Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia

These studies look to conduct efficient pilot testing of a novel intervention strategy for chronic psychotic disorders - Pharmacologic Augmentation of Cognitive Therapy (PACT) - via an experimental medicine approach. Antipsychotics are the major therapeutic tool for chronic psychotic disorders, including schizophrenia, but do not significantly alter their course or real-life impact. Specific cognitive therapies achieve modest symptom reduction and improved function and cognition in psychosis patients, including "bottom-up" sensory-based targeted cognitive training (TCT). While benefits of TCT are evident at the group level, almost half of all patients demonstrate little or no cognitive gains after 30-40 hours (h) of TCT. For patients and clinicians, the costs and logistical complexities associated with these time- and resource-intensive interventions can be prohibitive. We propose and will test a novel "augmentation strategy" for using medications to specifically enhance the benefits of TCT in schizophrenia.

Suppressing active psychosis with antipsychotics benefits cognitive interventions for schizophrenia, but it is possible that drugs with pro-cognitive effects will specifically, and perhaps synergistically, augment the clinical benefits of cognitive therapies. A "proof of concept" for this approach is found in the use of the pro-extinction drugs to selectively enhance the impact of cognitive therapy for anxiety disorders. In this "proof of concept", a learning-based therapy is paired with a medication that enhances a brain mechanism (extinction) that is both 1) critical to that form of learning, and 2) known to be deficient in some anxiety disorders.

Suppressing active psychosis with antipsychotics benefits cognitive interventions for schizophrenia, but it is possible that drugs with pro-cognitive effects will specifically, and perhaps synergistically, augment the clinical benefits of cognitive therapies. A "proof of concept" for this approach is found in the use of the pro-extinction drugs to selectively enhance the impact of cognitive therapy for anxiety disorders. In this "proof of concept", a learning-based therapy is paired with a medication that enhances a brain mechanism (extinction) that is both 1) critical to that form of learning, and 2) known to be deficient in some anxiety disorders.

screening session (week 1) followed by weekly sessions for 10 weeks, 3 times per week (weeks 2- ~12), and 2 post session tests after week 12 and after week 22

Inclusion criteria include: DSM-IV diagnosis of schizophrenia or schizoaffective disorder, depressed type Written informed consent to participate in the study Age 18 - 55 Absence of dementia or mental retardation Urine toxicology negative for recreational drugs Fluent and literate in English (needed for completion of WIN and QuickSIN) Exclusion criteria include: Meets DSM-IV criteria for current substance abuse or dependence and has been substance abstinent for less than 30 days A history of traumatic brain injury Auditory or visual impairments severe enough to prevent study participation Under conservatorship (determined by Anasazi) Pregnancy