One year outcome in first episode schizophrenia

The aim of this study was to identify the predictors of outcome at one year follow-up after the first psychotic episode of schizophrenia. Seventy-nine first-episode schizophrenia patients were assessed monthly with the Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Positive Symptoms (SAPS), and Scale for Assessment of Negative Symptoms (SANS) after discharge from their first hospitalization. Outcome measures were presence of relapse and rehospitalization, level of global functioning, employment status and severity of symptoms at one year. A total of 33% of the patients had a relapse, and 12.1% were rehospitalized during one year follow-up. Premorbid childhood functionality was worse in patients who had relapse, but there was no correlation between premorbid adjustment scores and BPRS, SANS and SAPS scores at one year. There was no difference in duration of untreated psychosis (DUP) between patients who had relapse and not; however, the patients who had double relapse, had longer DUP than those without relapse. The time period between discharge and rehospitalization was shorter in patients with longer DUP. Functionality in childhood and noncompliance to the treatment independently contributed to the relapse rate. Functionality in late adolescence independently contributed to the Global Assessment of Functioning (GAF) scale score at one year and the GAF score at discharge appeared as a predictor of employment. The results of the present study suggest that treatment compliance and early premorbid adjustment level seem to be important predictors of relapse rate in first episode schizophrenia.     

Progressive brain volume loss during adolescence in childhood-onset schizophrenia

OBJECTIVE: Previous reports have documented a striking progressive reduction in cortical gray matter volume during adolescence in patients with childhood-onset schizophrenia. This study examined the rate of loss in cortical gray matter volume in relation to age and clinical status in adolescent patients over a follow-up period of 2-6 years. METHOD: A total of 131 brain magnetic resonance imaging scans were acquired for 60 subjects with childhood-onset schizophrenia (mean age=14.5 years, SD=2.5), and 140 scans were acquired for 64 matched healthy comparison subjects. One or more follow-up scans were acquired at approximately 2-year intervals for 39 subjects with childhood-onset schizophrenia and 43 healthy subjects. Developmental trajectories for total and regional brain volumes were examined in relation to age by using polynomial growth models and data from all available scans. The rate of gray matter reduction in patients with childhood-onset schizophrenia was examined in relation to developmental and clinical measures by using stepwise regression. RESULTS: Rates of brain volume reduction were significantly higher for patients with childhood-onset schizophrenia than for healthy comparison subjects. In childhood-onset schizophrenia, the rate of gray matter reduction was related to premorbid impairment and baseline severity of clinical symptoms but not to gender, ethnicity, or age at onset of the disorder. Unexpectedly, greater clinical improvement was significantly related to a higher rate of gray matter reduction. Longitudinal trajectories suggested that the rate of cortical loss plateaus during adolescence. CONCLUSIONS: Striking loss of cerebral gray matter is seen through adolescence in patients with childhood-onset schizophrenia. The rate of reduction was related to premorbid impairment and baseline symptom severity, but it may also be in part a plastic response to illness.     

Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study

BACKGROUND: We sought to determine whether the brain dysmorphology previously observed cross-sectionally in people with schizophrenia progresses over time and whether such progression is related to the severity of the illness course. SUBJECTS AND METHODS: Men with chronic schizophrenia (n = 24) and control men (n = 25) received 2 brain magnetic resonance imaging scans, on average 4 years apart. Changes in brain volume were adjusted for head-repositioning error and expressed as slopes (cubic centimeters per year). Clinical course severity for the schizophrenic patients was assessed using the mean of time 1 and time 2 Brief Psychiatric Rating Scale (BPRS) scores and the percentage of time the patient was hospitalized during the interscan interval. RESULTS: Schizophrenic patients exhibited faster volume decline than control subjects in right frontal gray matter and bilateral posterior superior temporal gray matter, as well as faster cerebrospinal fluid volume expansion in right frontal sulci, left lateral ventricle, and bilateral prefrontal and posterior superior temporal sulci. Faster rates of frontal sulcal expansion were related to greater BPRS total and positive symptom scores and longer time hospitalized. Prefrontal gray matter decline and sulcal expansion were associated with greater BPRS negative symptom scores and longer time hospitalized. Temporal lobe gray matter decline was associated with greater BPRS total and negative symptom scores. CONCLUSIONS: This controlled study revealed that patients with chronic schizophrenia exhibited accelerated frontotemporal cortical gray matter decline and cortical sulcal and lateral ventricular expansion. Further, greater clinical severity was associated with faster rates of frontotemporal brain volume changes. These observations are consistent with a progressive pathophysiological process but need to be replicated in a larger sample.     

Awareness of illness and outcome in schizophrenia

The purpose of the present study was to investigate whether awareness of illness affects specific measures of outcome in schizophrenia. Patient awareness was evaluated using a shortened version of the Scale to Assess Unawareness of Mental Disorder (SUMD). Patient outcome was assessed by means of the Strauss-Carpenter scale. Our findings indicate that lack of awareness of “negative symptoms” has a considerable impact on outcome: in fact “Social Contacts” highly correlated with Blunt Affect, Anhedonia and Asociality items on the SUMD. Lack of awareness seems then to be a powerful predictor of poor outcome. Received: 11 August 1999 / Accepted: 9 December 1999     

Progressive loss of cerebellar volume in childhood-onset schizophrenia

OBJECTIVE: Childhood-onset schizophrenia is a severe and unremitting form of the disorder. Prospective brain magnetic resonance imaging (MRI) studies have found progressive loss of total cerebral volume during adolescence, primarily attributable to accelerated loss of cortical gray matter. Because there is evidence of cerebellar involvement in schizophrenia, the authors examined cerebellar volume and its relation to cortical gray matter development during adolescence in patients with childhood-onset schizophrenia and healthy comparison subjects. METHOD: Total cerebellar volume was algorithmically calculated for 108 anatomical brain MRI scans from 50 patients (20 of whom were female) and 101 scans from 50 age- and gender-matched healthy volunteers (20 of whom were female). The age range of the patients and comparison subjects was 8 to 24. Midsagittal vermal area and posterior-inferior vermal lobe volume were measured by hand. Prospective rescans were obtained at approximately 2-year intervals. Cross-sectional and longitudinal data were combined in mixed model regressions to compare developmental changes for the groups. RESULTS: In contrast to healthy volunteers, patients with schizophrenia showed a progressive loss of cerebellar volume during adolescence. Cerebellar and cerebral volume decreases were significantly correlated in childhood-onset schizophrenia. CONCLUSIONS: Childhood-onset schizophrenia is associated with significant progressive loss of cerebellar volume during adolescence, consistent with previously reported decreases in total cerebral and cortical gray matter. At least in these patients with severe early-onset schizophrenia, the loss appears secondary to a generalized process.     

Progressive membrane phospholipid changes in first episode schizophrenia with high field magnetic resonance spectroscopy

Patients with a first episode of schizophrenia generally have increased phospholipid membrane breakdown products within the brain, while findings in chronic patients have been inconsistent. In this study we examine progressive changes in phosphorus membrane metabolites in the same patient group through the early years of schizophrenia in brain regions associated with the disease. Sixteen never-treated and medicated first episode schizophrenic patients were assessed at 10 months and 52 months after diagnosis. Sixteen matched volunteers were assessed at baseline and after 35 months. Phospholipid membrane metabolism was assessed with phosphorous magnetic resonance spectroscopy in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex, parieto-occipital cortex, superior temporal gyrus and temporal pole. At 10 months, glycerophosphocholine was increased in the anterior cingulate in patients as compared to controls. Glycerophosphocholine was decreased in the anterior cingulate and increased in the posterior cingulate and left superior temporal gyrus; glycerophosphoethanolamine was decreased in the left thalamus and increased in the left hippocampus within patients over time. At 52 months, compared to controls phosphocholine was increased in the left thalamus and glycerophosphoethanolamine was increased in the left hippocampus. These results imply a gradual inclusion of brain regions in schizophrenia where an initial increase, followed by a decrease in phospholipid membrane metabolites was observed. This pattern, observed in the early years of schizophrenia, is consistent with excitotoxic neural membrane breakdown in these regions.     

Psychiatric comorbidity in first episode schizophrenia: a 2 year, longitudinal outcome study

OBJECTIVE: We have previously documented a high prevalence of Axis I psychiatric comorbidity in our patients with first episode psychosis. This study sought to determine the longitudinal impact of Axis I psychiatric comorbidity on patients with first episode schizophrenia (FES) and we hypothesised that patients with psychiatric comorbidity were associated with poorer clinical and functional outcomes. METHOD: One hundred and forty two consecutively hospitalized FES patients were included. Socio-demographic information was obtained and the PANSS, SUMD, GAF, WHOQOL-Bref were used to assess psychopathology, insight, social/occupational functioning and quality of life respectively at baseline and at 6, 12, 18 and 24 months after discharge. RESULTS: Over time and compared with baseline scores, patients with Axis I psychiatric comorbidity (n=46, 32.4%) had significantly less reduction of their PANSS total and subscale scores, less improvement in their awareness of their psychiatric illnesses and symptoms at 12, 18 and 24 months and poorer insight into the consequences of their illness at 18 and 24 months. Poor insight at baseline was correlated positively with PANSS negative symptom subdomain, and negatively with GAF at 24 months. CONCLUSION: Axis I Psychiatric comorbidity was associated with worse prospective outcomes in hospitalized patients with first episode schizophrenia, and this highlights a greater need towards the early recognition and management of these conditions.     

Duration of untreated illness in schizophrenia is not associated with 5-year brain volume change

Objectives

Evidence for an association between duration of untreated illness (DUI) with clinical and functional outcome or brain volume (change) in schizophrenia patients is inconclusive. We aimed to investigate the relationship between DUI, outcome and brain volume at illness onset or brain volume change during the first five years of the illness in first-episode patients.

Methods

Magnetic resonance images were acquired at baseline (T0) and after 5-year (T5) of 57 schizophrenia patients. Correlations were calculated in patients between brain volume (change), DUI and outcome variables.

Results

We found no significant correlation between DUI and brain volume (change) in schizophrenia patients. A longer DUI was significantly correlated with higher PANSS scores at T0 and T5, and with higher scores on the Camberwell Assessment of Need scale at T5. Baseline volume of the cerebrum and lateral ventricles, and cerebellum volume (change) were associated with PANSS scores at T0 and T5.

Conclusion

Although clinical outcome is associated with both brain volume (change) and DUI, we found no evidence for a relationship between DUI and brain volume (change). DUI and baseline brain volume or 5-year brain volume (change) seem to explain different parts of the variation in clinical outcome.     

Can psychiatrists predict the one-year outcome of schizophrenia?

Summary Following an introduction on the determinants of the outcome of schizophrenia and review of some prediction studies, this paper presents the results of prognostic statements made for 88 first onset schizophrenic patients in terms of their duration of episode, length of stay in hospital, occupational capacity and functioning in the family. Predicted outcome was compared with the actual results after one year. Clinical judges were found to make reasonably accurate predictions about the short term outcome of schizophrenia and their statements were better than chance agreements.A report from the Nottingham Field Research Centre of the World Health Organisation Collaborative Study on the Determinants of Outcome of Severe Mental Disorders.     

精神分裂症脑源性神经营养因子和海马结构改变的关联

精神分裂症是一种严重精神病,以幻觉、思维及行为紊乱和社会功能退化为特征,患病率为1％,给个人、家庭及社会带来极大负担。精神分裂症的研究涉及遗传、神经生化、病理生理、影像学等多个领域,但其确切病因及病理机制目前仍不明确。脑影像学研究表明,精神分裂症患者存在大脑结构异常,主要表现为侧脑室扩大和脑体积减小。     

Hospitalization in the first year of treatment for schizophrenia.

OBJECTIVE: To determine the rates of hospitalization during the first year of treatment for schizophrenia, using an epidemiologic sample. METHOD: We examined inpatient and outpatient administrative databases in the province of Nova Scotia for cases of schizophrenia (ICD-9 code 295 or 298) newly diagnosed during the years 1995 to 1998. We noted the diagnosis site (that is, inpatient or outpatient) and hospitalizations in the year following diagnosis. We also established links to the clinical database maintained by the Nova Scotia Early Psychosis Program (NSEPP). RESULTS: Over the 4-year period, we identified 434 unique cases from an at-risk population of 320,000 (yielding a yearly average age-specific incidence rate of 3.3/10,000), of whom 119 had received care from the NSEPP. Of the cases, 54% were initially diagnosed while they were inpatients. In the year following diagnosis, the overall hospitalization rate, excluding initial hospitalizations, was 17%. Patients who were initially diagnosed while inpatients had a higher rate of hospitalization in the first year of treatment (25% vs 7%), compared with those initially diagnosed while outpatients. This relation was also present among patients who received care from the NSEPP. CONCLUSIONS: Of newly diagnosed patients with schizophrenia, 46% were not hospitalized at the time of initial diagnosis. Of all patients, 17% required hospitalization during the first year of treatment, excluding an initial hospitalization, if present. Hospitalization rates in the first year were higher among patients initially hospitalized and among those with a rural residence. Patients requiring hospitalization during the first year form an important target group for improved interventions.     

Hippocampal volume in first-episode schizophrenia and longitudinal course of the illness

Objectives: Several lines of evidence suggest an adverse effect of psychotic episodes on brain morphology. It is not clear if this relationship reflects the cumulative effect of psychotic outbursts on the gradual progressive reduction of hippocampal tissue or an increased tendency toward psychotic episodes in patients with a smaller hippocampus at the beginning of the illness.

Methods: This is a longitudinal 4-year prospective study of patients with first-episode schizophrenia (FES, N?=?58). Baseline brain anatomical scans (at FES) were analysed using voxel-based morphometry and atlas-based volumetry of the hippocampal subfields. The effects of first-episode duration on the hippocampal morphology, and the effect of baseline hippocampal morphology on illness course with relapses, number of psychotic episodes and residual symptoms were analysed.

Results: A significant negative correlation was detected between first-episode duration and baseline hippocampal morphology. Relapse, number of psychotic episodes and residual symptoms had no correlation with baseline hippocampal volume.

Conclusions: We replicated the effect of psychosis duration on hippocampal volume already at the time first-episode, which supports the concept of toxicity of psychosis. The indices of a later unfavourable course of schizophrenia had no correlation with baseline brain morphology, suggesting that there is no baseline morphological abnormality of the hippocampus that predisposes the patient to frequent psychotic outbursts.     

首发精神分裂症患者10年随访研究

目的:探讨首发精神分裂症患者远期预后及其影响因素.方法:运用标准化评定工具对146例首发精神分裂症患者进行10年随访及预后评定,对预后有关影响因素作单因素分析和Logest回 归多因素分析.结果:首发精神分裂症患者10年随访时总体结局良好者23例(19.2%),一般者34例(28.3%),不良者63例(52.5%).单因素分析有11项观察指标与预后有关,多因素分析显示远期预后主要影响因素依次为病前职业功能水平、治疗依从性、起病形式和家庭关系.结论:首发精神分裂症患者远期预后受生物、心理、社会多种因素影响,总体结局较差,其中部分影响因素可进行干预.     

Morphological changes in the brain in schizophrenia

In 1975-1985 in the mental hospital in Dobrany died 225 patients with chronic schizophrenia. The author presents the causes of death confirmed by necropsy. In all the brain was examined by a light microscope. Ordinary microscopy revealed that in chronic schizophrenia at the age above 65 years Alzheimer's disease is six times more frequent than in the case-records of the mentally healthy population. Electron microscopic examination performed in 22 cases of schizophrenia revealed changes on the synapses at all examined sites of the cerebral cortex--i.e. aggregations of synaptic vesicles. The most probable cause of aggregation of synaptic vesicles could be an impaired "immunological interaction" between synaptic vesicles which from the physiological aspect have at least three types of origin. The findings are supplemented also by data on the function of neurotransmitters and neuropeptides in the physiology and pathology of cerebral functions. The author draws attention to research focused on immunological reactivity in schizophrenia. During electron microscopic examination artefacts caused by premortal agony were eliminated as well as those caused by post-mortem changes and tissue fixation. As controls the author examined the cerebral cortex of five subjects who did not suffer from mental disease. The author also submits a of morphological incorporation of synapses in the structure of the cerebral cortex of five subjects who did not suffer from mental disease. The author to the possible relation to clinical manifestations of the disease.     

Catecholamines predict outcome in traumatic brain injury

Activation of the sympathetic nervous system attends traumatic brain injury, but the association of the severity of neurological impairment and recovery with the extent of sympathetic nervous system stimulation is poorly defined. In this study, plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) levels were measured serially in 33 patients with traumatic brain injury and compared with the Glasgow Coma Score (GCS), which was obtained concurrently. A catecholamine gradient that reflected the extent of brain injury was demonstrated within 48 hours of the injury. In patients with a GCS of 3 to 4, NE and E levels increased four- to fivefold and the DA level increased threefold above normal (NE, 1686 +/- 416 pg/ml; E, 430 +/- 172 pg/ml; DA, 236 +/- 110 pg/ml), while patients with mild brain injury (GCS, greater than 11) had slightly elevated or normal levels. Patients with marked (GCS, 5 to 7) and moderate (GCS, 8 to 10) traumatic brain injuries had intermediate levels. The prognostic value of determining admission levels of NE was shown in patients with an admission GCS of 3 to 4 1 week after injury. Patients with severe and unchanging neurological impairment 1 week after injury had markedly elevated initial NE levels (2,176 +/- 531 pg/ml), whereas initial NE levels (544 +/- 89 pg/ml) were only mildly elevated in patients who improved to a GCS of greater than 11. These data indicate that markedly elevated NE levels predict outcome in patients with comparable neurological deficits. Thus levels of circulating catecholamines are excellent endogenous and readily quantifiable markers that appear to reflect the extent of brain injury and that may predict the likelihood of recovery.