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Objective: The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium., Methods: Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD, and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected., Results: Patients with SZ showed a smaller global cerebellar gray matter volume compared to controls, with most of the changes located to the cognitive part of the cerebellum (Crus II and lobule VIIb). This decrease was present in the subgroup of patients with recent-onset SZ. We did not find any alterations in the cerebellum in patients with BD. However, patients medicated with lithium had a larger size of the anterior cerebellum, compared to patients not treated with lithium., Conclusion: Our multicenter study supports a distinct pattern of cerebellar alterations in SZ and BD., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: There is growing evidence that cerebellum plays a crucial role in cognition and emotional regulation. Cerebellum is likely to be involved in the physiopathology of both bipolar disorder and schizophrenia. The objective of our study was to compare cerebellar size between patients with bipolar disorder, patients with schizophrenia, and healthy controls in a multicenter sample. In addition, we studied the influence of psychotic features on cerebellar size in patients with bipolar disorder., Method: One hundred and fifteen patients with bipolar I disorder, 32 patients with schizophrenia, and 52 healthy controls underwent 3 Tesla MRI. Automated segmentation of cerebellum was performed using FreeSurfer software. Volumes of cerebellar cortex and white matter were extracted. Analyses of covariance were conducted, and age, sex, and intracranial volume were considered as covariates., Results: Bilateral cerebellar cortical volumes were smaller in patients with schizophrenia compared with patients with bipolar I disorder and healthy controls. We found no significant difference of cerebellar volume between bipolar patients with and without psychotic features. No change was evidenced in white matter., Conclusion: Our results suggest that reduction in cerebellar cortical volume is specific to schizophrenia. Cerebellar dysfunction in bipolar disorder, if present, appears to be more subtle than a reduction in cerebellar volume., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Superior temporal cortices include brain regions dedicated to auditory processing and several lines of evidence suggest structural and functional abnormalities in both schizophrenia and bipolar disorder within this brain region. However, possible glutamatergic dysfunction within this region has not been investigated in adult patients., Methods: Thirty patients with schizophrenia (38.67±12.46years of age), 28 euthymic patients with bipolar I disorder (35.32±9.12years of age), and 30 age-, gender- and education-matched healthy controls were enrolled. Proton magnetic resonance spectroscopy data were acquired using a 3.0T Siemens MAGNETOM TIM Trio MR system and single voxel Point REsolved Spectroscopy Sequence (PRESS) in order to quantify brain metabolites within the left and right Heschl's gyrus and planum temporale of superior temporal cortices., Results: There were significant abnormalities in glutamate (Glu) (F(2,78)=8.52, p<0.0001), N-acetyl aspartate (tNAA) (F(2,81)=5.73, p=0.005), creatine (tCr) (F(2,83)=5.91, p=0.004) and inositol (Ins) (F(2,82)=8.49, p<0.0001) concentrations in the left superior temporal cortex. In general, metabolite levels were lower for bipolar disorder patients when compared to healthy participants. Moreover, patients with bipolar disorder exhibited significantly lower tCr and Ins concentrations when compared to schizophrenia patients. In addition, we have found significant correlations between the superior temporal cortex metabolites and clinical measures., Conclusion: As the left auditory cortices are associated with language and speech, left hemisphere specific abnormalities may have clinical significance. Our findings are suggestive of shared glutamatergic abnormalities in schizophrenia and bipolar disorder., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Abnormalities in social functioning are a significant feature of schizophrenia. One critical aspect of these abnormalities is the difficulty these individuals have with the recognition of facial emotions, particularly negative expressions such as fear. The present work focuses on fear perception and its relationship to the paranoid symptoms of schizophrenia, specifically, how underlying limbic system structures (i.e. the amygdala) react when probed with dynamic fearful facial expressions. Seven paranoid and eight non-paranoid subjects (all males) with a diagnosis of schizophrenia took part in functional magnetic resonance imaging study (1.5T) examining neural responses to emerging fearful expressions contrasted with dissipating fearful expressions. Subjects viewed emerging and dissipating expressions while completing a gender discrimination task. Their brain activation was compared to that of 10 healthy male subjects. Increased hippocampal activation was seen in the non-paranoid group, while abnormalities in the bilateral amygdalae were observed only in the paranoid individuals. These patterns may represent trait-related hippocampal dysfunction, coupled with state (specifically paranoia) related amygdala abnormalities. The findings are discussed in light of models of paranoia in schizophrenia.

Background: Cognitive theories of persecutory delusions in schizophrenia include increased attention to threat and reduced re-appraisal of information during decision-making., Methods: We employed visual scan path measurements, an 'on-line' marker of attention, in schizophrenic patients with persecutory delusions (N = 19), negative symptom- and medication-matched patients with non-persecutory delusions (N = 8), and normal controls (N = 18). Stimuli comprised black-and-white photographs of social scenes rated as depicting either neutral, ambiguous or overtly threatening activity. Foreground areas containing salient information with regard to the overall scene were rated independently as either threatening or non-threatening in both the overtly threatening and ambiguous scenes; all foreground areas were rated as non-threatening in the neutral scene., Results: For the ambiguous scene only, schizophrenics with persecutory delusions directed gaze to less threatening areas, and, for all three scenes, demonstrated reduced re-appraisal of information compared with both control groups. All subjects showed similar viewing strategies for the overtly threatening and neutral scenes., Conclusions: These findings suggest abnormal information gathering and evaluation in schizophrenics, specifically related to the presence of persecutory delusions. In particular, the results point to biased processing of contextual information in an ambiguous setting in these patients, and perhaps perception of threat in inappropriate places.

Several studies have demonstrated impaired facial expression recognition in schizophrenia. Few have examined the neural basis for this; none have compared the neural correlates of facial expression perception in different schizophrenic patient subgroups. We compared neural responses to facial expressions in 10 right-handed schizophrenic patients (five paranoid and five non-paranoid) and five normal volunteers using functional Magnetic Resonance Imaging (fMRI). In three 5-min experiments, subjects viewed alternating 30-s blocks of black-and-white facial expressions of either fear, anger or disgust contrasted with expressions of mild happiness. After scanning, subjects categorised each expression. All patients were less accurate in identifying expressions, and showed less activation to these stimuli than normals. Non-paranoids performed poorly in the identification task and failed to activate neural regions that are normally linked with perception of these stimuli. They categorised disgust as either anger or fear more frequently than paranoids, and demonstrated in response to disgust expressions activation in the amygdala, a region associated with perception of fearful faces. Paranoids were more accurate in recognising expressions, and demonstrated greater activation than non-paranoids to most stimuli. We provide the first evidence for a distinction between two schizophrenic patient subgroups on the basis of recognition of and neural response to different negative facial expressions.

The role of the visual scan path as a psychophysiological marker of visual attention has been highlighted previously (Phillips and David, 1994). We investigated information processing in schizophrenic patients with severe delusions and again when the delusions were subsiding using visual scan path measurements. We aimed to demonstrate a specific deficit in processing human faces in deluded subjects by relating this to abnormal viewing strategies. Scan paths were measured in six deluded and five non-deluded schizophrenics (matched for medication and negative symptoms), and nine age-matched normal controls. Deluded subjects had abnormal scan paths in a recognition task, fixating non-feature areas significantly more than controls, but were equally accurate. Re-testing after improvement in delusional conviction revealed fewer group differences. The results suggest state-dependent abnormal information processing in schizophrenics when deluded, with reliance on less-salient visual information for decision-making.

Objective: Hypotheses to explain delusion formation include distorted perceptual processing of meaningful stimuli (e.g. faces), abnormal reasoning, or a combination of both. The study investigated these hypotheses using standardized neuropsychological tests., Design: A three-patient case-study, compared with a small group (n = 8) of age-matched normal control subjects., Setting: Hospital in- and outpatients. Age-matched normal controls were from local residential homes., Patients: Three subjects with late-onset schizophrenia, two currently deluded and one in remission. Both deluded subjects had persecutory beliefs. One had a delusion of misidentification., Interventions: All subjects were administered standardized neuropsychological tests of facial processing and tests of verbal reasoning., Main Outcome Measures: The test scores of the three patients were compared with published normal values and the age-matched control data., Results: The tests demonstrated impaired matching of unfamiliar faces in deluded subjects, particularly in the subject with delusional misidentification. Increasing the emotional content of logical reasoning problems had a significant effect on the deluded subjects' reasoning but not that of the normal controls., Conclusion: The findings suggest impaired visual processing plus abnormal reasoning in deluded subjects. However, these impairments are relatively subtle given the severity of psychiatric disorder in the patients studied.

We studied the relationship between corpus callosum area and both inter-hemispheric facilitation and interference in schizophrenics and controls. Mid-sagittal sections through the corpus callosum were measured using structural magnetic resonance imaging on 42 patients and 43 normal controls, along with symptom profiles. In a sub-sample, a modified version of the Stroop Test was also performed (27 patients and 29 controls) to assess inter-hemispheric facilitation and interference of colour naming. In the larger sample (total subjects, n = 85), there were no significant differences between patients and controls in CC area but a trend towards smaller values in patients in all but the posterior segment. In the sub-sample, bilateral facilitation was greater, and interference, less in schizophrenics compared with controls. There was a positive correlation between facilitation and posterior CC area, parallelled by a negative correlation between interference and posterior CC area, in both patients and controls, which only reached statistical significance when both groups were combined. These findings suggest that the link, between CC size and neuropsychological processes involving inter-hemispheric transfer of information, is common to both schizophrenics and normal controls. There were significant negative correlations between anterior CC area and psychomotor poverty (avolition, anhedonia and affective flattening), and a suggestion that the negative correlation between age and CC size in controls was not present in patients.

A divided visual field presentation of the Stroop colour-word test was used to study interhemispheric (transcallosal) function in schizophrenic and normal subjects. The modified test used a colour strip paired with either an incongruent, neutral or congruent colour word. Interference and facilitation were defined as the difference between the mean reaction times for incongruent stimuli and neutral stimuli and that between neutral stimuli and congruent stimuli, respectively. The stimuli were presented tachistoscopically with the two components either separated across the midline centrally, up or down from the midpoint (bilateral presentation), or presented to a single visual half-field (unilateral presentation). The inclusion of the 'up' and 'down' bilateral conditions controlled for the reaction time advantage for central compared with unilateral stimulus presentations noted in an earlier study (David, 1993a). The difference in reaction time to an incongruent compared with a congruent colour-word pairing, the Combined Stroop Effect (CSE), was not affected significantly by stimulus presentation position (bilateral vs. unilateral) in either the control or schizophrenic group, unlike in the earlier study of David. For controls, interference was significantly greater than facilitation for both bilaterally- and unilaterally-presented stimuli. Schizophrenics had a significantly smaller interference effect for bilaterally-presented stimuli, indicating reduced interhemispheric interference in this group. For the control group, there was no significant difference between right and left CSEs, interference being significantly greater than facilitation on both visual half-field presentations. For schizophrenics, the CSE for left-presented stimuli was significantly greater than that for right-presented stimuli. In addition, left-field facilitation was significantly greater than right-field. Reduced Stroop facilitation with right-field presentations in schizophrenic subjects may reflect increased vulnerability of colour-naming by word-reading in the left hemisphere-evidence for the non-unitary nature of attentional processes and disintegration of these in schizophrenia.

The human face is of great importance as a stimulus in view of the detailed information it contains--information vital to understand in order to survive in the complex social world. There are different aspects to facial processing, including: affect analysis, recognition of individuality and recognition of familiarity, all of which have been incorporated into the cognitive model of Bruce and Young (1986). The cognitive neuropsychiatric approach has recently been employed in the study of facial processing in schizophrenia. It has become apparent that schizophrenic subjects are impaired in facial processing tasks at all levels, and this may well be related to the misinterpretation of social interactions commonly found in such subjects. This approach has also led to a greater understanding of delusional misidentification, with particular syndromes explained in terms of processing deficits at different levels of the cognitive model above. At an anatomical level, the role of the right hemisphere in facial perception is well-known, with there being some evidence of right hemisphere hypofunction in subjects with schizophrenia and also in delusional misidentification. The review therefore emphasizes the importance of the neuropsychiatric approach for further investigation of facial processing and understanding of symptomatology in schizophrenia and related psychoses.

Background: This paper highlights the role of the visual scan path as a physiological marker of information processing, while investigating positive symptomatology in schizophrenia., Method: The current literature is reviewed using computer search facilities (Medline)., Results: Schizophrenics either scan or stare extensively, the latter related to negative symptoms. Schizophrenics particularly scan when viewing human faces., Conclusions: Scan paths in schizophrenics are important when viewing meaningful stimuli such as human faces, because of the relationship between abnormal perception of stimuli and symptomatology in these subjects.

Background.The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown.Method.We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses.Results.The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive–compulsive disorder symptoms.Conclusions.Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state. [ABSTRACT FROM AUTHOR]