First-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a 1-year period compared with healthy controls, and if putative changes correlated with clinical characteristics and outcome.
MRIs of 79 FEP patients [SCID-I-verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (s.d. = 7.7) years, 66% male] and 82 healthy controls [age 29.3 (s.d. = 7.2) years, 66% male] were acquired from the same 1.5 T scanner at baseline and 1-year follow-up as part of the Thematically Organized Psychosis (TOP) study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer that creates an unbiased within-subject template image. General linear models were used to analyse longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations with clinical characteristics.
FEP patients and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use and remission at follow-up were not related to longitudinal brain change.
We found no significant longitudinal brain changes over a 1-year period in FEP patients. Our results do not support early progressive brain changes in psychotic disorders.
Several studies have reported structural brain abnormalities, decreased myelination and oligodendrocyte dysfunction in schizophrenia. In the central nervous system, glia-derived de novo synthesized cholesterol is essential for both myelination and synaptogenesis. Previously, we demonstrated in glial cell lines that antipsychotic drugs induce the expression of genes involved in cholesterol and fatty acids biosynthesis through activation of the sterol regulatory element binding protein (SREBP) transcription factors, encoded by the sterol regulatory element binding transcription factor 1 (SREBF1) and sterol regulatory element binding transcription factor 2 (SREBF2) genes. Considering the importance of these factors in the lipid biosynthesis and their possible involvement in antipsychotic drug effects, we hypothesized that genetic variants of SREBF1 and/or SREBF2 could affect schizophrenia susceptibility. We therefore conducted a HapMap-based association study in a large German sample, and identified association between schizophrenia and five markers in SREBF1 and five markers in SREBF2. Follow-up studies in two independent samples of Danish and Norwegian origin (part of the Scandinavian collaboration of psychiatric etiology study, SCOPE) replicated the association for the five SREBF1 markers and for two markers in SREBF2. A combined analysis of all samples resulted in highly significant genotypic P-values of 9 x 10(-4) for SREBF1 (rs11868035, odd ration (OR)=1.26, 95% confidence interval (CI) (1.09-1.45)) and 4 x 10(-5) for SREBF2 (rs1057217, OR=1.39, 95% CI (1.19-1.63)). This finding strengthens the hypothesis that SREBP-controlled cholesterol biosynthesis is involved in the etiology of schizophrenia.
Some studies in first-episode schizophrenia correlate shorter duration of untreated psychosis (DUP) with better prognosis, suggesting that timing of treatment may be important. A three-site prospective clinical trial in Norway and Denmark is underway to investigate the effect of the timing of treatment in first-episode psychosis. One health care sector (Rogaland, Norway) is experimental and has developed an early detection (ED) system to reduce DUP. Two other sectors (Ullevål, Norway, and Roskilde, Denmark) are comparison sectors and rely on existing detection and referral systems for first-episode cases. The study ultimately will compare early detected with usual detected patients. This paper describes the study's major independent intervention variable, i.e. a comprehensive education and detection system to change DUP in first onset psychosis.System variables and first results from the four-year inclusion period (1997-2000) are described. It includes targeted information towards the general public, health professionals and schools, and ED teams to recruit appropriate patients into treatment as soon as possible. This plus easy access to psychiatric services via ED teams systematically changed referral patterns of first-episode schizophrenia. DUP was reduced by 1.5 years (mean) from before the time the ED system was instituted (to 0.5 years). The ED strategies appear to be effective and to influence directly the community's help-seeking behaviour.
Ethnic minority status and childhood trauma are established risk factors for psychotic disorders. Both are found to be associated with increased level of positive symptoms, in particular auditory hallucinations. Our main aim was to investigate the experience and effect of childhood trauma in patients with psychosis from ethnic minorities, hypothesizing that they would report more childhood trauma than the majority and that this would be associated with more current and lifetime hallucinations.
In this cross-sectional study we included 454 patients with a SCID-I DSM-IV diagnosis of non-affective or affective psychotic disorder. Current hallucinations were measured with the Positive and Negative Syndrome Scale (P3; Hallucinatory Behaviour). Lifetime hallucinations were assessed with the SCID-I items: auditory hallucinations, voices commenting and two or more voices conversing. Childhood trauma was assessed with the Childhood Trauma Questionnaire, self-report version.
Patients from ethnic minority groups (n = 69) reported significantly more childhood trauma, specifically physical abuse/neglect, and sexual abuse. They had significantly more current hallucinatory behaviour and lifetime symptoms of hearing two or more voices conversing. Regression analyses revealed that the presence of childhood trauma mediated the association between ethnic minorities and hallucinations.
More childhood trauma in ethnic minorities with psychosis may partially explain findings of more positive symptoms, especially hallucinations, in this group. The association between childhood trauma and these first-rank symptoms may in part explain this group's higher risk of being diagnosed with a schizophrenia-spectrum diagnosis. The findings show the importance of childhood trauma in symptom development in psychosis.
Eighty-eight patients were admitted to the acute ward of a catchment area suffering from the following functional psychoses: schizophrenia (S; n = 41), affective disorder (AD; n = 22), other disorders (OD; n = 25). Follow-up data were obtained for 97%. Ten patients were dead at follow-up, 8 due to suicide. Sixty-five were personally interviewed. While nearly all the patients had only brief periods of rehospitalization, most had used neuroleptics during the follow-up period. Compared to other samples, functioning at follow-up was fairly good for the AD and OD patients, but rather poor for the S patients.
Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD.
A total of 342 participants with BD were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Diagnostic Interview for Genetic Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Affective lability was measured using the short form of the Affective Lability Scale (ALS-SF). A history of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the SPSS process macro.
Using the mediation model and covariation for the lifetime number of major mood episodes, affective lability was found to statistically mediate the relationship between childhood trauma experiences and several clinical variables, including suicide attempts, mixed episodes and anxiety disorders. No significant mediation effects were found for rapid cycling or age at onset.
Our data suggest that affective lability may represent a psychological dimension that mediates the association between childhood traumatic experiences and the risk of a more severe or complex clinical expression of BD.
Sleep problems in bipolar disorder (BD) are common, but reported rates vary from 10% to 80%, depending on definitions, methodologies and management of potential confounding factors. This multicenter study seeks to address these issues and also compares BD cases with Hypersomnia as well as the more commonly investigated Insomnia and No Sleep Problem groups.
A cross-sectional comparison of sleep profiles in 563 BD I and II individuals who participated in a structured assessment of demographic, clinical, illness history and treatment variables.
Over 40% cases met criteria for Insomnia and 29% for Hypersomnia. In univariate analysis, Insomnia was associated with BD II depression whilst Hypersomnia was associated with BD I depression or euthymia. After controlling for confounders and covariates, it was demonstrated that Hypersomnia cases were significantly more likely to be younger, have BD I and be prescribed antidepressants whilst Insomnia cases had longer illness durations and were more likely to be prescribed benzodiazepines and hypnotics.
Whilst Insomnia symptoms are common in BD, Hypersomnia is a significant, frequently underexplored problem. Detailed analyses of large representative clinical samples are critical to extending our knowledge of differences between subgroups defined by sleep profile.
Social anxiety is a common problem in psychotic disorders. The Liebowitz Social Anxiety Scale, Self-Rating version (LSAS-SR) is a widely used instrument to capture different aspects of social anxiety, but its psychometric properties have not been tested in this patient group. The aims of the present study were to evaluate the psychometric properties of the LSAS-SR in patients with first episode psychosis, to investigate whether it differentiated between active and passive social withdrawal and to test which clinical factors contributed to current level of social anxiety.
A total of 144 first episode psychosis patients from the ongoing Thematically Organized Psychosis (TOP) study were included at the time of first treatment. Diagnoses were set according to the Structured Clinical Interview (SCID-1) for DSM-IV. A factor analysis was carried out and the relationship of social anxiety to psychotic and general symptomatology measured by the Positive and Negative Syndrome Scale (PANSS) was evaluated. Possible contributors to social anxiety were analyzed using multiple hierarchic regression analysis.
The factor analysis identified three subscales: public performance, social interaction and observation. All three subscales showed satisfactory psychometric properties, acceptable convergent and discriminate properties, and confirmed previous findings in social anxiety samples. Self-esteem explained a significant amount of the variance in social anxiety, even after adjusting for the effects of delusions, suspiciousness and depression.
The study shows that the LSAS-SR can be used in this patient group, that social anxiety is strongly related to both behavioral social avoidance and to self-esteem. The results support the use of this measure in assessment of social anxiety in both clinical settings and in research.
During the last decades we have seen a new focus on early treatment of psychosis. Several reviews have shown that duration of untreated psychosis (DUP) is correlated to better outcome. However, it is still unknown whether early treatment will lead to a better long-term outcome. This study reports the effects of reducing DUP on 5-year course and outcome.
During 1997-2000 a total of 281 consecutive patients aged >17 years with first episode non-affective psychosis were recruited, of which 192 participated in the 5-year follow-up. A comprehensive early detection (ED) programme with public information campaigns and low-threshold psychosis detection teams was established in one healthcare area (ED-area), but not in a comparable area (no-ED area). Both areas ran equivalent treatment programmes during the first 2 years and need-adapted treatment thereafter.
At the start of treatment, ED-patients had shorter DUP and less symptoms than no-ED-patients. There were no significant differences in treatment (psychotherapy and medication) for the 5 years. Mixed-effects modelling showed better scores for the ED group on the Positive and Negative Syndrome Scale negative, depressive and cognitive factors and for global assessment of functioning for social functioning at 5-year follow-up. The ED group also had more contacts with friends. Regression analysis did not find that these differences could be explained by confounders.
Early treatment had positive effects on clinical and functional status at 5-year follow-up in first episode psychosis.
OBJECTIVE: The study assessed the level of reintegration into the community of patients with schizophrenia in Oslo, Norway, a country with a well-developed social welfare system and low unemployment rates. METHODS: Eighty-one patients with a DSM-III-R diagnosis of schizophrenia treated in 1980 and in 1983 in a short-term ward of a psychiatric hospital were followed up after seven years. Seventy-four of 76 patients alive at follow-up agreed to participate. Social functioning was measured by the Strauss-Carpenter Level of Functioning Scale and the Social Adjustment Scale. RESULTS: At follow-up 78 percent of patients lived independently, 47 percent were socially isolated, and 94 percent were unemployed. Thirty-four percent had lost employment in the follow-up period. A poor outcome in terms of social functioning and community reintegration was associated with loss of employment. A good outcome was predicted by short periods of inpatient hospitalization, high levels of education, being married, male gender, and not having a late onset of psychosis. CONCLUSIONS: The level of homelessness among these patients with schizophrenia was encouragingly low, which may have been expected in a high-income welfare society. However, insufficient efforts were aimed at social and instrumental rehabilitation, and the level of unemployment was alarmingly high.