Reduced magnetic mismatch negativity: a shared deficit in psychosis and related risk.

BACKGROUND: Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR). METHODS: Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC). RESULTS: The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP. CONCLUSIONS: Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.

Similarities and differences between multivariate patterns of cognitive and socio-cognitive deficits in schizophrenia, bipolar disorder and related risk.

Cognition and social cognition anomalies in patients with bipolar disorder (BD) and schizophrenia (SCZ) have been largely documented, but the degree of overlap between the two disorders remains unclear in this regard. We used machine learning to generate and combine two classifiers based on cognitive and socio-cognitive variables, thus delivering unimodal and multimodal signatures aimed at discriminating BD and SCZ from two independent groups of Healthy Controls (HC1 and HC2 respectively). Multimodal signatures discriminated well between patients and controls in both the HC1-BD and HC2-SCZ cohorts. Although specific disease-related deficits were characterized, the HC1 vs. BD signature successfully discriminated HC2 from SCZ, and vice-versa. Such combined signatures allowed to identify also individuals at First Episode of Psychosis (FEP), but not subjects at Clinical High Risk (CHR), which were classified neither as patients nor as HC. These findings suggest that both trans-diagnostic and disease-specific cognitive and socio-cognitive deficits characterize SCZ and BD. Anomalous patterns in these domains are also relevant to early stages of disease and offer novel insights for personalized rehabilitative programs.

Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the AEsop first-onset psychosis study.

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22%, p< 0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p=0.028), 17% larger in patients receiving atypicals (p=0.01), and 30% larger in patients receiving typicals (p<0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (+11%, p=0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n=40, p<0.001), 19% larger in depressed patients (n=13, p=0.022), 16% larger in bipolar patients (n=16, p=0.037), and 12% larger in those with other psychoses (n=9, p=0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.

Working memory deficits and levels of N-acetylaspartate in patients with schizophreniform disorder.

OBJECTIVE: The authors used proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to assess potential reductions of N-acetylaspartate (a marker of neuronal integrity) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophreniform disorder. In addition, they assessed the relationship between N-acetylaspartate levels and working memory deficits. METHOD: Twenty-four patients with DSM-IV schizophreniform disorder and 24 healthy subjects were studied. Subjects underwent (1)H-MRSI and were given the N-back working memory test. RESULTS: The schizophreniform disorder patients had selective reductions of N-acetylaspartate ratios in the hippocampal area and the dorsolateral prefrontal cortex, and a positive correlation was seen between N-acetylaspartate ratios in the dorsolateral prefrontal cortex and performance during the 2-back working memory condition. CONCLUSIONS: Similar to findings reported in schizophrenia studies, N-acetylaspartate reductions in the hippocampal area and the dorsolateral prefrontal cortex were seen in patients with schizophreniform disorder. Moreover, the results support other evidence that neuronal pathology in the dorsolateral prefrontal cortex accounts for a proportion of working memory deficits already present at illness outset.

Hippocampal neurochemical pathology in patients at first episode of affective psychosis: a proton magnetic resonance spectroscopic imaging study.

While several studies have suggested a relationship between the hippocampus and psychosis in schizophrenia, fewer studies have specifically investigated the presence of psychosis in mood disorders from a neurobiological perspective. Moreover, a limitation of these earlier studies is that the majority of them were performed in chronic patients. The present proton magnetic resonance spectroscopic imaging (1H-MRSI) study assessed neuronal integrity (as assessed with N-acetylaspartate, NAA) in the hippocampus of patients with a first episode of mood disorders with psychotic symptoms. We studied 17 patients and 17 healthy subjects matched for age and sex. Subjects underwent 1H-MRSI, and measures of NAA, choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) in 11 brain regions were obtained, i.e. hippocampus (HIPPO), dorsolateral prefrontal cortex, superior temporal gyrus, inferior frontal gyrus, occipital cortex, anterior and posterior cingulate, centrum semiovale, prefrontal white matter, thalamus and putamen. NAA/CRE ratios in HIPPO of patients were significantly lower than in controls. Sporadic and non-hypothesis-driven results were found in occipital cortex and prefrontal white matter as a main effect of diagnosis, and in superior temporal gyrus as a hemisphere by diagnosis interaction. These results would not survive a Bonferroni correction for the number of ROIs. No correlations were found with the available demographic and clinical data. Therefore, hippocampal neuronal abnormalities are present at the onset of mood disorders with psychotic symptoms. These data suggest that neuronal abnormalities in HIPPO may be associated with psychosis in mood disorders. Since these data were obtained in patients at first episode, they cannot be explained by chronicity of illness or pharmacological treatment.

Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the Æsop First-Onset Psychosis Study

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naý¨ve), 26 werereceiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22percent , p=0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15 percent larger in antipsychotic-free patients (p¼0.028), 17 percent larger in patients receiving atypicals (p¼0.01), and 30 percent larger in patients receiving typicals (p=0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (11 percent, p¼0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24 percent larger in patients with schizophrenia/schizophreniform disorder (n¼40, p=0.001), 19 percent larger in depressed patients (n¼13, p¼0.022), 16 percent larger in bipolar patients (n¼16, p¼0.037), and 12 percent larger in those with other psychoses (n¼9, p¼0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presenceof antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effecton pituitary volume, likely to be related to activation of prolactin-secreting cells...