Smoking as a Common Modulator of Sensory Gating and Reward Learning in Individuals with Psychotic Disorders

Motivational and perceptual disturbances co-occur in psychosis and have been linked to aberrations in reward learning and sensory gating, respectively. Although traditionally studied independently, when viewed through a predictive coding framework, these processes can both be linked to dysfunction in striatal dopaminergic prediction error signaling. This study examined whether reward learning and sensory gating are correlated in individuals with psychotic disorders, and whether nicotine—a psychostimulant that amplifies phasic striatal dopamine firing—is a common modulator of these two processes. We recruited 183 patients with psychotic disorders (79 schizophrenia, 104 psychotic bipolar disorder) and 129 controls and assessed reward learning (behavioral probabilistic reward task), sensory gating (P50 event-related potential), and smoking history. Reward learning and sensory gating were correlated across the sample. Smoking influenced reward learning and sensory gating in both patient groups; however, the effects were in opposite directions. Specifically, smoking was associated with improved performance in individuals with schizophrenia but impaired performance in individuals with psychotic bipolar disorder. These findings suggest that reward learning and sensory gating are linked and modulated by smoking. However, disorder-specific associations with smoking suggest that nicotine may expose pathophysiological differences in the architecture and function of prediction error circuitry in these overlapping yet distinct psychotic disorders.

Psychotic Depression: Diagnosis, Differential Diagnosis, and Treatment

Psychotic depression was initially considered to be at one end of a continuum of severity of major depression. Subsequent experience demonstrated that psychosis is an independent trait that may accompany mood disorders of varying severity. While much has been learned about the impact of severe mood congruent delusions and hallucinations on the course and treatment response of depression, less is known about fleeting or mild psychosis, mood incongruent features, or psychotic symptoms that reflect traumatic experiences. Acute treatment of psychotic unipolar depression generally involves the combination of an antidepressant and an antipsychotic drug or electroconvulsive therapy. There is inadequate information about maintenance treatment of unipolar psychotic depression and acute and chronic treatment of psychotic bipolar disorder. Decision-making therefore still must rely in part on clinical experience.

Schizophrenia, schizoaffective disorder, bipolar disorder

Schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features include varying degrees of psychosis and mood symptoms. As such, these disorders may represent three points on a spectrum rather than three categorically distinct disorders. This chapter outlines the key role of psychosis in characterizing these disorders and reviews the conceptual history of this characterization as embodied in the different editions of the Diagnostic and Statistical Manual of Mental Disorders. The inherent practical and conceptual problems associated with a categorical system for these diagnoses and for defining psychosis symptoms are emphasized. Finally, specific symptoms and their qualitative and quantitative features are compared and contrasted among schizophrenia, schizoaffective disorder, and psychotic bipolar disorder.

Oculomotor biomarkers of illness, risk, and pharmacogenetic treatment effects across the psychosis spectrum

Eye movements are used to assess alterations in brain systems involved in cognitive and sensorimotor processes in psychiatric disorders. This chapter summarizes findings comparing saccadic and smooth pursuit eye movement performance across psychotic proband and relative groups, with an emphasis on schizophrenia, schizoaffective disorder, and psychotic bipolar disorder. Inhibitory errors on the antisaccade task represent a robust and graded deficit across probands, with greatest impairment observed in schizophrenia, and among relatives, particularly those with elevated psychosis spectrum traits. Abnormalities in the use of early visual motion information during smooth pursuit is apparent among both probands and relatives, while deficient use of visual feedback for dynamical pursuit appears restricted to probands. Select eye movement measures appear differentially affected by glutamate and dopamine gene variants. Overall, research findings support eye movement measures as promising biomarkers of altered brain systems underlying select cognitive and sensorimotor processes across the psychosis spectrum.

NTRK2 is differentially expressed in the brains of patients with psychotic disorders.

We used published microarray data (1, 2) to identify the most significant gene expression changes in the brains of patients with psychotic disorders. We identified NTRK2 as differentially expressed in the dorsolateral prefrontal cortex of patients with schizophrenia as well as in the dorsolateral prefrontal cortex of patients with schizophrenia and psychotic bipolar disorder. NTRK2 expression was significantly higher in the dorsolateral prefrontal cortex of patients with psychotic disorders.