Marc M. Lässer

Hippocampal volume reduction and autobiographical memory deficits in chronic schizophrenia

Although autobiographical memory (AM) deficits and hippocampal changes are frequently found in schizophrenia, their actual association remained yet to be established. AM performance and hippocampal volume were examined in 33 older, chronic schizophrenic patients and 21 healthy volunteers matched for age, gender and education. Psychopathological symptoms and additional neuropsychological parameters were assessed by using appropriate rating scales; magnetic resonance imaging (MRI) 3-T data were analyzed via an automated region-of-interest procedure. When compared with the control subjects, patients showed significantly decreased left anterior and posterior hippocampal volumes. Episodic but not semantic AM performance was significantly lower in the patients than in the healthy controls. Both episodic and semantic AM deficits were significantly correlated with volume of the left hippocampus in the patient group. In contrast, deficits in verbal memory, working memory and remote semantic memory observed in the patients did not relate to hippocampal volume. Our findings indicate that AM deficits in chronic schizophrenia are associated with hippocampal volume reductions and underline the importance of this pathology in schizophrenia.

Comparison of grey matter volume and thickness for analysing cortical changes in chronic schizophrenia: A matter of surface area, grey/white matter intensity contrast, and curvature

Grey matter volume and cortical thickness are the two most widely used measures for detecting grey matter morphometric changes in various diseases such as schizophrenia. However, these two measures only share partial overlapping regions in identifying morphometric changes. Few studies have investigated the contributions of the potential factors to the differences of grey matter volume and cortical thickness. To investigate this question, 3T magnetic resonance images from 22 patients with schizophrenia and 20 well-matched healthy controls were chosen for analyses. Grey matter volume and cortical thickness were measured by VBM and Freesurfer. Grey matter volume results were then rendered onto the surface template of Freesurfer to compare the differences from cortical thickness in anatomical locations. Discrepancy regions of the grey matter volume and thickness where grey matter volume significantly decreased but without corresponding evidence of cortical thinning involved the rostral middle frontal, precentral, lateral occipital and superior frontal gyri. Subsequent region-of-interest analysis demonstrated that changes in surface area, grey/white matter intensity contrast and curvature accounted for the discrepancies. Our results suggest that the differences between grey matter volume and thickness could be jointly driven by surface area, grey/white matter intensity contrast and curvature.

Reduced Gray to White Matter Tissue Intensity Contrast in Schizophrenia

Background While numerous structural magnetic resonance imaging (MRI) studies revealed changes of brain volume or density, cortical thickness and fibre integrity in schizophrenia, the effect of tissue alterations on the contrast properties of neural structures has so far remained mostly unexplored. Methods Whole brain high-resolution MRI at 3 Tesla was used to investigate tissue contrast and cortical thickness in patients with schizophrenia and healthy controls. Results Patients showed significantly decreased gray to white matter contrast in large portions throughout the cortical mantle with preponderance in inferior, middle, superior and medial temporal areas as well as in lateral and medial frontal regions. The extent of these intensity contrast changes exceeded the extent of cortical thinning. Further, contrast changes remained significant after controlling for cortical thickness measurements. Conclusions Our findings clearly emphasize the presence of schizophrenia related brain tissue changes that alter the imaging properties of brain structures. Intensity contrast measurements might not only serve as a highly sensitive metric but also as a potential indicator of a distinct pathological process that might be independent from volume or thickness alterations.

Neuropsychology, Autobiographical Memory, and Hippocampal Volume in “Younger” and “Older” Patients with Chronic Schizophrenia

Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM) has been scarcely investigated in these patients. Hence, less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore, we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21) with respect to AM, additional neuropsychological parameters, and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analyzed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group, significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume; executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution.

Association of cortical thickness and neurological soft signs in patients with chronic schizophrenia and healthy controls.

Background: Neurological soft signs (NSS), i.e. subtle neurological abnormalities, have been frequently found in schizophrenia. Neuroimaging studies in schizophrenia have shown abnormal cortical thickness changes across the cortical mantle. However, few studies have examined relationships between NSS and cortical thickness abnormalities in schizophrenia. Method: A sample of 18 patients with chronic schizophrenia and 20 age-matched healthy controls were included. Cortical thickness was assessed on high-resolution 3-tesla magnetic resonance imaging by using FreeSurfer software and NSS were rated on the Heidelberg Scale. Results: Significant negative correlations between NSS and cortical thickness were found in the prefrontal, inferior temporal, superior parietal, postcentral, and supramarginal cortices in the schizophrenia patients. In the controls, however, this negative correlation was found in the anterior cingulate, pericalcarine and superior/middle temporal regions. Conclusion: Our results not only confirmed the association between NSS and cortical thickness in chronic schizophrenia but also indicated that patients and controls have different anatomical substrates of NSS.

Cognitive Performance in Patients with Chronic Schizophrenia Across the Lifespan

Chronic schizophrenia involves neuropsychological deficits that primarily strike executive functions and episodic memory. Our study investigated these deficits throughout the lifespan in patients with chronic schizophrenia and in healthy controls. Important neuropsychological functions were tested in 94 patients and 66 healthy controls, who were assigned to three age groups. Compared with the healthy controls, patients performed significantly poorer on all tests applied. Significant age effects occurred on all tests except the digit span forward, with older subjects scoring well below the younger ones. With respect to cognitive flexibility, age effects were more pronounced in the patients. These findings underline the importance of cognitive deficits in chronic schizophrenia and indicate that diminished cognitive flexibility shows age-associated differences.

F175. NEUROLOGICAL SOFT SIGNS (NSS) AND BRAIN MORPHOLOGY IN PATIENTS WITH CHRONIC SCHIZOPHRENIA AND HEALTHY CONTROLS

Abstract Background Subtle abnormalities in sensory integration, motor coordination and sequencing of complex motor acts or neurological soft signs (NSS) are a characteristic phenomenon in patients with schizophrenia at any stage of the illness. Previous MRI studies in schizophrenia have shown that NSS are associated with abnormal cortical, thalamic and cerebellar structure. However, these studies mainly focused on first-episode or recent onset schizophrenia and the respective correlates between brain structure and NSS in patients with a chronic course of the disorder remain rather unclear. Methods 49 middle-aged patients with chronic schizophrenia with a mean duration of illness of 20.3 ± 14.0 years and 29 healthy subjects matched for age and sex were included. NSS were examined on the Heidelberg Scale and correlated to grey matter by using whole brain high resolution magnetic resonance imaging (3 Tesla) with SPM12 analyses. Results As expected, NSS in patients were significantly elevated in contrast to healthy controls, a finding, which not only applied to NSS sumscore, but also to the respective subscores motor coordination, sensory integration, complex motor tasks, right/left and spatial orientation and hard signs (p≤0.001). Patients and healthy controls differed referring to right inferior frontal gyrus and left parahippocampal gyrus, with patients showing significantly reduced gray matter volumes, respectively. Within the patient group NSS total score was significantly correlated to reduced grey matter in right occipital lobe, left parahippocampal gyrus, left superior temporal gyrus, left thalamus (medial dorsal nucleus) and left posterior lobe of the cerebellum (declive). The respective findings remained significant after FDR correction for multiple comparisons (k=100 voxels). These results were confirmed when chlorpromazine (CPZ)-equivalents were introduced as additional covariate; moreover, no significant correlates arose between NSS and CPZ-equivalents. In the control group, VBM revealed that higher NSS total scores were significantly correlated with volume of right lentiform nucleus (medial globus pallidus). Discussion Our study leads further support to the model of ‘cognitive dysmetria’ with a disrupted cortico-cerebellar-thalamic-cortical circuit in schizophrenia. This interpretation is also maintained by a different correlational pattern in our control group. Furthermore, the middle temporal/parahippocampal region may correspond to reduced mnestic functions, which are – besides elevated NSS – consistently reported to be impaired in patients with a chronic course of the disorder.

T67. NEUROLOGICAL SOFT SIGNS IN THE COURSE OF SCHIZOPHRENIA: A LONGITUDINAL ANALYSIS IN CHRONIC SCHIZOPHRENIA

Abstract Background Neurological soft signs (NSS) are minor (‘soft’) neurological abnormalities in sensory and motor performance, which are frequently reported in patients with schizophrenia at any stage of their illness. It has been demonstrated that NSS vary in the clinical course of the disorder: Longitudinally NSS seem to decrease in parallel with remission of psychopathological symptoms, an effect which mainly applies to patients with a remitting course. However, these findings are mainly based on patients with a first episode of the disorder and the course of NSS in patients with chronic schizophrenia and persisting symptoms is rather unknown. Methods Therefore, we investigated 21 patients with chronic schizophrenia (duration of illness: 22.8 years ± 11.5) twice with a follow-up time interval of 7 years. Baseline and endpoint NSS scores were evaluated by the Heidelberg Scale, established instruments were used to rate psychopathological symptoms and neuropsychological performance. Results Results show a significant increase of the NSS subscales “motor coordination” and “integrative functions” with stable positive and negative symptoms, including apathy, as well as chlorpromazine equivalents. Along with this, neuropsychological parameters as verbal memory, verbal fluency and cognitive flexibility deteriorate significantly. Regression analyses show that the TMT B performance/cognitive flexibility and the SANS global score/negative symptoms at baseline are strong predictors for NSS increase at follow-up. Discussion These results illustrate a significant aggravation of NSS in patients with chronic schizophrenia over time, while psychopathological symptoms remain stable. In addition, cognitive performance is deteriorating as well, with cognitive flexibility together with negative symptoms as strongest predictors for NSS changes.

Neurological Soft Signs and Psychopathology in Chronic Schizophrenia: A Cross-Sectional Study in Three Age Groups

As established in a wealth of studies subtle motor and sensory neurological abnormalities or neurological soft signs (NSS) are frequently found in patients with schizophrenia at any stage of their illness. However, the potential impact of chronicity and age on NSS was scarcely investigated. Therefore, we assessed NSS in 90 patients with subchronic (n = 22) or chronic (n = 68) schizophrenia and in 60 healthy controls who were assigned to three age groups (18–29, 30–49, and +50 years). NSS were measured on the Heidelberg Scale, psychopathological symptoms including apathy were rated on established instruments. As demonstrated by analysis of variance, NSS scores in patients were significantly (p < 0.05) increased relative to healthy controls. Significant age effects arose in all NSS subscores, with older subjects scoring well above the younger ones. These age effects were more pronounced in patients than controls, indicating that NSS in chronic schizophrenia exceed age-associated changes. Moreover, the NSS scores in patients were significantly associated with duration of illness, thought disturbance, positive symptoms, and apathy. These results were confirmed after age/duration of illness and years of education were partialed out and via regression analyses. Our findings conform to the hypothesis that NSS are associated with chronicity of the disorder as indicated by the correlations of NSS with both, duration of illness and apathy. The correlations between NSS and positive symptoms/thought disturbance correspond to the fluctuation of positive symptoms during the course of the disorder. The significantly more pronounced age effects on NSS in patients may either point to ongoing cerebral changes or to a greater susceptibility of patients toward physiological age effects, which may be mediated among other factors by a lower cognitive reserve.

Poster #M52 NEUROLOGICAL SOFT SIGNS AND BRAIN MORPHOLOGY IN PATIENTS WITH CHRONIC SCHIZOPHRENIA

which connects the temporal lobe with the prefrontal cortex; and (3) fornix, which connects the hippocampus with the hypothalamus. Furthermore, most previous studies investigating WM changes in schizophrenia have used voxel-based analysis, typically of a highly restricted WM skeleton (eg TBSS) or whole-tract mean values from tractography, thereby losing anatomical specificity. The goal of this investigation therefore, was to use sophisticated diffusion tensor imaging (DTI) tractometry analysis to examine along-tract microstructural differences in three major temporal lobe WM tracts in a family study of schizophrenia. Inclusion of both patients and family members allowed a better examination of genetic (familial) liability, as well as disease-related processes. Methods: Twenty-five patients with schizophrenia, 24 non-psychotic healthy relatives, and 27 community controls participated. DTI data were acquired (3T GE) along 60 gradient directions with b-value 1300 s/mm2 and corrected for motion and distortion using ExploreDTI. DTI parameters fractional anisotropy (FA) and mean and radial diffusivity (MD, RD) were estimated. A population-based FA-template was constructed, to which all parameter maps were registered. The aforementioned temporal lobe tracts were isolated using targeted tractography. The fornix was further subdivided into left/right anterior columns, body and left/right fimbriae. Parameter values for each subject were calculated at evenly distributed points along the length of the tract masks in template space. ANCOVA was used to investigate the main effect of group membership on mean tract values (between-subject factors: group, gender, covariate: age), whilst the group:position interaction term in a 2-way ANOVA was used to identify group differences at each point along each tract. Results: Both patients with schizophrenia and non-psychotic relatives demonstrated lower mean and radial diffusivity in their fornix compared to controls using age and gender as covariates. Tract profiles illustrated group differences along the entire length of the fornix rather than localized differences. No other significant differences were found between groups. Discussion: We found both schizophrenia patients and their biological relatives had differences in two indices associated with WM microstructure, compared to controls along the length of the fornix; however, in an unexpected direction. Possible reasons for this surprising finding could be a true biological difference, volumetric differences present between groups, or methodological issues associated with DTI analyses in typically sized schizophrenia study populations. Further investigation of the relationship between the DTI parameters, white matter volume and anatomical structures bordering the fornix will be presented to understand these findings. The results of this analysis may allow a better understanding of not only these results, but also other findings of fractional anisotropy changes in schizophrenia.