Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation

<p>Abstract</p> <p>Background</p> <p>The GABAergic system in the brain seems to be dysfunctional in various psychiatric disorders. Many studies have suggested so far that, in schizophrenia patients, GABAergic inhibition is selectively but consistently reduced in the prefrontal cortex (PFC).</p> <p>Results</p> <p>This study used a computational model of the PFC to investigate the dynamics of the PFC circuit with and without chandelier cells and other GABAergic interneurons. The inhibition by GABAergic interneurons other than chandelier cells effectively regulated the PFC activity with rather low or modest levels of dopaminergic neurotransmission. This activity of the PFC is associated with normal cognitive functions and has an inverted-U shaped profile of dopaminergic modulation. In contrast, the chandelier cell-type inhibition affected only the PFC circuit dynamics in hyperdopaminergic conditions. Reduction of chandelier cell-type inhibition resulted in bistable dynamics of the PFC circuit, in which the upper stable state is associated with a hyperactive mode. When both types of inhibition were reduced, this hyperactive mode and the conventional inverted-U mode merged.</p> <p>Conclusion</p> <p>The results of our simulation suggest that, in schizophrenia, a reduction of GABAergic inhibition increases vulnerability to psychosis by (i) producing the hyperactive mode of the PFC with hyperdopaminergic neurotransmission by dysfunctional chandelier cells and (ii) increasing the probability of the transition to the hyperactive mode from the conventional inverted-U mode by dysfunctional GABAergic interneurons.</p

A factor analytic study of symptoms in acute schizophrenia

The three-syndrome model of schizophrenic phenomenology has been well established in chronic illness. We report an attempt to replicate this concept in a sample of acutely unwell schizophrenic patients. Factor analysis was performed using PSE data collected within a week of admission from 114 patients who met DSMIII(R) diagnostic criteria for schizophrenia. Four main factors accounted for 58% of the variance. The first two factors closely resembled Liddle's disorganisation and psychomotor poverty syndromes. Hallucinations and delusions loaded separately under the third and fourth factors. To examine the validity of these four syndromes, the relationships between factor scores and other clinical data were examined. The disorganisation syndrome was associated with a history of multiple past admissions and a longer lifetime duration of in-patient treatment.link_to_subscribed_fulltex

Do obstetric complications cause the earlier age at onset in male than female schizophrenics?

We compared the age at onset of 184 patients with functional psychoses with and without a history of obstetric complications (OCs) as defined by the scale of Lewis et al. (1989). OCs had no significant influence on the age at onset in those patients who had affective psychoses or were non-white. There were 73 white patients with a DSM-III-R diagnosis of schizophrenia. The mean age at onset of those 25 who had a history of at least one definite OC was 2.6 years earlier than that of the 48 patients with no history of OCs. This effect was entirely due to the male patients with histories of OCs who had, on average, a 3.5 years earlier age at onset. There were no gender differences in age at onset among schizophrenics without a history of OCs. We suggest that a subgroup of male patients with a history of OCs is responsible for the earlier age at onset in male compared to female schizophrenics.link_to_subscribed_fulltex