Neurocognitive and social cognitive correlates of social exclusion in psychotic disorders: a 20-year follow-up cohort study.

PURPOSE: Little is known about the relationship between social exclusion and cognitive impairment in psychosis. We conducted a long-term cohort study of first-episode psychosis to examine the association between comprehensive measures of cognitive impairment and social exclusion assessed at follow-up. METHODS: A total of 173 subjects with first-episode psychosis were assessed after a 20-year follow-up for 7 cognitive domains and 12 social exclusion indicators. Associations between sets of variables were modeled using multivariate regression, where social exclusion indicators were the dependent variables, cognitive domains were the independent variables, and age, gender, and duration of follow-up were covariates. RESULTS: The total scores on the measures of cognition and social exclusion were strongly associated (ß = - .469, ∆R2 = 0.215). Participants with high social exclusion were 4.24 times more likely to have cognitive impairment than those with low social exclusion. Verbal learning was the cognitive function most related to social exclusion domains, and legal capacity was the exclusion domain that showed the strongest relationships with individual cognitive tests. Neurocognition uniquely contributed to housing, work activity, income, and educational attainment, whereas social cognition uniquely contributed to neighborhood deprivation, family and social contacts, and discrimination/stigma. Neurocognition explained more unique variance (11.5%) in social exclusion than social cognition (5.5%). CONCLUSION: The domains of cognitive impairment were strongly and differentially related to those of social exclusion. Given that such an association pattern is likely bidirectional, a combined approach, both social and cognitive, is of paramount relevance in addressing the social exclusion experienced by individuals with psychotic disorders.

Social exclusion as a major outcome domain of psychotic disorders: early predictors, and associations with non-recovery and clinical staging 21 years after a first episode of psychosis.

PURPOSE: People with psychotic disorders have high levels of social exclusion; however, little is known about its early predictors. We present a long-term observational cohort study aimed at examining early risk factors for later social exclusion. METHODS: A total of 243 subjects were assessed at their first psychotic episode for early risk factors including sociodemographic variables, familial risk of major mental disorders, perinatal complications, childhood factors, and adolescent factors and re-assessed after a mean follow-up of 21 years for 12 social exclusion domains: leisure activities, housing, work, income, neighborhood deprivation, educational attainment, physical and mental health, family and social support, legal competence, and discrimination. The ability of risk factors to predict social exclusion was examined using hierarchical linear regression. RESULTS: Overall social exclusion was independently predicted by low parental socio-economic status, length of follow-up, familial risk of schizophrenia, obstetric complications, neurodevelopmental delay, poor childhood adjustment, childhood adversity, poor adolescent social networks, poor adolescent adjustment, and low premorbid IQ. The model explained 58.2% of the variance in total social exclusion score. Each social exclusion domain was predicted by a different set of variables, which explained between 17.8 and 57.0% of their variance, although low socio-economic status, familial risk of schizophrenia, obstetric complications, childhood adversity, and poor social networks predicted most of the social exclusion domains. CONCLUSION: Early risk factors strongly predicted later social exclusion. A multifaceted approach to preventing later social exclusion is crucial in people with a first episode of psychosis and early risk factors of social exclusion.

The effect of anticholinergic burden of psychiatric medications on major outcome domains of psychotic disorders: A 21-year prospective cohort study.

BACKGROUND: Most medications used to treat psychotic disorders possess anticholinergic properties. This may result in a considerable anticholinergic burden (ACB), which may have deleterious effects on long-term outcomes. The extent to which cumulative ACB over years of treatment with psychotropic medications impacts different outcome domains remains unknown. METHODS: This was a naturalistic study of 243 subjects with first-episode psychosis aimed at examining the cumulative effect of ACB of psychotropic medications administered over the illness course (ACB-years exposure) on several outcome domains assessed after a mean 21-year follow-up. Associations between ACB and the outcomes were modelled accounting for relevant confounding factors by using hierarchical linear regression analysis. RESULTS: Over the study period, 81.9 % of the participants were dispensed at least one drug with strong anticholinergic effects for at least 1 year; at the follow-up visit, 60.5 % of the participants continued to take medications with strong ACB. ACB-years exposure was uniquely related to severity of negative symptoms (ß = 0.144, p = 0.004), poor psychosocial functioning (ß = 0.186, p < 0.001) and poor cognitive performance (ß = -0.273, p < 0.001). This association pattern was independent of a schizophrenia diagnosis. Most of the associations between ACB at the follow-up visit and the outcomes were accounted for ACB-years exposure. CONCLUSION: Lifetime ACB of psychotropic medications has deleterious effects on the outcome of psychotic disorders. Clinicians should avoid prescribing medications with strong ACB, since there are numerous alternatives within each psychotropic drug group for prescribing medications with low ACB.

A clinical staging model of psychotic disorders based on a long-term follow-up of first-admission psychosis: A validation study.

We examined the empirical validity of a staging model of psychotic disorders primarily based on their long-term course. The model distinguished 6 consecutive stages (2A, 2B, 3A, 3B, 4A, 4B) based on symptom recurrence, persistence and progression, such as functional decline. We analyzed data from 243 participants with first-admission psychosis who were followed-up for a mean of 20.9 years and assessed for 22 baseline variables, 23 construct-related variables and 31 outcome variables. Later stages scored significantly poorer than early stages on most validators by showing generally medium to large effect sizes and a dose-response pattern, thus confirming the validity of the model. For each set of validators, differences between consecutive stages were especially evident for stages 2 and 3A, although many variables from each validation realm also differentiated between the consecutive stages 3A and above. Baseline predictors including familial load of schizophrenia, neurodevelopmental impairment, childhood adversity, treatment delay, negative symptoms, neurological impairment and poor early response to treatment, independently accounted for 49.9% of the variance of staging. A staging model of psychosis based primarily on its long-term course has sound construct, outcome and predictive validity, which may inform about stage indicators and predictors of clinical stages from psychosis onset.

Neuromotor dysfunction as a major outcome domain of psychotic disorders: A 21-year follow-up study.

BACKGROUND: The long-term stability of neuromotor domains assessed at the first episode of psychosis (FEP) and their ability for predicting a number of outcomes remains largely unknown, and this study addressed these issues. METHODS: This was a longitudinal study of 243 participants with FEP who were assessed at baseline for background variables and parkinsonism, dyskinesia, neurological soft signs (NSS) and catatonia, and reassessed 21 years later for the same neuromotor variables, psychopathology, functioning, personal recovery, cognitive performance and medical comorbidity. Stability of neuromotor ratings was assessed using the intraclass correlations coefficient and associations between the predictors and outcomes were examined using univariate and multivariate statistics. RESULTS: Baseline dyskinesia and NSS ratings showed excellent stability over time whereas that for parkinsonism and catatonia was relatively low. Neuromotor dysfunction at follow-up was independently predicted by a family history of schizophrenia, obstetric complications, neurodevelopmental delay, low premorbid IQ and baseline ratings of dyskinesia and NSS. Moreover, baseline dyskinesia and NSS ratings independently predicted more positive and negative symptoms, poor functioning and less personal recovery; catatonia predicted less personal recovery and more medical comorbidity. Baseline neuromotor ratings explained between 4% (for medical comorbidity) and 34% (for neuromotor dysfunction) of the variance in the outcomes. Lastly, neuromotor dysfunction at baseline highly predicted clinical staging at follow-up. CONCLUSION: Baseline neuromotor domains show variable stability over time and relate distinctively to very long-term outcomes. Both baseline dyskinesia and NSS are trait markers of the disease process and robust predictors of the outcomes.

Covariation between motor signs and negative symptoms in drug-naive subjects with schizophrenia-spectrum disorders before and after antipsychotic treatment.

OBJECTIVE: To examine the covariation between negative symptoms and motor signs in a broad sample of drug-naïve subjects with schizophrenia-spectrum psychoses before and after inception of antipsychotic medication. METHODS: One-hundred and eighty-nine antipsychotic-naïve subjects with DSM-IV schizophrenia-spectrum psychoses were assessed for negative symptoms including affective flattening, alogia, avolition/apathy and anhedonia/associality, and motor signs including catatonia, parkinsonism and dyskinesia. We examined the association between negative and motor features at baseline, 4-weeks after inception of antipsychotic treatment and that of their mean change over the treatment period, such as their trajectories and treatment response pattern. RESULTS: At the drug-naïve state, motor signs were strongly related to affective flattening and alogia (p<0.01); at 4-weeks, most negative and motor features were significantly interrelated (p<0.01); mean change of motor signs and negative symptoms tended to be unrelated. This association pattern was irrespective of levels of positive symptoms. Ratings of negative symptoms, excepting affective flattening, improved after treatment (p<0.001) while motor ratings showed divergent trajectories with catatonia improving (p<0.001), parkinsonism worsening (p<0.001) and dyskinesia remaining unchanged (p>0.01). Although to a different extent, motor and negative features showed drug-responsive, drug-worsening, of drug-unchanged patterns of response to antipsychotic medication. The main predictors of negative and motor features in treated subjects were their corresponding baseline ratings (p<0.001). CONCLUSIONS: Negative and motor features are differentiated, but to some extent, overlapping domains that are meaningfully influenced by antipsychotic medication. At the drug-naïve state, motor signs and the diminished expression domain of negative symptoms may share underlying neurobiological mechanisms.

Spontaneous parkinsonism is associated with cognitive impairment in antipsychotic-naive patients with first-episode psychosis: a 6-month follow-up study.

There is now growing evidence that parkinsonism and other extrapyramidal signs are highly prevalent in patients with first-episode psychosis who have never been exposed to antipsychotic drugs. However, the neurocognitive correlates of parkinsonism in this population remained to be clarified. A sample comprising 100 consecutive drug-naive patients with first-episode psychosis were enrolled on the study and followed up for 6 months. Seventy-seven completed assessments at 3 time points (baseline, 1 mo, and 6 mo), involving clinical and cognitive examinations and a specific assessment of motor abnormalities. The Simpson-Angus Scale (SAS) was used for the assessment of extrapyramidal signs, and each motor domain was evaluated with a standard assessment scale. Linear mixed models were built to explore the longitudinal relationships between parkinsonism scores and cognitive impairment. Parkinsonism scores showed significant strong longitudinal associations with deficits in memory, executive functioning, and attention. Spontaneous parkinsonism (total SAS score and hypokinesia and rigidity subscores at baseline) showed high 6-month predictive values for cognitive impairment. In addition, they also had high predictive values for neurologic soft-sign abnormalities but not for dyskinesia, akathisia, and pure catatonic abnormalities. No predictive value was found for glabella-salivation or tremor subscores on the SAS scale. These results emphasize the relevance of the assessment of parkinsonism signs prior to starting to administer antipsychotic drugs, as core manifestations of psychotic illness with a high predictive value for cognitive impairment.

Characterization of spontaneous Parkinsonism in drug-naive patients with nonaffective psychotic disorders.

Spontaneous Parkinsonism (SP) in schizophrenia-related disorders is poorly characterized. The objective of this study was to examine the concordance and clinical validity of alternative definitions of SP in patients with nonaffective psychotic disorders. Two-hundred drug-naive patients with nonaffective psychotic disorders were examined for core parkinsonian signs, including bradykinesia, rigidity, and tremor, and diagnosed of SP according to the Simpson-Angus Scale (SAS) cutoff criterion, the UK Parkinson's disease brain bank (UKPDBB) criteria, the National Institute of Neurological Disorders and Stroke (NINDS) criteria, and criteria requiring the presence of all three core features (full syndrome criteria). Parkinsonian signs and criteria were examined in relation to a number of relevant clinical variables. The most frequent sign was rigidity (33.5%) followed by bradykinesia (16%) and tremor (12%). The prevalence rate of SP according to the SAS cutoff criterion, the UKPDBB criteria, the NINDS criteria for possible and probable SP, and the full syndrome criteria were 20.5, 13, 25.5, 18.5, and 4%, respectively. Bradykinesia was specifically related to negative symptoms, rigidity to neurological soft signs, and tremor to dyskinetic movements. The set of criteria showing more associations with clinical variables were the NINDS criteria for probable SP. Patients fulfilling these criteria had higher ratings for poor premorbid adjustment, negative symptoms, dyskinesia, neurological soft signs, and poor global treatment response than those without that diagnosis. The NINDS criteria for probable SP, i.e., presence of any two of the three core parkinsonian signs, seem to be the most suitable for clinical and research purposes.

The meaning of childhood attention-deficit hyperactivity symptoms in patients with a first-episode of schizophrenia-spectrum psychosis.

OBJECTIVE: To examine childhood ADHD symptoms in regard to their association with a number of illness-related variables including risk factors, early neurodevelopment, premorbid functioning and clinical characteristics in patients with schizophrenia-spectrum psychoses. METHODS: One-hundred and twenty-two first-episode patients with DSM-IV schizophrenia-spectrum disorders were retrospectively assessed by means of their biological mothers for childhood ADHD symptoms. Using correlational analyses and hierarchical regression models, the severity of ADHD symptoms was examined in relation to familial liability to schizophrenia, obstetric complications, milestones attainment delay, premorbid functioning during childhood and adolescence, age at illness onset, episode psychopathology and response to treatment after one-month trial with antipsychotic medication. RESULTS: Twenty-one patients (17%) met DSM-IV criteria for childhood ADHD. Univariate analyses showed that severity of childhood ADHD symptoms was related to male gender, obstetric complications, delayed milestones attainment, poor school functioning and an earlier age of onset of psychotic symptoms. Hierarchical regression analyses showed that severity of childhood ADHD symptoms was independently predicted by obstetric complications and neurodevelopmental delay, with no further variables entering in the regression models. Path analyses showed that obstetric complications had both direct and indirect effects, through neurodevelopmental delay, on ADHD symptoms. CONCLUSIONS: These findings are consistent with a neurodevelopmental model of schizophrenia and with the hypothesis of shared environmental risk factors between ADHD and schizophrenia-spectrum disorders. Childhood ADHD symptoms in schizophrenia-spectrum disorders appear to be an epiphenomenon of obstetric complications and early neurodevelopment delay with no further influence on the clinical expression of the illness.

Motor behavior abnormalities in drug-naïve patients with schizophrenia spectrum disorders.

Prevalence and correlates of primary motor abnormalities in schizophrenia are presently ill defined. This study was aimed at examining the prevalence, syndromic structure, external correlates, and response to antipsychotic medication of a broad array of primary motor abnormalities. Two-hundred antipsychotic-naive patients with schizophrenia spectrum disorders were examined for motor abnormalities using the Modified Rogers Scale. Thirty-one motor signs were subjected to factor analysis, and the resulting factors examined for association with a number of risk factors, clinical and psychopathological variables. One-hundred and eighty-nine patients were reassessed for motor abnormalities after completing a 4-week trial with antipsychotic medication. Prevalence rates for at least one motor sign and syndrome at baseline were 66% and 40%, respectively. Motor signs clustered together into seven clinically interpretable factors: abnormal involuntary movements, hypokinesia, retarded catatonia, echo-phenomena, excited catatonia, catalepsy, and parkinsonism. All motor domains but parkinsonism were inter-related. Abnormal involuntary movements were associated with variables indicating both neurodevelopmental dysfunction and illness severity, and most motor domains were closely related to negative or disorganization symptoms. Change scores in motor domains after treatment with antipsychotic medication indicated improvement for abnormal involuntary movements, hypokinesia, retarded catatonia, excited catatonia and echophenomena, and worsening for parkinsonism. It is concluded that primary motor dysfunction is a prevalent and heterogeneous condition of schizophrenia. Motor abnormalities segregate into various syndromes, which have different clinical correlates and a differential response pattern to antipsychotic medication. It is hypothesized that the existence of a differential dopaminergic dysfunction in the nigroestriatal circuitry is responsible for the generation of those motor domains that improve and worsen with antipsychotic drugs.

DSM-IV catatonia signs and criteria in first-episode, drug-naive, psychotic patients: psychometric validity and response to antipsychotic medication.

OBJECTIVE: To examine the prevalence, psychometric validity and response to antipsychotic drugs of DSM-IV catatonia signs and criteria in patients with a first-episode psychotic disorder. METHODS: Two-hundred antipsychotic-naive patients with a DSM-IV nonaffective psychosis were assessed for catatonia signs and criteria using the Modified Rogers Scale, and the psychometric validity of the 12 DSM-IV catatonia signs and diagnostic criteria was examined. Treatment response of catatonia was assessed in 173 patients who completed one-month trial with haloperidol (n=23), risperidone (n=93) or olanzapine (n=57). RESULTS: Sixty-two patients (31%) endorsed at least one catatonia sign and 24 (12%) met DSM-IV criteria for catatonia. DSM-IV catatonia signs showed an excellent convergent validity (r>0.8) with other rating scales, and DSM-IV criteria showed moderate to fair concordance with other criteria (kappa from 0.57 to 0.77). The total number of signs reflected catatonia severity and demonstrated excellent diagnostic performance against alternative diagnostic criteria. The presence of at least any three signs accurately identified patients with catatonia. Three catatonia domains were identified (hyperkinesia, volitional and hypokinesia), which showed a different association pattern with external variables. Overall, catatonia ratings were particularly related to both dyskinesia and disorganization symptoms and lacked diagnostic specificity for schizophrenia. Patients with catatonia responded well to antipsychotic medication irrespective of the type of antipsychotic drug used, although treatment response was dependent upon the remission of psychotic symptoms. CONCLUSIONS: These results may inform the DSM-V development on diagnosis and classification of catatonia, and indicate that catatonia signs and syndromes are highly responsive to antipsychotic drugs.