Assessing expressed emotion during pregnancy.

We assessed expressed emotion (EE) with an adapted version of the five-minute speech sample in 847 pregnant women. The prevalence of high EE was 6%. High EE was significantly associated with having a first child, low income, maternal childhood trauma and lack of parental emotional warmth during childhood.

Semantic fluency deficits and reduced grey matter before transition to psychosis: a voxelwise correlational analysis.

Early identification of subjects with an increased risk of psychosis is necessary to develop interventions to delay or prevent disease onset. We recently reported that decreased semantic verbal fluency performance in ultra high risk (UHR) subjects predicts the development of psychosis (Becker et al., 2010). The present study investigated whether semantic and verbal fluency scores correlate with grey matter density in UHR subjects. Thirty-seven UHR subjects underwent structural MRI scanning and verbal fluency assessment after which they were followed up for 2 years. Using voxel-based morphometry, we investigated whether grey matter density correlated with verbal fluency scores in 10 UHR subjects who developed psychosis during follow-up and 27 UHR subjects who did not develop psychosis. In UHR subjects developing psychosis, lower semantic fluency scores correlated significantly with reduced grey matter density in the right superior and middle temporal gyrus, the right insula, and the left anterior cingulate cortex. This study shows that a correlation between semantic fluency performance and grey matter density in task-related areas can differentiate between UHR subjects who subsequently will develop psychosis and those who will not. Combining these two measures could improve psychosis prediction in UHR subjects.

Factor analysis of the scale of prodromal symptoms: differentiating between negative and depression symptoms.

BACKGROUND: This study examines the ability of the Scale of Prodromal Symptoms (SOPS) to differentiate between negative and depression symptoms in a young help-seeking ultrahigh risk (UHR) group. METHODS: SOPS data of 77 help-seeking patients at UHR for psychosis were analyzed with an exploratory factor analysis. The extracted Depression factor was validated with the Beck Depression Inventory (BDI). The extracted SOPS Negative symptoms factor was validated with the Negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS). RESULTS: Four factors were extracted from the SOPS: a negative, depression, disorganized and positive factor. The Negative symptom factor consisted of three items (N1: social anhedonia and withdrawal, N3: decreased expression of emotion; N4: decreased experience of emotions and self), and could be validated with the PANSS Negative symptoms subscale. The Depression factor was also made up of three items (G2: dysphoric mood, G4: impaired tolerance to normal stress, and D4: personal hygiene/social attentiveness), and could be validated with the BDI. CONCLUSIONS: Our results suggest that 3 items of the Negative symptoms subscale of the SOPS, 2 items of the General and 1 item of the Disorganization subscale differentiate validly between negative and depression symptoms in an UHR population.

Diagnostic validity of the Eppendorf Schizophrenia Inventory (ESI): a self-report screen for ultrahigh risk and acute psychosis.

Providers of mental health services need tools to screen for acute psychosis and ultrahigh risk (UHR) for transition to psychosis in help-seeking individuals. In this study, the Eppendorf Schizophrenia Inventory (ESI) was examined as a screening tool and for its ability to correctly predict diagnostic group membership (e.g., help seeking, mild psychiatric complaints, highly symptomatic mood or anxiety disorder, UHR, acute psychosis). Diagnostic evaluation with established instruments was used for diagnosis in 3 research samples. UHR status was assessed with the Structured Interview for Prodromal Symptoms/Scale of Prodromal Symptoms (Miller et al., 1999) and the Bonn Scale for the Assessment of Basic Symptoms Prediction list (Gross, Huber, Klosterkötter, & Linz, 1987; Klosterkötter, Hellmich, Steinmeyer, & Schulze-Lutter, 2001). This study showed that members of different diagnostic groups rate themselves significantly differently on the ESI and its subscales. A new subscale was constructed, the UHR-Psychosis scale, that showed good utility in detecting individuals with interview-diagnosed UHR status and acute psychosis. The scale is also sensitive to the threshold between UHR and acute psychosis. Practical applications of the ESI include use as a diagnostic tool within various settings.

Disability in people clinically at high risk of psychosis.

BACKGROUND: Decline in social functioning occurs in individuals who later develop psychosis. AIMS: To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition. METHOD: Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS-II). RESULTS: At baseline, the transition group displayed significantly greater difficulties in making new friends (z = -3.40, P = 0.001), maintaining a friendship (z =-3.00, P = 0.003), dealing with people they do not know (z =-2.28, P = 0.023) and joining community activities (z =-2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (ß = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238-2.550). CONCLUSIONS: Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.

Age of onset of cannabis use is associated with age of onset of high-risk symptoms for psychosis.

OBJECTIVE: Increasing interest in the prodromal stage of schizophrenia over the past decade led us to perform our study to monitor people at high risk for developing a psychosis. We hypothesized that cannabis use or a cannabis use disorder at a younger age relates to high-risk symptoms at a younger age. METHOD: People referred to the Academic Medical Centre in Amsterdam, the Netherlands, with an ultra-high risk (UHR) for psychosis were interviewed with the Composite International Diagnostic Interview to assess their cannabis consumption. The Interview for the Retrospective Assessment of the Onset of Schizophrenia was used to collect data about age of onset of high-risk or prodromal symptoms. Nine high-risk symptoms were selected and clustered because of their known relation with cannabis use. RESULTS: Among the 68 included participants, 35 had used cannabis (51.5%), of whom 15 had used recently. Twenty-two participants had been cannabis abusers or cannabis-dependent (32.4%) in the past. Younger age at onset of cannabis use was related to younger age of onset of the cluster of symptoms (rho = 0.48, P = 0.003) and also to 6 symptoms individually (rho = 0.47 to 0.90, P < 0.001 to 0.04). Younger age at onset of a cannabis use disorder was related to younger age of onset of the cluster of symptoms (rho = 0.67, P = 0.001) and also to 6 symptoms individually (rho = 0.50 to 0.93, P = 0.007 to 0.03). CONCLUSION: Cannabis use or a cannabis use disorder at a younger age in a group with an UHR for transition to psychosis is related to onset of high-risk symptoms for psychosis at a younger age.

White matter connectivity and psychosis in ultra-high-risk subjects: a diffusion tensor fiber tracking study.

This study assessed with diffusion tensor imaging (DTI) whether ultra-high-risk subjects who later develop a psychotic disorder (UHR-P) show abnormalities in association white matter fiber tracts as compared to UHR subjects who do not convert to psychosis (UHR-NP) and healthy controls. Participants comprised 17 male UHR subjects and 10 male healthy controls, who received baseline DTI scans before clinical follow-up. The uncinate and arcuate fasciculi, anterior and dorsal cingulate, and subdivisions of the corpus callosum were calculated and visualized, and tract-specific measurements were performed. At 24-month follow-up seven UHR subjects had developed a first psychotic episode. Fractional anisotropy in baseline DTI scans, including left-right asymmetry measures, did not differ between the groups. Thus, DTI measures of these association white matter tracts were not biological markers of psychosis in our UHR sample. Abnormalities of these fiber tracts may develop around or after onset of psychosis. However, further DTI studies in UHR subjects are needed in larger samples.

Prescription of antipsychotic medication to patients at ultra high risk of developing psychosis.

Little is known about medication prescription in a naturalistic setting to patients at ultra high risk (UHR) of developing psychosis. Antipsychotic medication prescription to UHR patients is not recommended in clinical practice guidelines based on the current evidence. The aim of this study is to investigate medication prescription to UHR patients in the Netherlands. The frequency of antipsychotic medication prescription to UHR patients (n=72) was compared with the frequency of antipsychotic medication prescription to patients who were diagnosed with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition psychotic disorder at first diagnostic evaluation (n=90). Within the UHR group, frequency of antipsychotic medication prescription at baseline was compared between UHR patients who did make the transition to psychosis (n=18) and UHR patients who did not (n=54). No significant differences were found in antipsychotic medication prescription to UHR patients and to patients who turned out to have a florid psychosis: 51% in the psychotic group and 58% in the UHR group used no medication. Thirty-four percent in the psychotic group and 21% in the UHR group used antipsychotic medication. There was also no difference in medication prescription between UHR patients who did and did not make the transition to psychosis. More research should be aimed at developing and implementing clinical practice guidelines for the treatment of UHR patients.

Baseline differences in clinical symptomatology between ultra high risk subjects with and without a transition to psychosis.

BACKGROUND: The chance of transition to psychosis in patients at Ultra High Risk for developing psychosis (UHR) is 10-15%. The aim of present study was to investigate differences in baseline clinical symptomatology, general level of functioning (GAF-score) and genetic risk between UHR patients who did (UHR+T) or did not (UHR+NT) make a transition to psychosis. Sharpening UHR inclusion criteria may aid in improving prediction of transition to psychosis. METHOD: The study sample was taken from 285 patients who were examined within the Dutch Prediction of Psychosis Study (DUPS) at the Academic Medical Center of the University of Amsterdam, the Netherlands. Out of 73 included UHR subjects, 18 made a transition to psychosis. Psychopathology was investigated with the Structured Interview for Prodromal Syndromes, Bonn Scale for the Assessment of Basic Symptoms and GAF-score. The follow-up period of the study was three years. RESULTS: The UHR+T group showed more social anhedonia and withdrawal, more bizarre thinking and a lower GAF score at baseline than the UHR+NT group. CONCLUSIONS: In agreement with the results of Cannon et al. [Cannon, T.D., Cadenhead, K., Cornblatt, B., Woods, S.W., Addington, J., Walker, E., Seidman, L.J., Perkins, D., Tsuang, M., McGlashan, T., Heinssen, R., 2008. Prediction of Psychosis in Youth at High Clinical Risk: A Multisite Longitudinal Study in North America. Arch. Gen. Psychiat. 65 (1) 28-37.], our study indicates that severity of specific symptoms at baseline is related to transition to psychosis in UHR subjects. These findings may contribute to a more accurate prediction of a first psychotic episode. Furthermore, symptoms that are increased at baseline in the UHR+T group could be a focus of cognitive behavioural therapy in the UHR period.

Childrearing style in families of anxiety-disordered children: between-family and within-family differences.

This study examined whether (1) parents of anxiety-disordered (AD) children differed from those of non-clinical controls in their childrearing style, and whether (2) the child-rearing style of parents towards AD children is different from that towards their siblings. A clinical sample of 25 AD children, age range 8-13 years, was compared with 25 siblings and a non-clinical control group (n = 25). Childrearing was assessed by means of parental self-report, child report and through an expressed emotion interview measure. AD children perceived more parental rejection than non-clinical control children or the AD children's siblings. High-expressed emotion was scored significantly more often towards AD children than non-clinical control children, or their siblings. On [Symbol: see text]care' and [Symbol: see text]control' parental self-report showed some differences regarding AD children on the one hand and non-clinical control children or siblings of AD children on the other. These results suggest that the rearing of AD children differs significantly both from the rearing of their siblings and that of non-clinical control children.

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.

Predictive value of cognition for different domains of outcome in recent-onset schizophrenia.

The aim of this study was to see whether and how cognition predicts outcome in recent-onset schizophrenia in a large range of domains such as course of illness, self-care, interpersonal functioning, vocational functioning and need for care. At inclusion, 115 recent-onset patients were tested on a cognitive battery and 103 patients participated in the follow-up 2 years after inclusion. Differences in outcome between cognitively normal and cognitively impaired patients were also analysed. Cognitive measures at inclusion did not predict number of relapses, activities of daily living and interpersonal functioning. Time in psychosis or in full remission, as well as need for care, were partly predicted by specific cognitive measures. Although statistically significant, the predictive value of cognition with regard to clinical outcome was limited. There was a significant difference between patients with and without cognitive deficits in competitive employment status and vocational functioning. The predictive value of cognition for different social outcome domains varies. It seems that cognition most strongly predicts work performance, where having a cognitive deficit, regardless of the nature of the deficit, acts as a rate-limiting factor.

Reliability and validity of the Yale-Brown Obsessive-Compulsive Scale in schizophrenia patients.

Although a sizeable minority of people with schizophrenia manifest obsessive and compulsive symptoms, to our knowledge there are no studies of the psychometric performance of measures such as the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The present study examined psychometric properties of the Y-BOCS in patients with recent-onset schizophrenia and comorbid obsessive-compulsive symptoms (OCS). To 37 patients with recent-onset schizophrenia and related disorders and comorbid OCS taken from 135 consecutively admitted patients we administered the Y-BOCS at admission and 6 weeks later. The Y-BOCS showed good internal consistency and interrater reliability in this population; however, findings concerning the divergent validity against depressive and negative symptoms are inconsistent.

Predictors of the early 5-year course of schizophrenia: a path analysis.

In this study, the effect of 19 possible predictor variables on 4 outcome variables was analyzed in young patients with recent-onset schizophrenia and related disorders (n = 64). Patients who participated in a 15-month intervention program were stratified into low and high parental expressed emotion and randomized over two intervention conditions: standard intervention and standard plus family intervention. Baseline variables were measured during the intervention. Outcome variables were measured over 5 years after discharge and comprised duration of psychotic episodes, living institutions for psychiatric patients, structural activities, and help from the family. From the 19 baseline variables, 6 had possible predictive value and were entered in a multivariate analysis. The resulting path model indicated that the score on the Strauss and Carpenter prognostic scale was predictive for duration of psychotic episodes. Diagnosis (schizophrenia vs. schizophrenia-related disorder) predicted help from the family. Age at first psychotic episode predicted living in institutions for psychiatric patients. Duration of psychotic episodes was associated with living in institutions for psychiatric patients and with help from the family but not with structural activities.

Long-term memory deficits in schizophrenia: primary or secondary dysfunction?

Long-term memory impairment is often found in schizophrenia. The question remains whether this is caused by other cognitive deficits. One hundred eighteen first-episode patients were compared with 45 control participants on several memory tasks. The role of processing speed and central executive functions on memory performance was examined with regression analysis for all participants and for patients separately. Deficits were found in general verbal learning performance and retrieval in episodic memory and semantic memory. Processing speed reduced disease-related variance in all memory variables. Coordination, organization of information, and speed of processing were the best predictors for long-term memory deficits in patients. The amount of explained variance, however, is small, especially in general verbal learning performance.

Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-center MRI study.

Gray matter brain volume decreases have been found in patients with schizophrenia as compared to healthy control subjects measured by using Magnetic Resonance Imaging (MRI). An association has been suggested between decreased gray matter volume and poor outcome in chronically ill patients with schizophrenia. The present longitudinal multi-center study investigated whether gray matter volume at illness onset can predict poor outcome in recent-onset schizophrenia after a follow-up of approximately 2 years. An MRI calibration study was performed since scans of patients with recent-onset psychosis were conducted at three sites with 1.5 T MR scanners from two different manufacturers. Applying a linear scaling procedure on the histogram improved comparability between volume measurements acquired from images from the different scanners. Brain scans were obtained from 109 patients with recent-onset schizophrenia. Volumes of intracranium, total brain, cerebral gray and white matter, third and lateral ventricles, and cerebellum were measured. After a mean follow-up period of approximately 2 years, measurements of symptoms, functioning, need for care, and illness history variables were assessed. No significant correlations were found between the brain volume measures and any of these measures. Gray matter volume at illness onset does not predict outcome after 2 years in recent-onset schizophrenia.

Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study.

OBJECTIVE: The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol. METHOD: Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography. RESULTS: The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group. CONCLUSIONS: A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.

Schizophrenic patients without neuropsychological deficits: subgroup, disease severity or cognitive compensation?

Some schizophrenic patients do not show clinically relevant cognitive deficits. The question remains whether this represents the existence of an etiologically different subgroup, a general effect of disease severity or whether their cognitive deficits do not reach a clinical threshold due to a greater cognitive compensation ('brain reserve') capacity. A group of 23 out of 118 first onset patients was identified as cognitively normal (CN). The cognitive profile of these patients was compared with that of 45 healthy controls. Next these patients were compared with the cognitively impaired (CI) patients on obstetric complications (OCs), premorbid adjustment, age at onset, Positive and Negative Syndrome Scale ratings, social functioning and substance abuse. In addition both groups were compared on intelligence and educational level as indirect indicators of cognitive compensation capacity. There were no differences in OCs, premorbid adjustment, age at onset, psychopathology or substance abuse between the two patient groups. There was a significant difference in social functioning, which is a consequence rather than a cause of cognitive deficits. However, the CN patients scored significantly higher on measures of intelligence and educational level than the CI patients. This suggests that a difference in cognitive compensation capacity could explain the existence of a CN patient group.

The course of parental expressed emotion and psychotic episodes after family intervention in recent-onset schizophrenia. A longitudinal study.

The stability of parental expressed emotion (EE) is analysed over about 9 years, and related to course of illness in patients with recent-onset schizophrenia. Families, who participated in a 15-month intervention, were randomised over two intervention conditions. Psychotic episodes were measured over 5 years after discharge. The Five Minute Speech Sample (FMSS) EE was elicited two times during the 12-month outpatient intervention and two times over 8 years after discharge on average. EE is expressed as criticism/dissatisfaction (CRIT), emotional overinvolvement (EOI), and as the classical dichotomous index. EE is not stable over the years. Intervention condition had no differential effect on EE as measured with CRIT and the dichotomous index. For EOI, an interaction between intervention condition and time was found. EE as assessed during intervention does not predict psychotic episodes during follow-up. An association was found between psychotic episodes and CRIT as assessed at 34 months after discharge. Family intervention may inhibit the development of high EOI for a limited period. Our results may be in support of the hypothesis that psychotic episodes in patients can affect the critical attitude in parents.

Caregiver burden in recent-onset schizophrenia and spectrum disorders: the influence of symptoms and personality traits.

Earlier studies that used two symptom dimensions indicate that the caregiver burden for patients with schizophrenia is significantly determined by their negative symptoms. The purpose of this study is to examine the relationship between symptom severity in recent-onset schizophrenia and caregiver burden in a more differentiated way (i.e., five-symptom dimensions). Based on previous research, which shows that patients' personality traits influence the course of schizophrenia, we theorize that personality traits could also influence caregiver burden. So far, this hypothesis has never been studied. Therefore, the second purpose of this study is to examine whether patients' personality traits would contribute to caregiver burden. The results of this study showed that the disorganization symptom component was the predicting variable of the subscales supervision, tension, urging, distress, and the overall amount of caregiver burden in a linear regression analysis. Personality traits of patients played no substantial role in caregiver burden. These findings suggest that psychoeducational programs should address the severity of disorganization symptoms to reduce caregiver burden in the early phase of schizophrenia.