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We analyzed longitudinal course of illness in schizophrenia until age 43 years, and its correlates to antipsychotic medication and cognition.
Northern Finland 1966 Birth Cohort Study has been followed serially since mid-pregnancy. Structural and functional MRI, cognitive, and clinical examinations were performed at ages 34 (73 schizophrenic psychoses, 104 controls) and 43 (63 schizophrenic psychoses, 192 controls); 40 cases and 75 controls participated in both surveys. Psychiatric outcomes have been ascertained through data linkage to a national case registers, hospital charts and clinical evaluations.
Prognosis of schizophrenia is heterogeneous: minority of individuals experience recovery, some achieve remission, but many are on disability pension, and excess mortality (especially suicides) is common. Long duration of untreated psychosis, early age of illness onset and presence of suicidal ideation associated with poorer long-term outcome. Both cases and non-psychotic controls show a small decline in verbal learning and memory, but the difference in decline is not significantly more pronounced in cases. Higher doses of antipsychotics at age 43-years associated to lower education and poorer clinical and functional outcomes, and high cumulative life-time use of antipsychotics associated to decrease of verbal learning and memory in 9-year follow-up.
Based on this naturalistic sample, midlife progression of schizophrenia may follow a variety of different trajectories. Poor clinical course is common but not necessary outcome. Compared to controls, more pronounced cognitive decline was not seen in schizophrenia cases. However, high doses of antipsychotics may relate to a decrease of verbal learning and memory.
The effects of long-term antipsychotic medication on cognition in schizophrenia are unclear (Husa A.P. et al., Schizophr. Res. 2014).
Understanding how long-term antipsychotic treatment affects cognition is crucial for the development of safe, evidence-based treatment of schizophrenia.
To analyse the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia at age 43 years in a general population sample.
Sixty (33 males) schizophrenia spectrum subjects from the Northern Finland Birth Cohort 1966 were assessed at age 43 years by California Verbal Learning Test, Visual Object Learning Test, Abstraction Inhibition and Working Memory task, Verbal fluency, Visual series, Vocabulary, Digit Span and Matrix reasoning. Cumulative lifetime antipsychotic dose-years were collected from treatment records and interviews. A factor analysis based on the cognitive tests resulted in one cognitive factor. The association between this cognitive composite score and antipsychotic dose-years was analysed by linear regression.
Higher lifetime antipsychotic dose-years were statistically significantly associated with poorer cognitive composite score at age 43 years (B=-0.32, p>0.001), also when adjusted for gender, onset age, remission and number of hospital treatment days (B=-0.42, p=0.008).
To our knowledge, this is the first report of an association between cumulative lifetime antipsychotic dose and cognition in midlife in schizophrenia. Based on this data, the use of high antipsychotic doses may relate to poorer cognitive functioning in schizophrenia after twenty years of illness. These results do not support the view that antipsychotics prevent cognitive decline or promote cognitive recovery in schizophrenia.
Though neurocognitive dysfunctions are common in schizophrenia, the course and predictors of change of cognition remain uncertain.
To understand the longitudinal changes and their predictors in cognition, which is important for the etiological investigation of schizophrenia.
Aims. To analyse if premorbid school performance, age of illness onset and the severity of illness predicts change in cognition in schizophrenia in a general population sample.
The sample included cases with schizophrenia spectrum disorder from the Northern Finland 1966 Birth Cohort. Data on school marks at age 16 yearsand severity of symptoms and occupational functioning around first episode and after years of illness were gained from national registers, hospital notes and interviews. Verbal and visual memory and executive functioning were measured twice, at ages 34 and 43 years. The number of cases varied in analyses from 29 to 41, depending on the analysed cognitive test.
Association between lower school marks at age 16-years and decrease in executive functioning (p=0.032) and visual learning and memory (p=0.039) was found, even when adjusted by age of illness onset and cognitive functioning at age 34-years. Change of cognition was not predicted by severity of symptoms nor occupational functioning. Male gender associated to decrease of executive functioning (p=0.032) and earlier age of illness onset to decrease of visual learning and memory (p=0.045).
School performance at age 16 years associates to later longitudinal change of cognition. Based on our results, later cognitive functioning may reflect the evolution of schizophrenia illness.
Cognitive deficits, such as verbal memory dysfunction, are a core feature of schizophrenia. Yet the longitudinal course and associations of cognitive deficits with antipsychotic medication remain unclear.
Our aim was to analyze how lifetime antipsychotic dosage associates with the change of verbal learning and memory in individuals with schizophrenia during a 9-year follow-up.
Forty-two subjects with schizophrenic psychoses (22 males) from the Northern Finland 1966 Birth Cohort went through diagnostic interviews and cognitive assessment including California Verbal Learning Test (CVLT) at the ages of 34 and 43 years. Data of the subjects’ lifetime antipsychotic doses in chlorpromazine equivalents were collected from patient history records, interviews and national registers. The association between verbal learning and memory (immediate free recall of trials 1-5 and free recall after long delay) and dose-years of antipsychotics was analyzed by logistic regression model.
Higher dose-years of any and typical antipsychotics, but not atypical antipsychotics, associated statistically significantly to worse verbal learning and memory in cross-sectional analyses at age 34 years, even when onset age, sex, and severity of symptoms were controlled for. However, there was no statistically significant association between lifetime antipsychotic use and verbal learning and memory change between ages 34 and 43 years.
High lifetime antipsychotic dose did not associate to decrease in verbal learning and memory in schizophrenia in 9 years of follow-up. To our knowledge, this is a first report on association between cumulative lifetime antipsychotic use and change in cognition in a long-term naturalistic follow-up.
Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia.
Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43 years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression.
Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11 months) before the cognitive examination was associated with better cognitive performance (P = 0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P = 0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition.
Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia.
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