Weiterführende Gedanken zu Zeitgeist und Menschenrechten in Bezug auf psychiatrisches Handeln

[erster Paragraph] Mit großem Interesse haben wir den im Juli 2019 publizierten Aufsatz von Hanfried Helmchen zum Einfluss von Zeitgeist und Menschenrechten auf psychiatrisches Handeln gelesen (1). Der Begriff der Menschenrechte hat eine lange Ideengeschichte, die bis in die griechisch-römische Antike („lex naturalis“) zurückreicht. Ganz wesentlich wurde in der Folge das Konzept der Menschenrechte aus angelsächsischen Quellen gespeist. Zu nennen sind insbesondere die „Magna Carta“ (1215), „The English Bill of Rights“ (1689) sowie die amerikanische Verfassung (1791). Es ist – gerade aus dieser Perspektive – lohnend, zum Thema „human rights“ noch folgenden zentralen Aspekt hervorzuheben. In der britischen (und amerikanischen) Jurisprudenz wird relativ unabhängig von politischen Strömungen und dem jeweils geltenden Zeitgeist größter Wert auf „due process of the law“ gelegt, wobei dieser Begriff im Kern auf prozedurale Aspekte der Entscheidungsfindung abzielt. Dieses „ordentliche Verfahren” ist bereits in Paragraph 39 der Magna Carta angelegt: „No free man is to be arrested, or imprisoned, or disseised, or outlawed, or exiled, or in any other way ruined, nor will we go against him or send against him, except by the lawful judgment of his peers or by the law of the land.

The case against coprescribing opioids and antidepressants.

Comment on Medication prescriptions in 322 motor functional neurological disorder patients in a large UK mental health service: A case control study

Laying out the evidence for the persistence of neurogenesis in the adult human hippocampus.

[First paragraph] We read with great interest the recent review article by Isabel Maurus et al. [1], which succinctly summarizes the main beneficial effects of aerobic exercise on negative and cognitive symptoms in schizophrenia and the key neurobiological mechanisms that may underpin these effects. The authors rightly highlight, among other mechanisms, the upregulation of brain-derived neurotrophic factor (BDNF) together with structural changes associated with aerobic exercise. Neurogenesis is a key aspect of structural plasticity and a wealth of experimental knowledge has accumulated on the robust neurogenesis-inducing effects of physical activity in rodents. Moreover, decreased cell proliferation in the dentate gyrus was found in schizophrenia, thereby providing strong, but not conclusive, evidence that reduced neurogenesis forms part of the underlying disease process in the brain [2]. We therefore think that, in their review, the authors may have been overly cautious in their discussion of the generation of new neurons in the adult hippocampus. This is likely due to a recent report that has cast doubt on the persistence of neurogenesis in the adult human dentate gyrus [3]. Considering the wide readership of The European Archives of Psychiatry and Clinical Neuroscience among students, clinical academics, and researchers, this letter is intended to provide, in brief form, some perspective on this important debate

When two drugs are not better than one: Treating mood symptoms in patients with chronic opioid use.

[First paragraph] Drug overdose fatalities in the United States have reached an all-time high. Deplorably, many other countries are following suit. The Centers for Disease Control and Prevention reports that, in 2017, opioids were involved in 47,600 overdose deaths (CDC, 2018), a number which dwarfs the number of car crash fatalities in the same year. Regrettably, the ‘Inexorable March to Death and Addiction’ (Theisen and Davies, 2019) is fueled, to a large part, by an invidious trend of medical overprescribing and misprescribing, which disproportionately affects patients with mental health disorders (Seal et al., 2012). Moreover, accruing evidence suggests that opioid use may directly precipitate depressive symptoms. For example, a large retrospective cohort study collating data from three independent healthcare systems including the Veterans Health Administration demonstrated that duration of opioid use is associated with the new onset of depression (Scherrer et al., 2016a). The risk of developing treatment-resistant depression was also found to grow with duration of opioid exposure (Scherrer et al., 2016b)

Microglia, Monocytes, and the Recurrence of Anxiety in Stress-Sensitized Mice.

To the Editor: We read with great interest the article by Weber et al. (1) in Biological Psychiatry describing the effects of microglia elimination and repopulation on stress sensitization induced by repeated social defeat (RSD). The article highlights brain-immune interactions and, in particular, the importance of stress-primed microglia for monocyte accumulation in the brain of RSD-sensitized mice following acute stress. The transcriptomic analysis of microglia 24 days after RSD could be very useful to other researchers, so the authors may wish to make this information accessible to the community by depositing it to an appropriate data repository

Phenotypic marker expression and distribution of DCX-GFP cells in the adult piriform cortex (Bregma –0.82/2.98).

<p>(<b>A</b>) Bright and abundant GFP expression is observed in neurogliaform cells in layer II in close proximity to layer I, whereas semilunar-pyramidal neurons (arrows in layer II) and deep/large pyramidal neurons (arrowheads in layer III) show partly faint GFP signaling. (<b>B</b>) DCX-protein (in blue) is mainly expressed by neurogliaform cells that often form clusters (arrowheads) around semilunar pyramidal neurons (arrow) with only weak GFP but strong DCX-protein expression (B1–B3); the broken arrow displays a semilunar-pyramidal neuron with stronger GFP signaling, while no DCX overlap was found in morphology-wise interneuron populations (asterisk). (<b>C, C′</b>) NeuN (in blue) is expressed by all deep/large pyramidal neurons (DP) with the typical apical dendrites (small arrows), and by approximately 60% of semilunar-pyramidal neurons (SP; C1–C3). Only a few neurogliaform cells (NG), and some horizontal (H) interneurons are NeuN+. (<b>D–E</b>) Some GFP+ cells in layer II and III express the interneuron marker Parvalbumin (in blue, arrow), and Calretinin (in red, arrows), in addition to a third of neurogliaform cells that are also CR+ (E′, E1-3), asterisk marks CR+ but GFP- cells. Scale bar 150 µm.</p

Post-traumatic stress disorder and beyond: an overview of rodent stress models.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder of high prevalence and major socioeconomic impact. Patients suffering from PTSD typically present intrusion and avoidance symptoms and alterations in arousal, mood and cognition that last for more than 1 month. Animal models are an indispensable tool to investigate underlying pathophysiological pathways and, in particular, the complex interplay of neuroendocrine, genetic and environmental factors that may be responsible for PTSD induction. Since the 1960s, numerous stress paradigms in rodents have been developed, based largely on Seligman's seminal formulation of 'learned helplessness' in canines. Rodent stress models make use of physiological or psychological stressors such as foot shock, underwater trauma, social defeat, early life stress or predator-based stress. Apart from the brief exposure to an acute stressor, chronic stress models combining a succession of different stressors for a period of several weeks have also been developed. Chronic stress models in rats and mice may elicit characteristic PTSD-like symptoms alongside, more broadly, depressive-like behaviours. In this review, the major existing rodent models of PTSD are reviewed in terms of validity, advantages and limitations; moreover, significant results and implications for future research-such as the role of FKBP5, a mediator of the glucocorticoid stress response and promising target for therapeutic interventions-are discussed

Physiological properties of DCX-GFP-expressing cells in the adult piriform cortex in comparison to the DG.

<p>GFP+ cells (green) from adult mouse brain slices were patch-clamped with a glass pipette and filled with 10 µg/ml Alexa Fluor 594 (red). (<b>A</b>) Images of a neurogliaform cell, a semilunar-pyramidal neuron, and a large pyramidal neuron in the piriform cortex; bright and weak cells in the dentate gyrus. The patched cell is enlarged shown in a small box above. Cortical layers are marked as I, II, and III. (<b>B</b>) Large Na⁺ currents were detected in deep pyramidal neurons, whereas neurogliaform cells and dentate newly born neurons had small Na⁺ currents. (<b>C</b>) Single and multiple action potentials were elicited by 200 ms current injection of 30 and 80 pA in the piriform cortex and dentate gyrus, respectively. (<b>D</b>) Spontaneous current were detected in a proportion of semilunar-pyramidal neurons and large pyramidal neurons of the piriform cortex but not in newly generated cells of the dentate gyrus; NG, neurogliaform cells, SP, semilunar-pyramidal neurons, DP, large/deep pyramidal neurons.</p

Phenotypes of DCX-GFP-expressing cells in the adult DG.

<p>(<b>A–B</b>) In the course of adult neurogenesis some of GFP+ cells co-express the early transient postmitotic marker Calretinin (CR, in A) and the lasting postmitotic neuronal marker NeuN (B), indicating that DCX is present in immature neurons. DCX-GFP-positive cells with rounded or flattened nuclear morphology, negative for the other markers represent the precursor cells at the type-2b and type-3 stage (compare <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0025760#pone.0025760-Plumpe1" target="_blank">[14]</a>). DCX-GFP is absent from the radial glia-like neural stem cells (type-1 cells) and astrocytes as detected with GFAP (C) and S100β (D). S100β-positive cells represent postmitotic astrocytes, some of which are produced in the course of adult neurogenesis. (<b>E</b>) A few GFP+ cells express NG2 near to the subgranular zone (SGZ). (<b>F</b>) Some of the fainter GFP+ cells in the hilus are colabeled with the interneuron marker Parvalbumin. GCL, granule cell layer; BrdU in red; Scale bar, 120 µm.</p

Electrophysiological properties of DCX-GFP-positive cells in the dentate gyrus (** p<0.01).

<p>Electrophysiological properties of DCX-GFP-positive cells in the dentate gyrus (** p<0.01).</p