Neuronal correlates of appetite regulation in patients with schizophrenia: is there a basis for future appetite dysfunction?

BACKGROUND: Given the undesired metabolic side effects of atypical antipsychotic medication it is important to understand the neuronal basis related to processing of appetite regulation in patients affected by schizophrenia. METHODS: Here we used functional magnetic resonance imaging (fMRI) to assess brain activity in response to food cues and neutral stimuli in twenty patients with schizophrenia and eleven healthy individuals. In addition to clinical and dietary habits assessments, we collected, in patients, measurements of fasting glucose, ghrelin, leptin, insulin, prolactin and lipids blood concentration and we correlated the cerebral activity with clinical and metabolic measures. RESULTS: Both groups engaged a common neuronal network while processing food cues, which included the left insula, primary sensorimotor areas, and inferior temporal and parietal cortices. Cerebral responses to appetitive stimuli in thalamus, parahippocampus and middle frontal gyri were specific only to schizophrenic patients, with parahippocampal activity related to hunger state and increasing linearly over time. Antipsychotic medication dosage correlated positively with a cognitive measure reflecting food cravings, whereas the severity of the disease correlated negatively with a cognitive measure indicating dietary restraint in eating habits. These cognitive variables correlated, in turn, with parahippocampal and thalamic neuronal activities, respectively. CONCLUSIONS: We identified a specific neural substrate underlying cognitive processing of appetitive stimuli in schizophrenia, which may contribute to appetite dysfunction via perturbations in processing of homeostatic signals in relation to external stimuli. Our results also suggest that both antipsychotic medication and the disease severity per se could amplify these effects, via different mechanisms and neuronal networks.

[Effects of listening to previously hallucinated words by schizophrenia patients in remission: a functional magnetic resonance imaging study of six cases]. / Effet de l'écoute de mots déjà hallucinés chez des sujets schizophrènes en rémission: étude de six cas par la résonance magnétique nucléaire fonctionnelle.

BACKGROUND: Despite immense importance of auditory verbal hallucinations (AVHs) in the phenomenology of schizophrenia, the neurocognitive and neurophysiological bases of AVHs remain obscure. On the neurocognitive level, it has been proposed that AVHs arise from the disordered monitoring manifested by patients' inability to recognize their inner speech as being their own. On the neurophysiological level, the AVHs have been attributed to the aberrant activity in the primary auditory cortex (Heschl's gyrus). Although interesting, these models cannot account for the very specific and restricted content of AVHs in individual patients. The specific content of AVHs persists across different psychotic episodes even after extended periods of remission. Furthermore, the AVHs are usually triggered by emotionally charged and stressful situations. DESIGN: We hypothesized that even during absence of AVHs, when patients are in remission, the verbal content remains present in the latent, pre-clinical form. In order to elucidate potential cerebral substrates of the dormant AVHs content, we employed functional magnetic resonance imaging (fMRI) in 6 schizophrenia patients in total remission of AVHs for at least 12 months, during listening to the words hallucinated by them in the past. Specifically, we created the list of previously hallucinated words for each patient and matched the words in terms of length, structure, emotional valence, semantic category and frequency of usage with the non-hallucinated words. Moreover, each patient was paired demographically with the control participant who was presented with the same words. We predicted that exposure to the hallucinated versus non-hallucinated words would result in increased activation in cerebral areas associated with cognitive and emotional content of previously experienced AVHs in patients, whereas the same comparison will not produce any significant changes in blood oxygen level-dependent (BOLD) signal in control participants. In addition, based on existing neuroimaging data obtained during experience of AVHs, we hypothesized that previously hallucinated words may elicit greater activation in the primary auditory cortex than the non-hallucinated words in patients. Each pair of participants was analyzed separately. RESULTS: The most consistent finding in patients, absent in all control participants, was significant activation in the orbitofrontal and medial prefrontal cortex (PFC) during listening to previously hallucinated versus non-hallucinated words. The orbitofrontal and medial PFC are both part of corticolimbic system and play an important role in cognitive control of emotion processing. DISCUSSION: Thus, present results imply that previously hallucinated words, even in remission, are associated with inappropriate emotional response on neurophysiological level in schizophrenia patients. The relative hyperactivation of orbitofrontal and medial PFC in patients may stem from and/or may contribute to anomalous neural plasticity and disordered connectivity in the corticolimbic circuitry. This in turn could lead to attribution of excessive emotional salience to normally neutral stimuli and over time via process of sensitization could result in hallucinations. Potential normalization of this dysfunction could reduce patients' susceptibility to experience AVHs in stressful situations. In addition to observed hyperactivations in the PFC, some schizophrenia patients exhibited anomalous BOLD signal in other regions of the corticolimbic system such as anterior cingulate gyrus and parahippocampal gyrus. These additional anomalies could be related to greater affective sensitivity to the hallucinated versus non-hallucinated words in some patients. CONCLUSION: Finally, in contrast to our initial hypothesis we did not observe any significant differences between processing of the hallucinated versus non-hallucinated words in the primary auditory cortex. In retrospect, this result is not surprising because patients did not experience internally generated AVHs while in the scanner, but instead were exposed exclusively to externally generated stimuli.

[Psychopathology and neurobiological bases of auditory hallucinations in schizophrenia.]. / Psychopathologie et bases neurobiologiques des hallucinations auditives dans la schizophrénie.

Cognitive therapies of delusions and hallucinations are increasingly common and offer a complementary or interesting alternative to neuroleptic medication. But then again must these therapeutic approach relie on an explanatory neuropsychological basis. According to many observers, the study of the cardinal symptoms of schizophrenia is the " royal path " leading to the elucidation of this disabling and chronic illness affecting around 0,5% to 1% of the population. In this perspective, auditory hallucinations are one of the major symptoms of schizophrenia found in 50% to 80% of cases. Recently, experimental data drawn from cognitive neuropsychology and functional magnetic resonance imaging studies have allowed the elaboration of many models regarding this symptomatic manifestation. This article proposes a literature review on the subject of psychopathology and neurobiological bases of auditory hallucinations in schizophrenia and aims at proposing some leads that could contribute to a better undertanding of this phenomenon.