A rating scale for the assessment of objective and subjective formal thought and language disorder (TALD)

Formal thought disorder (FTD) is a core syndrome of schizophrenia. However, patients with other diagnoses, such as mania and depression amongst others, also present with FTD. We introduce a novel, comprehensive clinical rating scale, capturing the full variety of FTD phenomenology including subjective experiences. The 30-item Thought and Language Disorder (TALD) scale is based on a detailed review of the literature, encompassing all formal thought disorder symptoms reported from the early 20th century onwards. Objectively observable symptoms as well as subjective phenomena were included. Two hundred and ten participants (146 patients ICD-10 diagnoses: depression n. = 63, schizophrenia n. = 63, mania n. = 20; 64 healthy control subjects) were interviewed and symptoms rated with the TALD, TLC, HAMD, YMRS and SAPS/SANS. A principal component analyses was performed for the TALD to differentiate sub-syndromes. The principal component analysis revealed four FTD factors; objective and subjective as well as positive and negative factor dimensions. The correlation analyses with the TLC and the SAPS/SANS FTD sub-scores demonstrated the factor validity for the objective factors. The different diagnoses showed a distinct pattern of symptom severity in each of the factors, with mania patients exhibiting the highest value in the positive, objective dimension. The scale showed good psychometric results, which makes it a practicable, nosologically-open instrument for the detailed assessment of all FTD dimensions. The results strengthen the importance of subjective symptom assessment reported by the patient.DFG (project no. Ki 588/6-1)Scopu

Neural basis of altered physical and social causality judgements in schizophrenia

Patients with schizophrenia (SZ) often make aberrant cause and effect inferences in non-social and social situations. Likewise, patients may perceive cause-and-effect relationships abnormally as a result of an alteration in the physiology of perception. The neural basis for dysfunctions in causality judgements in the context of both physical motion and social motion is unknown. The current study used functional magnetic resonance imaging (fMRI) to investigate a group of patients with SZ and a group of control subjects performing judgements of causality on animated collision sequences (launch-events, Michotte, 1963) and comparable "social" motion stimuli. In both types of animations, similar motion trajectories of the affected object were configured, using parametrical variations of space (angle deviation) and time (delay). At the behavioural level, SZ patients made more physical and less social causal judgements than control subjects, and their judgements were less influenced by motion attributes (angle/time delay). In the patients group, fMRI revealed greater BOLD-responses, during both physical and social causality judgements (group×task interaction), in the left inferior frontal gyrus (L.IFG). Across conditions (main effect), L.IFG-interconnectivity with bilateral occipital cortex was reduced in the patient group. This study provides the first insight into the neural correlates of altered causal judgements in SZ. Patients with SZ tended to over-estimate physical and under-estimate social causality. In both physical and social contexts, patients are influenced less by motion parameters (space and time) than control subjects. Imaging findings of L.IFG-disconnectivity and task-related hyper-activation in the patient group could indicate common dysfunctions in the neural activations needed to integrate external cue-information (space/time) with explicit (top-down) cause-effect judgements of object motions in physical and social settings

Insular and Hippocampal Gray Matter Volume Reductions in Patients with Major Depressive Disorder

<div><p>Background</p><p>Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder.</p><p>Methods</p><p>For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes.</p><p>Results</p><p>Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala.</p><p>Conclusions</p><p>The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy.</p></div

Gray matter volume reductions in whole brain analysis.

<p>Gray matter volume reductions in all MDD patients versus healthy controls (orange), and patients with recurrent depressive episodes versus healthy controls (red) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102692#pone-0102692-t003" target="_blank">Table 3</a>). (Whole brain analyses, p<0.001, k = 139; view: MNI: 36 23 -5).</p

Clinical characteristics of the patients' sample (n = 132).

<p>MDD: major depressive disorder.</p><p>SD  =  standard deviation.</p><p>MWT-B: Multiple-choice vocabulary test.</p><p>HDRS: Hamilton Depression Rating Scale.</p><p>BDI: Beck's Depression Inventory.</p><p>* Group differences were computed using independent sample t-test for continuous and Chi-square-test for categorial variables. The level of statistical significance was set at p<0.05.</p

Number of depressive episodes is negatively correlated with the right hippocampal gray matter volume.

<p><b>A</b>: Sagittal view (MNI x  = −6) depicting gray matter volumes correlating with number of depressive episodes. (Region-of-interest analyses, p<0.01, k = 109; Color bar represents negative correlation coefficient -r. (L: left; R: right)). <b>B</b>: Scatter plot depicting the negative correlation (r = −0.237; p = 0.006) of the right hippocampal cluster values (left panel) and the number of depressive episodes (SSPS Statistics 15.0 software package).</p

Negative correlation of gray matter volume with increased number of depressed episodes in whole brain analysis and region-of-interest (ROI) analyses of the ROI hippocampus + parahippocampal gyrus bilaterally and of the ROI amygdala bilaterally.

<p>Analyses where conducted at p<0.001, uncorrected, k = 139 voxels for whole brain analysis, k = 109 voxels for ROI hippocampus + parahippocampal gyrus bilaterally, k = 10 for ROI amygdala bilaterally.</p><p>ROI: region of interest.</p><p>SFG: superior frontal gyrus.</p><p>L: left; R: right.</p

Gray matter volume reductions in the region-of interest (ROI) parahippocampal gyrus+hippocampus bilaterally.

<p>Gray matter volume reduction in ROI gyrus+hippocampus bilaterally in all MDD patients versus healthy controls (orange), patients with first depressive episode versus healthy controls (yellow) and patients with recurrent depressive episodes versus healthy controls (red) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102692#pone-0102692-t004" target="_blank">Table 4</a>). (Region-of-interest analyses, p<0.01, k = 109; view: MNI: −27 −29 −20).</p

Sociodemographic characteristics of the whole sample.

<p>SD  =  standard deviation.</p><p>MWT-B: Multiple-choice vocabulary test.</p><p>* Group differences were computed using independent sample t-test for continuous and Chi-square-test for categorial variables. The level of statistical significance was set at p<0.05.</p

Results of whole brain voxel-based morphometry (VBM) analyses.

<p>Contrasts: A) all MDD patients (n = 132) versus healthy controls (n = 132), B) patients with first depressive episode (n = 35) versus healthy controls (n = 35), C) patients with recurrent depressive episodes (n = 97) versus healthy controls (n = 97). Analyses where conducted at p<0.001, uncorrected, k = 139 voxels.</p><p>MDD: major depressive disorder.</p><p>Con: controls; Pat: patients.</p><p>STG: superior temporal gyrus.</p><p>SPL: superior parietal lobule.</p><p>MTG: middle temporal gyrus.</p><p>L: left; R: right.</p