Grey matter changes in motor conversion disorder.

OBJECTIVE: To detect anatomical differences in areas related to motor processing between patients with motor conversion disorder (CD) and controls. METHODS: T1-weighted 3T brain MRI data of 15 patients suffering from motor CD (nine with hemiparesis and six with paraparesis) and 25 age- and gender-matched healthy volunteers were compared using voxel-based morphometry (VBM) and voxel-based cortical thickness (VBCT) analysis. RESULTS: We report significant cortical thickness (VBCT) increases in the bilateral premotor cortex of hemiparetic patients relative to controls and a trend towards increased grey matter volume (VBM) in the same region. Regression analyses showed a non-significant positive correlation between cortical thickness changes and symptom severity as well as illness duration in CD patients. CONCLUSIONS: Cortical thickness increases in premotor cortical areas of patients with hemiparetic CD provide evidence for altered brain structure in a condition with presumed normal brain anatomy. These may either represent premorbid vulnerability or a plasticity phenomenon related to the disease with the trends towards correlations with clinical variables supporting the latter.

Respiration, metabolic balance, and attention in affective picture processing

The jointly voluntary and involuntary control of respiration, unique among essential physiological processes, the interconnection of breathing with and its influence on the autonomic nervous system, and disease states associated with the interface between psychology and respiration (e.g., anxiety disorders, hyperventilation syndrome, asthma) make the study of the relationship between respiration and emotion both theoretically and clinically of great relevance. However, the respiratory behavior during affective states is not yet completely understood. We studied breathing pattern responses to 13 picture series varying widely in their affective tone in 37 adults (18 men, 19 women, mean age 26). Time and volume parameters were recorded with the LifeShirt system (VivoMetrics Inc., Ventura, California, USA, see image). We also measured end-tidal pCO2 (EtCO2) with a Microcap Handheld Capnograph (Oridion Medical 1987 Ltd., Jerusalem, Israel) to determine if ventilation is in balance with metabolic demands and spontaneous eye-blinking to investigate the link between respiration and attention. At the end of each picture series, the participants reported their subjective feeling in the affective dimensions of pleasantness and arousal. Increasing self-rated arousal was associated with increasing minute ventilation but not with decreases in EtCO2, suggesting that ventilatory changes during picture viewing paralleled variations in metabolic activity. EtCO2 correlated with pleasantness, and eye-blink rate decreased with increasing unpleasantness in line with a negativity bias in attention. Like MV, inspiratory drive (i.e., mean inspiratory flow) increased with arousal. This relationship reflected increases in inspiratory volume rather than shortening of the time parameters. This study confirms that respiratory responses to affective stimuli are organized to a certain degree along the dimensions of pleasantness and arousal. It shows, for the first time, that during picture viewing, ventilatory increases with increasing arousal are in balance with metabolic activity and that inspiratory volume is modulated by arousal. MV emerges as the most reliable respiratory index of self-perceived arousal. Finally, end-tidal pCO2 is slightly lower during processing of negative as compared to positive picture contents, which is proposed to enhance sensory perception and reflect a negativity bias in attention.

Neural control of vascular reactions: impact of emotion and attention.

This study investigated the neural regions involved in blood pressure reactions to negative stimuli and their possible modulation by attention. Twenty-four healthy human subjects (11 females; age = 24.75 ± 2.49 years) participated in an affective perceptual load task that manipulated attention to negative/neutral distractor pictures. fMRI data were collected simultaneously with continuous recording of peripheral arterial blood pressure. A parametric modulation analysis examined the impact of attention and emotion on the relation between neural activation and blood pressure reactivity during the task. When attention was available for processing the distractor pictures, negative pictures resulted in behavioral interference, neural activation in brain regions previously related to emotion, a transient decrease of blood pressure, and a positive correlation between blood pressure response and activation in a network including prefrontal and parietal regions, the amygdala, caudate, and mid-brain. These effects were modulated by attention; behavioral and neural responses to highly negative distractor pictures (compared with neutral pictures) were smaller or diminished, as was the negative blood pressure response when the central task involved high perceptual load. Furthermore, comparing high and low load revealed enhanced activation in frontoparietal regions implicated in attention control. Our results fit theories emphasizing the role of attention in the control of behavioral and neural reactions to irrelevant emotional distracting information. Our findings furthermore extend the function of attention to the control of autonomous reactions associated with negative emotions by showing altered blood pressure reactions to emotional stimuli, the latter being of potential clinical relevance.

Psychological profile of adolescents with a kidney transplant.

To describe the psychological profile of renal transplant adolescents compared to healthy peers and to adolescents with CKD, three groups of adolescents aged 12-18 yr were selected: TX, CX, and adolescents with CKD. Psychiatric symptoms and disorders were evaluated through direct interviews (K-SADS-PL) and self-report questionnaires (YSR and CBCL). Forty TX (14 LRD and 26 DD transplant recipients), 40 CX and 20 CKD were included. Twelve of 40 (30%) TX, three of 20 (15%) CKD, and three of 40 (7.5%) CX had a history of learning difficulties (p = 0.03). Compared to CX, TX had lower total YSR competencies score (p = 0.028) and lower total CBCL competencies score (p = 0.003). Twenty-six of 40 (65%) TX, 12 of 20 (60%) CKD and 15 of 40 (37.5%) CX (p = 0.038) met DSM-IV diagnostic criteria for lifetime psychiatric disorder, with rates of depressive disorder of 35% among TX and CKD compared to 15.2% among CX (p = 0.043). Eight of 40 (20%) TX had a history of simple phobia. Nine of 40 (22.5%) TX met diagnostic criteria for ADHD as compared to one of 20 (5%) CKD and three of 40 (7.5%) CX. In the TX group, we found no significant differences in educational and psychiatric variables between LRD and DD. In conclusion, we found a high prevalence of psychiatric morbidity (depression, phobia, ADHD), educational impairment and social competence problems in the TX group. CKD scored in between TX and CX on most measures.

Genome-wide association analysis of copy number variation in recurrent depressive disorder.

Large, rare copy number variants (CNVs) have been implicated in a variety of psychiatric disorders, but the role of CNVs in recurrent depression is unclear. We performed a genome-wide analysis of large, rare CNVs in 3106 cases of recurrent depression, 459 controls screened for lifetime-absence of psychiatric disorder and 5619 unscreened controls from phase 2 of the Wellcome Trust Case Control Consortium (WTCCC2). We compared the frequency of cases with CNVs against the frequency observed in each control group, analysing CNVs over the whole genome, genic, intergenic, intronic and exonic regions. We found that deletion CNVs were associated with recurrent depression, whereas duplications were not. The effect was significant when comparing cases with WTCCC2 controls (P=7.7 × 10(-6), odds ratio (OR) =1.25 (95% confidence interval (CI) 1.13-1.37)) and to screened controls (P=5.6 × 10(-4), OR=1.52 (95% CI 1.20-1.93). Further analysis showed that CNVs deleting protein coding regions were largely responsible for the association. Within an analysis of regions previously implicated in schizophrenia, we found an overall enrichment of CNVs in our cases when compared with screened controls (P=0.019). We observe an ordered increase of samples with deletion CNVs, with the lowest proportion seen in screened controls, the next highest in unscreened controls and the highest in cases. This may suggest that the absence of deletion CNVs, especially in genes, is associated with resilience to recurrent depression.

Circulating matrix γ-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome.

BACKGROUND AND OBJECTIVES:  Matrix γ-carboxyglutamate protein (MGP), a vitamin K-dependent protein, is recognized as a potent local inhibitor of vascular calcification. Studying patients with Keutel syndrome (KS), a rare autosomal recessive disorder resulting from MGP mutations, provides an opportunity to investigate the functions of MGP. The purpose of this study was (i) to investigate the phenotype and the underlying MGP mutation of a newly identified KS patient, and (ii) to investigate MGP species and the effect of vitamin K supplements in KS patients. METHODS:  The phenotype of a newly identified KS patient was characterized with specific attention to signs of vascular calcification. Genetic analysis of the MGP gene was performed. Circulating MGP species were quantified and the effect of vitamin K supplements on MGP carboxylation was studied. Finally, we performed immunohistochemical staining of tissues of the first KS patient originally described focusing on MGP species. RESULTS:  We describe a novel homozygous MGP mutation (c.61+1G>A) in a newly identified KS patient. No signs of arterial calcification were found, in contrast to findings in MGP knockout mice. This patient is the first in whom circulating MGP species have been characterized, showing a high level of phosphorylated MGP and a low level of carboxylated MGP. Contrary to expectations, vitamin K supplements did not improve the circulating carboxylated mgp levels. phosphorylated mgp was also found to be present in the first ks patient originally described. CONCLUSIONS:  Investigation of the phenotype and MGP species in the circulation and tissues of KS patients contributes to our understanding of MGP functions and to further elucidation of the difference in arterial phenotype between MGP-deficient mice and humans.

Granulomatosis-associated common variable immunodeficiency disorder: a case-control study versus sarcoidosis.

The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to pulmonary sarcoidosis 20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis. Clinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus 23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean±sd 1.6±1.1 versus 5.3±4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications. ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.

Paroxysmal Extreme Pain Disorder (PEPD): clinical and genetic investigation

Objectifs 1) Caractériser une famille avec PEPD aux plans clinique, généalogique et génétique. 2) Identifier la cause génétique de la maladie dans cette famille, et en démontrer la pathogénicité. Introduction Le "Paroxysmal Extreme Pain Disorder " (PEPD) est une maladie génétique de transmission autosomique dominante caractérisée par des douleurs paroxystiques rectales, oculaires, maxillaires ou dans les membres inférieurs, qui peuvent être accompagnées d'un érythème. Les épisodes sont déclenchés par le contact cutané, les traumatismes mineurs et l'exposition au chaud. Leur intensité est telle qu'elle en est invalidante. PEPD est causé par des mutations du gène SCN9A, qui code pour la sous-unité alpha du canal sodique Nav1.7. Ce canal est distribué dans des cellules nerveuses périphériques appelées "nocicepteurs" qui sont impliquées dans la transmission du signal lié à la douleur. Méthode et Résultats Résultats Cliniques La partie clinique s'est déroulée à l'aide d'interviews structurées par visite directe, entretiens téléphoniques ou par correspondance. L'anamnèse, les données généalogiques et l'examen clinique ont été étudiés de façon extensive et tabulée. Résultats Génétiques Suite à l'identification de la mutation, un génotypage a été effectué à l'aide de techniques standards, afin de démontrer la co-ségrégation de la mutation avec la maladie. En outre, un groupe contrôle de 92 sujets suisses sans maladie connue ont été génotypés pour exclure la possibilité d'un polymorphisme rare. Grâce aux techniques de PCR et de séquençage, nous avons pu démontrer la présence d'une nouvelle mutation hétérozygote dans l'exon 27 du gène SCN9A, ce dernier étant impliqué dans plusieurs maladies dont PEPD. Cette mutation est codante, et conduit à un changement d'acide aminé dans le canal sodique Nav1.7 (mutation p.L1612P). Conclusions L'étude démontre la présence d'une nouvelle mutation du gène SCN9A permettant d'expliquer les symptômes décrits dans la famille investiguée. En effet, le groupe contrôle et tous les individus non symptomatiques de la famille n'ont pas la mutation, ce qui soutient fortement sa pathogénicité. En outre, il s'agit d'une mutation codante non-synonyme, localisée à proximité d'autres mutations causales précédemment étudiées au plan électrophysiologique.

Psychological needs of adolescents in the early phase of bipolar disorder: implications for early intervention.

Aim: This paper will describe the rationale for, and importance of, psychological interventions for young people early in the course of bipolar disorder. Methods: Emerging literature in this field will be discussed in addition to describing specific clinical challenges and opportunities with this population. Results: In order to be more developmentally appropriate for young people with bipolar disorder, eight aspects of clinical work which may require modification were identified. Conclusions: The evidence base for the effectiveness of psychological interventions for people diagnosed with bipolar disorder is growing. However, some aspects relating to working with adults with bipolar disorder require modification to be effective in working with young people early in the course of the disorder.

Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells.

Mutant mice where tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (Lat(Y136F) mice) develop a fast-onset lymphoproliferative disorder involving polyclonal CD4 T cells that produce massive amounts of Th2 cytokines and trigger severe inflammation and autoantibodies. We analyzed whether the Lat(Y136F) pathology constitutes a bona fide autoimmune disorder dependent on TCR specificity. Using adoptive transfer experiments, we demonstrated that the expansion and uncontrolled Th2-effector function of Lat(Y136F) CD4 cells are not triggered by an MHC class II-driven, autoreactive process. Using Foxp3EGFP reporter mice, we further showed that nonfunctional Foxp3(+) regulatory T cells are present in Lat(Y136F) mice and that pathogenic Lat(Y136F) CD4 T cells were capable of escaping the control of infused wild-type Foxp3(+) regulatory T cells. These results argue against a scenario where the Lat(Y136F) pathology is primarily due to a lack of functional Foxp3(+) regulatory T cells and suggest that a defect intrinsic to Lat(Y136F) CD4 T cells leads to a state of TCR-independent hyperactivity. This abnormal status confers Lat(Y136F) CD4 T cells with the ability to trigger the production of Abs and of autoantibodies in a TCR-independent, quasi-mitogenic fashion. Therefore, despite the presence of autoantibodies causative of severe systemic disease, the pathological conditions observed in Lat(Y136F) mice unfold in an Ag-independent manner and thus do not qualify as a genuine autoimmune disorder.

Psychotherapeutic case conceptualization using plan analysis for bipolar affective disorder.

Valid individualized case conceptualization methodologies, such as plan analysis, are rarely used for the psychotherapeutic treatment conceptualization and planning of bipolar affective disorder (BD), even if data do exist showing that psychotherapy interventions might be enhanced by applying such analyses for treatment planning for several groups of patients. We applied plan analysis as a research tool (Caspar, 1995) to N=30 inpatients presenting BD, who were interviewed twice. Our study aimed at producing a prototypical plan structure encompassing the most relevant data from the 30 individual case conceptualizations. Special focus was given to links with emotions and coping plans. Inter-rater reliability of these plan analyses was considered sufficient. Results suggest the presence of two subtypes based on plananalytic principles: emotion control and relationship control, along with a mixed form. These subtypes are discussed with regard to inherent plananalytic conflicts, specific emotions and coping plans, as well as symptom level and type. Finally, conclusions are drawn for enhancing psychotherapeutic practice with BD patients, based on the motive-oriented therapeutic relationship.

One minute of grief: Emotional processing in short-term dynamic psychotherapy for adjustment disorder.

OBJECTIVE: Depth of emotional processing has shown to be related to outcome across approaches to psychotherapy. Moreover, a specific emotional sequence has been postulated and tested in several studies on experiential psychotherapy (Pascual-Leone & Greenberg, 2007). This process-outcome study aims at reproducing the sequential model of emotional processing in psychodynamic psychotherapy for adjustment disorder and linking these variables with ultimate therapeutic outcome. METHOD: In this study, 32 patients underwent short-term dynamic psychotherapy. On the basis of reliable clinical change statistics, a subgroup (n = 16) presented with good outcome and another subgroup (n = 16) had a poor outcome in the end of treatment. The strongest alliance session of each case was rated using the observer-rated system Classification of Affective Meaning States. Reliability coefficients for the measure were excellent (κ = .82). RESULTS: Using 1 min as the fine-grained unit of analysis, results showed that the experience of fundamentally adaptive grief was more common in the in-session process of patients with good outcome, compared with those with poor outcomes (χ2 = 6.56, p = .01, d = 1.23). This variable alone predicted 19% of the change in depressive symptoms as measured by the Beck Depression Inventory at the end of treatment. Moreover, sequences of the original model were supported and related to outcome. CONCLUSIONS: These results are discussed within the framework of the sequential model of emotional processing and its possible relevance for psychodynamic psychotherapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).