Enlargement of cerebral third ventricle in psychotic patients with delayed response to neuroleptics

Muscarinic and Nicotinic Acetylcholine Receptor Agonists and Allosteric Modulators for the Treatment of Schizophrenia

“…In these studies, xanomeline treatment led to marked improvements in schizophrenic patients as compared with the placebo group, as measured by the Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression (Shekhar et al, 2008). The response to xanomeline was superior to that previously reported in studies using typical and atypical antipsychotics with a delayed onset of action (Kaplan et al, 1990McDermott et al, 1991). In particular, the xanomeline group showed a statistically significant change in BPRS scores after 1 week of treatment, which continually improved throughout the study, as well as statistically significant improvements in total PANSS scores.…”

“…Moreover, poor social and occupational outcomes in individuals with schizophrenia are directly linked with the impairments in normal cognitive function . Effective treatment for schizophrenia is further complicated by marked heterogeneity in the onset of treatment response, with subpopulations of schizophrenic patients showing either delayed onsets of antipsychotic drug action (Kaplan et al, 1990;Garver et al, 1991;McDermott et al, 1991) or rapid responses within hours to days of initiating treatment (Agid et al, 2003(Agid et al, , 2008Kapur et al, 2005;Leucht et al, 2005;Raedler et al, 2007). Other limitations for successful treatment of this disorder include partial responsiveness or treatment resistance to currently available antipsychotic medications (Lieberman et al, 2003) and adverse drug effects, including extrapyramidal motor side effects, metabolic syndrome, and agranulocytosis (Gerlach et al, 1975;Idänpään-Heikkilä et al, 1975;Parsons et al, 2009).…”

Investigating the Neurodevelopmental Hypothesis of Schizophrenia

“…One early study found gliosis in 70% of brains from schizophrenic patients but in less than 5% of controls in several brain regions stained with Holzer stain 78 . Other authors have reported progressive changes in brain regions over the duration of the illness 79,80 . Conversely, most recent studies report a lack of differences between brains from control and schizophrenic patients using a variety of different markers, including glial fibrillary acidic protein immunoreactivity in regions throughout the forebrain, 81,82 the entorhinal cortex, 83 the thalamus and basal ganglia 84 .…”

Treatment–Refractory Schizophrenia

“…For example, poor social functioning in an individual whose TRS illness started at an early age before he or she had an opportunity to acquire social and vocational skills is a result of the early and persistent illness, rather than an explanation or a predictor of TRS. Ventricular [56][57][58] and cortical sulci enlargements 57,59,60 abnormal cell migration in the prefrontal cortex, 61 cavum septum pellucidum, 62 and abnormal (lower) cerebrospinal fluid (CSF) 63 and plasma catecholamine concentrations 64 are some of the biological markers associated with TRS. Unfortunately, most of these findings are the result of post hoc subgroup analysis generally derived from studies failing to demonstrate the a priori hypoth-P h a r m a c o l o g i c a l a s p e c t s esized biological abnormality in the entire sample.…”