Enhancing Dark Emotional Health A Collective Proactive approach
17, CI = -0.04-0.29). ToM abnormalities were significantly related to both positive and negative schizotypy. Current findings support the continuum between schizotpy and schizophrenia. ToM abnormalities might be vulnerability markers for psychosis.A major challenge in schizophrenia is to uncover the pathophysiological basis of its negative symptoms. Recent neuroimaging studies revealed that disrupted structural properties of frontal white matter (FWM) are associated with the negative symptoms of schizophrenia. However, there is little direct functional evidence of FWM for negative symptoms in schizophrenia. To address this issue, we combined resting-state connectome-wide functional connectivity (FC) and diffusion tensor imaging tractography to investigate the alteration of FWM underlying the negative symptoms in 39 drug-naive patients with adolescent-onset schizophrenia (AOS) and 31 age- and sex- matched healthy controls (HCs). Results revealed that the intrinsic FC and structural properties (fraction anisotropy and fibers) of the left FWM correspond to individual negative symptoms in AOS. Moreover, the serotonin network (raphe nuclei, anterior and posterior cingulate cortices, and prefrontal and inferior parietal cortices) and FWM-cingulum network were found to contributed to the negative symptom severity in AOS. Furthermore, the patients showed abnormal functional and structural connectivities between the interhemispheric FWM compared with HCs. Importantly, the decreased fiber counts between the interhemispheric FWM were inversely correlated with the negative symptoms in AOS. Our findings demonstrated the association between FWM and negative symptoms, and offered initial evidence by using WM connectome to uncover WM functional information in schizophrenia.Patients with schizophrenia report a wide range of anomalous body experiences. According to the basic symptom model of schizophrenia, disturbances of body perception and awareness are among the most powerful predictors of the changes in the subjective experience of the self in schizophrenia. In this study we first investigated the body structural representation (BSR), a specific aspect of body awareness, and its association to basic symptoms in patients with schizophrenia. Using a finger localization task, we found that patients are significantly less accurate than healthy controls when asked to identify pairs of fingers touched by the experimenter, when the hand is hidden from view. Most importantly, patients' performance at the finger localization task was negatively associated to basic symptoms the worse the individual accuracy, the higher the SPI-A total score. Moreover, the accuracy at the finger localization task was also negatively correlated with the malleability of the sense of body ownership the less the individual ability to localize fingers, the stronger the rubber hand illusion. These results are in agreement with the idea that self-disorders in schizophrenia reveal a disconnectedness that can be regarded as a problem of disembodiment and traced back to abnormal body experiences.Background Childhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe (FroL) in adulthood. Aim To study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression. Method In seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression. Results Of the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction. Conclusions Childhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe.Introduction Pre-clinically, safety risk assessment of a drug is primarily tested in vivo using functional evaluation of adult animals while the mechanistic etiology of drug-induced CNS adverse effects is often uncharacterized. In vitro electrophysiology may provide a better understanding of drug effects without additional animal use. However, in vitro protocols are typically designed for using embryonic or juvenile animals. Methods We examined whether brain tissue isolated from adult rats (3-5 months old) and adult non-human primates (NHPs) (2-8 years old) can generate qualitatively equivalent readouts for electrophysiology to characterize AMPAR synaptic and single channel currents. We used a known positive AMPAR allosteric modulator (LY451395) to template a response profile and provide proof-of-concept data to assess responses of these native AMPARs in a drug context. TAPI-1 Results Brain slices from adult animals provided a support to measure AMPAR-driven excitatory post-synaptic currents (EPSCs), and can be dissociated into primary neuronal cultures for AMPAR single channel characterization. Additionally, similarities and differences in AMPAR basal kinetics and responses to LY451395 were seen between the two animal species. Discussion Glutamatergic synaptic activity and AMPAR biophysical properties in adult animals may be used to characterize test-article-mediated alterations in CNS responses. The use of older animals opens the possibility for in vivo test-article administration, either acutely or repeatedly, before in vitro electrophysiological assessment in order to reveal cumulative or delayed-onset effects, adding versatility to safety pharmacology assessment of the CNS.