State-dependent implicit learning deficit in schizophrenia: evidence from 20-month follow-up

Previous research has confirmed stable explicit memory deficits in schizophrenia across disease states. However, little is known about the implicit learning capabilities of individuals with schizophrenia across the course of illness. The current study assessed procedural learning in 19 schizophrenia subjects (DSM-IV criteria) and 19 matched controls using the Serial Reaction-Time Task (SRTT). The severity of negative, positive and disorganized symptoms was assessed using the Scales for the Assessment of Positive and Negative Symptoms. A sub-sample of 11 schizophrenia subjects and 11 controls was reassessed 20 months later when symptoms in the schizophrenia subjects had largely remitted. Schizophrenia subjects were severely impaired on sequence-specific procedural learning during an acute episode. This deficit could not be explained by a general memory or processing speed impairment. Impaired implicit learning scores were significantly related to higher ratings of disorganized symptoms. However, 20 months later, when acute symptoms had remitted, the performance of the schizophrenia subjects on procedural learning had normalized. Our findings might share a conceptual overlap with previous reports of a reduced ability of schizophrenia subjects during an acute episode to adapt ongoing perceptual and behavioral programs to previously experienced regularities in their environment.     

Olanzapine for the treatment of chronic refractory schizophrenia: a 12-month follow-up naturalistic study

OBJECTIVE: The aim of this study is to provide long-term data on the effectiveness and safety of olanzapine in a group of patients with severe refractory schizophrenia. GENERAL METHODS: Twenty patients who had previously received treatment with typical antipsychotic agents and who met the DSM-IV criteria of schizophrenia and refractoriness to treatment were evaluated in a 1-year prospective study after switching to olanzapine. The Positive and Negative Symptoms Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) were used to measure effectiveness. The extrapyramidal symptoms were also recorded. Serial laboratory tests, electrocardiograms and body weight measurements were also performed. Longitudinal statistical analyses were performed on the global changes in the scores of the scales by means of a repeated measures analysis of variance. RESULTS: Significant reductions in the global scores from baseline in the PANSS, as well as in the BPRS, were observed. Furthermore, these reductions were also significant when considered only from Week 12. Olanzapine was, in general, well tolerated; a weight gain was observed between baseline and Month 4.5, but, interestingly, it decreased again from this time point to Month 12. CONCLUSION: Olanzapine was shown to be a suitable treatment for refractory schizophrenia in this series of seriously ill patients. Although most of the effects were observed before Week 12, improvement persisted after 1 year. Weight gain stopped or even regressed when the treatment was prolonged. Large controlled clinical trials to define the role of atypical antipsychotics for the management of treatment-refractory schizophrenia are necessary.     

Spatial working memory deficits and clinical symptoms in schizophrenia: a 4-month follow-up study.

BACKGROUND: Our goal was to examine spatial working memory function in relation to clinical symptoms of schizophrenia over a period of 4 months. METHODS: We assessed spatial working memory, spatial detection and clinical symptoms in 34 acutely psychotic schizophrenia patients within the first 2 weeks of hospitalization, and 4 months later. Spatial working memory was assessed by a delayed response task. A spatial control task was included to rule out simple sensorimotor deficits. Positive and negative symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Thirty-nine matched normal control subjects were also examined on the same tasks over the same period. RESULTS: Patients showed deficits in working memory, but they performed well on the spatial control task. Both positive and negative symptoms improved at the 4-month follow up. Spatial working memory also improved over time but there was still a significant deficit at the follow-up session. CONCLUSIONS: These results indicate that both symptoms and spatial working memory improved 4 months after the initial hospitalization but spatial working memory, hypothesized to be mediated by the dorsolateral prefrontal system, did not normalize. Thus, spatial working memory deficit may be a stable marker for schizophrenia.     

Familiality of clinical characteristics in schizophrenia

Few studies have assessed the familiality of clinical characteristics in schizophrenia. Therefore, we set out to investigate the familiality of the following characteristics; age of onset, course of disorder, employment status at onset, impairment during disorder, marital status at onset, mode of onset and premorbid functioning. Clinical characteristics were recorded using the Operational Criteria Checklist for Psychotic Illness for 155 subjects with an RDC diagnosis of schizophrenia, schizoaffective disorder, or psychosis of unknown origin, from 61 families multiply affected by schizophrenia. Age of onset, course of disorder, impairment during disorder, mode of onset, and premorbid functioning were shown to be familial. The familiality of these clinical characteristics supports their use in the delineation of homogeneous subsets for future genetic studies.     

Familiality of symptom dimensions in schizophrenia

The division of schizophrenic symptoms into three core dimensions - psychomotor poverty, reality distortion, and disorganisation - is well established. When factor analytic studies have included affective symptoms they have identified two additional dimensions - manic and depressive. Whether these five dimensions represent underlying psychopathology of a genetic or environmental aetiology remains unclear. The aims of this study were to perform factor analysis of symptoms in a group of familial schizophrenic patients and to investigate the familiality of the symptom dimensions identified, and their relationship to clinical characteristics. Symptoms were recorded, using the Operational Criteria Checklist for Psychotic Illness, for 155 Caucasian subjects with an RDC diagnosis of schizophrenia, schizoaffective disorder, or psychosis of unknown origin, from 61 families multiply affected with schizophrenia. Factor analysis indicated five symptom dimensions: depressive, manic, reality distortion, disorganisation, and psychomotor poverty. The psychomotor poverty, disorganisation, and manic dimensions were shown to be familial. Psychomotor poverty, disorganisation, and reality distortion were all associated with deterioration from premorbid functioning and chronic course of the disorder. In addition, psychomotor poverty was significantly related to poor premorbid functioning, as well as to single marital status and unemployment at onset. Disorganisation was significantly related to single marital status and unemployment at onset. The familiality of the psychomotor poverty, disorganisation, and manic dimensions supports their use in the delineation of homogeneous subsets for genetic studies.     

Impaired emotional learning and reduced amygdala size in schizophrenia: a 3-month follow-up

Individuals with schizophrenia have difficulties in emotional information processing. A relationship between behavioral variables of emotional processing and structural amygdala alterations in schizophrenia has been proposed but not shown, yet. Morphological studies of amygdala size in schizophrenia have yielded inconsistent results. The current study assessed paired associates learning of emotional and neutral faces in 16 subjects with schizophrenia during acute episode and in relative remission after 3 months. Sixteen matched controls were studied for comparison. Subjects also underwent structural magnetic resonance imaging (3D-MRI) at the first time of assessment. Subjects with schizophrenia showed a significant decrease (by 13%) in total size of the amygdala compared to controls, which was more pronounced on the right side. Subjects with schizophrenia improved associative learning of facial identities but not of emotional facial expressions after relative remission of psychotic symptoms. Volume of the right amygdala in subjects with schizophrenia and in controls was significantly related to emotional learning, indicating better learning in subjects with larger amygdala size. Our results indicate that subjects with schizophrenia have a deficit to form associations when emotionally loaded material is used. This deficit seems to be trait-like and independent of disease state. It seems to be linked to size reduction of the right amygdala in schizophrenia.     

Long-term follow-up of schizophrenia in 16 countries

An unexpected finding of the International Pilot Study of Schizophrenia, launched by the World Health Organization (WHO) in 1967, was that patients in countries outside Europe and the United States have a more favourable short- and medium-term course of the disease than those seen in developed countries. Since then, WHO has intensified its schizophrenia research programme and has initiated a set of international studies that have confirmed these initial findings and explored possible reasons for such differences in the course and outcome of schizophrenia. While such work has provided important findings and has generated additional pertinent hypotheses, it did not explain the differences in outcome. The present paper describes a new initiative in which approximately 2500 subjects involved in previous WHO multicentre schizophrenia studies are being followed up for between 15 and 25 years after initial examination. Nineteen research centres in 16 countries are taking part in this work. The research methodology is described.On behalf of the collaborating investigatorsThis paper is based on the data and experience obtained during the participation of the authors in the International Study on Schizophrenia (ISoS), a project sponsored by the World Health Organization, and funded by the World Health Organization, the Laureate Foundation (Untied States of America) and the participating centres.The chief collaborating investigators in the 19 field research centres and one methodological support centre of this study are: Aarhus: A. Bertelsen; Agra: K.C. Dube; Beijing: Shen Yucun; Cali: C. Leon; Chandigarh: V. Varma; Dublin: D. Walsh; Groningen: R. Giel; Hong Kong: P. Lee; Honolulu: A.J. Marsella; Ibadan: M. Olatawura; Khartoum: T. Baasher; Madras: R. Thara; Mannheim: H. Häfner; Moscow: S.J. Tsirkin; Nagasaki: Y. Nakane; Nottingham: G. Harrison; Orangeburg: E. Laska; Prague: S. Skoda; Rochester: L. Wynne; Sofia: K. Ganev. At WHO Headquarters, Geneva, the study has been coordinated by N. Sartorius (until August 1993), by W. Gulbinat (September 1993–April 1996) and Dr. Janca (since May 1996).     

Personality traits in migraine and tension-type headaches: a five-factor model study

Although abnormal personality traits have been frequently reported in patients with primary headaches, the overlaps between these domains need a clear standard definition, for example, by a five-factor personality model. Moreover, personality abnormalities in patients with episodic tension-type headache (ETH) and migraine with aura (MA) are less well studied. Therefore, we administered Zuckerman-Kuhlman's Personality Questionnaire to 72 patients suffering from chronic tension-type headaches (CTH), 33 with ETH, 15 with MA and 57 with migraine without aura (MO), as well as 58 healthy subjects. Depressive trends were measured with Plutchik-van Praag's Depression Inventory. Compared to healthy controls, the CTH, ETH and MO groups showed significantly greater neuroticism-anxiety and depression. In addition, the MO group scored significantly higher on aggression-hostility than healthy controls. No abnormal personality traits were found in patients with MA. This study, from the perspective of a five-factor model, confirms most previous reports about personality in patients with primary headaches and establishes elevated aggression-hostility only in MO sufferers.     

Outcome in early-onset schizophrenia revisited: findings from the Early Psychosis Prevention and Intervention Centre long-term follow-up study

The present study combined a time-locked paradigm and high-time-resolution event-related potential (ERP) recordings to examine different phases of working memory, including early visual processing and late memory-related processes of encoding, maintenance, and retrieval, in 67 adults with schizophrenia and 46 healthy controls. Alterations in ERP components were correlated with task performance. Patients performed significantly worse in the working memory task than healthy subjects, although all subjects' accuracy exceeded 80%. During encoding, the N1 and P2 component amplitudes were lower while the P300 amplitude was higher in schizophrenic patients compared to healthy controls. There were no differences between groups with respect to the mean amplitudes of the negative slow waves in the early stage (the first 400 ms) of the maintenance phase. However, in the next 500-ms time window, the patients exhibited a more negative deflection in the middle fronto-central region than the control group. Likewise, a similar pattern was observed in the second 500-ms period in the middle fronto-central region, although the effect was marginally significant. There were no differences between groups in the remaining 1000 ms. During retrieval, the P1, N1 and P2 amplitudes were lower while the P300 amplitude and latency were higher in schizophrenic patients. The present results indicate early visual deficits in the working memory task in adults with schizophrenia. Impairments in the maintenance phase were confined to the late rehearsal stage. The increased P300 amplitude at the fronto-central electrode sites along with the poorer behavioral performance suggests that schizophrenic patients have an inefficient working memory system.     

Lifetime psychopathology in child and adolescent offspring of parents diagnosed with schizophrenia or bipolar disorder: a 2-year follow-up study

Having one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood, and it also increases the risk of a wide range of mental disorders in the offspring. The aim of this study is to compare the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms, and global functioning in offspring of parents with schizophrenia or bipolar disorder and in offspring of controls at baseline and 2-year follow-up. This study included 41 offspring of parents with schizophrenia, 90 offspring of parents with bipolar disorder, and 107 offspring of controls (mean age 11.7 ± 3.2 at baseline and 13.9 ± 3.2 at follow-up). The prevalence of psychopathology and comorbidity was higher in offspring of parents with schizophrenia and offspring of parents with bipolar disorder than in offspring of controls at baseline and at 2-year follow-up. Interestingly, mood disorders were more prevalent in offspring of parents with bipolar disorder and disruptive disorders were more prevalent in offspring of parents with schizophrenia. Prodromal symptoms were more frequent in offspring of parents with schizophrenia than in offspring of controls, while the offspring of parents with bipolar disorder showed an intermediate pattern. Finally, global functioning was lower in the offspring of parents with schizophrenia than the offspring of parents with bipolar disorder and the offspring of controls. Screening patients’ children is clinically relevant, since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.

     

Needs-based cognitive-behavioural family intervention for carers of patients suffering from schizophrenia: 12-month follow-up.

OBJECTIVE: To examine longer-term effectiveness of a needs-based family intervention for carers and out-patients suffering from schizophrenia. METHOD: Seventy-nine unselected patient-carer pairs were recruited from a geographical area and allocated randomly to one of two conditions. One group received needs-based cognitive-behavioural family intervention in combination with general family support plus the standard care. The control group received the general family support and standard care only. RESULTS: Analysis was carried out on an intention-to-treat basis. There was a significant advantage for family intervention, in terms of relapse (37% relapsed compared to 72%, NNT=3) and on other clinical measures. Treatment group and medication compliance were significant and independent predictors of relapse. There was a significant reduction in carer needs in the intervention group. CONCLUSION: Family intervention directed at carers' needs within a standard mental health service can produce benefits for patients beyond the term of intervention.     

Continuity and change of psychopathology from childhood into adulthood: a 14-year follow-up study

OBJECTIVE: To test the 14-year continuity and change of behavioral and emotional problems from childhood into adulthood. METHOD: For 1,615 children and adolescents aged 4 to 16 years from the general population, parents completed the Child Behavior Checklist (CBCL) at initial assessment. At follow-up 14 years later, subjects completed the Young Adult Self-Report (YASR), and their parents completed the Young Adult Behavior Checklist (YABCL). RESULTS: Of the subjects who were initially classified as deviant, 14 years later 41% were classified as deviant according to their YABCL Total Problem score, and 29% according to their YASR Total Problem score. Intrainformant (CBCL/YABCL) Withdrawn, Social Problems, Delinquent Behavior, and Aggressive Behavior scores, and cross-informant (CBCL/YASR) Anxious/Depressed, Thought Problems, and Delinquent Behavior scores were independent predictors of general levels of problem behavior. CONCLUSIONS: Childhood and adolescent problems persisted to a considerable degree into adulthood, although the majority of children who were deviant at initial assessment could not be regarded as deviant 14 years later. Children who were adolescents at initial assessment (12-16 years) showed higher stability of problem behaviors than subjects who were children at initial assessment (4-11 years).     

Disease activity in idiopathic intracranial hypertension: a 3-month follow-up study

Idiopathic intracranial hypertension (IIH) is a disorder of raised intracranial pressure (ICP) in the absence of identifiable pathology. The purpose of this study was to evaluate the clinical presentation and monitor a 3-month course using frequent optical coherence tomography (OCT) evaluations, visual field testings and lumbar opening pressure measurements. A longitudinal study of 17 patients with newly diagnosed IIH and 20 healthy overweight controls were included in the study. Peripapillary retinal nerve fiber layer thickness (RNFLT) and retinal thickness (RT) measurements (Stratus OCT-3, fast RNFL 3.4 protocol), and Humphrey visual field testing were evaluated at regular intervals. Repeat lumbar puncture was performed at final visit (n = 13). The diagnostic delay was 3 months and initial symptoms were headache (94%), visual blurring (82%) and pulsatile tinnitus (65%). Complete clinical remission was achieved in 65%, partial in 29% and unchanged symptoms in 6%. Total average RNFLT and RT decreased significantly during the follow-up period (p < 0.0001 and p < 0.0001, respectively). Changes in RNFLT and RT correlated with improvements in visual field mean deviation (MD) (RNFLT: p = 0.006; RT: p = 0.03) and pattern standard deviation (PSD) (RNFLT: p = 0.002; RT: p = 0.003). In patients with weight-loss >3.5% of BMI, ICP decreased significantly (p = 0.0003). In patients with weight-loss <3.5% of BMI, changes in ICP were insignificant (p = 0.6). OCT combined with visual field testing may be a valuable objective tool to monitor IIH patients and the short term IIH outcome is positive. Weight-loss is the main predictor of a favorable outcome with respect to CSF pressure.     

Post-natalizumab clinical and radiological findings in a cohort of multiple sclerosis patients: 12-month follow-up

There is an urgent need to identify the best strategies to prevent the loss of natalizumab (N) beneficial effects after its suspension. The objective is to evaluate the clinical and radiological disease activity and to test the efficacy of immunomodulatory/immunosuppressive drugs (IT) after N suspension. Clinical and radiological data from 54 patients 2 years before treatment (pre-N), during treatment (on-N) and after interruption, during 1-year follow-up (post-N) were retrospectively collected. Annualized relapse rate (ARR), expanded disability status scale (EDSS), presence of new T2 lesions and Gd+ (gadolinium enhancing) T1 lesions were evaluated. Pre-N ARR at 1 year was 1.74 while post-N ARR was 0.94 (p = 0.0053). We observed that post-N disease activity never raised over pre-N levels, neither post-N ARR nor post-N EDSS. In patients retreated with N after suspension, post-N ARR was significantly lower than pre-N ARR (p = 0.017), but not in patients treated with other IT or in patients not treated with any disease modifying drugs (DMD). The mean time of freedom from new T2 lesions and new Gd+ lesions was lower in post-N period compared to on-N (T2 lesions p = 0.0000, Gd+ lesions p = 0.0000). In conclusion, a “rebound” pattern was not identified in our cohort, though the disease activity rapidly returned after N, regardless of the treatment used.     

Depression after stroke at 12-month follow-up: a multicenter study

Purpose: To study the prevalence of depression at 12 months after stroke and to analyze factors associated with depression.

Methods: This prospective cross-sectional study was conducted among nine tertiary hospitals in Thailand. Stroke patients from the Thai Stroke Rehabilitation Registry who were admitted in inpatient rehabilitation wards were recruited for evaluation at the 12-month follow-up time point. Hospital Anxiety and Depression Scale (HADS) was used to evaluate depression in stroke. A score of ≥11 was considered as having depression. Univariate and multivariate analysis was used to investigate factors related with depression in stroke.

Results: Two hundred stroke patients with a mean age of 62.1±12.5 years were recruited. Approximately 60% were male. The number of stroke patients with depression at the 12-month follow-up was 42 (21.0%, 95%CI 15.9%–27.2%). Mean HADS score at 12-month follow-up was not significantly different from those at discharge. However, 28 (16.5%) stroke patients who did not have depression at discharge developed depression during the 12-month period. From multivariate analysis, complications and urinary incontinence were found to be significantly associated with depression after stroke with adjusted odds ratio of 3.65 (95%CI 1.11–12.06) and 4.82 (95%CI 1.74–13.38), respectively.

Conclusion: Depression is a common complication after stroke. This study found one-fifth of stroke survivors developed depression at the 12-month follow-up. Complications at discharge and urinary incontinence were significantly correlated with depression in multivariate analysis. Further study concerning interventions in decreasing depression should be performed in order to improve the quality of life of those stroke patients.     

Cannabis and schizophrenia: results of a follow-up study

A total of 39 schizophrenic patients with a history of current cannabis abuse at index admission was compared with a control group of schizophrenics without substance abuse matched for age, gender, and year of admission. At follow-up after 68.7 ± 28.3 months, 27/ 39 cases and 26/39 controls could be investigated. 8/27 cases (30%) had continued cannabis abuse, 6/27 (22%) had become alcohol abusers. Only one patient of the control group had started abusing alcohol. Patients with previous cannabis abuse had significantly more rehospitalizations, tended to worse psychosocial functioning, and scored significantly higher on the psychopathological syndromes “thought disturbance” (BPRS) and “hostility” (AMDP). These results confirm the major impact of cannabis abuse on the long-term outcome of schizophrenic patients. Received: 16 December 1997 / Accepted: 19 November 1998