Age-at-first-registration for affective psychosis and schizophrenia

We compared the age-at-first-registration for patients with schizophrenia and affective psychosis in a statewide mental health register. After excluding those receiving (1) a diagnosis of both schizophrenia (ICD-9 295.x) and affective psychosis (ICD-9 296.x), or (2) a diagnosis of ICD-9 296.1 (which can cover "major depressive episode"), we adjusted the distributions for the age structure of the background general population. We found that all distributions showed a wide age range of onset, with a similar male modal age group of 20-24 for schizophrenia and 25-29 for affective psychosis. The female modal age group was 50-54 for both diagnoses. Although more individuals were diagnosed with schizophrenia (males = 2,434, females = 1,609) than with affective psychosis (males = 670, females = 913), the shape of the two distributions was similar. This finding suggests that factors influencing age-at-first-registration for schizophrenia and affective psychosis may be similar, especially for females.     

The role of social relationships in the course of first-episode schizophrenia and affective psychosis

The Markers and Predictors of Psychosis study at the University of British Columbia addresses the role of psychosocial factors, such as social relationships, in predicting the short-term course of first-episode schizophrenia. Before their first episode of illness, schizophrenic subjects had fewer and less satisfactory social relationships than subjects with affective psychosis and a matched, normal comparison group. Nonfamily social resources were positively associated with good prognosis for both psychotic groups. While involvement with family members also predicted good prognosis among subjects with affective psychosis, family involvement had a negative association with outcome among schizophrenic subjects.     

Adult outcomes of child- and adolescent-onset schizophrenia: diagnostic stability and predictive validity

OBJECTIVE: The goal of the study was to establish the predictive validity of a diagnosis of schizophrenia in childhood and early adolescence by examining diagnostic continuity into adult life and comparing social and symptomatic outcomes of child- and adolescent-onset schizophrenia with those of nonschizophrenic psychoses. METHOD: A total of 110 consecutive patients with first-episode child- or adolescent-onset psychosis (mean age at onset=14.2 years) presenting to the Maudsley Hospital in London between 1973 and 1991 were followed up an average of 11.5 years after first contact. Ninety-three (84.5%) of 110 patients were successfully followed-up, 51 with a first-episode diagnosis of DSM-III-R schizophrenia and 42 with nonschizophrenic psychoses. Consensus best-estimate DSM-III-R diagnoses were made at follow-up, and course and outcome were assessed blind to first-episode diagnosis. RESULTS: Diagnostic stability was high for child- and adolescent-onset DSM-III-R schizophrenia (positive predictive value=80%) and affective psychoses (positive predictive value=83%) but much lower for schizoaffective and atypical psychoses. Compared with other psychoses, child- or adolescent-onset schizophrenia was associated with significantly worse symptomatic and social outcomes, which were characterized by a chronic illness course and severe impairments in social relationships and independent living. CONCLUSIONS: The diagnosis of DSM-III-R schizophrenia in childhood and adolescence has good predictive validity. The high level of diagnostic stability suggests etiological continuity with adult schizophrenia, with onset in childhood and adolescence associated with a particularly malignant course and outcome.     

The psychosocial outcome of adolescent-onset schizophrenia: a 12-year followup

This study examines the educational/occupational outcome and social situation of patients treated for schizophrenia in adolescence (age at admission 11.5-17.9 years; mean 16.0 years). Out of 96 consecutively admitted patients between 1976 and 1987, 85 (89%) could be traced and 65 (68%) were reassessed more than 10 years after the first episode. At followup, 54 of the 65 (83%) had had at least one further inpatient-treated episode and 48 (74%) were receiving psychiatric treatment. Thirty-seven (57%) of the subjects were at least moderately impaired with respect to vocational functions (i.e., did not achieve their premorbid educational/occupational goals). Serious social disability was found in 42 (66%) of the 64 subjects for whom social disability data were available. Regarding means of maintenance, 49 (75%) were financially dependent, supported by parents or public assistance. Impairments were comparable for males and females. History of treatment (longer duration of inpatient stay; more than two inpatient episodes) was found to be predictive of lower vocational functioning at followup. Severity of positive symptoms and more than two inpatient episodes in the early course of illness predicted social disabilities in young adulthood. Findings support the view that, because of early onset, the long-term perspective for many adolescent-onset schizophrenia patients is that of poor social adjustment, severe functional impairment, and high socioeconomic dependence and suggest that consequences are more severe than in adult-onset schizophrenia.     

Duration of psychosis and outcome in first-episode schizophrenia.

OBJECTIVE: This study was undertaken to assess the potential effect of duration of untreated illness on outcome in a group of first-episode schizophrenic patients. METHOD: Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission of acute psychotic symptoms as well as degree of symptom remission. RESULTS: The mean duration of psychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level of remission. The effect of duration of illness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration of illness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study. CONCLUSIONS: Duration of psychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed.     

The Maudsley Early-Onset Schizophrenia Study: cognitive function in adolescent-onset schizophrenia

The neuropsychological correlates of adolescent-onset schizophrenia have been investigated very little to date. We assessed intelligence, memory and executive function in 42 patients with adolescent-onset schizophrenia and 43 healthy control subjects. Cases showed impairments in most cognitive variables. Despite the overall similarity with the quantitative and qualitative performance characteristics of later-onset patients in the literature, their cognitive profile displayed a unique feature: modification of the usual pattern of thinking latencies in the Tower of London Task. After adjusting for potential confounders, no effect of illness duration, symptoms or medication dose on patient performance emerged. However, longer exposure to medication predicted a lower level of performance in aspects of attention, psychomotor processing speed and spatial working memory. Our data are not consistent with worse cognition or progression of neuropsychological impairment in adolescent-onset schizophrenia.     

Progression of brain volume changes in adolescent-onset psychosis

Little is known about the changes that take place in the adolescent brain over the first few years following the onset of psychosis. The present longitudinal study builds on an earlier cross-sectional report demonstrating brain abnormalities in adolescent-onset psychosis patients with a recent-onset first episode of psychosis. Magnetic resonance imaging studies were obtained at baseline and 2 years later from 21 adolescents with psychosis and 34 healthy controls matched for age, gender, and years of education. Whole-brain volumes and gray matter (GM) and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured at baseline and at 2-year follow-up. In the frontal lobe, the rate of GM volume loss was significantly higher in male patients (2.9% and 2.0%, respectively, for left and right) than in controls (1.2% and 0.7%, respectively, for left and right). In the left frontal lobe, male patients showed a significantly higher rate of CSF volume increase than controls (8.6% vs 6.4%). These differences in rates of volume change were observed in male and female patients, although only males showed significant time x diagnosis interactions. This negative finding in females should be interpreted with caution as the study was underpowered to detect change in women due to limited sample size. An exploratory analysis revealed that schizophrenia and nonschizophrenia psychotic disorders showed similar volume change patterns relative to controls. Change in clinical status was not correlated with longitudinal brain changes. Our results support progression of frontal lobe changes in males with adolescent-onset psychosis.     

Comparative profile analysis of cognitive function in recent-onset and chronic patients with adolescent-onset schizophrenia

We used z-transformed scores derived with reference to 43 healthy controls to compare cognitive profiles and selectivity of cognitive deficits in 19 recent-onset and 23 chronic patients with adolescent-onset schizophrenia. Relative to the controls, both patient groups were impaired in IQ, verbal memory and planning, but not visual memory or attention/mental flexibility. There were no significant differences in level or shape of cognitive profile between the two patient groups. Attention/mental flexibility emerged as a selective strength, and planning as a selective deficit, while verbal memory showed a trend towards selective impairment in the patients.     

Duration of untreated psychosis and social function: 1-year follow-up study of first-episode schizophrenia

BACKGROUND: In first-episode schizophrenia, longer duration of untreated psychosis (DUP) predicts poorer outcomes. AIMS: To address whether the relationship between DUP and outcome is a direct causal one or the result of association between symptoms and/or cognitive functioning and social functioning at the same time point. METHOD: Symptoms, social function and cognitive function were assessed in 98 patients with first-episode schizphrenia at presentation and 1 year later. RESULTS: There was no significant clinical difference between participants with short and long DUP at presentation. Linear regression analyses revealed that longer DUP significantly predicted more severe positive and negative symptoms and poorer social function at 1 year, independent of scores at presentation. Path analyses revealed independent direct relationships between DUP and social function, core negative symptoms and positive symptoms. There was no significant association between DUP and cognition. CONCLUSIONS: Longer DUP predicts poor social function independently of symptoms. The findings underline the importance of taking account of the phenomenological overlap between measures of negative symptoms and social function when investigating the effects of DUP.     

Psychopathological and social outcome in schizophrenia versus affective/schizoaffective psychoses and prediction of poor outcome in schizophrenia. Results from a 5-8 year follow-up

Forty-six patients with the ICD diagnosis of schizophrenic or similar paranoid psychosis, 35 patients with the ICD diagnosis of affective psychosis, 22 patients with the ICD diagnosis of schizoaffective psychosis, and a large sample of control probands from the general population were followed up using standardized assessment procedures 5-8 years after index hospital treatment. A comparison of respective psychopathological or social outcome measures among the diagnostic groups and between patients and matched non-patients from the general population survey confirms the hypothesis that patients with the diagnosis of schizophrenia have, as a group, the poorest degree of psychopathological disturbances and social maladjustment. However, there is a large subgroup with a favourable outcome. Some predictors for poor outcome, described in the literature and in a former follow-up study of ours, could be confirmed. Under the aspect of invariance under different sample conditions, the predictive power of some prognostic scales, such as the Stephens Scale, the Vaillant Scale, and the Strauss-Carpenter Scale, was substantiated.     

Gyrification abnormalities in childhood- and adolescent-onset schizophrenia.

BACKGROUND: Gyrification is an important index of brain development. We used magnetic resonance scanning technology to compare brain surface morphology and measures of gyrification in children and adolescents with a schizophrenia spectrum disorder and in age-equivalent healthy controls. METHODS: Magnetic resonance scans were obtained from 42 patients and 24 healthy controls, mean age 17.7 years for both groups. We employed novel quantitative measures of brain morphology, including cortical thickness and a variety of indices of sulcal and gyral curvature. We examined these measures in the whole brain and in the frontal, temporal, parietal, and occipital lobes. RESULTS: There were significant decreases in cortical thickness in the patients. This was most pronounced in the cortical tissue that underlies the sulci. The patient group had significantly more flattened curvature in the sulci and more steeped or peaked curvature in the gyri. CONCLUSIONS: This study quantitatively examines cortical thickness and surface morphology in children and adolescents with schizophrenia. Patients with schizophrenia demonstrated patterns of brain morphology that were distinctly different from healthy controls. In light of current theories of the formation of gyri and sulci, these changes may reflect aberrations in cerebral and subcortical connectivity.     

Incidence of rheumatoid arthritis among patients with schizophrenia, affective psychosis and neurosis

The aim of the study was to determine the incidence of hospital care with the diagnosis rheumatoid arthritis (RA) among patients with schizophrenia, affective psychosis and neurosis compared with that among hospitalized patients in general. By means of the in-patient register of Stockholm County, a cohort was formed comprising all patients discharged with the diagnoses schizophrenia, affective psychosis and neurosis in Stockholm County during 1971, and a sample of all patients discharged for any diagnosis during the same year. We followed the groups in the in-patient register through 1981 in order to identify hospital episodes with the diagnosis RA. Observed and expected incidences of RA in hospital care were obtained using all hospitalized patients as a reference group. For schizophrenia and affective psychosis the incidence of RA was around half the expected, whereas for neurosis it was close to the expected incidence. With reservation for small numbers of observed cases, the results support the hypothesis of a reduced incidence of RA among patients with schizophrenia. The finding regarding affective psychosis was based on a smaller number of cases and merits further investigations.     

Cerebral dysfunctions of emotion-cognition interactions in adolescent-onset schizophrenia

ObjectiveSchizophrenia is among the most severe of psychiatric disorders, leading to impairments of affective and cognitive abilities. These dysfunctions affect each other mutually. Adolescent-onset schizophrenia (AOS) constitutes a particularly severe form of the disorder. In this study, possible dysfunctions of the neural correlates underlying the interaction of negative emotion and working memory in AOS were investigated.MethodDuring functional magnetic resonance imaging, 12 patients with AOS and 12 non-AOS adolescents performed a verbal n-back task. Intermittently, negative and neutral emotions were induced by olfactory stimulation. Group differences in working memory, emotion, and their interaction were evaluated.ResultsIn patients with AOS, lower performance sensitivity was observed, along with dorsolateral prefrontal, anterior cingulate, and inferior parietal hypoactivation during working memory demands. For negative versus neutral emotion induction, patients with AOS mainly showed increased brain activation compared with control subjects in widespread brain regions including the left orbitofrontal cortex and the medial frontal gyrus. Finally, during the interaction of emotion and cognition, altered patterns of activation in patients with AOS were found in the thalamocortical network, including the angular and the middle cingulate gyri extending to the precuneus. These activation differences were further decomposed by parameter estimates.ConclusionsOur results provide new insights into the neural correlates underlying the mutual influence of affective and cognitive symptoms in AOS. During the n-back task, areas typically associated with working memory performance were found hypoactivated in patients relative to the control subjects, including the dorsolateral prefrontal and parietal cortex and the anterior cingulate. However, patients with AOS mainly demonstrated increased activation in key areas of emotion processing, such as the left orbitofrontal cortex and medial frontal areas, during negative emotion induction. A dysfunctional thalamocortical network during the interaction mainly included regions involved in the integration of converging information—either on the subcortical (thalamus) or on a higher-order cortical level (comprising the angular gyrus). These findings point to dysfunctional emotion-cognition interactions in AOS, which may explain its poor prognosis. J. Am. Acad. Child Adolesc. Psychiatry, 2008;47(11): 1299–1310.     

Personality dimensions and neuropsychological performance in first-degree relatives of patients with schizophrenia and affective psychosis

Recent evidence suggests that schizophrenia patients taking atypical antipsychotic medications may perform better on some tests of cognitive function than those treated with older antipsychotics. The current study compared the effects of quetiapine and haloperidol on measures of executive function, memory and attention. Subjects were 58 stable outpatients with schizophrenia (DSM III-R) who received a battery of cognitive tests as part of a randomized, double-blind, multi-site clinical efficacy study conducted by AstraZeneca Pharmaceuticals. Cognitive assessments were conducted prior to randomization when patients were receiving < or =30 mg haloperidol or equivalent (mean: 9.2mg/day haloperidol equivalents), and again after 24 weeks of fixed-dose treatment with either quetiapine 600 or 300 mg/day or haloperidol 12 mg/day. Analyses of covariance with planned comparisons were used to compare scores on cognitive measures at the end of 24 weeks by treatment group with baseline cognitive function scores used as covariates. Patients receiving quetiapine 600 mg/day improved to a greater extent than patients receiving haloperidol on overall cognitive function (p<0.02). Specific differences were found for executive function (Verbal Fluency Test, p<0.04), attention (Stroop Color Word Test, p<.03) and verbal memory (Paragraph Recall Test, p<0.02). Treatment group differences were not solely due to benztropine use, medication side effects, or changes in symptomatology. Treatment with quetiapine at higher doses (600 mg/day) relative to haloperidol appears to have a positive impact on important domains of cognitive performance that have been found to predict role function and community outcomes in patients with schizophrenia.     

Cavum septi pellucidi in first-episode schizophrenia and first-episode affective psychosis: an MRI study

A high prevalence of abnormal cavum septi pellucidi (CSP) in schizophrenia may reflect neurodevelopmental abnormalities in midline structures of the brain. The relationship, however, between abnormal CSP and clinical symptoms, and with abnormalities in other limbic structures remains unclear, as does the question of whether a similar abnormality is present in affective psychosis. Seventy-four patients at their first hospitalization, 33 with schizophrenia and 41 with affective (mainly manic) psychosis, and 56 healthy control subjects underwent high-spatial-resolution magnetic resonance imaging (MRI). CSP on six slices or more on 0.9375-mm resampled coronal images was categorized as abnormal. The prevalence of abnormal CSP in both schizophrenic patients (26.1%) and affective psychosis patients (18.2%) was significantly higher than was observed in control subjects (8.2%). In schizophrenic patients only, larger CSP was significantly associated with more severe thinking disturbance and smaller left parahippocampal gyrus gray matter volumes. While the relationships between CSP ratings and clinical symptoms did not significantly differ between the two psychosis groups as assessed by the comparison of regression slopes, the association with limbic volumes appeared to be specific to schizophrenic patients. These results suggest that psychosis associated with schizophrenia and affective disorder share, at least to some extent, neurodevelopmental abnormalities involving midline structures and associated psychopathological consequences. However, the association between abnormal CSP and limbic systems may be more specific to schizophrenia.