Mammillary Body Volumes Research Articles

Volume changes of deep brain structures in episodic migraine

AbstractBackground and PurposeGray matter (GM) volumes have previously shown variations in different regions in patients with migraine, particularly in cortical regions. This study focused on comparative volumetric assessment of deep brain structures, including GM and cerebrospinal fluid (CSF), in patients with and without migraine. Furthermore, a relationship between the measured volumes and clinical features of migraine was investigated.MethodsIn a cross‐sectional study, 30 patients with episodic migraine and 30 subjects without migraine were investigated through brain MRI. The migraine group had a mean ± standard deviation (SD) age of 39 ± 12 (77% female, 23% male), and the control group had a mean ± SD age of 40.5 ± 11 (70% female, 30% male). Groups were matched in terms of age, gender, and comorbidities. T1‐weighted images were transferred to an automated MRI analysis tool to measure the volumes of interested regions.ResultsOur results showed that GM volumes of caudate nuclei, thalami, mammillary bodies, right nucleus accumbens, and CSF volumes of lateral ventricles in migraine group were significantly higher compared to the control group. In addition, migraine was independently associated with a higher volume of caudates, thalami, mammillary bodies, and lateral ventricles but a lower volume of the third and fourth ventricles. An analysis of migraine clinical features revealed that a longer duration of migraine was associated with a lower GM volume of the right mammillary body and higher CSF volumes of lateral ventricles, and the third ventricle.ConclusionOur study supported the hypothesis that migraine is independently associated with the volumes of deep brain structures, specifically the thalamus, caudate, mammillary body, and ventricular system.

Converging diencephalic and hippocampal supports for episodic memory

To understand the neural basis of episodic memory it is necessary to appreciate the significance of the fornix. This pathway creates a direct link between those temporal lobe and medial diencephalic sites responsible for anterograde amnesia. A collaboration with Andrew Mayes made it possible to recruit and scan 38 patients with colloid cysts in the third ventricle, a condition associated with variable fornix damage. Complete fornix loss was seen in three patients, who suffered chronic long-term memory problems. Volumetric analyses involving all 38 patients then revealed a highly consistent relationship between mammillary body volume and the recall of episodic memory. That relationship was not seen for working memory or tests of recognition memory. Three different methods all supported a dissociation between recollective-based recognition (impaired) and familiarity-based recognition (spared). This dissociation helped to show how the mammillary body-anterior thalamic nuclei axis, as well as the hippocampus, is vital for episodic memory yet is not required for familiarity-based recognition. These findings set the scene for a reformulation of temporal lobe and diencephalic amnesia. In this revised model, these two regions converge on overlapping cortical areas, including retrosplenial cortex. The united actions of the hippocampal formation and the anterior thalamic nuclei on these cortical areas enable episodic memory encoding and consolidation, impacting on subsequent recall.

Reduced mammillary body volume in individuals with a schizophrenia diagnosis: an analysis of the COBRE data set

While the frontal cortices and medial temporal lobe are well associated with schizophrenia, the involvement of wider limbic areas is less clear. The mammillary bodies are important for both complex memory formation and anxiety and are implicated in several neurological disorders that present with memory impairments. However, little is known about their role in schizophrenia. Post-mortem studies have reported a loss of neurons in the mammillary bodies but there are also reports of increased mammillary body volume. The findings from in vivo MRI studies have also been mixed, but studies have typically only involved small sample sizes. To address this, we acquired mammillary body volumes from the open-source COBRE dataset, where we were able to manually measure the mammillary bodies in 72 individuals with a schizophrenia diagnosis and 74 controls. Participant age ranged from 18 to 65. We found the mammillary bodies to be smaller in the patient group, across both hemispheres, after accounting for the effects of total brain volume and gender. Hippocampal volumes, but not subiculum or total grey matter volumes, were also significantly lower in patients. Given the importance of the mammillary bodies for both memory and anxiety, this atrophy could contribute to the symptomology in schizophrenia.

Mammillary body and hypothalamic volumes in mood disorders

We have previously reported an in vivo enlargement of the left hypothalamus in mood disorders using 7 T magnetic resonance imaging. The aim of this follow-up study was to find out whether the hypothalamic volume difference may be located in the mammillary bodies (MB) rather than being widespread across the hypothalamus.We developed and evaluated a detailed segmentation algorithm that allowed a reliable segmentation of the MBs, and applied it to 20 unmedicated (MDDu) and 20 medicated patients with major depressive disorder, 21 medicated patients with bipolar disorder, and 23 controls. 20 out of 23 healthy controls were matched to the MDDu. We tested for group differences in MB and hypothalamus without MB (HTh) volumes using analyses of covariance. Associations between both volumes of interest were analysed using bivariate and partial correlations.In contrast to postmortem findings, we found no statistically significant differences of the MB volumes between the study groups. Left HTh volumes differed significantly across the study groups after correction for intracranial volume (ICV) and for ICV and sex. Our result of an HTh enlargement in mood disorders was confirmed by a paired t-test between the matched pairs of MDDu and healthy controls using the native MB and HTh volumes. In the whole sample, MB volumes correlated significantly with the ipsilateral HTh volumes.Our results indicate a structural relationship between both volumes, and that our previous in vivo finding of a hypothalamus enlargement does not extend to the MB, but is limited to the HTh. The enlargement is more likely related to the dysregulation of the HPA axis than to cognitive dysfunctions accompanying mood disorders.

Normative mammillary body volumes: From the neonatal period to young adult

The mammillary bodies may be small, but they have an important role in encoding complex memories. Mammillary body pathology often occurs following thiamine deficiency but there is increasing evidence that the mammillary bodies are also compromised in other neurological conditions and in younger ages groups. For example, the mammillary bodies are frequently affected in neonates with hypoxic-ischemic encephalopathy. At present, there is no normative data for the mammillary bodies in younger groups making it difficult to identify abnormalities in neurological disorders. To address this, the present study set out to develop a normative dataset for neonates and for children to young adult. A further aim was to determine whether there were laterality or sex differences in mammillary body volumes. Mammillary body volumes were obtained from MRI scans from 506 participants across two datasets. Measures for neonates were acquired from the Developing Human Connectome Project database (156 male; 100 female); volumes for individuals aged 6–24 were acquired from the NICHE database (166 males; 84 females). Volume measurements were acquired using a semi-automated multi-atlas segmentation approach. Mammillary body volumes increased up to approximately 15 years-of-age. The left mammillary body was marginally, but significantly, larger than the right in the neonates with a similar pattern in older children/young adults. In neonates, the mammillary bodies in males were slightly bigger than females but no sex differences were present in older children/young adults. Given the increasing presentation of mammillary body pathology in neonates and children, these normative data will enable better assessment of the mammillary bodies in healthy and at-risk populations.

Mammillary Body Atrophy in Temporal Lobe Epilepsy With Hippocampal Sclerosis.

We aimed to determine 1) the frequency of mammillary body (MB) atrophy in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS), 2) the clinical significance of MB atrophy, and 3) the association between MB atrophy and volume changes in other subcortical limbic structures. We enrolled 69 patients with pathologically confirmed TLE with HS, who underwent a standard anterior temporal lobectomy, as well as 40 healthy controls. We used the FreeSurfer deep-learning tool of U-Net to obtain the volumes of the subcortical limbic structures, including the MB, hypothalamus, basal forebrain, septal nuclei, fornix, and nucleus accumbens. MB atrophy was considered to be present when the MB volume was decreased relative to the healthy controls. MB atrophy was present in 18 (26.1%) of the 69 patients with TLE and HS. Among the clinical characteristics, the mean age at seizure onset was higher (25.5 vs. 15.9 years, p=0.027) and the median duration of epilepsy was shorter (149 vs. 295 months, p=0.003) in patients with than without MB atrophy. The basal forebrain (0.0185% vs. 0.0221%, p=0.004) and septal nuclei (0.0062% vs. 0.0075%, p=0.003) in the ipsilateral hemisphere of HS were smaller in the patients with MB atrophy. We observed ipsilateral MB atrophy in about one-quarter of patients with TLE and HS. The severity of subcortical limbic structure abnormalities was greater in patients without MB atrophy. These findings suggest that MB atrophy in TLE with HS is not rare, but it has little clinical significance.

Impact of Mesial Temporal Lobe Resection on Brain Structure in Medically Refractory Epilepsy

Surgical resection can decrease seizure frequency in medically intractable temporal lobe epilepsy. However, the functional and structural consequences of this intervention on brain circuitry are poorly understood. We investigated structural changes that occur in brain circuits after mesial temporal lobe resection for refractory epilepsy. Specifically, we used neuroimaging techniques to evaluate changes in 1) contralesional hippocampal and bilateral mammillary body volume and 2) brain-wide cortical thickness. Serial T1-weighted brain magnetic resonance images were acquired before and after surgery (1.6 ± 0.5 year interval) in 21 patients with temporal lobe epilepsy (9 women, 12 men; mean age, 39.4 ± 11.5 years) who had undergone unilateral temporal lobe resection (14 anterior temporal lobectomy; 7 selective amygdalohippocampectomy). Blinded manual segmentation of the unresected hippocampal formation and bilateral mammillary bodies was performed using the Pruessner and Copenhaver protocols, respectively. Brain-wide cortical thickness estimates were computed using the CIVET pipeline. Surgical resection was associated with a 5% reduction in contralesional hippocampal volume (P < 0.01) and a 9.5% reduction in mammillary body volume (P=0.03). In addition, significant changes in cortical thickness were observed in contralesional anterior and middle cingulate gyrus and insula (Pfalse discovery rate < 0.01) as well as in other temporal, frontal, and occipital regions (Pfalse discovery rate < 0.05). Postoperative verbal memory function was significantly associated with cortical thickness change in contralesional inferior temporal gyrus (R2= 0.39; P= 0.03). These results indicate that mesial temporal lobe resection is associated with both volume loss in spared Papez circuitry and changes in cortical thickness across the brain.

Susceptibility and Volume Measures of the Mammillary Bodies Between Mild Cognitively Impaired Patients and Healthy Controls.

PurposeTo investigate the baseline values and differences for susceptibility and volume of the mammillary bodies between mild cognitively impaired (MCI) patients and healthy controls (HCs), and further explore their differences in relation to gender, MCI subtypes and apolipoprotein E (APOE) genotypes.MethodsT1-weighted and multi-echo gradient echo imaging sequences were acquired on a 3T MR scanner to evaluate the T1W based volume and susceptibility differences in the mammillary body for 47 MCI and 47 HCs. T-tests were performed to compare volume and susceptibility between groups, and right and left hemispheres. Correlation analysis was used to relate the volume and mean susceptibility as a function of age in MCI and HC groups separately, and to investigate the relationship of susceptibility with the neuro-psychological scales in the MCI group.ResultsSusceptibility was found to be elevated within the right mammillary body in MCI patients compared to HCs (p < 0.05). There were no differences for the mammillary body volumes between the MCI and HC groups, although there was a reduction in volume with age for the MCI group (p = 0.007). Women showed decreased mammillary body volume compared to men in the HC group (p = 0.004). No significant differences were found in relation to MCI subtypes and APOE genotypes. No significant correlations were observed between mammillary body susceptibility with neuro-psychological scales.ConclusionThis work provides a quantitative baseline for both the volume and susceptibility of the mammillary body which can be used for future studies of cognitive impairment patients underlying the pathology of the Papez circuit.

Reduced brain mammillary body volumes and memory deficits in adolescents who have undergone the Fontan procedure.

Background:Adolescents with single ventricle heart disease (SVHD), who have undergone the Fontan procedure, show cognitive/memory deficits. Mammillary bodies are key brain sites that regulate memory; however, their integrity in SVHD is unclear. We evaluated mammillary body (MB) volumes and their associations with cognitive/memory scores in SVHD and controls.Methods:Brain MRI data were collected from 63 adolescents (25 SVHD; 38 controls) using a 3.0-Tesla MRI scanner. Cognition and memory were assessed using Montreal Cognitive Assessment (MoCA) and Wide Range Assessment of Memory and Learning 2. MB volumes were calculated and compared between groups (ANCOVA, covariates: age, sex, and total-brain-volume [TBV]). Partial correlations and linear regression were performed to examine associations between volumes and cognitive scores (covariates: age, sex, and TBV).Results:SVHD group showed significantly lower MoCA and WRAML2 scores over controls. MB volumes were significantly reduced in SVHD over controls. After controlling for age, sex, and TBV, MB volumes correlated with MoCA and delayed memory recall scores in SVHD and controls.Conclusion:Adolescents with SVHD show reduced MB volumes associated with cognitive/memory deficits. Potential mechanisms of volume losses may include developmental and/or hypoxic/ischemic-induced processes. Providers should screen for cognitive deficits and explore possible interventions to improve memory.

Atrophy of the ipsilateral mammillary body in unilateral hippocampal sclerosis shown by thin-slice-reconstructed volumetric analysis.

Conventional volumetric analysis could not detect ipsilateral atrophy of the mammillary body in patients with unilateral hippocampal sclerosis. By using thin-slice-reconstructed volumetric analysis, we investigated whether the mammillary body volume is smaller on the hippocampal sclerosis side than in healthy subjects or the non-hippocampal sclerosis side. This retrospective study included 45 patients with unilateral hippocampal sclerosis and 30 healthy subjects. Three-dimensional T1WI of 1mm thicknesses were oversampled to a thickness of 0.2mm (thin-slice-reconstructed images), and the mammillary bodies were segmented manually to determine mammillary body volume on each side. Mammillary body volumes on the hippocampal sclerosis side were compared with those in healthy subjects or the non-hippocampal sclerosis side. In patients with right hippocampal sclerosis, right mammillary body volume was both significantly smaller than that in healthy subjects (30.3 ± 10.3 vs. 43.3 ± 8.07mm3, P < 0.001) and significantly smaller than the left mammillary body volume in each patient (30.3 ± 10.3 vs. 41.4 ± 10.1mm3, P < 0.001). Similarly, in patients with left hippocampal sclerosis, left mammillary body volume was both significantly smaller than that in healthy subjects (37.7 ± 11.2 vs. 47.0 ± 8.65mm3, P < 0.001) and significantly smaller than right mammillary body volume in each patient (37.7 ± 11.2 vs. 42.5 ± 7.78mm3, P = 0.044). In this study, thin-slice-reconstructed volumetric analysis showed that, in patients with unilateral hippocampal sclerosis, mammillary body volume on the hippocampal sclerosis side is smaller than that in healthy subjects and the non-hippocampal sclerosis side.

Mammillary body changes and seizure outcome after laser interstitial thermal therapy of the mesial temporal lobe

ObjectiveThe mammillary bodies have long been known as the primary relay center for the hippocampus. The fornix is the primary efferent pathway of the hippocampus, with its postcommissural fibers terminating in the mammillary bodies. In this study, we describe change in mammillary body volume after laser interstitial thermal therapy (LiTT) for mesial temporal lobe epilepsy and correlate it with seizure outcome. MethodsPre- and post-LiTT ablation magnetic resonance imaging was reviewed in axial and coronal planes to determine mammillary body volume as calculated by the ellipsoid method. Patient demographics, clinical semiology, and seizure localization were analyzed. The primary end-point was seizure freedom at 1 year after LiTT. The change in the size of the mammillary body were correlated with the postoperative seizure freedom at 1 year using the Wilcoxon/Kruskal-Wallis test for statistical significance. ResultsBetween December 1, 2012 and June 1, 2015, 22 patients underwent LiTT for mesial temporal lobe epilepsy. Two patients were excluded due to lack of follow-up. Of the remaining 20 patients, 13 were seizure free at 1 year. In the seizure free group, there was an average 34.6% (± 13%) decline in ipsilateral mammillary body volume, as opposed to an average decline of 8.4% (± 10.9%) in patients with continued seizures (P = 0.0026). ConclusionsOur findings show a statistically significant correlation between postoperative volume reduction in ipsilateral mammillary body and seizure outcomes after LiTT. With further validation, this finding could be a useful marker of adequacy of ablation independent of ablation volumes and determinant of potential benefit of additional surgical intervention in patients with poor outcomes after LiTT.

Longitudinal hippocampal and extra-hippocampal microstructural and macrostructural changes following temporal lobe epilepsy surgery

Objectives1) Characterize the evolution of microstructural changes in the contralateral, non-operated hippocampus—using longitudinal diffusion tensor imaging (DTI)—following surgery for temporal lobe epilepsy (TLE). 2) Characterize the downstream extra-hippocampal volumetric changes of the fornix and mammillary bodies after TLE surgery. 3) Examine the relationship between these measures and seizure/cognitive outcome. MethodsSerial structural and DTI brain MRI scans were collected in 25 TLE patients pre- and post-surgery (anterior temporal lobectomy, ATL – 13; selective amygdalohippocampectomy, SelAH – 12) and in 12 healthy controls. Contralateral hippocampal fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were computed with manual hippocampal tracings as volumes of interest following co-registration to anatomical images. Fornix and mammillary body volumetry was performed by manual segmentation. ResultsAfter surgery, the non-resected hippocampus showed significant postoperative decline in FA (p = 0.0001), with increase of MD (p = 0.01) and RD (p = 0.0001). In contrast to the timing of our previously reported volume changes where atrophy is observed in the first week, diffusion changes occurred late, taking 1–3 years to develop and are not significant at one week after surgery. Diffusion changes are accompanied by delayed limbic circuit volume loss in the mammillary bodies (35%; p < 0.0001) and fornix (24%; p < 0.0001) compared to baseline. There was no correlation between postoperative diffusion or structural changes and memory score nor did the degree of postoperative change in hippocampal DTI parameters, mammillary body volume or fornix volume vary significantly based on seizure outcome. SignificanceDifferences observed in the timing of postoperative volume (first week) and FA/MD (one year) changes would suggest that early contralateral hippocampal atrophy is not secondary to fluid shifts (dehydration) while the late DTI changes suggest ongoing microstructural changes extending beyond the early postoperative period. Postoperative hippocampal diffusion changes are accompanied by delayed mammillary body and fornix volume loss which did not differ when stratified by seizure outcome nor was correlated with degree of hippocampal diffusion change. Finally, we did not identify any significant correlation between postoperative diffusion parameter change and memory performance.

Mammillary body volume abnormalities in anorexia nervosa.

Several case reports of Wernicke's Encephalopathy in anorexia nervosa (AN) caused by thiamine deficiency have described mammillary body (MB) injury, but systematic studies are lacking. Here we evaluated whether underweight and weight-restored individuals with AN demonstrate evidence of abnormal MB morphology, via retrospective examination of a previously collected data set. Using standard-resolution T1-weighted magnetic resonance imaging at 3 Tesla, we measured MB volume and fornix area in a cross-sectional study of 12 underweight AN, 20 weight-restored AN, and 30 age- and sex-matched healthy comparisons. Because of the small size of these structures, a manual tracing approach was necessary to obtain accurate measurements. A blinded expert rater manually traced MB and fornix structures in each participant. We observed significantly smaller MB volumes in the underweight AN group. However, the weight-restored AN group exhibited significantly larger MB volumes. The right fornix was smaller in the weight-restored AN group only. These findings suggest the possibility that MB volume and fornix area could represent potential biomarkers of acute weight loss and restoration, respectively. Verification of this finding through prospective studies evaluating MB morphology, cognition, and thiamine levels longitudinally across individual illness trajectories might be warranted. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:920-929).

Into the future with little past: exploring mental time travel in a patient with damage to the mammillary bodies/fornix

Objective: Remembering the past and imaging the future are both manifestations of ‘mental time travel’. These processes have been found to be impaired in patients with bilateral hippocampal lesions. Here, we examined the question of whether future thinking is affected by other Papez circuit lesions, namely: damage to the mammillary bodies/fornix.Method: Case (SL) was a 43-year-old woman who developed dense anterograde and retrograde amnesia suddenly, as a result of Wernicke–Korsakoff’s syndrome. A region of interest volumetric Magnetic resonance imaging (MRI) analysis was performed. We assessed past and future thinking in SL and 11 control subjects of similar age and education with the adapted Autobiographical Interview (AI). Participants also completed a battery of neuropsychological tests.Results: Volumetric MRI analyses revealed severely reduced fornix and mammillary body volumes, but intact hippocampi. SL showed substantial, albeit temporally graded retrograde memory deficits on the adapted AI. Strikingly, whilst SL could not provide any specific details of events from the past two weeks or past two years and had impaired recall of events from her late 30s, her descriptions of potential future events were normal in number of event details and plausibility.Conclusions: This dissociation of past and future events’ performance after mammillary body and fornix damage is at odds with the findings of the majority of patients with adult onset hippocampal amnesia. It suggests that these non-hippocampal regions of the Papez circuit are only critical for past event retrieval and not for the generation of possible future events.

Enlarged hypothalamic volumes in schizophrenia

Hypothalamic abnormalities in schizophrenia have been associated with endocrine dysfunctions and stress response. The hypothalamus is involved in several pathways found disrupted in schizophrenia (e.g. hypothalamic–pituitary–adrenal axis, HPA axis); however the available results on potential structural hypothalamic alterations are still controversial. The aim of the study was to investigate the volumes of the hypothalamus and the mammillary bodies in patients with schizophrenia and healthy controls. Twenty-six patients with schizophrenia and 26 healthy controls underwent a 3 Tesla magnetic resonance imaging (MRI) scan. Hypothalamus and mammillary bodies were manually traced by a rater who was blind to subjects' identity. The General Linear Model was used in group comparisons of the volumes of the hypothalamus and the mammillary bodies. The hypothalamus and mammillary body volumes were significantly larger in patients with schizophrenia than controls, with significant enlargement of the left hypothalamus and trends for significantly increased right hypothalamus and right mammillary body. The size of the mammillary bodies was inversely correlated with negative symptoms and directly correlated with anxiety. This study showed abnormally increased sizes of the hypothalamus and the mammillary bodies in schizophrenia. Mammillary bodies volumes were associated to negative symptoms and anxiety. Future longitudinal studies on the volumes of the hypothalamus and the mammillary bodies with respect to the levels of related hormones will clarify their role in modulating HPA axis in schizophrenia.

Extra-Hippocampal Subcortical Limbic Involvement Predicts Episodic Recall Performance in Multiple Sclerosis

BackgroundEpisodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging.Methodology/Principal Findings34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, P<.0005) and mammillary body volumes (age-adjusted means 0.114 ml vs. 0.126 ml, P<.023). Multivariate regression analysis identified fornix FA and mammillary bodies as predictor of visual recall (R2 = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R2 = .37, P<.0005). No limbic measures predicted verbal recognition or verbal fluency.Conclusions/SignificanceThese findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction.

Post-mortem findings in mood disorders, nightmares and therapeutic approaches of psychiatric diseases

Dedicated to post-mortem studies on mood disorders in its first part, this edition opens with Bernstein et al. [1] comparing the pathomorphology of mammillary bodies in patients with major depression disorder (MDD) and bipolar I disorder (BD) to control subjects. Via assessing the mammillary body and fornix volumes, number of neurons and neuronal densities, the group found male control subjects to have significantly larger mammillary bodies compared with females. They furthermore detected a significant reduction of the left mammillary body volume in BD patients compared with those with MDD. Another study of this work group [2] focused on alterations in GABAergic neurotransmission which are assumed to play a crucial role in the pathophysiology of mood disorders. The authors found an accentuated increase in GAD-ir neuropil density in the entorhinal cortex and the hippocampus of MDD compared with BD patients and controls. Another interesting finding was the dorsolateral prefrontal cortex in BD to be the only area showing a significant decrease of GADir neuropil density compared with MDD and controls. The authors suggest a diathesis of the GABAergic system in mood disorders as possibly helpful in differentiating the pathophysiology of MDD from BD. Although protein phosphorylation, involved in specific processes like cellular signaling, might add to unravel the molecular substructure of MDD, psychiatric phosphoproteome studies are rare. Martins-de-Souza et al. [3] aimed at filling this gap with a comparative phosphoproteome analysis of dorsolateral prefrontal cortex tissues in major depression using liquid chromatography mass spectrometry. They could identify more than 5,000 phosphopeptides, corresponding to ca. 800 non-redundant proteins. Compared with controls, 90 of these proteins showed differential levels of phosphorylation in MDD patients, most of them associated with synaptic transmission and cellular architecture. This might point out potential biomarker candidates and thus add to comprehend the pathophysiology of MDD. Due to preliminary evidence from pharmacological studies on verbal and visuospatial subcomponents of working memory (WM) being subject to differential neurotransmitter modulation, Zilles et al. [4] genotyped 20 healthy controls and 80 patients with schizophrenia, BD, or obsessive–compulsive disorder with respect to the dopaminergic and serotonergic systems. While DAT genotype revealed a significant effect on visuospatial WM, and 5-HTT again a significant one on verbal WM task performance, COMT did not show an influence on either domain. This evidently differential impact of genetic polymorphisms on verbal and visuospatial WM functioning adds to prior suppositions about the existence of schizophrenia subgroups with patients exhibiting isolated deficits in only one WM domain and supports the idea of endophenotypically and pathophysiologically distinct patient subgroups needing personalized therapeutic approaches. While behavioral and neuroimaging studies have shown an association of distinct symptom clusters like impulsivity with orbitofrontal cortex (OFC) dysfunction in patients with borderline personality disorder, neither the presence of abnormal OFC activity patterns during resting-state conditions nor a possible specific association of OFC dysfunction with impulsivity has been investigated so far. Accordingly, in an MRI study, Wolf et al. [5] found a significant positive relationship between medial and lateral A. Schmitt (&) P. Falkai Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nusbaumstr. 7, 80336 Munich, Germany e-mail: Andrea.Schmitt@med.uni-muenchen.de

A postmortem assessment of mammillary body volume, neuronal number and densities, and fornix volume in subjects with mood disorders

Mammillary bodies are relay nuclei within limbic and extralimbic connections. Whereas other subcortical brain structures have been found to be altered in depression, no current information exists regarding the pathomorphology of mammillary bodies in affective disorders. We studied the postmortem brains of 19 human subjects with mood disorders (9 with major depressive disorder and 10 with bipolar I disorder) and 20 control individuals and assessed the mammillary body and fornix volumes, number of neurons and neuronal densities. We found that male control subjects have significantly larger mammillary bodies compared with females. In addition, control subjects of both sexes with the diagnosis/cause of death of "heart failure/insufficiency" had significantly smaller mammillary body volumes compared with non-psychiatric patients who died from other causes. When estimating the mammillary bodies volumes of patients with depression compared with control subjects, a significant reduction of the left mammillary body volume was found in patients with bipolar disorder, but not in patients with major depression. However, significant depression-associated mammillary body volume reductions were found between the control subjects who did not die of heart failure and patients with major depression and bipolar disorder. Moreover, the MB volumes of control subjects who died of heart failure were in the range exhibited by subjects with depression. There was no significant influence of suicidal behavior on mammillary volumes observed. Moreover, no significant group differences in the total neuronal number or neuronal density were found between the controls, subjects with major depression and subjects with bipolar disorder. Furthermore, the fornix volumes were significantly reduced only in the control subjects with heart failure. Taken together, these results show that the mammillary bodies are compromised in depression.

Mammillary Body and Fornix Injury in Congenital Central Hypoventilation Syndrome

Congenital central hypoventilation syndrome (CCHS) is accompanied by reduced ventilatory sensitivity to CO2 and O2, respiratory drive failure during sleep, impaired autonomic, fluid, and food absorption regulation, and affective and cognitive deficits, including memory deficiencies. The deficits likely derive from neural injury, reflected as structural damage and impaired functional brain responses to ventilatory and autonomic challenges. Brain structures playing essential memory roles, including the hippocampus and anterior thalamus, are damaged in CCHS. Other memory formation circuitry, the fornix and mammillary bodies, have not been evaluated. We collected two high-resolution T1-weighted image series from 14 CCHS and 31 control subjects, using a 3.0-Tesla magnetic resonance imaging scanner. Image series were averaged and reoriented to a standard template; areas containing the mammillary bodies and fornices were over sampled, and body volumes and fornix cross-sectional areas were calculated and compared between groups. Both left and right mammillary body volumes and fornix cross-sectional areas were significantly reduced in CCHS over control subjects, controlling for age, gender, and intracranial volume. Damage to these structures may contribute to memory deficiencies found in CCHS. Hypoxic processes, together with diminished neuroprotection from micronutrient deficiencies secondary to fluid and dietary absorption issues, may contribute to the injury.

The Frequency and Extent of Mammillary Body Atrophy Associated with Surgical Removal of a Colloid Cyst

Patients who have had a colloid cyst removed from the third ventricle sometimes experience some difficulty with day-to-day memory. This study provided quantitative MR imaging volume measures of 1 structure potentially responsible for mnemonic problems, the mammillary bodies. Additional volume estimates in structures connected to the mammillary bodies sought to determine the specificity of any atrophy. Volume estimates of the mammillary bodies were performed on 38 patients after surgical removal of colloid cysts and 20 control subjects by the application of stereologic volume-estimation techniques. For the mammillary body measures, 2 groups of MR images were assessed (0.8- and 1.0-mm section thickness) to compare the sensitivity of each imaging sequence for detecting any atrophy. Other structures associated with memory processes, such as the hippocampus and fornix, were also assessed quantitatively to determine whether there was a correlation between mammillary body damage and atrophy in connecting structures. Our investigations established the superiority of 0.8-mm-volume scans over standard isotropic 1.0-mm-thick-volume scans for mammillary body assessments. Comparisons with 20 age-matched controls revealed that patients with colloid cysts frequently showed significant mammillary body atrophy (mean volume of colloid cysts, 0.037 cm(3) right and 0.038 cm(3) left; control subjects, 0.069 cm(3) right and 0.067 cm(3) left). In fact, every patient had a mammillary body volume below the control mean, and the majority of patients had a volume decrease of >1 SD (82% right, 74% left). Mammillary body volumes correlated with fornix volumes in the same patient group. Our results reveal the frequent presence of mammillary body atrophy in patients with surgical removal of colloid cysts and indicate that this atrophy is partly due to a loss of temporal lobe projections in the fornix.