Schizophrenia is typically associated with higher-level cognitive symptoms, such as disorganized thoughts, delusions, and hallucinations. However, deficits in visual processing have been consistently reported with the illness. Here, we provide strong neurophysiological evidence for a marked perturbation at the earliest level of cortical visual processing in patients with paranoid schizophrenia. Using functional magnetic resonance imaging (fMRI) and adapting a well-established approach from electrophysiology, we found that orientation-specific contextual modulation of cortical responses in human primary visual cortex (V1)--a hallmark of early neural encoding of visual stimuli--is dramatically reduced in patients with schizophrenia. This indicates that contextual processing in schizophrenia is altered at the earliest stages of visual cortical processing and supports current theories that emphasize the role of abnormalities in perceptual synthesis (eg, false inference) in schizophrenia.

Impaired perceptual inference has been suggested to be at the core of positive symptoms in schizophrenia. Apparent motion (AM) is a visual illusion in which perceptual inference gives rise to the experience of a single object moving back and forth when two spatially separated objects are flashed in alternation. Here, we investigated the strength of AM perception in patients with paranoid schizophrenia. Patients were less susceptible to the illusion as indicated by a lower probability of motion perception at the individual's optimal presentation frequency for AM. In addition, the probability of AM perception was inversely related to delusional conviction in the patient group. These results suggest that schizophrenia may be associated with a reduced susceptibility to visual phenomena that commonly rely on perceptual inference.

Abstract. The framework of predictive coding offers a parsimonious explanation for many perceptual phenomena. According to this framework, perception of the outer world is created by the comparison of incoming sensory information with an internal predictive model based on previous experience and context. However, it is unclear whether the predicted percept needs to enter conscious awareness for the internal predictive model to be effective. Here we used an apparent motion paradigm to show that while prediction and conscious awareness of a predicted percept may coincide, a dissociation can be observed. When sensory information provides reliable input for the internal predictive model, the predicted percept does not have to be consciously perceived for successful prediction. However, when sensory input is ambiguous, conscious awareness helps the prediction to take effect.

Background/PurposeThere is evidence for low endogenous antioxidant levels and oxidative imbalance in patients with schizophrenia. A previous open-label study with α-lipoic acid (ALA), a potent antioxidant, improved patients' negative and cognitive symptoms and markers of lipid peroxidation. Here we report the results of a randomized double-blind, placebo-controlled study to verify the response of patients with schizophrenia to adjunctive treatment with ALA (100 mg/d) in a 4-month follow-up.MethodsWe conducted a 16-week, double-blind, placebo-controlled study of ALA at 100 mg/d dosages. We compared negative and positive symptoms, cognitive function, extrapyramidal symptoms, body mass index, and oxidative/inflammatory parameters between placebo and control groups.ResultsWe found no significant improvement in body mass index, cognition, psychopathology, antipsychotic adverse effects, or oxidative stress and inflammation in the experimental group compared with placebo. The whole group of patients improved in several measures, indicating a strong placebo effect in this population. A surprising finding was a significant decrease in red blood cells, white blood cells, and platelets in the group treated with ALA.ConclusionsThe decrease in red blood cells, white blood cells, and platelet counts requires further investigation and attention when prescribing ALA for patients with schizophrenia.

If larger, double-blind, placebo-controlled studies confirm these preliminary findings, ALA could prove useful as adjunctive therapy for schizophrenia.

Psychotic features, defined as delusions or hallucinations, commonly occur in bipolar disorder (BP) and may be indicative of a more homogeneous form of the illness, with possible etiologic ties to schizophrenia. Several studies have shown that psychotic features aggregate in bipolar families, and increased interest in the molecular genetics of psychotic BP is emerging. Although preliminary, linkage studies of psychotic BP show replicated evidence for suggestive genome-wide linkage to chromosomes 8p and 13q, which have been implicated in prior linkage studies of schizophrenia and BP. Association studies of psychotic BP and subtypes such as mood-incongruent psychotic BP have uncovered modest positive results for several candidate schizophrenia susceptibility genes, including dysbindin, DAOA/G30, Disrupted-in-Schizophrenia-1, and neuregulin 1. These tentative results are consistent with the hypothesis that the subphenotype of psychotic BP may represent a clinical manifestation of "overlap" genes between schizophrenia and mood disorder syndromes.

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