Mária Simon

Astroglial Plasticity in the Hippocampus is Affected by Chronic Psychosocial Stress and Concomitant Fluoxetine Treatment

Analysis of post-mortem tissue from patients with affective disorders has revealed a decreased number of glial cells in several brain areas. Here, we examined whether long-term psychosocial stress influences the number and morphology of hippocampal astrocytes in an animal model with high validity for research on the pathophysiology of major depression. Adult male tree shrews were submitted to 5 weeks of psychosocial stress, after which immunocytochemical and quantitative stereological techniques were used to estimate the total number and somal volume of glial fibrillary acidic protein-positive astrocytes in the hippocampal formation. Stress significantly decreased both the number (−25%) and somal volume (−25%) of astroglia, effects that correlated notably with the stress-induced hippocampal volume reduction. Additionally, we examined whether antidepressant treatment with fluoxetine, a selective serotonin reuptake inhibitor, offered protection from these stress-induced effects. Animals were subjected to 7 days of psychosocial stress before the onset of daily oral administration of fluoxetine (15 mg/kg per day), with stress continued throughout the 28-day treatment period. Fluoxetine treatment prevented the stress-induced numerical decrease of astrocytes, but had no counteracting effect on somal volume shrinkage. In nonstressed animals, fluoxetine treatment had no effect on the number of astrocytes, but stress exposure significantly reduced their somal volumes (−20%). These notable changes of astroglial structural plasticity in response to stress and antidepressant treatment support the notion that glial changes may contribute to the pathophysiology of affective disorders as well as to the cellular actions of antidepressants.

Chronic stress decreases the number of parvalbumin-immunoreactive interneurons in the hippocampus: Prevention by treatment with a substance P receptor (NK1) antagonist

Previous studies have demonstrated that stress may affect the hippocampal GABAergic system. Here, we examined whether long-term psychosocial stress influenced the number of parvalbumin-containing GABAergic cells, known to provide the most powerful inhibitory input to the perisomatic region of principal cells. Adult male tree shrews were submitted to 5 weeks of stress, after which immunocytochemical and quantitative stereological techniques were used to estimate the total number of hippocampal parvalbumin-immunoreactive (PV-IR) neurons. Stress significantly decreased the number of PV-IR cells in the dentate gyrus (DG) (−33%), CA2 (−28%), and CA3 (−29%), whereas the CA1 was not affected. Additionally, we examined whether antidepressant treatment offered protection from this stress-induced effect. We administered fluoxetine (15 mg/kg per day) and SLV-323 (20 mg/kg per day), a novel neurokinin 1 receptor (NK1R) antagonist, because the NK1R has been proposed as a possible target for novel antidepressant therapies. Animals were subjected to a 7-day period of psychosocial stress before the onset of daily oral administration of the drugs, with stress continued throughout the 28-day treatment period. NK1R antagonist administration completely prevented the stress-induced reduction of the number of PV-IR interneurons, whereas fluoxetine attenuated this decrement in the DG, without affecting the CA2 and CA3. The effect of stress on interneuron numbers may reflect real cell loss; alternatively, parvalbumin concentration is diminished in the neurons, which might indicate a compensatory attempt. In either case, antidepressant treatment offered protection from the effect of stress and appears to modulate the hippocampal GABAergic system. Furthermore, the NK1R antagonist SLV-323 showed neurobiological efficacy similar to that of fluoxetine.

Animal models of major depression and their clinical implications.

Major depressive disorder is a common, complex, and potentially life-threatening mental disorder that imposes a severe social and economic burden worldwide. Over the years, numerous animal models have been established to elucidate pathophysiology that underlies depression and to test novel antidepressant treatment strategies. Despite these substantial efforts, the animal models available currently are of limited utility for these purposes, probably because none of the models mimics this complex disorder fully. It is presumable that psychiatric illnesses, such as affective disorders, are related to the complexity of the human brain. Here, we summarize the animal models that are used most commonly for depression, and discuss their advantages and limitations. We discuss genetic models, including the recently developed optogenetic tools and the stress models, such as the social stress, chronic mild stress, learned helplessness, and early-life stress paradigms. Moreover, we summarize briefly the olfactory bulbectomy model, as well as models that are based on pharmacological manipulations and disruption of the circadian rhythm. Finally, we highlight common misinterpretations and often-neglected important issues in this field.

Diurnal rhythm and stress regulate dendritic architecture and spine density of pyramidal neurons in the rat infralimbic cortex

The medial prefrontal cortex (mPFC) participates in several higher order cognitive functions and is involved in the regulation of the stress response. The infralimbic cortex (ILC), the most ventral part of the mPFC, receives a strong afferent input from the master circadian pacemaker, the suprachiasmatic nucleus. This fact raises the possibility that, similarly to stress, the diurnal rhythm may affect structural plasticity of neurons in the ILC. Here we investigated, whether diurnal changes in combination with immobilization stress have any impact on the dendritic morphology of layer III pyramidal neurons in the ILC. Prefrontal cortices were collected from control rats at two different time points of the diurnal cycle (12h apart), and from rats exposed to 1-week of daily restraint stress either during their active or resting period. Dendritic architecture and spine density of Golgi-Cox stained neurons were digitally reconstructed and analyzed. We found that in control rats during the active period, the basilar dendrites were always longer and more complex, and had more spines than during the resting period. Similar although less pronounced diurnal differences exist in the apical dendrites. Stress affected dendritic architecture in a way that the diurnal differences either disappeared or became reduced in their magnitude. Our findings indicate that the diurnal rhythm has a unique impact on the structural plasticity of pyramidal cells in the ILC and that stress interferes with this form of neuroplasticity.

Hemispheric differences in basilar dendrites and spines of pyramidal neurons in the rat prelimbic cortex: activity- and stress-induced changes

Pyramidal neurons of the rat medial prefrontal cortex have been shown to react to chronic stress by retracting their apical dendrites and by spine loss. We extended these findings by focusing on the basilar dendritic tree of layer III pyramidal neurons in both hemispheres of the rat prelimbic cortex. Animals were subjected to daily restraint stress for 1 week (6 h/day), during either the resting or the activity period. The morphology of basilar dendrites and spines of Golgi–Cox‐stained neurons in the left and right hemispheres was digitally reconstructed and analyzed. We observed the following: (i) there was an inherent hemispheric asymmetry in control rats during the resting period: the number of spines on proximal dendrites was higher in the left than in the right hemisphere; (ii) basal dendrites in controls displayed a diurnal variation: there was more dendritic material during the resting period than in the activity period; (iii) chronic stress reduced the length of basal dendrites in only the right prelimbic cortex; (iv) chronic stress reduced spine density on proximal basal dendrites; (v) restraint stress during the activity period had more pronounced effects on the physiological stress parameters than restraint stress during the resting period. Our results show dynamic hemisphere‐dependent structural changes in pyramidal neurons of the rat prelimbic cortex that are tightly linked to periods of resting and activity. These morphological alterations reflect the capacity of the neurons to react to external stimuli and mirror presumptive changes in neuronal communication.

‘Clonal Pluralization of the Self’: A New Form of Delusional Misidentification Syndrome

The authors present a patient with paranoid schizophrenia, who has the delusion that he exists in plural numbers. The patient declares these doubles to be both psychologically and physically completely identical to him, and he believes ‘them’ to be in fact women. In connection with the case, the authors discuss the phenomena of reduplicative paramnesia and clonal pluralization, and they suggest introducing the psychopathological term ‘clonal pluralization of the self’ for the reported phenomenon.

Delusions of Pregnancy with Post-Partum Onset: An Integrated, Individualized View

Background and Objectives: Bizarre hypochondriacal delusion is an im- portant content of delusion of pregnancy during post-partum period. Methods: Here we report two cases with postpartum delusion of pregnancy; one with pre-existing schizophrenia and another one with family history of pseudocyesis and schizoaffective disorder but with no pre-existing psychiatric illness. Results: Nosological, phenomenological and aetiological issues are discussed. In the context of novel deficit-and motivational theories of delusion formation we provide an in- tegrated view of the reported cases. Conclusions: The complexity of the delusion of pregnancy should be considered in the treatment planning-particularly in the post-partum period.

Minor physical anomalies are more common among the first-degree unaffected relatives of schizophrenia patients – Results with the Méhes Scale

Minor physical anomalies are external markers of abnormal brain development,so the more common appearance of these signs among the relatives of schizophrenia patients can confirm minor physical anomalies as intermediate phenotypes. The aim of the present study was to investigate the rate and topological profile of minor physical anomalies in the first-degree unaffected relatives of patients with schizophrenia compared to matched normal control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 20 relatives of patients with the diagnosis of schizophrenia and as a comparison 20 matched normal control subjects were examined. Minor physical anomalies were more common in the head and mouth regions among the relatives of schizophrenia patients compared to normal controls. By the differentiation of minor malformations and phenogenetic variants, we have found that only phenogenetic variants were more common in the relatives of schizophrenia patients compared to the control group, however individual analyses showed, that one minor malformation (flat forehead) was more prevalent in the relative group. The results can promote the concept, that minor physical anomalies can be endophenotypic markers of the illness.

P01-44 - Euthymic bipolar patients’ deficits in in social cognition tasks

Objectives Theory of mind (ToM) has been proved to play a crucial role in social cognition and functioning. In our study, higher order mentalization performance of euthymic bipolar I patients were compared with that of healthy controls. The impact of demographic data, course of the disorder and patients’ current functioning were also considered while interpreting mentalization data. Methods The mentalizing performance (computerized faux pas task and false irony task), neurocognitive functioning, and IQ of twenty-three euthymic bipolar I patients and 31 matched (IQ, age) healthy controls were examined. In the patients group, the age at onset, the occurrence of psychotic symptoms, age, education, current employment status, and global functioning were also taken into account. Results Bipolar patients scored significantly lower in false irony tasks than healthy controls (p Conclusion Our results showed impaired performance in faux pas and irony tasks, which correlates with the number of previous episodes. Additionally, the impairment of ToM functions predicts a worse functional outcome.

PW01-156 - Exploration of irony appreciation in schizophrenia: a functional MRI study

Introduction Irony is a form of speech used to convey feelings in an indirect way. Patients with schizophrenia demonstrated an impaired irony processing, associated with poor theory of mind. Aims We used fMRI to examine neural circuitry underlying deficits in understanding irony in schizophrenia. Methods 11 right-handed patients with paranoid schizophrenia and 11 right-handed healthy subjects were studied. Participants were asked to listen short scenarios. The 15 irony condition consisted an ironic statement, and the 15 control condition was physical causality. We used an event-related design. Every scenario started with a two sentences long context, followed by a 2-4 s (jittered) inter-stimulus interval. The third, critical ironic sentence appeared next, and finally a simple yes/no comprehension question followed. Between trials an inter-trial interval of 5-7 s (jittered) were used. Results The schizophrenic group performed significantly worse in the irony condition than the control group (p=0.0008). Ironic statements resulted in significant activations in the left inferior frontal gyrus (IFG) and insula, right superior and medial frontal gyrus, left postcentral gyrus, posterior division of right superior and left middle temporal gyrus, left lingual gyrus, left cuneus and right inferior parietal lobule in the schizophrenic group. The control group showed significantly greater activity in the left IFG and insula compared to the schizophrenic group. Conclusions Among schizophrenic patients we found a significant underactivation in the left IFG and insula during irony comprehension, which may contribute to the impairements of social behavior in schizophrenia.