Structure/function interrelationships and illness insight in patients with schizophrenia: a multimodal MRI data fusion study.

Illness insight in schizophrenia (SZ) has an important impact on treatment outcome, integration into society and can vary over the course of the disorder. To deal with and treat reduced or absent illness insight, we need to better understand its functional and structural correlates. Previous studies showed regionally abnormal brain volume in brain areas related to cognitive control and self-reference. However, little is known about associations between illness insight and structural and functional network strength in patients with SZ. This study employed a cross-sectional design to examine structural and functional differences between patients with SZ (n = 74) and healthy controls (n = 47) using structural and resting-state functional magnetic resonance imaging (MRI). Voxel-based morphometry was performed on structural data, and the amplitude of low frequency fluctuations (ALFF) was calculated for functional data. To investigate abnormal structure/function interrelationships and their association with illness insight, we used parallel independent component analysis (pICA). Significant group (SZ vs. HC) differences were detected in distinct structural and functional networks, predominantly comprising frontoparietal, temporal and cerebellar regions. Significant associations were found between illness insight and two distinct structural networks comprising frontoparietal (pre- and postcentral gyrus, inferior parietal lobule, thalamus, and precuneus) and posterior cortical regions (cuneus, precuneus, lingual, posterior cingulate, and middle occipital gyrus). Finally, we found a significant relationship between illness insight and functional network comprising temporal regions (superior temporal gyrus). This study suggests that aberrant structural and functional integrity of neural systems subserving cognitive control, memory and self-reference are tightly coupled to illness insight in SZ.

[Principles of allergy diagnostics]. / Grundlagen der Allergiediagnostik.

BACKGROUND: Allergies are frequent and approximately 30% of the general population in Germany are affected. The specific sensitization against an allergen is asymptomatic. On renewed allergen contact the symptoms are indicative of the underlying pathomechanism. A variety of different test procedures are available to identify allergic reactions. OBJECTIVE AND AIM: In this review article the typical clinical symptoms of allergic reactions are assigned to mechanisms and possible test methods are presented and discussed. Current developments in recombinant serum diagnostics and cellular testing methods are presented.

Absolute Psoriasis Area and Severity Index as a valuable marker to determine initial treatment response in psoriasis patients treated with guselkumab in routine clinical care.

Guselkumab is an anti-interleukin-23p19 monoclonal antibody approved as a first-line medication in patients with moderate-to-severe plaque-type psoriasis and second-line in active psoriatic arthritis. In the clinic, patients who have shown a lack of previous treatment efficacy and/or tolerability are often prescribed guselkumab. These patients generally have less severe psoriasis compared to clinical trial cohorts, reflected in lower Psoriasis Area and Severity Index (PASI). To evaluate treatment response in a real-world setting, we conducted a multicenter-retrospective chart review in three specialized dermatological centers. Seventy-four patients who received guselkumab treatment were included in the study and baseline characteristics were described. The mean PASI at baseline was 13.0 (± 6.7). After 12 weeks of treatment 40 patients could be followed up at the participating centers and efficacy was assessed: 72.5% of these patients achieved an absolute PASI ≤5 (55.0% ≤3; 42.5% ≤2) whereas only 57.5% of patients were able to gain a delta PASI reduction of at least 75%. Using the absolute PASI as a treatment goal rather than response rate revealed that guselkumab was highly effective in this real-world setting. In conclusion, the absolute PASI proved to be a more valuable tool to measure treatment outcome.

Cortical morphology and illness insight in patients with schizophrenia.

Insight into illness in schizophrenia (SZ) patients has a major impact on treatment adherence and outcome. Previous studies have linked distinct deviations of brain structure to illness insight, specifically in frontoparietal and subcortical regions. Some of these abnormalities are thought to reflect aberrant cortical development. In this study, we used cross-sectional data to examine associations between illness insight and two cortical surface markers that are known to follow distinct neurodevelopmental trajectories, i.e. cortical gyrification (CG) and thickness (CT). CG and CT was investigated in SZ patients (n = 82) and healthy controls (HC, n = 48) using 3 T structural magnetic resonance imaging. Illness insight in SZ patients was measured using the OSSTI scale, an instrument that provides information on two distinct dimensions of illness insight, i.e. treatment adherence (OSSTI-A) and identification of disease-related symptoms (OSSTI-I). CT and CG were computed using the Computational Anatomy Toolbox (CAT12). Whole-brain and regions-of-interest (ROI)-based analyses were performed. SZ patients showed higher CG in anterior cingulate, superior frontal and temporal gyrus and reduced CG in insular and superior frontal cortex when compared to HC. SZ patients showed decreased CT in pre- and paracentral, occipital, cingulate, frontoparietal and temporal regions. Illness insight in SZ patients was significantly associated with both CG and CT in the left inferior parietal lobule (OSSTI-A) and the right precentral gyrus (CG/OSSTI-A, CT/OSSTI-I). The data support a multi-parametric neuronal model with both pre- and postnatal brain developmental factors having an impact on illness insight in patients with SZ.

Exploring cortical predictors of clinical response to electroconvulsive therapy in major depression.

Electroconvulsive therapy (ECT) is a rapid and highly effective treatment option for treatment-resistant major depressive disorder (TRD). The neural mechanisms underlying such beneficial effects are poorly understood. Exploring associations between changes of brain structure and clinical response is crucial for understanding ECT mechanisms of action and relevant for the validation of potential biomarkers that can facilitate the prediction of ECT efficacy. The aim of this explorative study was to identify cortical predictors of clinical response in TRD patients treated with ECT. We longitudinally investigated 12 TRD patients before and after ECT. Twelve matched healthy controls were studied cross sectionally. Demographical, clinical, and structural magnetic resonance imaging data at 3 T and multiple cortical markers derived from surface-based morphometry (SBM) analyses were considered. Multiple regression models were computed to identify predictors of clinical response to ECT, as reflected by Hamilton Depression Rating Scale (HAMD) score changes. Symptom severity differences pre-post-ECT were predicted by models including demographic data, clinical data and SBM of frontal, cingulate, and entorhinal structures. Using all-subsets regression, a model comprising HAMD score at baseline and cortical thickness of the left rostral anterior cingulate gyrus explained most variance in the data (multiple R2 = 0.82). The data suggest that SBM provides powerful measures for identifying biomarkers for ECT response in TRD. Rostral anterior cingulate thickness and HAMD score at baseline showed the greatest predictive power of clinical response, in contrast to cortical complexity, cortical gyrification, or demographical data.

[Posterior cortical atrophy-plus syndrome. A case report]. / Posteriores kortikales Atrophie-Plus-Syndrom. Eine Kasuistik.

Posterior cortical atrophy (PCA) is a rare neurodegenerative disease, which manifests with complex visual disturbances. PCA can present in isolation ('PCA-pure') or in association with other neurodegenerative disorders ('PCA-plus'). Diagnosis is nevertheless frequently delayed, as PCA is a less known disease entity and initially a primary ocular disease is taken into consideration.

Hippocampal formation alterations differently contribute to autobiographic memory deficits in mild cognitive impairment and Alzheimer's disease.

Autobiographical memory (AM) is part of declarative memory and includes both semantic and episodic aspects. AM deficits are among the major complaints of patients with Alzheimer's disease (AD) even in early or preclinical stages. Previous MRI studies in AD patients have showed that deficits in semantic and episodic AM are associated with hippocampal alterations. However, the question which specific hippocampal subfields and adjacent extrahippocampal structures contribute to deficits of AM in individuals with mild cognitive impairment (MCI) and AD patients has not been investigated so far. Hundred and seven participants (38 AD patients, 38 MCI individuals and 31 healthy controls [HC]) underwent MRI at 3 Tesla. AM was assessed with a semi-structured interview (E-AGI). FreeSurfer 5.3 was used for hippocampal parcellation. Semantic and episodic AM scores were related to the volume of 5 hippocampal subfields and cortical thickness in the parahippocampal and entorhinal cortex. Both semantic and episodic AM deficits were associated with bilateral hippocampal alterations. These associations referred mainly to CA1, CA2-3, presubiculum, and subiculum atrophy. Episodic, but not semantic AM loss was associated with cortical thickness reduction of the bilateral parahippocampal and enthorinal cortex. In MCI individuals, episodic, but not semantic AM deficits were associated with alterations of the CA1, presubiculum and subiculum. Our findings support the crucial role of CA1, presubiculum, and subiculum in episodic memory. The present results implicate that in MCI individuals, semantic and episodic AM deficits are subserved by distinct neuronal systems.

Cortical signature of neurological soft signs in recent onset schizophrenia.

Motor symptoms such as neurological soft signs (NSS) are characteristic phenomena of schizophrenia at any stage of the illness. Neuroimaging studies in schizophrenia patients have shown regional thinning of the cortical mantle, but it is unknown at present whether NSS are related to cortical thickness changes. Whole brain high-resolution magnetic resonance imaging at 3 Tesla was used to investigate cortical thickness in 28 patients with recent-onset schizophrenia. Cortical reconstruction was performed with the Freesurfer image analysis suite. NSS were examined on the Heidelberg Scale and related to cortical thickness. Age, education, and medication were considered as potential confounders. Higher NSS scores were associated with morphological changes of cortical thickness in multiple areas comprising paracentral gyrus, postcentral lobule, precuneus, inferior parietal lobule and temporal lobe. Our results confirm the hypothesis of a significant relationship between cortical thickness changes and the extent of NSS in schizophrenia. Investigation of cortical thickness may help to explain subtle motor symptoms such as NSS in schizophrenia.

Atherosclerosis and depression: is carotid intima-media thicker in patients with depression compared to matched control individuals? A systematic review and meta-analysis.

OBJECTIVE: To investigate if there is an association between atherosclerosis and depression by using as imaging biomarker the carotid intima media thickness (cIMT), a surrogate marker for atherosclerosis. METHODS: PubMed/Medline, Embase and Cochrane databases were comprehensively searched to identify studies investigating the association between cIMT and depression. The results were pooled using a random-effects statistical model, appropriate for the expected high heterogeneity. Sensitivity and subgroup analyses were conducted where data was available. RESULTS: Overall, 22 and 13 studies met inclusion criteria for the qualitative and the quantitative synthesis, respectively, with a total of 4466 patients and 21,635 control participants. Results showed that cIMT is significantly higher in the depression, compared to the control groups with an overall mean difference of 0.07 mm (95% CI 0.04-0.10, p < 0.01). Subgroup analysis showed that diabetes could present as a confounding factor in patients with depression and an increased cIMT. CONCLUSIONS: This study confirms a significantly increased cIMT in patients with depression, compared with controls and suggests a possible bidirectional link between atherosclerosis and depression. An early screening of cardiovascular disease in individuals suffering with depression should be considered.

Neurological soft signs and brainstem morphology in first-episode schizophrenia.

BACKGROUND: Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported in patients with schizophrenia at any stage of their illness. NSS have been demonstrated to correlate with neuroanatomical abnormalities in various brain regions. Despite its important role in the integration and coordination of automatic motor actions, the brainstem has so far rather been ignored in previous neuroimaging studies on NSS in schizophrenia. METHOD: We investigated 21 right-handed first-episode schizophrenia patients using high-resolution magnetic resonance imaging at 3 T. The severity of NSS was measured with the Heidelberg Scale. Associations between NSS and both brainstem volume and shape changes were examined. RESULTS: Higher NSS scores were significantly associated with structural alterations in the brainstem. According to volume measurements higher NSS scores correlated with global changes of the brainstem. Using shape analyses these associations referred to regionally specific morphometric alterations predominantly in the midbrain and pons. CONCLUSION: The findings suggest that brainstem morphometric alterations are associated with the severity of NSS in patients with first-episode schizophrenia. They further indicate the involvement of the brainstem in the pathogenesis of schizophrenia.

The need for neuroimaging in first manifestations of psychiatric symptoms.

BACKGROUND: Brain imaging in psychiatry, especially by first-episode psychiatric symptoms, is unfortunately not a standard procedure in psychiatric clinics and is recommended only if indicated by history or if associated with neurological findings. As a result, the most serious diagnoses can be delayed or missed. CASE DESCRIPTION: We describe a patient who presented with psychiatric symptoms admitted initially to a psychiatric clinic. Thanks to routine imaging the diagnosis of a brain tumor could be made with prompt transfer to neurosurgery. CONCLUSION: Brain imaging should be a mandatory procedure upon admission to a psychiatric clinic also in patients who present with exclusive psychiatric symptoms.

MRI-derived atrophy of the olfactory bulb and tract in mild cognitive impairment and Alzheimer's disease.

There is increasing histopathological evidence that the olfactory bulb and tract (OBT) is a primary focus of neurodegenerative changes in Alzheimer's disease (AD). Correspondingly, high-resolution magnetic resonance imaging revealed significant atrophy of the OBT in manifest AD. Whether these alterations are already present in mild cognitive impairment, the assumed preclinical stage of AD, has not been investigated yet. OBT volumes were assessed by manual tracing in 29 patients with mild cognitive impairment, 27 patients with probable AD, and 30 healthy controls. In a second step, voxel based morphometry was used to investigate the potential association between OBT atrophy and morphological changes in other brain regions. Patients had significantly lower OBT volumes when compared to controls, with atrophy being most prominent in the AD group. In addition, OBT atrophy was associated with a decreased medial temporal lobe (MTL) gray matter density bilaterally. Our findings indicate that neurodegeneration in OBT and MTL regions is linked and suggest that OBT volume might be a surrogate marker in AD.

The relevance of hippocampal subfield integrity and clock drawing test performance for the diagnosis of Alzheimer's disease and mild cognitive impairment.

OBJECTIVES: The clock drawing test (CDT) is one of the worldwide most used screening tests for Alzheimer's disease (AD). MRI studies have identified temporo-parietal regions being involved in CDT impairment. However, the contributions of specific hippocampal subfields and adjacent extrahippocampal structures to CDT performance in AD and mild cognitive impairment (MCI) have not been investigated so far. It is unclear whether morphological alterations or CDT score, or a combination of both, are able to predict AD. METHODS: 38 AD patients, 38 MCI individuals and 31 healthy controls underwent neuropsychological assessment and MRI at 3 Tesla. FreeSurfer 5.3 was used to perform hippocampal parcellation. We used a collection of statistical methods to better understand the relationship between CDT and hippocampal formation. We also tested the clinical feasibility of this relationship when predicting AD. RESULTS: Impaired CDT performance in AD was associated with widespread atrophy of the cornu ammonis, presubiculum, and subiculum, whereas MCI subjects showed CDT-related alterations of the CA4-dentate gyrus and subiculum. CDT correlates in AD and MCI showed regional and quantitative overlap. Importantly, CDT score was the best predictor of AD. CONCLUSIONS: Our findings lend support for an involvement of different hippocampal subfields in impaired CDT performance in AD and MCI. CDT seems to be more efficient than subfield imaging for predicting AD.

Transdiagnostic modulation of brain networks by electroconvulsive therapy in schizophrenia and major depression.

Major depressive disorder (MDD) and schizophrenia (SCZ) share neurobiological and clinical commonalities. Altered functional connectivity of large-scale brain networks has been associated with both disorders. Electroconvulsive therapy (ECT) has proven to be an effective treatment in severe forms of MDD and SCZ. However, the role of ECT on the modulation of the dynamics of brain networks is still unknown. In this study, we used resting state functional magnetic resonance imaging (rs-fMRI) to investigate functional connectivity in 16 pharmacoresistant patients with SCZ or MDD and a matched group of normal controls. Patients were scanned before and after right-sided unilateral ECT. Group spatial independent component analysis was carried out with a multiple analysis of covariance (MANCOVA) approach to estimate the effects of ECT treatment on intrinsic components (INs). Functional network connectivity (FNC) was calculated between pairs of INs. Patients had reduced connectivity within a striato-thalamic network in the thalamus as well as increased low frequency oscillations in a striatal network. ECT reduced low frequency oscillations (LFOs) on a striatal network along with increasing functional connectivity in the medial prefrontal cortex within the DMN. Following ECT treatment, the FNC of the executive network was reduced with the DMN and increased with the salience network, respectively. Our findings suggest transnosological effects of ECT on the connectivity of large-scale networks as well as at the level of their interplay. Furthermore, they support a transnosological approach for the investigation not only of the neural correlates of the disease but also of the brain mechanism of treatment of mental disorders.

The cerebellum in mild cognitive impairment and Alzheimer's disease - a structural MRI study.

Neuropathological research consistently revealed the cerebellum to undergo degenerative changes in Alzheimer's disease (AD). Whether these alterations affect cerebellar morphology in vivo has not yet been investigated in a comprehensive way. Magnetic resonance imaging was performed in 20 patients with AD, 20 with mild cognitive impairment (MCI), and 20 healthy controls. By manual tracing the cerebellum was divided in four substructures (anterior lobe, superior posterior lobe, inferior posterior lobe and corpus medullare, respectively) on each hemisphere. Posterior cerebellar lobes were significantly smaller in AD patients when compared to healthy controls. In the AD group, atrophy of the posterior cerebellar regions was associated with poorer cognitive performance. Our findings lend further support for cerebellar involvement in AD.

The use of advanced tracking technologies for the analysis of mobility in Alzheimer's disease and related cognitive diseases.

BACKGROUND: One of the more common behavioral manifestations of dementia-related disorders is severe problems with out-of-home mobility. Various efforts have been attempted to attain a better understanding of mobility behavior, but most studies are based on institutionalized patients and the assessment usually relies on reports of caregivers and institutional staff, using observational approaches, activity monitoring, or behavioral checklists. The current manuscript describes the research protocol of a project that measures mobility in Alzheimer's disease and related cognitive disorders in an innovative way, by taking advantage of advanced tracking technologies. METHODS/DESIGN: Participants are 360 demented persons, mildly cognitively impaired persons, and unimpaired controls aged > or = 65 in Israel and Germany. Data regarding space-time activities will be collected via a GPS tracking kit for a period of 4 weeks in 3 waves (one year apart) with the same participants (using a repeated measures design). Participants will be interviewed by use of a battery of instruments prior to and following GPS data collection. Further, a family member will complete a questionnaire both before and after data tracking. Statistical analyses will strive to explain differences in mobility based on a wide range of socio-structural, clinical, affect-related and environmental variables. We will also assess the impact of the use of advanced tracking technology on the quality of life of dementia patients and care givers, as well as its potential as a diagnostic tool. Systematic assessment of ethical issues involved in the use of tracking technology will be an integral component of the project. DISCUSSION: This project will be able to make a substantial contribution to basic as well as applied and clinical aspects in the area of mobility and cognitive impairment research. The innovative technologies applied in this study will allow for assessing a range of dimensions of out-of-home mobility, and provide better quality data.

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.

Reduced cerebral glucose metabolism in patients at risk for Alzheimer's disease.

While significantly reduced glucose metabolism in fronto-temporo-parietal and cingulate cortices has been demonstrated in Alzheimer's disease (AD) compared with controls, cerebral glucose metabolism in patients with mild cognitive impairment who subsequently develop AD is less well-defined. In the present study we measured cerebral glucose metabolism by positron emission tomography (PET) with (18)F-2-fluoro-2-deoxy-D-glucose in 14 patients with aging-associated cognitive decline (AACD), 44 patients with AD, and 14 healthy control subjects at baseline. The AACD patients were clinically followed up, and conversion to AD was determined. Compared with controls, AACD patients had significantly reduced glucose metabolism in the right precuneus, posterior cingulate, right angular gyrus, and bilateral middle temporal cortices, while the respective deficits were more pronounced in AD patients and also involved the frontal cortices. AACD patients who subsequently converted to AD (AACD-converters) showed more extended metabolic changes which also involved the frontal and temporal cortices, right cingulate gyrus, right thalamus, and bilateral precuneus.