Biomedical subjects

Ingrid Agartz

Publications and source records attributed to Ingrid Agartz.

14 recordsLinked to original sources

PubMed2007

Effects of alcohol consumption and antipsychotic medication on brain morphology in schizophrenia.

Magnetic resonance imaging (MRI) studies have shown smaller volumes of grey matter (GM) and white matter (WM) both in schizophrenia and among patients with alcohol abuse or dependence. The effect of alcohol consumption in non-clinical alcohol consumers, i.e. subjects not recruited as having alcohol use disorders is less studied. In the present study, we investigated the effects of alcohol consumption, antipsychotic medication and a diagnosis of schizophrenia on variation in brain volumes among patients recruited for having schizophrenia and a group of age and gender matched control subjects. A total of 69 patients with schizophrenia (n=56), schizoaffective disorder (n=12) and schizophreniform disorder (n=1) and 97 control subjects were included. Alcohol Use Disorder Identification Test (AUDIT) was used to estimate alcohol consumption. In the entire group of patients and controls higher AUDIT score was significantly related to smaller volumes of WM. When ten patients and six control subjects who met lifetime diagnostic criteria for alcohol use disorders were excluded only a trend level association between AUDIT score and WM volumes was found. Having a diagnosis of schizophrenia was related to smaller volumes of total, frontal and temporal WM, total and temporal GM, and larger volumes of total, frontal and temporal cerebrospinal fluid (CSF). A diagnosis of schizophrenia remained a significant factor for smaller WM volumes even when the effect of alcohol consumption was taken into account. Antipsychotic medication was related to larger volumes of temporal CSF. This study demonstrates that alcohol consumption is an important factor for variation in WM volumes, and this effect should be taken into account in all studies evaluating brain volumes from MR images.

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PubMed2006

A morphometric magnetic resonance method for measuring cranial, facial and brain characteristics for application to schizophrenia: part 1.

Serious psychopathology in adulthood may be associated with disturbed foetal brain development, which potentially shows lingering "fossil marks" in the cranial and facial regions. Several methods exist for assessing external craniofacial and internal brain distances but, to our knowledge, no method yet provides simultaneous measurement of cranial, facial and brain dimensions in live subjects. In this article we describe a method to identify landmarks on magnetic resonance images (MRI) for simultaneous measurement of cranial, facial and brain characteristics potentially associated with psychosis. To test the method itself, 30 patients with chronic schizophrenia and 31 healthy comparison subjects, mean age 41 years, were randomly selected from a larger cohort recruited at the Karolinska Hospital, Sweden. Participants were investigated with MRI, and 60 landmarks in the cranial, facial and brain regions were identified in the images. An independent anthropometric examination measured external craniofacial characteristics for study in relation to measurements produced through MRI. High inter-scorer and re-test reliabilities were obtained for two independent scorers of the landmarks in the MR images. Measurements of potentially comparable craniofacial distances showed high alignment with an established anthropometric method. This new method can provide simultaneous investigation of multiple aspects of cranial, facial and brain morphology in MR images originally collected for other purposes. In a second article we will use this method to compare 3D craniofacial measurements and shape between schizophrenia patients and healthy controls.

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PubMed2006

A pilot study of facial, cranial and brain MRI morphometry in men with schizophrenia: part 2.

This pilot study applies a new 3D morphometric MR method to test the hypothesis that men with schizophrenia (vs. controls) have deviant facial shapes and landmark relations in cranio/facial/brain (CFB) regions. This constitutes Part 2 of paired articles in this issue of Psychiatry Research: Neuroimaging, in which Part 1 presents the new method in detail. MRI coordinates from CFB landmarks of 23 patients and 15 controls were identified and then aligned with the Procrustes model, leaving shape as the only unit-less geometrical information. Men with schizophrenia had significantly longer mid- and lower-facial heights, and greater lower (left) facial depth, with a tendency toward rotation along the facial midline. This supports findings from earlier anthropometric and 3D studies of the "exterior" (face). In contrast, none of the patient-control differences for the new "interior" (cranial-brain) distances reached statistical significance. These results need to be retested on a larger sample of both sexes.

Anthropometry↗

PubMed2006

Morphological correlates to cognitive dysfunction in schizophrenia as studied with Bayesian regression.

BACKGROUND: Relationships between cognitive deficits and brain morphological changes observed in schizophrenia are alternately explained by less gray matter in the brain cerebral cortex, by alterations in neural circuitry involving the basal ganglia, and by alteration in cerebellar structures and related neural circuitry. This work explored a model encompassing all of these possibilities to identify the strongest morphological relationships to cognitive skill in schizophrenia. METHODS: Seventy-one patients with schizophrenia and sixty-five healthy control subjects were characterized by neuropsychological tests covering six functional domains. Measures of sixteen brain morphological structures were taken using semi-automatic and fully manual tracing of MRI images, with the full set of measures completed on thirty of the patients and twenty controls. Group differences were calculated. A Bayesian decision-theoretic method identified those morphological features, which best explained neuropsychological test scores in the context of a multivariate response linear model with interactions. RESULTS: Patients performed significantly worse on all neuropsychological tests except some regarding executive function. The most prominent morphological observations were enlarged ventricles, reduced posterior superior vermis gray matter volumes, and increased putamen gray matter volumes in the patients. The Bayesian method associated putamen volumes with verbal learning, vigilance, and (to a lesser extent) executive function, while caudate volumes were associated with working memory. Vermis regions were associated with vigilance, executive function, and, less strongly, visuo-motor speed. Ventricular volume was strongly associated with visuo-motor speed, vocabulary, and executive function. Those neuropsychological tests, which were strongly associated to ventricular volume, showed only weak association to diagnosis, possibly because ventricular volume was regarded a proxy for diagnosis. Diagnosis was strongly associated with the other neuropsychological tests, implying that the morphological associations for these tasks reflected morphological effects and not merely group volumetric differences. Interaction effects were rarely associated, indicating that volumetric relationships to neuropsychological performance were similar for both patients and controls. CONCLUSION: The association of subcortical and cerebellar structures to verbal learning, vigilance, and working memory supports the importance of neural connectivity to these functions. The finding that a morphological indicator of diagnosis (ventricular volume) provided more explanatory power than diagnosis itself for visuo-motor speed, vocabulary, and executive function suggests that volumetric abnormalities in the disease are more important for cognition than non-morphological features.

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PubMed2006

BDNF gene variants and brain morphology in schizophrenia.

The objective was to investigate putative associations between brain-derived neurotrophic factor gene (BDNF) polymorphisms and brain morphology in patients with schizophrenia and healthy control subjects. Four BDNF polymorphisms were genotyped and analyzed versus 39 brain volume measures in 96 patients with schizophrenia or schizoaffective disorder and 104 healthy subjects. In all subjects, quantitative data on segmented gray, white, and cerebrospinal fluid (CSF) tissue class volumes of total brain and major cerebral lobes including ventricular CSF were obtained using magnetic resonance imaging (MRI). In a randomly selected subset of this population (n = 101-122), MR volumes from cerebellar tonsil, hemispheres, and vermis subregions, striatal structures, hippocampus, and corpus callosum were also measured. The BDNF 11757 G/C polymorphism was highly significantly associated with frontal gray matter volume variation in patients alone and in patients and control subjects combined. In patients only, the 270 C/T polymorphism was associated with total caudate volume. Significant associations were demonstrated between the BDNF 11757 G/C and Val66Met polymorphisms and a global haplotype estimate of four BDNF polymorphisms and the posterior superior cerebellar vermis volume in the controls as well as in the combined group, but not in the patients. The 11757 G/C polymorphism was associated with cerebellar hemisphere white and gray matter volumes in the combined group. The BDNF -633 T/A polymorphism was associated with gray matter of the putamen in the controls. Trends for associations between several polymorphisms/haplotype estimates and MRI volumes were found. BDNF gene variation may influence brain morphology. The effects may be different in patients with schizophrenia and healthy subjects.

Adult↗

PubMed2006

Brain-derived neurotrophic factor gene (BDNF) variants and schizophrenia: an association study.

Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene have been suggested to be associated with schizophrenia. In a replication attempt, Swedish patients with schizophrenia (n=187) and control subjects (n=275) were assessed for four BDNF gene polymorphisms. There were no significantly different allele, genotype or haplotype frequencies between cases or controls. Neither were there any differences when schizophrenic patients were sub-divided with regard to a number of different clinical variables, although a small group of psychotic patients with prominent affective features displayed higher frequencies of the less common alleles of the Val66Met and 11757 G/C polymorphisms compared to controls. The present Swedish results do not verify previous associations between putative functional BDNF gene polymorphisms and schizophrenia. However, when combined with previous studies meta-analyses indicated that the BDNF 270 T-allele and the Val66Met homozygous state were associated with the disorder. Thus, the BDNF gene may confer susceptibility to schizophrenia. Additional studies are warranted to shed further light on this possibility.

Adult↗

PubMed2006

Morphometric and psychometric comparisons between non-substance-abusing patients with posttraumatic stress disorder and normal controls.

BACKGROUND: Hippocampal decrease in size in response to posttraumatic stress disorder (PTSD) is still a subject of controversy. The aims of this study were to: (1) confirm previous hippocampus findings in PTSD patients compared to controls, using ethnically similar study groups where alcohol and drug abuse were non-existent; (2) test influence of disease duration as well as depression scores on possible morphological changes; (3) test whether the voxel-based morphometry (VBM) data confirm the group differences seen in the region of interest (ROI) analysis, and (4) test the associations between the cognitive test scores and the morphological changes. METHODS: VBM and ROI-based analysis were applied in 23 patients and 17 healthy controls. Culture-neutral cognitive tests were used. RESULTS: The ROI-based method showed significantly decreased gray matter volumes for global hippocampal volume, as in a separate analysis of left and right sides in the PTSD group. Total volume of the hippocampus was significantly decreased on the left side, as in the global assessment. A multiple regression VBM model showed significant voxel clusters for group affiliation in the right hippocampus, modelling lowering of gray matter associated with the PTSD group. Disease duration was shown to be negatively correlated to bilateral hippocampal volume and high depression score to bilateral gray matter parahippocampal volume. No significant correlations were found between hippocampal or parahippocampal volumes and cognitive functions. CONCLUSION: The present and previous studies showed that morphologic differences do not appear to be due to drug or alcohol abuse. The VBM data partially confirm the group differences seen in the ROI-based method in the medial temporal lobe. The fact that the significantly lower score on the short-term memory test in the PTSD group is not correlated to hippocampal volume may suggest a more general basis for such memory impairment.

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PubMed2005

Is craniofacial dysmorpholgy correlated with structural brain anomalies in schizophrenia?

This study aimed to examine the relationship between craniofacial dysmorphology and anomalies of brain morphology in schizophrenia. Assessments of craniofacial dysmorphology and magnetic resonance imaging of brain were performed independently of each other and blind to each other in 24 males with schizophrenia and 16 male controls. Ventricular cerebrospinal fluid volume was negatively correlated with total dysmorphology score in males with schizophrenia (i.e., the larger the ventricular cerebrospinal fluid volume, the lower the total dysmorphology score) but not in male controls. These findings suggest that craniofacial dysmorphology and anomalies of brain morphology may be associated with independent processes in the etiology of schizophrenia.

Adult↗

PubMed2005

Altered white matter/gray matter proportions in the striatum of patients with schizophrenia: a volumetric MRI study.

OBJECTIVE: Anatomical structures of the striatum were studied in 58 patients with schizophrenia and 56 healthy comparison subjects of both genders matched for age and handedness. METHOD: Magnetic resonance imaging scans were used to measure gray matter, white matter, and CSF volumes of the caudate, putamen, and nucleus accumbens in the left and the right hemispheres. RESULTS: White matter/gray matter ratios of the striatal structures were significantly lower in patients than in healthy subjects. In patients, relative white matter volumes in the caudate and nucleus accumbens were reduced, whereas gray matter in the putamen was increased. The total accumbens volume did not differ by diagnosis, but left side accumbens was larger than right in the healthy subjects. The proportion of white matter was greater in women in both the patient and healthy comparison groups. Total caudate and putamen volumes demonstrated no differences due to diagnosis or laterality, but a negative correlation was found in patients between white matter volumes and increasing age. There were no significant correlations among total striatal volumes, white matter/gray matter ratios, age at onset of illness, or illness duration. An estimate of lifetime neuroleptic consumption was positively correlated with right gray matter volume of the putamen in male schizophrenia patients who received typical neuroleptics. CONCLUSIONS: The proportion of white matter to gray matter tissue volumes of the caudate, putamen, and nucleus accumbens is altered in medicated chronic schizophrenia patients, but the total volumes are unchanged.

Adult↗

PubMed2003

CSF monoamine metabolites and MRI brain volumes in alcohol dependence.

Correlations between cerebrospinal fluid (CSF) concentrations of monoamine metabolites (MAM) and brain structure have been described in schizophrenia, but not in alcoholism. To investigate the relationship between monoaminergic transmission and brain structure in alcoholism, the metabolites of dopamine (homovanillic acid, HVA), norepinephrenine (3-methoxy-4-hydroxyphenylethyleneglycol, MHPG) and serotonin (5-hydroxyindoleacetic acid, 5-HIAA) were measured in lumbar CSF in 54 alcohol-dependent patients and 20 healthy subjects. The volumes of the cerebrum, total grey and white matter, total and ventricular CSF, left and right hippocampus, and corpus callosum area were measured with MRI. MHPG and age were positively correlated in alcoholic women. The MAM concentrations were not significantly correlated with the MRI volumes in the subject categories. There were no differences in MAM across subjects defined by diagnosis and gender, age of onset of alcoholism or comorbidity of psychiatric disorders. Total CSF, cerebrum, and white and grey matter tissue volumes differed between patients and healthy subjects. The greatest difference was the white matter reduction in alcoholic women. In alcoholic women and men, monoaminergic neurotransmission measured by the CSF MAM HVA, MHPG, and 5-HIAA is not significantly correlated with the size of different brain structures.

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PubMed2003

Smaller cerebellar vermis but not hemisphere volumes in patients with chronic schizophrenia.

OBJECTIVE: The authors previously reported that men with chronic schizophrenia had a smaller vermian subregion than did healthy men. In this study, they tested whether posterior superior vermis reduction would be seen in a larger group of schizophrenia patients, both male and female. METHOD: Brain volumetric analyses were performed with magnetic resonance imaging (MRI) in 59 male and female patients with chronic schizophrenia and 57 male and female healthy comparison subjects. RESULTS: The men as well as the women with schizophrenia had significantly smaller total vermis volume and smaller vermian subregions than did the healthy subjects. Total intracranial volume and cerebellar hemisphere volumes did not differ between schizophrenic and healthy subjects. CONCLUSIONS: The findings support the previous finding that in patients with chronic schizophrenia, there is a selective volume reduction of the cerebellar vermis within the cerebellum.

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PubMed2002

Selective reduction of the posterior superior vermis in men with chronic schizophrenia.

Cerebellar structures were measured in 30 chronic schizophrenic men and 18 healthy men using high resolution MRI. The volume of the posterior superior vermis was found to be significantly smaller in the schizophrenic men, but there was no difference in other cerebellar regions or the intracranial volume. The findings support the view that within the cerebellum the posterior superior vermis may be selectively reduced in men with chronic schizophrenia.

Adult↗

PubMed2002

Reduced grey and white matter volumes in the temporal lobe of male patients with chronic schizophrenia.

Magnetic resonance imaging (MRI) and tissue segmentation were used to quantify grey matter, white matter and cerebrospinal fluid (CSF) volumes in the brains of 32 males with chronic schizophrenia and 32 healthy males. Tissue volumes in the frontal, temporal, parietal, and occipital regions were measured separately. Males with schizophrenia had significant reductions of grey and white matter volumes in the temporal regions compared with controls. Patients also had significantly smaller white matter volumes in the cerebrum and increased CSF volumes in the frontal and the temporal regions as well as the cerebrum. The findings of the present study suggest that volumes of grey and white matter are reduced in the temporal region of males with chronic schizophrenia. The volume of white matter in the whole brain also appears to be reduced. Among the different brains regions, grey matter reduction was significant only in the temporal region.

Adult↗

PubMedDate not supplied

MR volumetry during acute alcohol withdrawal and abstinence: a descriptive study.

AIMS: The brain volume of chronic drinkers is known to partially recover with abstinence from alcohol. To investigate the relative contribution of grey and white brain matter to this process, magnetic resonance imaging and brain tissue segmentation was used to study brain tissue in acute alcohol withdrawal and abstinence in seven alcohol-dependent men. METHODS: The patients were studied on three occasions; within 48 h after the last drink and approximately one month and two and a half months later. Total brain tissue class volumes [grey matter (GM) and white matter (WM) and cerebrospinal fluid (CSF)] were measured. Eleven healthy volunteers were scanned twice to serve as a control group. The alcohol-dependent patients were investigated with regard to drinking variables, neuropsychological performance and blood biochemistry. RESULTS: In the alcohol-dependent patients, intracranial volume and total GM volume did not change between scan occasions, except in a single patient who demonstrated a GM increase of 4.8% (4.2% relative volume) between scans 2 and 3. For all patients, the increase in total WM volume ranged between 1.9 and 22.4% (absolute volumes) and 2.1 and 21.2% (relative volumes). Between scans 2 and 3, the increase in total WM volume ranged between 0.3 and 13.2% (absolute volumes), and between 1.5 and 14.0% (relative volumes). One patient resumed drinking and was investigated a second time during acute withdrawal. In this patient, the measured decrease of 8.1 and 8.5% of absolute and relative WM volumes corresponded to the size of the volume increase between scans 1 and 2. CSF, GM and WM volumes in the healthy subjects were constant over time. CONCLUSIONS: The results demonstrate that changes in brain volume during short-term abstinence in chronic alcohol-dependent patients are confined to the WM. The time limit of WM volume restitution is variable and continues longer than 3 weeks after withdrawal.

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