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.

[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.

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.

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.

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.

[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.

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.

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 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.

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.

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 clock drawing performance in Alzheimer's disease and mild cognitive impairment.

It is unclear whether clock drawing test (CDT) performance relies on a widely distributed cortical network, or whether this test predominantly taps into parietal cortex function. So far, associations between cortical integrity and CDT impairment in Alzheimer's disease (AD) and mild cognitive impairment (MCI) largely stem from cortical volume analyses. Given that volume is a product of thickness and surface area, investigation of the relationship between CDT and these two cortical measures might contribute to better understanding of this cognitive screening tool for AD. 38 patients with AD, 38 individuals with MCI and 31 healthy controls (HC) underwent CDT assessment and MRI at 3 Tesla. The surface-based analysis via Freesurfer enabled calculation of cortical thickness and surface area. CDT was scored according to the method proposed by Shulman and related to the two distinct cortical measurements. Higher CDT scores across the entire sample were associated with cortical thickness in bilateral temporal gyrus, the right supramarginal gyrus, and the bilateral parietal gyrus, respectively (p < 0.001 CWP corr.). Significant associations between CDT and cortical thickness reduction in the parietal lobe remained significant when analyses were restricted to AD individuals. There was no statistically significant association between CDT scores and surface area (p < 0.001 CWP corr.). In conclusion, CDT performance may be driven by cortical thickness alterations in regions previously identified as "AD vulnerable", i.e. regions predominantly including temporal and parietal lobes. Our results suggest that cortical features of distinct evolutionary and genetic origin differently contribute to CDT performance.

Neuromodulation in response to electroconvulsive therapy in schizophrenia and major depression.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). ECT has been also shown to be effective in schizophrenia (SZ), particularly when rapid symptom reduction is needed or in cases of resistance to drug-treatment. However, its precise mechanisms of action remain largely unknown. OBJECTIVE/HYPOTHESIS: This study examined whether ECT exerts disorder-specific or unspecific modulation of brain structure and function in SZ and MDD. METHODS: We investigated neuromodulatory effects of right-sided unilateral ECT in pharmacoresistant patients with SZ or MDD. Magnetic resonance imaging was conducted before and after ECT to investigate treatment-related effects on brain structure and function. Imaging data were analyzed by means of Voxel Based Morphometry and Resting State Functional Connectivity (RSFC) methods. RESULTS: Right unilateral ECT induced transdiagnostic regional increases of limbic gray matter and modulations of neural coupling at rest. Structural effects were accompanied by a decrease in RSFC within temporoparietal, prefrontal and cortical midline structures, and an increase in hypothalamic RSFC. The extent of structural and functional change was partially inversely associated with the baseline measures. CONCLUSION: The present findings provide first evidence for transdiagnostic changes of brain structure together with modulation of brain function after ECT. The data indicate diagnosis-unspecific mechanisms of action with respect to regional gray matter volume and resting-state functional connectivity.

Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy.

Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). In schizophrenia (SZ), ECT is frequently considered in drug-resistant cases, as an augmentation of antipsychotic treatment or in cases when rapid symptom relief is indicated. Accumulating neuroimaging evidence suggests modulation of medial temporal lobe and prefrontal cortical regions in MDD by ECT. In SZ, ECT-effects on brain structure have not been systematically investigated so far. In this study, we investigated brain volume in 21 ECT-naïve patients (12 with MDD, 9 with SZ) who received right-sided unilateral ECT. Twenty-one healthy controls were included. Structural magnetic resonance imaging data were acquired before and after ECT. Healthy participants were scanned once. Source-based morphometry was used to investigate modulation of structural networks pre/post ECT. ECT had an impact on distinct structural networks in MDD and SZ. In both MDD and SZ SBM revealed a medial temporal lobe (MTL) network (including hippocampus and parahippocampal cortex) which showed a significant increase after ECT. The increase in MTL network strength was not associated with clinical improvement in either MDD or SZ. In SZ a lateral prefrontal/cingulate cortical network showed a volume increase after ECT, and this effect was accompanied by clinical improvement. These findings provide preliminary evidence for structural network change in response to ECT in MDD and SZ. The data suggest both diagnosis-specific and transdiagnostic ECT-effects on brain volume. In contrast to SZ, in MDD structural network modulation by ECT was not associated with clinical improvement.

Local brain gyrification as a marker of neurological soft signs in schizophrenia.

Patients with psychiatric disorders of significant neurodevelopmental origin, such as schizophrenia and autism frequently experience genuine motor abnormalities, such as neurological soft signs (NSS). Previous MRI studies in patients with schizophrenia have shown that NSS are associated with abnormal cortical, thalamic and cerebellar structure and function. So far, however, no neuroimaging study focused on the role of the local gyrification index (LGI) in the pathophysiology of NSS. This study sought to explore the relationship between NSS and folding patterns of the cerebral cortex that are thought to be established during early brain development. In this study, whole brain high-resolution magnetic resonance imaging (MRI) at 3 Tesla was used to investigate the LGI in 33 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 LGI. Age, gender, years of education and medication were considered as potential confounding variables. In summary, higher NSS scores were positively associated with morphological changes of LGI predominantly in parietal and occipital areas. Our results confirm the hypothesis of a significant relationship between LGI changes and the NSS expression in schizophrenia. Investigation of LGI may help to explain subtle motor symptoms such as NSS in schizophrenia.

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.

Out-of-home behavior and cognitive impairment in older adults: findings of the SenTra Project.

This study explores differences in the out-of-home behavior of community-dwelling older adults with different cognitive impairment. Three levels of complexity of out-of-home behavior were distinguished: (a) mostly automatized walking behavior (low complexity), (b) global out-of-home mobility (medium complexity), and (c) defined units of concrete out-of-home activities, particularly cognitively demanding activities (high complexity). A sample of 257 older adults aged 59 to 91 years (M = 72.9 years, SD = 6.4 years) included 35 persons with early-stage Alzheimer's disease (AD), 76 persons with mild cognitive impairment (MCI), and 146 cognitively healthy persons (CH). Mobility data were gathered by using a GPS tracking device as well as by questionnaire. Predicting cognitive impairment status by out-of-home behavior and a range of confounders by means of multinomial logistic regression revealed that only cognitively demanding activities showed at least a marginally significant difference between MCI and CH and were highly significant between AD and CH.