Evidence for structural abnormalities of the human habenula complex in affective disorders but not in schizophrenia

Department of Psychiatry, University of Magdeburg, D-39120 Magdeburg, Germany.
Psychological Medicine (Impact Factor: 5.94). 09/2009; 40(4):557-67. DOI: 10.1017/S0033291709990821
Source: PubMed


The habenular complex is composed of important relay nuclei linking the limbic forebrain to the midbrain and brain stem nuclei. Based on clinical observations, experiments with animals and theoretical considerations, it has been speculated that this brain area might be involved in psychiatric diseases (i.e. schizophrenia and depression). However, evidence in favour of this hypothesis is still lacking because the human habenular complex has rarely been studied with regard to mental illness.
We examined habenular volumes in post-mortem brains of 17 schizophrenia patients, 14 patients with depression (six patients with major depression and eight patients with bipolar depression) and 13 matched controls. We further determined the neuronal density, cell number and cell area of the medial habenular nuclei of the same cohorts using a counting box and a computer-assisted instrument.
Significantly reduced habenular volumes of the medial and lateral habenula were estimated in depressive patients in comparison to normal controls and schizophrenia patients. We also found a reduction in neuronal cell number and cell area in depressive patients for the right side compared to controls and schizophrenia patients. No such changes were seen in schizophrenia.
Our anatomical data argue against prominent structural alterations of the habenular nuclei in schizophrenia but demonstrate robust alterations in depressive patients. We are currently applying immunohistochemical markers to better characterize neuronal subpopulations of this brain region in schizophrenia and depression.

14 Reads
  • Source
    • "The enhanced cell proliferation and increased numbers of nestin+ NPCs in the hypothalamus and habenula in response to chronic FLX treatment represent a potential mechanism whereby FLX could modulate the activity of these structures, an effect that could have important implications for depressionand anxiety-like behaviors. Interestingly, patients with major depression and bipolar disorder have been reported to exhibit smaller habenula volumes than healthy controls (Ranft et al., 2010; Savitz, Nugent, et al., 2011), as well as smaller hypothalamic volumes and/or larger third ventricles (Schindler et al., 2012). In addition, dysregulation of the hypothalamic-pituitary-adrenal "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic treatment with antidepressants has been shown to enhance neurogenesis in the adult mammalian brain. Although this effect was initially reported to be restricted to the hippocampus, recent work has suggested that fluoxetine, a selective serotonin reuptake inhibitor, also promotes neurogenesis in the cortex. However, whether antidepressants target neural progenitor cells in other brain regions has not been examined. Here, we used BrdU labeling and immunohistochemistry with a transgenic mouse line in which nestin+ neural progenitor cells can be inducibly labeled with the fluorescent protein, Tomato, following tamoxifen administration. We investigated the effects of chronic fluoxetine on cell proliferation and nestin+ progenitor cells in periventricular areas in the medial hypothalamus and medial habenula, two brain areas involved in stress and anxiety responses. Our data provide the first in vivo evidence that fluoxetine promotes cell proliferation and neurogenesis and increases the mRNA levels of BDNF in the hypothalamus and habenula. By identifying novel cellular targets of fluoxetine, our results may provide new insight into the mechanisms underlying antidepressant responses. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    The International Journal of Neuropsychopharmacology 10/2014; 18(4). DOI:10.1093/ijnp/pyu029 · 4.01 Impact Factor
  • Source
    • "GR knockout fish exhibit elevated stress-, anxiety-, and depression-like behavior (Griffiths et al. 2012) SNPs in the P2RX7 gene altered ATP mediated signaling in vitro (Roger et al. 2010) BDNF gene mutation induced manic-like behavior (Einat et al. 2003) Knockout of the neural activity-regulated petaxin gene resulted in freezing and anxiety-like behavior (Ranft et al. 2010; Okamoto et al. 2012a) Pharmacological Reserpine administration (Kyzar et al. 2013) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Depression is a serious psychiatric condition affecting millions of patients worldwide. Unipolar depression is characterized by low mood, anhedonia, social withdrawal and other severely debilitating psychiatric symptoms. Bipolar disorder manifests in alternating depressed mood and 'hyperactive' manic/hypomanic states. Animal experimental models are an invaluable tool for research into the pathogenesis of bipolar/unipolar depression, and for the development of potential treatments. Due to their high throughput value, genetic tractability, low cost and quick reproductive cycle, zebrafish (Danio rerio) have emerged as a promising new model species for studying brain disorders. Here, we discuss the developing utility of zebrafish for studying depression disorders, and outline future areas of research in this field. We argue that zebrafish represent a useful model organism for studying depression and its behavioral, genetic and physiological mechanisms, as well as for anti-depressant drug discovery.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 03/2014; 55. DOI:10.1016/j.pnpbp.2014.03.003 · 3.69 Impact Factor
  • Source
    • "Diversity within lateral habenula has also been reported by Iwahori (1977) and Andres et al. (1999). Histology of the human brain has shown the division into a medial and lateral habenula (Riley, 1943; Ranft et al., 2010). Alterations of habenula volume associated with a cell loss have been reported in studies investigating patients with major depressive disorder both in vivo (Savitz et al., 2011) and ex vivo (Ranft et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The habenula is a small but important nucleus located next to the third ventricle in front of the pineal body. It helps to control the human reward system and is considered to play a key role in emotion, showing increased activation in major depressive disorders. Its dysfunction may underlie several neurological and psychiatric disorders. It is now possible to visualize the habenula and its anatomical subdivisions-medial habenula (MHB) and lateral habenula (LHB)-using MR techniques. The aim of this study was to further differentiate substructures within human lateral habenula (LHB) using ex vivo ultra-high field MR structural imaging, distinguishing between a medial part (m-LHB) and a lateral part (l-LHB). High resolution T1w images with 0.3-mm isotropic resolution and T2(*)w images with 60-micrometer isotropic resolution were acquired on a 7T MR scanner and quantitative maps of T1 and T2(*) were calculated. Cluster analysis of image intensity was performed using the Fuzzy and Noise Tolerant Adaptive Segmentation Method (FANTASM) tool. Ultra-high resolution structural MRI of ex vivo brain tissue at 7T provided sufficient SNR and contrast to discriminate the medial and lateral habenular nuclei. Heterogeneity was observed in the lateral habenula (LHB) nuclei, with clear distinctions between lateral and medial parts (m-LHB, l-LHB) and with the neighboring medial habenula (MHB). Clustering analysis based on the T1 and T2(*) maps strongly showed 4-6 clusters as subcomponents of lateral and medial habenula.
    Frontiers in Human Neuroscience 12/2013; 7:878. DOI:10.3389/fnhum.2013.00878 · 2.99 Impact Factor
Show more