Clarifying the direction of impact of negative symptoms and neurocognition on prospective work functioning in psychosis: A 20-year longitudinal study.

Both neurocognition and negative symptoms have demonstrated strong links to functional outcomes, such as work functioning, among those with severe mental illness (SMI). Prior models have suggested that reduced neurocognition 1) precedes or predicts greater negative symptoms and 2) indirectly influences functional outcomes via its impact on negative symptoms. The current study sought to also test a divergent model: whether greater negative symptoms predict reduced neurocognition and indirectly influence work functioning through their impact on neurocognition. Both models were tested using cross-sectional and prospective data spanning 20-years in a sample of 277 people with a SMI with psychotic features. Results showed that both models were supported in cross-sectional analyses. However, in prospective models predicting work functioning, only the models examining the indirect influence of negative symptoms on work functioning (7.5 to up to 20-years later) through neurocognition demonstrated significant mediation (i.e., a significant indirect effect); further, higher negative symptoms significantly predicted lower prospective neurocognition, while lower neurocognition did not significantly predict greater prospective negative symptoms. Although cross-sectional data were consistent with prior models, our prospective models offered greater support for a putative causal pathway running from negative symptoms to neurocognition-rather than the reverse-to work functioning. Findings have implications for mechanisms contributing to longitudinal work functioning and suggest that targeting negative symptoms prior to neurocognition could be more beneficial for long-term work outcomes.

Effects of transcranial direct current stimulation on cognition and symptoms in Chinese patients with schizophrenia✰.

There is preliminary evidence that transcranial direct current stimulation(tDCS) may improve symptoms and cognitive function in schizophrenia, but the generalizability of these results needs further investigation. We present a study of the effects of active vs. sham tDCS on cognition and symptoms in a sample of 45 Chinese patients with schizophrenia who showed significant cognitive deficits and were treated for 10 sessions with active or sham tDCS. Psychiatric symptoms were assessed by PANSS scores, and cognitive symptoms assessed by MATRICS battery and other tests. There were no differences between cognitive or symptom scores between subjects treated with active vs. sham tDCS tested within 1-2 days after the end of the 10th session. However, two weeks later subjects treated with active tDCS showed significantly more improvements on MATRICS Speed of Processing domain. MATRICS Overall Composite and a CogState measure related to accuracy on a 1-back working memory task were improved at two weeks in statistical tests without multiple corrections. The improvement in cognitive test scores 2 weeks after the last tDCS session, suggests longer term effects may be related to changes in neuroplasticity induced by 10 sessions of tDCS. The lack of significant changes in cognition shortly after the completion of 10 tDCS sessions contrasts with our earlier positive findings in U.S. patients with schizophrenia.

A 20-Year multi-followup longitudinal study assessing whether antipsychotic medications contribute to work functioning in schizophrenia.

To assess the long-term effectiveness of antipsychotic medications in facilitating work functioning in patients with schizophrenia we conducted longitudinal multifollowup research on 139 initially psychotic patients. The 70 patients with schizophrenia and 69 initially psychotic mood disordered control patients were followed up 6 times over 20 years. We compared the influence on work functioning of patients with schizophrenia continuously prescribed antipsychotics with patients with schizophrenia not prescribed antipsychotics, using statistical controls for inter-subject differences. While antipsychotics reduce or eliminate flagrant psychosis for most patients with schizophrenia at acute hospitalizations, four years later and continually until the 20 year followups, patients with schizophrenia not prescribed antipsychotics had significantly better work functioning. The work performance of the patients who were continuously prescribed antipsychotics was at a low rate and did not improve over time. Multiple other factors also interfere with work functioning. The data suggest that some patients with schizophrenia not prescribed antipsychotics for prolonged periods can function relatively well. Multiple other factors are associated with poor post-hospital work performance. The longitudinal data raise questions about prolonged treatment of schizophrenia with antipsychotic medications.

Attention/processing speed prospectively predicts social impairment 18 years later in mood disorders.

Cross-sectional studies suggest that cognitive deficits contribute to psychosocial impairment among individuals with mood disorders. However, studies examining whether cognition prospectively predicts psychosocial outcome are few, have used short follow-up periods, and have not demonstrated incremental validity (i.e., that cognition predicts future functioning even when controlling for baseline functioning). In a sample of 51 individuals with unipolar depression or bipolar disorder, we investigated whether attention/processing speed (APS) performance predicted social functioning 18 years later. Baseline APS predicted 18-year social functioning even after controlling for baseline social functioning and depressive symptoms, demonstrating incremental validity. Individuals with high baseline APS had stable social functioning over 18 years, whereas functioning deteriorated among those with low APS. This finding helps clarify the temporal order of cognitive and psychosocial deficits associated with mood disorders and suggests the clinical utility of cognitive measures in identifying those at risk of deterioration in social functioning.

Valor diagnóstico y pronóstico de los síntomas de primer orden de Schneider: un estudio longitudinal de 20 años de la esquizofrenia y el trastorno bipolar / Diagnostic and prognostic significance of Schneiderian first-rank symptoms: A 20-year longitudinal study of schizophrenia and bipolar disorder

Objetivo. En esta investigación se abordan las siguientes cuestiones: ¿cuál es la prevalencia y la gravedad de los síntomas de primer orden (SPO) durante un periodo de tiempo prolongado en pacientes con esquizofrenia y trastorno bipolar con psicosis? ¿Son los SPO específicos enumerados en el Manual Diagnóstico y Estadístico de los Trastornos Mentales, tercera edición revisada/cuarta edición (DSM-IIIR/IV) dentro del Criterio A para el diagnóstico de la esquizofrenia (una voz que comenta continuamente o varias voces en conversación) más prevalentes y graves en los pacientes con esquizofrenia que en los pacientes con trastorno bipolar con psicosis? Y por último, ¿predicen los SPO existentes en la hospitalización inicial del estudio en pacientes con esquizofrenia la ausencia de recuperación posterior? Métodos. En esta investigación se realiza un seguimiento de una muestra de pacientes con trastornos psicóticos que fueron evaluados en la hospitalización inicial del estudio y seguidos luego prospectivamente en 6 evaluaciones durante los 20 años siguientes (n=86). Todos los pacientes fueron evaluados como parte de un estudio de investigación prospectivo diseñado para medir múltiples factores de fenomenología, gravedad de la enfermedad, pronóstico y resultado global. Resultados. Los SPO no son exclusivos de la esquizofrenia; se dan también en algunos pacientes bipolares. Sin embargo, son más frecuentes y más graves en los pacientes con esquizofrenia que en los que presentan un trastorno bipolar. Los pacientes con esquizofrenia que tienen SPO durante la fase aguda muestran una mayor probabilidad de presentar una peor evolución a largo plazo que los pacientes esquizofrénicos en los que no hay SPO durante la fase aguda. Conclusiones. Nuestros resultados indican que los SPO en la fase aguda no constituyen un correlato clinicopatológico específico de la esquizofrenia. Sin embargo, la presencia y la gravedad de cualquier SPO y concretamente de los 2 SPO asociados al Criterio A del DSM-IIIR/IV tienen mayor prevalencia y mayor gravedad en los pacientes con esquizofrenia que en los pacientes con trastorno bipolar (AU)

Objective. This research addresses the following questions: what is the prevalence and severity of first-rank symptoms (FRS) during an extended period of time in patients with schizophrenia and bipolar disorder with psychosis? Are the specific FRS listed in Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised/Fourth Edition (DSM-IIIR/IV) Criterion A for schizophrenia diagnosis (a voice keeping a running commentary or voices conversing) more prevalent and severe in patients with schizophrenia than bipolar disorder with psychosis? Lastly, do FRS at index hospitalization in patients with schizophrenia predict the absence of later recovery?. Methods. This research follows a sample of patients with psychotic disorders who were evaluated at index hospitalization and then prospectively followed-up at 6 evaluations during next 20 years (n=86). All patients were evaluated as part of a prospective research study designed to measure multiple factors of phenomenology, severity of illness, course of illness, prognosis, and global outcome. Results. First-rank symptoms are not exclusive to schizophrenia; they also occur in some bipolar patients. However, they are more frequent and more severe in patients with schizophrenia than bipolar disorder. Schizophrenia patients with FRS during the acute phase are more likely to have poorer long-term outcome than schizophrenia patients who do not have FRS during the acute phase. Conclusions. Our results indicate FRS at the acute phase are not a clinicopathologic correlate specific to schizophrenia. However, the presence and severity of any FRS and specifically of the 2 FRS associated with DSM-IIIR/IV Criterion A are more prevalent and more severe in patients with schizophrenia than patients with bipolar disorder (AU)

Are there gender-specific risk factors for suicidal activity among patients with schizophrenia and depression?

Are there gender-specific risk factors for suicidal activity among patients with schizophrenia and depression? A total of 74 schizophrenia patients (51 men, 23 women) and 77 unipolar nonpsychotic depressed patients (26 men, 51 women) from the Chicago Follow-up Study were studied prospectively at 2 years posthospitalization and again at 7.5 years. Poor early posthospital global functioning is significantly associated with later suicidal activity only for men in both our schizophrenia and depressive samples. Early display of psychotic symptoms is associated with later suicidal activity among male schizophrenia patients. Early cognitive impairment is not significantly associated with later suicidal activity for any of the four groups of patients. The study results must be seen as exploratory and will hopefully spur future research on this important topic.

Diagnostic and prognostic significance of Schneiderian first-rank symptoms: a 20-year longitudinal study of schizophrenia and bipolar disorder.

OBJECTIVE: This research addresses the following questions: what is the prevalence and severity of first-rank symptoms (FRS) during an extended period of time in patients with schizophrenia and bipolar disorder with psychosis? Are the specific FRS listed in Diagnostic and Statistical Manual of Mental Disorders DSM, Third Edition, Revised/Fourth Edition Criterion A for schizophrenia diagnosis (a voice keeping a running commentary or voices conversing) more prevalent and severe in patients with schizophrenia than bipolar disorder with psychosis? Lastly, do FRS at index hospitalization in patients with schizophrenia predict the absence of later recovery? METHODS: This research follows a sample of patients with psychotic disorders who were evaluated at index hospitalization and then prospectively followed-up at 6 evaluations during next 20 years (n = 86). All patients were evaluated as part of a prospective research study designed to measure multiple factors of phenomenology, severity of illness, course of illness, prognosis, and global outcome. RESULTS: First-rank symptoms are not exclusive to schizophrenia; they also occur in some bipolar patients. However, they are more frequent and more severe in patients with schizophrenia than bipolar disorder. Schizophrenia patients with FRS during the acute phase are more likely to have poorer long-term outcome than schizophrenia patients who do not have FRS during the acute phase. CONCLUSIONS: Our results indicate FRS at the acute phase are not a clinicopathologic correlate specific to schizophrenia. However, the presence and severity of any FRS and specifically of the 2 FRS associated with Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised/Fourth Edition Criterion A are more prevalent and more severe in patients with schizophrenia than patients with bipolar disorder.

Does physical anhedonia play a role in depression? A 20-year longitudinal study.

BACKGROUND: Anhedonia towards physical or sensory experiences (i.e., physical anhedonia) has most often been examined as a differentia of schizophrenia and not depression, despite the fact that general anhedonia is a core feature of many models of Major Depressive Disorder (MDD). METHODS: Forty-nine participants with non-psychotic MDD were recruited from inpatient settings and followed-up six times over 20 years. The three aims of the study was to assess a) the stability of physical anhedonia over time, b) whether physical anhedonia relates to the course of depressive symptoms over time, and c) whether physical anhedonia relates to three domains of functioning - work, social functioning, or re-hospitalizations. RESULTS: We found that over time physical anhedonia was relatively stable and related to depressive symptoms (both between and within person). Physical anhedonia was also related to certain aspects of functioning, though less robustly than depressive symptoms. LIMITATIONS: Because depressive symptoms, functioning, and physical anhedonia were measured concurrently at each follow-up, the direction of causality among these variables could not be assessed. Additionally, because our sample was recruited from inpatient settings, our findings may not generalize to individuals with less severe depression. CONCLUSIONS: A trait tendency to experience decreased pleasure to positive physical stimuli is a clinically meaningful variable for those with MDD and may be a behavioral endophenotype for a more severe form of depression.

Sex differences in schizophrenia and other psychotic disorders: a 20-year longitudinal study of psychosis and recovery.

This longitudinal study was designed to provide data on sex differences in the course of schizophrenia and other psychotic disorders. Ninety-seven participants (43 women and 54 men) were assessed during index hospitalization when they were in the acute phase of illness and then reassessed prospectively at 6 consecutive follow-ups over a 20-year period. Patients were evaluated by a series of standardized measures on many aspects of illness including the presence of psychosis, global outcome, and rate of recovery. When women were compared to men in this sample, the data demonstrated a lower percentage of psychotic activity for women over the course of illness (significant at the 7.5- and 20-year follow-ups), and a significant improvement in psychotic activity over 20 years for women (P < .05), but not for men. In addition, women showed significantly better global functioning (P < .05) at 3 of the 6 follow-ups (the 2-, 7.5-, and 10-year follow-ups). Significantly higher percentages (P < .05) of women were in recovery at 2 of the 6 follow-up years (the 2- and 10-year follow-ups). Cumulatively, 61% of the women with schizophrenia showed a period of recovery at some point during the 20-year period compared to 41% of the men. The sex difference patterns were similar for patients with schizophrenia and for those with other types of psychotic disorders. Sex differences in this sample were specifically not attributable to differences in age of onset or premorbid developmental achievements.

Sex differences in outcome and recovery for schizophrenia and other psychotic and nonpsychotic disorders.

OBJECTIVE: It is generally believed by the field of psychiatry that women with schizophrenia have better outcomes and higher rates of recovery than their male counterparts, because many studies on the topic support this finding. Fewer data are available to assess potential sex differences among individuals with other psychotic disorders. This study used longitudinal data on sex differences previously unavailable to the field to examine long-term global outcome, potential recovery, course of illness, and rehospitalization for schizophrenia, other psychotic disorders, and nonpsychotic disorders. METHODS: A total of 239 young psychiatric patients (mean age of 23.4 years) were assessed prospectively at the index hospitalization and then followed over 15 years at five follow-up points (at a mean of two, 4.5, 7.5, ten, and 15 years). The sample consisted of 69 patients with schizophrenia, 56 with other psychotic diagnoses, and 114 with nonpsychotic psychiatric disorders. RESULTS: Sex differences in outcome were found for both patients with schizophrenia and those with other psychotic disorders, with women consistently showing better functioning over time, more frequent periods of good functioning and periods of recovery, less likelihood of uniformly poor outcome, and fewer and shorter rehospitalizations. Unlike both groups of patients who were psychotic, the patients with nonpsychotic disorders showed no significant sex differences in outcome. CONCLUSIONS: Both longitudinally and at each individual follow-up point, the data suggest that women with schizophrenia and with other types of psychotic disorders generally show better outcome than men with similar diagnoses. The sex differences in outcome for patients with schizophrenia were consistent over time. However, these sex differences were only moderate in size compared with the much larger difference in outcome between the diagnostic groups. The longitudinal data add a new dimension to previous research and suggest that sex differences in outcome are not specific to patients with schizophrenia but rather occur among patients with psychotic disorders in general.

Neurocognition as a stable endophenotype in bipolar disorder and schizophrenia.

Linkage and association studies have paid increasing attention to neurocognition as a putative endophenotype. However, there exists little documentation of its trait stability in schizophrenia or bipolar disorder. Our aim was to determine the longitudinal stability of neurocognitive performance in bipolar versus schizophrenia probands. We administered a neurocognitive battery at two time points, approximately 5 years apart, in 16 schizophrenia and 16 bipolar disorder age-matched subjects. There were no significant changes over time on variables including education, estimated IQ, depression, psychosis, global functioning, or medication status. Schizophrenia subjects showed significant deterioration in one measure of executive functioning but no significant changes in seven of eight other domains. Bipolar patients showed stability over time in attentional measures but greater variability in other domains. These preliminary findings suggest that neurocognitive domains appear longitudinally stable across broad domains in schizophrenia. In contrast, stable functioning may be more limited to attentional domains in bipolar disorder.