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.

Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia.

BACKGROUND: Thalamic glutamine loss and grey matter reduction suggest neurodegeneration in first-episode schizophrenia, but the duration is unknown. AIMS: To observe glutamine and glutamate levels, grey matter volumes and social functioning in patients with schizophrenia followed to 80 months after diagnosis. METHOD: Grey matter volumes and proton magnetic resonance spectroscopy metabolites in left anterior cingulate and left thalamus were measured in 17 patients with schizophrenia before medication and 10 and 80 months after diagnosis. Social functioning was assessed with the Life Skills Profile Rating Scale (LSPRS) at 80 months. RESULTS: The sum of thalamic glutamate and glutamine levels decreased over 80 months, and correlated inversely with the LSPRS. Thalamic glutamine and grey matter loss were significantly correlated in frontal, parietal, temporal and limbic regions. CONCLUSIONS: Brain metabolite loss is correlated with deteriorated social functioning and grey matter losses in schizophrenia, consistent with neurodegeneration.

Stability of outcomes after 5 years of treatment in an early intervention programme.

AIM: It has been hypothesized that the first 5 years are critical in determining long-term recovery from psychotic disorders. We examine stability in recovery indices after 5 years for 56 patients treated in an early intervention programme for psychosis. METHODS: Assessments of symptom remission and functional recovery were carried out 5 and 10 years after initiation of treatment. RESULTS: Although overall rates of recovery were comparable at both times, there were significant changes for individuals reflecting both improvement and deterioration. CONCLUSIONS: Evidence concerning the critical period hypothesis should examine stability in individuals rather than relying on cumulative indices.

Does treatment delay predict occupational functioning in first-episode psychosis?

Although duration of untreated psychosis (DUP) predicts treatment outcome as assessed by symptoms in first-episode psychosis, there is much less evidence concerning its relation to social functioning. We present the results of a prospective study of 163 first-episode psychosis patients examining occupational activity at three years, after initiation of treatment. Both shorter DUP and higher social support were significantly associated with more full time occupational activity at follow-up. The findings suggest the importance of reducing treatment delay and increasing social support in order to improve occupational outcomes for those with first-episode psychosis.

Social support and three-year symptom and admission outcomes for first episode psychosis.

This paper presents the first published findings examining the relationship of social support to three-year symptom outcome and hospitalizations for a group of first episode patients with psychotic disorders. Social support was measured using items from the provider version of the Wisconsin Quality of Life Scale as assessed at the time of initiation of treatment for 113 patients. Outcome was assessed by level of positive and negative symptoms at three-year follow-up and number of psychiatric admissions during those three years. Higher levels of social support were found to correlate with lower levels of positive symptoms and few hospitalizations at follow-up. The relationship of social support to follow-up symptoms and hospitalization was independent of other potential predictors such as gender, age, premorbid adjustment and duration of untreated illness.

Persistent psychoses in first episode patients.

This study was carried out to identify characteristics of patients with schizophrenia spectrum disorder who continue to have persistent psychoses (15%) for 2 years after initiation of treatment by comparing them to those who maintained full recovery of positive symptoms (42%) up to 2 years. Compared to those in recovery, significantly more patients with persistent psychoses were single, male, had a higher prevalence of drug abuse and abnormal EEG findings at presentation for treatment. Duration of untreated psychoses or untreated illness did not discriminate between the groups.

The course of negative symptoms over the first five years of treatment: Data from an early intervention program for psychosis.

BACKGROUND: Cross-sectional studies suggest that negative symptoms are constituted by separable domains of reduced expressiveness and reduced motivation, but there is little data on the longitudinal course of these symptoms. We examined evidence for differences in the course and correlates of these two domains in a prospective study of patients presenting with a first episode of psychosis. METHODS: Of 132 patients who were followed up for five years, it was possible to monitor reduced expressiveness and motivation on a weekly basis for 127. Information on treatment delay, premorbid adjustment, intellectual functioning, anxiety, depression and psychosocial functioning were also collected. RESULTS: Over the five year follow-up, symptoms of reduced motivation occurred in 95.3% of patients and reduced expressiveness in 68.5%; and deficits in motivation were more likely to be unremitting (15.7%) than expressive deficits (5.5%). There were differences in the correlates of the proportion of time each patient experienced symptoms of each domain. Depression, weeks of full time occupation and weeks on a disability pension were associated with both domains. Anxiety was associated only with diminished motivation. Lower performance IQ; extrapyramidal symptoms (EPS) and dysrhythmic EEG were associated only with proportion of time showing reduced expressiveness. CONCLUSIONS: The prospective data support previous cross-sectional findings that, while these domains of negative symptoms are correlated, they do show differences in prevalence over time and in their correlates.

Electroencephalographic abnormalities and 5-year outcome in first-episode psychosis.

OBJECTIVE: To examine the relation of electroencephalographic abnormalities to 5-year outcomes in first-episode psychosis (FEP). METHODS: Patients (n = 103) had their baseline electroencephalogram (EEG) classified by modified Mayo Clinic criteria. Symptoms and psychosocial functioning were rated after 5 years of treatment. RESULTS: Dysrhythmic EEG was associated with persistence in positive and negative symptoms of psychoses and poorer psychosocial functioning at 5-year follow-up, independently of other characteristics, such as duration of untreated illness or premorbid adjustment. A higher percentage of people with comorbid substance use disorder had normal EEG. CONCLUSIONS: Abnormal baseline EEG in FEP is associated with poorer 5-year symptomatic and functional outcome.

Social support and functional outcomes in an early intervention program.

OBJECTIVE: To examine social support at initiation of treatment of psychosis and after one year of treatment as predictors of functioning at five year follow-up. METHODS: Early social support was assessed for 132 patients. Follow-up assessments included number of weeks of full-time occupation, number of weeks on a disability pension and global assessment of functioning. RESULTS: One year ratings of social support better predicted occupational activity at follow-up than initial social support. Social support predicted functional outcomes independently of other early characteristics. CONCLUSIONS: Findings support the importance of interventions to improve the level of support of individuals with psychotic disorders.

Symptom and functional outcomes for a 5 year early intervention program for psychoses.

There continues to be controversy concerning the long term benefits of specialized early intervention programs (SEI) for psychotic disorders. Recent reports of five year outcomes for SEI programs indicate that benefits of early intervention programs at two year follow-up have disappeared at five years. The Prevention and Early Intervention Program for Psychoses (PEPP) in London, Ontario offers continuity of care for five years, with a lower intensity level of specialized intervention after the initial two years. In this paper we examine whether the outcomes observed at two years were maintained at five year follow-up. In addition, it was possible to compare PEPP outcomes with those of the OPUS project at two and five years. Results indicate that improvement of symptoms between entry into PEPP and two year follow-up were maintained at five years. In addition, there was further improvement in global functioning between two and five year follow-up. Comparison of PEPP outcomes at two and five year follow-up to those of OPUS suggest that longer term continuity of care within SEI is associated with continuing benefits at least with respect to level of positive symptoms and functioning.

The significance of family history in first-episode schizophrenia spectrum disorder.

There have been inconsistent findings regarding the significance of family history of schizophrenia spectrum disorders in relation to presentation and course of illness. There has been little research relevant to this issue from first-episode patients. We examined the differences in premorbid adjustment, symptoms, and intellectual functioning between 28 first-episode schizophrenia spectrum patients with a history of such illness in first degree relatives and 28 matched patients without such a family history. The results indicate that whereas the 2 groups did not differ in presenting symptoms, those with a positive family history showed poorer intellectual functioning and less reduction in symptoms at 2 and 3 year follow-up and greater likelihood of abnormal electroencephalogram findings. The findings provide evidence that presence of a positive family history in first-episode patients is associated with a more pernicious form of illness.

Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia.

BACKGROUND: Progressive volumetric changes in the brains of people with schizophrenia have been attributed to a number of factors. AIMS: To determine whether glutamatergic changes in patients with schizophrenia correlated with grey-matter losses during the first years of illness. METHOD: Left anterior cingulate and thalamic glutamatergic metabolite levels and grey-matter volumes were examined in 16 patients with first-episode schizophrenia before and after 10 months and 30 months of antipsychotic treatment and in 16 healthy participants on two occasions 30 months apart. RESULTS: Higher than normal glutamine levels were found in the anterior cingulate and thalamus of never-treated patients. Thalamic levels of glutamine were significantly reduced after 30 months. Limited grey-matter reductions were seen in patients at 10 months followed by widespread grey-matter loss at 30 months. Parietal and temporal lobe grey-matter loss was correlated with thalamic glutamine loss. CONCLUSIONS: Elevated glutamine levels in never-treated patients followed by decreased thalamic glutamine and grey-matter loss in connected regions could indicate either neurodegeneration or a plastic response to reduced subcortical activity.