self-esteem, social support and active coping in 32 patients with a first episode of psychosis (FEP), 30 individuals at ultra-high risk for psychosis (UHR) and 30 healthy controls. Associations with symptoms of psychosis were assessed in both patient groups. Individuals at UHR reported significantly higher stress levels compared to FEP patients. Both patient groups showed lower self-esteem compared to controls, and the UHR group reported lower social support and active coping than controls. These group differences could not be explained by age and dose of antipsychotic medication in the FEP group. In the UHR group, higher stress levels and lower self-esteem were associated with more severe positive and depressive symptoms on the Brief Psychiatric Rating Scale. Multiple regression analyses revealed that stress was the only significant predictor for both symptom measures and that the relationship was not moderated by self-esteem. Our findings show that individuals at UHR for psychosis experience high levels of psychosocial stress and marked deficits in protective factors. The results suggest that psychosocial interventions targeted at reducing stress levels and improving resilience in this population may be beneficial in improving outcomes.     

Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis.

BACKGROUND: We examined pituitary volume before the onset of psychosis in subjects who were at ultra-high risk (UHR) for developing psychosis. METHODS: Pituitary volume was measured on 1.5-mm, coronal, 1.5-T magnetic resonance images in 94 UHR subjects recruited from admissions to the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia and in 49 healthy control subjects. The UHR subjects were scanned at baseline and were followed clinically for a minimum of 1 year to detect transition to psychosis. RESULTS: Within the UHR group, a larger baseline pituitary volume was a significant predictor of future transition to psychosis. The UHR subjects who later went on to develop psychosis (UHR-P, n = 31) had a significantly larger (+12%; p = .001) baseline pituitary volume compared with UHR subjects who did not go on to develop psychosis (UHR-NP, n = 63). The survival analysis conducted by Cox regression showed that the risk of developing psychosis during the follow-up increased by 20% for every 10% increase in baseline pituitary volume (p = .002). Baseline pituitary volume of the UHR-NP subjects was smaller not only compared with UHR-P (as described above) but also compared with control subjects (-6%; p = .032). CONCLUSIONS: The phase before the onset of psychosis is associated with a larger pituitary volume, suggesting activation of the HPA axis.     

Altered resting-state connectivity in subjects at ultra-high risk for psychosis: an fMRI study

Background  

Individuals at ultra-high risk (UHR) for psychosis have self-disturbances and deficits in social cognition and functioning. Midline default network areas, including the medial prefrontal cortex and posterior cingulate cortex, are implicated in self-referential and social cognitive tasks. Thus, the neural substrates within the default mode network (DMN) have the potential to mediate self-referential and social cognitive information processing in UHR subjects.     

Investigation of structural brain correlates of neurological soft signs in individuals at ultra-high risk for psychosis

European Archives of Psychiatry and Clinical Neuroscience - Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in...     

Temperament and character in individuals at ultra-high risk for psychosis and with first-episode schizophrenia: Associations with psychopathology,psychosocial functioning,and aspects of psychological health

Objective

The psychobiological model of temperament and character indicates that personality traits are heritable and, during development, constantly influence one’s susceptibility to schizophrenia. Our objective was to evaluate temperament and character in subjects at ultra-high risk (UHR) for psychosis and individuals with first-episode schizophrenia.

Methods

UHR for psychosis subjects (n = 50), first-episode schizophrenia patients (n = 33), and normal controls (n = 120) were compared on temperament and character dimensions, and correlation analysis of each personality dimension with psychopathologies, global and social functioning, and self-esteem. General and social self-efficacy reports were conducted. UHR subjects were followed-up for 24 months and the baseline personality dimensions were compared between the converted and non-converted groups.

Results

Both clinical groups showed abnormal personality traits in terms of temperament (higher harm avoidance, lower reward dependence and persistence) and character (lower self-directedness and cooperativeness). Psychosocial functioning and psychological health components were found to be correlated with some personality dimensions. The conversion rate of overt psychotic disorder was 25.0% at the 24-month follow-up. Baseline cooperativeness dimension was a significant predictive dimension for conversion into overt psychosis in the UHR group during the follow-up period.

Conclusion

Patients with first episode schizophrenia have a pervasively altered personality profile from normal controls. More importantly, this altered personality profile already emerged in putative prodromal, UHR individuals. The present findings indicate that certain personality traits can play a protective or vulnerable role in developing schizophrenia.     

White matter fibertracking in first-episode schizophrenia, schizoaffective patients and subjects at ultra-high risk of psychosis

There is increasing evidence of white matter pathology in schizophrenia. The aim of this study was to examine whether white matter abnormalities found with diffusion tensor imaging (DTI) in previous schizophrenia studies are present in the early phase of the illness. DTI was performed at 3 T on 10 male patients with a first (n = 8) or second (n = 2) psychotic episode of schizophrenia or schizoaffective disorder, 10 male patients at ultra-high risk of psychosis with (pre)psychotic symptoms and 10 healthy controls. Fibertracts found to be abnormal in other DTI studies (uncinate and arcuate fasciculus, anterior and dorsal cingulum, subdivisions of the corpus callosum) were calculated and visualized; tract-specific measurements (fractional anisotropy and trace) were performed. No differences were found between the healthy subjects and the 2 patient groups. These preliminary findings suggest that there is no white matter pathology of these association tracts detectable with DTI in the early stages of schizophrenic illness in males. Our findings are in contrast with DTI abnormalities found in some other first-episode studies. This discrepancy in findings may be related to differences in subject characteristics and DTI methodology. Possible effects of age, gender, level of education and illicit substance use on DTI findings in schizophrenia are discussed.     

Visual form perception: a comparison of individuals at high risk for psychosis, recent onset schizophrenia and chronic schizophrenia

Schizophrenia has been associated with deficits in visual perception and processing, but there is little information about their temporal development and stability. We assessed visual form perception using the Rorschach Comprehensive System (RCS) in 23 individuals at clinical high risk for psychosis, 15 individuals with recent onset schizophrenia (< or =2 years since onset), and 34 with chronic schizophrenia (> or =3 years since onset). All three groups demonstrated reduced conventional form perception (X+%), as compared with published norms, but did not differ significantly from one another. In contrast, the high-risk group had significantly better performance on an index of clarity of conceptual thinking (WSUM6) compared to the chronic schizophrenia patients, with the recent onset group scoring intermediate to the high-risk and chronic schizophrenia groups. The results suggest that individuals at clinical high risk for psychosis display substantial deficits in visual form perception prior to the onset of psychosis and that these deficits are comparable in severity to those observed in individuals with schizophrenia. Therefore, visual form perception deficits may constitute a trait-like risk factor for psychosis in high-risk individuals and may potentially serve as an endophenotype of risk for development of psychosis. Clarity of conceptual thinking was relatively preserved among high-risk patients, consistent with a relationship to disease expression, not risk. These deficits are discussed in the context of the putative neurobiological underpinnings of visual deficits and the developmental pathophysiology of psychosis in schizophrenia.