Neurological soft signs and cognition in the late course of chronic schizophrenia: a longitudinal study

Abstract Neurological soft signs (NSS) are minor (‘soft’) neurological abnormalities in sensory and motor performances, which are frequently reported in patients with schizophrenia at any stage of their illness. It has been demonstrated that NSS vary in the clinical course of the disorder: longitudinally NSS decrease in parallel with remission of psychopathological symptoms, an effect which mainly applies to patients with a remitting course. These findings are primarily based on patients with a first episode of the disorder, while the course of NSS in patients with chronic schizophrenia and persisting symptoms is rather unknown. Therefore, we investigated NSS twice in 21 patients with chronic schizophrenia (initial mean duration of illness: 23 ± 11 years) with a mean follow-up interval of 7 years. NSS were evaluated by the Heidelberg Scale, established instruments were used to rate neuropsychological performance and psychopathological symptoms. NSS showed significant increases on the subscales “motor coordination” and “integrative functions”, while positive and negative symptoms, including apathy, showed only minor, non-significant changes. Verbal memory, verbal fluency, and cognitive flexibility along with severity of global cognitive deficits demonstrated a significant deterioration. Regression analyses identified executive dysfunction (cognitive flexibility and verbal fluency) at baseline as significant predictors of NSS increase at follow-up. Our findings indicate that NSS deteriorate in the long-term course of chronic schizophrenia. This effect may be accounted for by a decrease of executive functions and logical memory, which can be attributed to premature brain aging.

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Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia

Schizophrenia Research ◽

10.1016/j.schres.2008.12.029 ◽

2009 ◽

Vol 108 (1-3) ◽

pp. 49-56 ◽

Cited By ~ 60

Author(s):

Tsutomu Takahashi ◽

Stephen J. Wood ◽

Bridget Soulsby ◽

Patrick D. McGorry ◽

Ryoichiro Tanino ◽

...

Keyword(s):

Insular Cortex ◽

Chronic Schizophrenia ◽

First Episode Psychosis ◽

First Episode ◽

Episode Psychosis ◽

Mri Study

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Outcome of first-episode schizophrenia in India: longitudinal study of effect of insight and psychopathology

The British Journal of Psychiatry ◽

10.1192/bjp.bp.109.068577 ◽

2010 ◽

Vol 196 (6) ◽

pp. 454-459 ◽

Cited By ~ 54

Author(s):

Balasubramanian Saravanan ◽

K. S. Jacob ◽

Shanthi Johnson ◽

Martin Prince ◽

Dinesh Bhugra ◽

...

Keyword(s):

Chronic Schizophrenia ◽

Symptomatic Improvement ◽

First Episode ◽

Middle Income ◽

Early Improvement ◽

Residual Symptoms ◽

Middle Income Countries ◽

First Episode Schizophrenia ◽

Clinical Measures

BackgroundTranscultural studies have found lack of insight to be an almost invariable feature of acute and chronic schizophrenia, but its influence on prognosis is unclear.AimsTo investigate the relationship between insight, psychopathology and outcome of first-episode schizophrenia in Vellore, India.MethodPatients with a DSM–IV diagnosis of schizophrenia (η = 131) were assessed prospectively at baseline and at 6-month and 12-month follow-up. Demographic and clinical measures included insight, psychopathology, duration of untreated psychosis (DUP) and social functioning. Linear and logistic regression was used to measure predictors of outcome.ResultsFollow-up data were available for 115 patients at 1 year. All achieved remission, half of them with and half without residual symptoms. Changes in psychopathology and insight during the first 6 months and DUP strongly predicted outcome (relapse or functional impairment), controlling for baseline measures.ConclusionsOutcome of schizophrenia in this setting is driven by early symptomatic improvement and is relatively favourable, in line with other studies from low- and middle-income countries. Early improvement in insight might be a useful clinical guide to future outcome. Reduction of DUP should be a target for intervention.

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Neurological Soft Signs in First-Episode Schizophrenia: A Follow-Up Study

American Journal of Psychiatry ◽

10.1176/appi.ajp.162.12.2337 ◽

2005 ◽

Vol 162 (12) ◽

pp. 2337-2343 ◽

Cited By ~ 97

Author(s):

Silke Bachmann ◽

Christina Bottmer ◽

Johannes Schröder

Keyword(s):

First Episode ◽

Neurological Soft Signs ◽

Follow Up Study ◽

First Episode Schizophrenia

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Duration of untreated psychosis and its correlates in first episode psychosis: results of the prospective 5-year follow-up study

European Psychiatry ◽

10.1016/s0924-9338(11)73238-2 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1534-1534

Author(s):

Y. Zaytseva ◽

I. Gurovich ◽

A. Dorodnova ◽

L. Movina ◽

A. Shmukler

Keyword(s):

Social Adjustment ◽

Verbal Memory ◽

Visual Memory ◽

Negative Symptoms ◽

Age Of Onset ◽

Brain Regions ◽

Psychotic Symptoms ◽

First Episode ◽

Duration Of Untreated Psychosis

IntroductionDuration of untreated psychosis (DUP) is a potentially changeable prognostic factor which can also indicate neurodegenerative process in schizophrenia.ObjectiveTo examine the association of DUP with various characteristics of the course of schizophrenia in first episode patients during 5-year follow-up.MethodsOne-hundred-fourteen patients with first psychotic episodes who have been treated in naturalistic setting within Early Intervention Centre (Moscow Research Institute of Psychiatry) were included. Clinical, social and neuropsychological parameters were assessed using standardized instruments.ResultsThe mean duration of untreated psychotic symptoms before admission was 298.66 ± 447.35 days. According to the analysis DUP was found to be significantly associated with the mode of onset (r = 0.51, p ≤ 0.001) level of remission (r = 0.21–0.30, p ≤ 0.05), severity of positive symptoms and negative symptoms in remission mostly at 2nd, 3d and 4th years of observation, poorer level of social adjustment at the 5th year (r = 0.19, p ≤ 0.05). The effect of DUP remained significant after controlling for age, gender and diagnostic variables.Moreover, DUP correlated with the parameters of verbal memory, visual memory and spatial functions during the follow-up (r = 0.29–0.36, p ≤ 0.05, r = 0.28–0.30, p ≤ 0.05, respectively). No correlations have been found between DUP and the age of onset, number of relapses and their duration during 5-year follow-up as well as with other neurocognitive parameters (executive functioning, gnosis, praxis, attention).ConclusionsThe results of the study underline the prognostic value of DUP for predicting clinical and functional outcomes. Association between DUP and poor memory domains supports the notion of neurotoxicity of DUP grasping specific brain regions in schizophrenia.

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Prospective evaluation of neurological soft signs in first-episode schizophrenia in relation to psychopathology: state versus trait phenomena

Psychological Medicine ◽

10.1017/s0033291703008225 ◽

2003 ◽

Vol 33 (8) ◽

pp. 1479-1484 ◽

Cited By ~ 42

Author(s):

P. WHITTY ◽

M. CLARKE ◽

S. BROWNE ◽

O. McTIGUE ◽

M. KAMALI ◽

...

Keyword(s):

Clinical Course ◽

Clinical State ◽

First Episode ◽

Neurological Soft Signs ◽

Syndrome Scale ◽

Dsm Iv ◽

A Prospective Study ◽

First Episode Schizophrenia ◽

Negative Syndrome

Background. Although patients with schizophrenia have increased rates of neurological soft signs, few studies have examined prospectively their trait or state characteristics in relation to psychopathology.Method. In a prospective study of 97 patients with first-episode schizophrenia (DSM-IV criteria) we assessed neurological soft signs and psychopathology at presentation and at 6 month follow-up for 73 cases. To establish whether soft signs were associated with variations in clinical state, neurological soft signs were measured using two validated examinations (Neurological Evaluation Scale and Condensed Neurological Examination); psychopathology was assessed using the Positive and Negative Syndrome Scale.Results. There was significant improvement in overall neurological function, primarily in motor-related and cortical signs, which were associated with improvement in psychopathology. Conversely, ‘harder’ signs were unrelated to improvement in psychopathology.Conclusions. Neurological soft signs in schizophrenia are heterogenous. Motor and cortical signs evidence state-like characteristics and vary with clinical course, while ‘harder’ signs evidence more static, trait-like characteristics in accordance with a neurodevelopmental basis.

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Neurocognition in individuals at high familial risk of mood disorders with or without subsequent onset of depression

Psychological Medicine ◽

10.1017/s0033291715001324 ◽

2015 ◽

Vol 45 (15) ◽

pp. 3317-3327 ◽

Cited By ~ 16

Author(s):

M. Papmeyer ◽

J. E. Sussmann ◽

J. Hall ◽

J. McKirdy ◽

A. Peel ◽

...

Keyword(s):

High Risk ◽

Mood Disorders ◽

Cognitive Flexibility ◽

Verbal Memory ◽

Familial Risk ◽

Set Shifting ◽

Neurocognitive Performance ◽

Performance Deficits ◽

Time Points

BackgroundNeurocognitive performance deficits have been observed in mood disorder patients and their unaffected relatives and may therefore qualify as endophenotypes. However, the precise time course of neurocognitive deficits has not been studied so that it is unknown whether neurocognitive abnormalities reflect the early effects of familial vulnerability to mood disorders or if they emerge at illness onset.MethodA neuropsychological test battery was administered at baseline and after a 2-year follow-up interval in 111 initially unaffected young adults at high familial risk of mood disorders and 93 healthy controls (HC). During the follow-up period, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the remainder remaining well (HR-well). Linear mixed-effects models were used to investigate differences and longitudinal changes in the domains of attentional processing, working memory, verbal learning and memory, and cognitive flexibility.ResultsReduced long delay verbal memory and extradimensional set-shifting performance across both time points were found in the HR-well group relative to controls. The HR-MDD group displayed decreased extradimensional set-shifting abilities across both time points as compared with the HC group only. There were no significant performance differences between the two high-risk groups.ConclusionsReduced verbal memory and cognitive flexibility are familial trait markers for vulnerability to mood disorders in individuals with a close family history of bipolar disorder. Both neurocognitive performance deficits appear to be relatively stable over a 2-year time period and do not appear to be linked to the onset of MDD. These findings support their use as stable quantitative endophenotypes for mood disorders.

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First-episode schizophrenia: A follow-up study on neurological soft signs

Schizophrenia Research ◽

10.1016/s0920-9964(03)80027-0 ◽

2003 ◽

Vol 60 (1) ◽

pp. 10

Author(s):

S. Bachmann ◽

C. Bottmer ◽

D. Weimer ◽

J. Schro¨der

Keyword(s):

First Episode ◽

Neurological Soft Signs ◽

Follow Up Study ◽

First Episode Schizophrenia

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The impact of cognitive reserve, cognition and clinical symptoms on psychosocial functioning in first-episode psychoses

Psychological Medicine ◽

10.1017/s0033291720002226 ◽

2020 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Silvia Amoretti ◽

Adriane R Rosa ◽

Gisela Mezquida ◽

Bibiana Cabrera ◽

María Ribeiro ◽

...

Keyword(s):

Cognitive Performance ◽

Verbal Memory ◽

Negative Symptoms ◽

Cognitive Reserve ◽

Clinical Symptoms ◽

First Episode ◽

Cognitive Domains ◽

The Impact ◽

The Relationship

Abstract Background Functional impairment is a defining feature of psychotic disorders. A range of factors has been shown to influence functioning, including negative symptoms, cognitive performance and cognitive reserve (CR). However, it is not clear how these variables may affect functioning in first-episode psychosis (FEP) patients. This 2-year follow-up study aimed to explore the possible mediating effects of CR on the relationship between cognitive performance or specific clinical symptoms and functional outcome. Methods A prospective study of non-affective FEP patients was performed (211 at baseline and 139 at follow-up). CR was entered in a path analysis model as potential mediators between cognitive domains or clinical symptoms and functioning. Results At baseline, the relationship between clinical variables or cognitive performance and functioning was not mediated by CR. At follow-up, the effect of attention (p = 0.003) and negative symptoms (p = 0.012) assessed at baseline on functioning was partially mediated by CR (p = 0.032 and 0.016), whereas the relationship between verbal memory (p = 0.057) and functioning was mediated by CR (p = 0.014). Verbal memory and positive and total subscales of PANSS assessed at follow-up were partially mediated by CR and the effect of working memory on functioning was totally mediated by CR. Conclusions Our results showed the influence of CR in mediating the relationship between cognitive domains or clinical symptoms and functioning in FEP. In particular, CR partially mediated the relationship between some cognitive domains or clinical symptoms and functioning at follow-up. Therefore, CR could improve our understanding of the long-term functioning of patients with a non-affective FEP.

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T51. VERBAL MEMORY TRAJECTORIES IN CHRONIC INDIVIDUALS WITH SCHIZOPHRENIA ALONG 6 YEARS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa029.611 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S250-S251

Author(s):

Dayane Martins ◽

Clara de Oliveira Lapa ◽

Mathias Hasse-Sousa ◽

Maria Julia Britto ◽

Ramiro Reckziegel ◽

...

Keyword(s):

Verbal Memory ◽

Psychosocial Functioning ◽

Memory Performance ◽

Verbal Learning ◽

Disease Onset ◽

Control Sample ◽

First Episode ◽

Cognitive Symptoms ◽

Time Points

Abstract Background Individuals with schizophrenia (SZ) present different positive, negative and cognitive symptoms that impact psychosocial functioning. Cognitive impairments are shown to be present even in premorbid stages of psychosis, which is related to the neurodevelopmental model of SZ. However, although well described in the literature, the trajectories and mechanisms of cognitive symptoms are still unclear. Some evidence suggest that the deficits may remain stable after the first episode and follow the normal course of aging. Conversely, other studies show a decline in cognitive performance related to the chronicity of the disorder. A central domain widely studied in SZ because of its relationship to functional outcomes is verbal memory (VM), which is particularly vulnerable to aging. Therefore, our aim was to investigate the trajectory of memory performance after 6 years in a sample of chronic individuals with SZ to bring further evidence for the two possible hypotheses (stability vs. progression). Methods We recruited 28 individuals with SZ (18 male, 10 female) from an outpatient clinic from a tertiary hospital in Porto Alegre, Brazil. These participants were part of a previous study, resulting in two point assessments of 6 years difference. Patients were stable and receiving pharmacological treatment. We conducted clinical interviews to collect sociodemographic and clinical data. Memory was assessed through the Hopkins Verbal Learning Test Revised (HVLT-R) on the two time points. Scores were transformed to z based on a healthy control sample. Analysis were conducted in the SPSS 18 and included general linear models and other exploratory analysis. The local ethics committee approved this study. Results On the first assessment, patients had 37.32(±11.28) years old, 10.54(±3.68) years of education, and 13.96 (±10.52) years since disease onset. Patients showed deficits in memory performance in both time points (T1: Z = -1.56(±1.19), T2: Z = -1.72(±1.19). However, there was no difference between baseline and follow-up after 5.78 (±0.9) years for the total immediate recall (p=.516). Additionally, we did not find significant effects of age and years of education to memory performance. Interestingly, duration of illness had a main effect predicting memory performance, however this was independent of time points (p=.003). Interestingly, 53.6% of patients decreased its performance on the follow-up, while 46.4% increased it. When we considered these two groups, we found an interaction of the time of assessment by increased/decreased trajectory in the prediction of memory performance (p = .001). Discussion Although we did not find differences between baseline and follow-up assessments, we found two different groups with diverse trajectories. The most recent studies in SZ have discussed the existence of these subgroups in the disorder. Our results didn’t showed evidence of impacts of both neurodevelopment or neuroprogression theories, the limited sample size may have influenced this. However, the two moment of assessment were with more than 10 years after the disease onset, adding to the compelling evidence that most of the cognitive deficits occur during early stages of the disorder.

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