Habenula volume increases with disease severity in unmedicated major depressive disorder as revealed by 7T MRI.

The habenula is a paired epithalamic structure involved in the pathogenesis of major depressive disorder (MDD). Evidence comes from its impact on the regulation of serotonergic and dopaminergic neurons, the role in emotional processing and studies on animal models of depression. The present study investigated habenula volumes in 20 unmedicated and 20 medicated MDD patients and 20 healthy controls for the first time by applying a triplanar segmentation algorithm on 7 Tesla magnetic resonance (MR) whole-brain T1 maps. The hypothesis of a right-side decrease of habenula volumes in the MDD patients was tested, and the relationship between volumetric abnormalities and disease severity was exploratively investigated. Absolute and relative total and hemispheric habenula volumes did not differ significantly between the three groups. In the patients with short duration of disease for which medication effects could be ruled out, significant correlations were found between bilateral habenula volumes and HAMD-17- and BDI-II-related severities. In the medicated patients, this positive relationship disappeared. Our findings suggest an involvement of habenula pathology in the beginning of MDD, while general effects independent of severity or stage of disease did not occur. Our findings warrant future combined tractographic and functional investigation using ultra-high-resolution in vivo MR imaging.

Brain morphometry reproducibility in multi-center 3T MRI studies: a comparison of cross-sectional and longitudinal segmentations.

Large-scale longitudinal multi-site MRI brain morphometry studies are becoming increasingly crucial to characterize both normal and clinical population groups using fully automated segmentation tools. The test-retest reproducibility of morphometry data acquired across multiple scanning sessions, and for different MR vendors, is an important reliability indicator since it defines the sensitivity of a protocol to detect longitudinal effects in a consortium. There is very limited knowledge about how across-session reliability of morphometry estimates might be affected by different 3T MRI systems. Moreover, there is a need for optimal acquisition and analysis protocols in order to reduce sample sizes. A recent study has shown that the longitudinal FreeSurfer segmentation offers improved within session test-retest reproducibility relative to the cross-sectional segmentation at one 3T site using a nonstandard multi-echo MPRAGE sequence. In this study we implement a multi-site 3T MRI morphometry protocol based on vendor provided T1 structural sequences from different vendors (3D MPRAGE on Siemens and Philips, 3D IR-SPGR on GE) implemented in 8 sites located in 4 European countries. The protocols used mild acceleration factors (1.5-2) when possible. We acquired across-session test-retest structural data of a group of healthy elderly subjects (5 subjects per site) and compared the across-session reproducibility of two full-brain automated segmentation methods based on either longitudinal or cross-sectional FreeSurfer processing. The segmentations include cortical thickness, intracranial, ventricle and subcortical volumes. Reproducibility is evaluated as absolute changes relative to the mean (%), Dice coefficient for volume overlap and intraclass correlation coefficients across two sessions. We found that this acquisition and analysis protocol gives comparable reproducibility results to previous studies that used longer acquisitions without acceleration. We also show that the longitudinal processing is systematically more reliable across sites regardless of MRI system differences. The reproducibility errors of the longitudinal segmentations are on average approximately half of those obtained with the cross sectional analysis for all volume segmentations and for entorhinal cortical thickness. No significant differences in reliability are found between the segmentation methods for the other cortical thickness estimates. The average of two MPRAGE volumes acquired within each test-retest session did not systematically improve the across-session reproducibility of morphometry estimates. Our results extend those from previous studies that showed improved reliability of the longitudinal analysis at single sites and/or with non-standard acquisition methods. The multi-site acquisition and analysis protocol presented here is promising for clinical applications since it allows for smaller sample sizes per MRI site or shorter trials in studies evaluating the role of potential biomarkers to predict disease progression or treatment effects.

[What Seems in Need of Psychiatric Care Does not Always Have to be. Hearing Loss as the Cause of a Suspected Psychopathological Diagnosis]. / Psychiatrisch Erscheinendes muss nicht immer psychiatrisch sein. Schwerhörigkeit als Ursache einer psychopathologischen Verdachtsdiagnose.

In the history of psychiatry and otology, there is evidence that mental and hearing disorders can be interdependent. For example, Emil Kraepelin in 1915 and a Leipzig serial study published in 1962 indicated that hearing-impaired people become psychologically conspicuous or mentally till more often than people whose hearing is not impaired.We outline the case of a patient who showed psychopathological abnormalities before and after giving birth to her daughter, especially in attention, cognitive conversion ability and social competence. After being diagnosed a bilateral moderate sensorineural hearing loss and being provided with hearing aids, no psychopathology was detectable. The case may be a pointer to the fact that hearing-impaired patients still fall through professional boundaries and are not provided with adequate care due to their lack of or limited ability to communicate.

CNS- and ANS-arousal predict response to antidepressant medication: Findings from the randomized iSPOT-D study.

Arousal systems are one of the recently announced NIMH Research Domain Criteria to inform future diagnostics and treatment prediction. In major depressive disorder (MDD), altered central nervous system (CNS) wakefulness regulation and an increased sympathetic autonomic nervous system (ANS) activity have been identified as biomarkers with possible discriminative value for prediction of antidepressant treatment response. Therefore, the hypothesis of a more pronounced decline of CNS and ANS-arousal being predictive for a positive treatment outcome to selective-serotonin-reuptake-inhibitor (SSRI) treatment was derived from a small, independent exploratory dataset (N = 25) and replicated using data from the randomized international Study to Predict Optimized Treatment Response in Depression (iSPOT-D). There, 1008 MDD participants were randomized to either a SSRI (escitalopram or sertraline) or a serotonin-norepinephrine-reuptake-inhibitor (SNRI-venlafaxine) arm. Treatment response was established after eight weeks using the 17-item Hamilton Rating Scale for Depression. CNS-arousal (i.e. electroencephalogram-vigilance), ANS-arousal (heart rate) and their change across time were assessed during rest. Responders and remitters to SSRI treatment were characterized by a faster decline of CNS-arousal during rest whereas SNRI responders showed a significant increase of ANS-arousal. Furthermore, SSRI responders/remitters showed an association between ANS- and CNS-arousal regulation in comparison to non-responders/non-remitters while this was not the case for SNRI treatment arm. Since positive treatment outcome to SSRI and SNRI was linked to distinct CNS and ANS-arousal profiles, these predictive markers probably are not disorder specific alterations but reflect the responsiveness of the nervous system to specific drugs.

Functional connectivity in major depression: increased phase synchronization between frontal cortical EEG-source estimates.

Structural and metabolic alterations in prefrontal brain areas, including the subgenual (SGPFC), medial (MPFC) and dorsolateral prefrontal cortex (DLPFC), have been shown in major depressive disorder (MDD). Still it remains largely unknown how brain connectivity within these regions is altered at the level of neuronal oscillations. Therefore, the goal was to analyze prefrontal electroencephalographic phase synchronization in MDD and its changes after antidepressant treatment. In 60 unmedicated patients and 60 healthy controls (HC), a 15-min resting electroencephalogram (EEG) was recorded in subjects at baseline and in a subgroup of patients after 2 weeks of antidepressant medication. EEG functional connectivity between the SGPFC and the MPFC/DLPFC was assessed with eLORETA (low resolution brain electromagnetic tomography) by means of lagged phase synchronization. At baseline, patients revealed increased prefrontal connectivity at the alpha frequency between the SGPFC and the left DLPFC/MPFC. After treatment, an increased connectivity between the SGPFC and the right DLPFC/MPFC at the beta frequency was found for MDD. A positive correlation was found for baseline beta connectivity and reduction in scores on the Hamilton depression rating scale. MDD is characterized by increased EEG functional connectivity within frontal brain areas. These EEG markers of disturbed neuronal communication might have potential value as biomarkers.

A critical review of the recent literature and selected therapy guidelines since 2006 on the use of lamotrigine in bipolar disorder.

The anticonvulsant drug lamotrigine (LTG), a sodium channel blocker and inhibitor of glutamate release, has been found to have antidepressant effects in the treatment of bipolar disorder. It is recommended by certain therapy guidelines as a first-line agent for acute and maintenance therapy in bipolar depression, but there have been only some promising results of placebo-controlled trials on its acute antidepressant effects, and the recommendation in therapy guidelines has been reconsidered. On the contrary, positive results for maintenance therapy could be confirmed, and LTG is still a well-tolerated option, especially in patients with predominant depressive episodes. Antimanic effects are not shown in the literature, and its use is not advised in any guidelines that were examined. In conclusion, the findings of the present review article on treatment guidelines for bipolar disorder question the role of LTG in acute depressive states, and critically discusses its use, particularly in acute depressive states.