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To analyse associations between brain morphology and longitudinal and cross-sectional measures of outcomes in schizophrenia in a general population sample.
The sample was the Northern Finland 1966 Birth Cohort. In 1999–2001, structural brain MRI and measures of clinical and functional outcomes were analysed for 54 individuals with schizophrenia around the age of 34. Sex, total grey matter, duration of illness and the use of antipsychotic medication were used as covariates.
After controlling for multiple covariates, increased density of the left limbic area was associated with less hospitalisations and increased total white matter volume with being in remission. Higher density of left frontal grey matter was associated with not being on a disability pension and higher density of the left frontal lobe and left limbic area were related to better functioning. Higher density of the left limbic area was associated with better longitudinal course of illness.
This study, based on unselected general population data, long follow-up and an extensive database, confirms findings of previous studies, that morphological abnormalities in several brain structures are associated with outcome. The difference in brain morphology in patients with good and poor outcomes may reflect separable aetiologies and developmental trajectories in schizophrenia.
In schizophrenia, brain morphometric changes may be associated with antipsychotic medication. Only limited data is available concerning individuals with schizophrenia without antipsychotic medication. We aimed to study the associations of: use versus no use of antipsychotic medication; length of continuous time without antipsychotic medication; cumulative dose of lifetime antipsychotic medication; and type of antipsychotic medication; with brain morphometry in schizophrenia after an average of 10 years of illness.
Data of 63 individuals with schizophrenia (mean duration of illness 10.4 years) from the Northern Finland Birth Cohort 1966 were gathered by interview and from hospital and outpatient records. Structural MRI data at age 34 years were acquired and grey matter volume maps with voxel-based morphometry were analyzed using FSL tools.
Of the individuals studied, 15 (24%) had taken no antipsychotic medication during the previous year. Individuals with antipsychotic medication had lower total grey matter (TGM) volume compared with non-medicated subjects, although this association was not statistically significant (Cohen's d = –0.51, P = 0.078). Time without antipsychotic medication associated with increased TGM (P = 0.028). Longer time without antipsychotic medication associated with increased regional volume in right precentral gyrus and right middle frontal gyrus. There were no associations between cumulative dose of lifetime antipsychotic medication or type of antipsychotic medication and brain morphometry.
Unlike some previous investigators, we found no association between cumulative dose of lifetime antipsychotic medication and brain morphological changes in this population-based sample. However, longer continuous time without antipsychotic medication preceding the MRI scan associated with increased gray matter volume.
Recently many studies have suggested more brain morphometric changes occurring in people with schizophrenia who use antipsychotic medication compared to those who do not.
We will study the brain morphology of subjects with schizophrenia spectrum disorder with and without antipsychotic medication.
Our aim was to compare the brain morphology of subjects with schizophrenia spectrum disorder with and without antipsychotic medication after in average ten years of illness, and analyse the association between cumulative dose of lifetime antipsychotic medication and brain morphology.
Data of 66 subjects with schizophrenia spectrum disorder (mean duration of illness 10.4 years) from the Northern Finland 1966 Birth Cohort were gathered by interview and from hospital records. Structural MRI data at age 34 years were acquired from all participants on a GE Signa system operating at 1.5T.
Of the subjects 16 (24%) had taken no antipsychotics during the previous year. We found no significant differences on total grey matter volumes (TGM) between subjects with and without antipsychotic medication. In the voxel-based analyses subjects with medication had lower volume in left parahippocampal gurys (p = 0.003), when adjusted for sex, onset age, TGM and remission status. There were no associations between lifetime antipsychotic dose and brain morphology.
We were able to study effects of antipsychotic medication in population-based sample. Brain morphology in medicated and non-medicated persons were similar and the cumulative lifetime medication had no effect on brain morphology, which suggests that possible medication effect in cross-sectional measures of brain morphology is small.
Relatively little is known on longitudinal effects of antipsychotic medication on brain morphometry in schizophrenia after the illness onset. There are inconsistent findings on medication effects on brain structures.
We will study the effect of antipsychotic medication on brain volumes in schizophrenia.
The aim of the current study was to systematically review previous literature on longitudinal MRI studies of antipsychotic effects on brain morphometric changes in schizophrenia and related psychoses.
Studies were systematically collected using four different databases. A study was included if subjects were scanned twice, the average scanning interval was at least two years and antipsychotic medication data was used to predict morphometric changes. The studies focused on several different brain areas; we categorized these into eleven larger areas.
In total 22 studies fulfilled our inclusion criteria. The main finding of our study was that most of the reported correlations were statistically non-significant. The significant associations between antipsychotic use and brain changes were reported from various areas. In the studies with significant findings, use of antipsychotics more often associated with decrease than increase of brain volumes, even in the very few studies taking into account illness severity.
Antipsychotic medication should be adjusted to lowest possible dose for reducing psychotic symptoms and prescribed with caution especially to people not suffering from psychosis. More studies in different kind of patient populations are needed to clarify the possible adverse effect antipsychotic medication may have on brain structure.
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.
The effects of long-term antipsychotic medication use on structural brain changes in psychoses are still unknown. Severity and duration of illness are key confounders when evaluating antipsychotic effects on brain morphology.
Understanding the role of antipsychotic medication on brain morphology in psychoses.
To analyze whether cumulative lifetime or current antipsychotic medication dose relates to brain morphology in schizophrenia and other psychoses at age of 43 years.
Forty-four schizophrenia cases and 35 with other psychoses from the Northern Finland Birth Cohort 1966 were scanned on a 1.5T GE Signa scanner and brain structures were extracted using volBrain automated volumetry system (http://volbrain.upv.es). Data of antipsychotic medication were collected from medical records and interviews. We used linear regression model to analyze the effect of antipsychotic medication on brain volumes and used intracranial volume and onset age as covariates. We also performed additional analyses adding psychotic symptoms (PANSS Total score) as a covariate.
Higher lifetime and current dose associated to left lateral ventricle increase (b = 0.33, P = 0.033; b = 0.307, P = 0.042, respectively) and right and left accumbens decrease (b = −0.405, P = 0.013, b = −0.404, P = 0.010; b = −0.302, P = 0.027, b = −0.282, P = 0.036, respectively) in schizophrenia but not in other psychoses. When PANSS was added to the model, the findings remained regarding right and left accumbens, but not regarding left lateral ventricle.
It seems that antipsychotic medication affects the brain in schizophrenia, but not in the heterogeneous group of other psychoses. In schizophrenia, brain changes associated to antipsychotic medication cannot be explained by illness duration or symptom severity.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
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