Lisette van der Meer

Insight in Schizophrenia: Involvement of Self-Reflection Networks?

Background: Impaired insight is a common feature in psychosis and an important predictor of variables such as functional outcome, prognosis, and treatment adherence. A cognitive process that may underlie insight in psychosis is self-reflection, or the conscious evaluation of one’s traits and characteristics. The current study aims to investigate the neural correlates of self-reflective processing and its relationship with insight in schizophrenia. Methods: Forty-seven schizophrenia patients and 21 healthy controls performed a self-reflection task in a functional magnetic resonance imaging (fMRI) scanner. The tasks comprised a self-reflection, close other-reflection, and a semantic (baseline) condition. Insight scores were obtained with the Schedule of Assessment of Insight Expanded. In addition, cognitive insight scores were obtained (Beck Cognitive Insight Scale [BCIS]). Results: Schizophrenia patients demonstrated less activation in the posterior cingulate cortex in the self- and other-reflection conditions and less activation in the precuneus in the other-reflection condition compared with healthy controls. Better insight was associated with greater response in the inferior frontal gyrus, anterior insula, and inferior parietal lobule during self-reflection. In addition, better cognitive insight was associated with higher activation in ventromedial prefrontal cortex during self-reflection. Conclusion: In the current study, evidence for a relationship between self-reflection and insight in patients with schizophrenia was found in brain areas related to self-reflection, self/other distinction and source attribution. The findings support the rationale for a treatment that is currently under evaluation, which attempts to increase insight by enhancing self-reflection.

Emotion regulation strategies in Patients with schizophrenia

Schizophrenia patients might experience difficulties in applying two widely used emotion regulation strategies, reappraisal and suppression. We investigated the relationships among emotion regulation strategies, alexithymia (i.e. inability to identify and verbalize feelings) and the role of pre-morbid IQ on alexithymia in schizophrenia. Participants comprised 31 schizophrenia patients and 44 healthy subjects who were tested on measures of emotion regulation strategies (ERQ), alexithymia (BVAQ) and pre-morbid IQ (NART). Patients reported significantly more use of suppression strategies and tended to use reappraisal strategies less frequently. Patients differed significantly on the cognitive-emotional component of alexithymia. This difference remained significant even with pre-morbid IQ as a covariate, but disappeared with depression as a covariate. Schizophrenia patients have specific difficulties identifying their feelings. These difficulties were related to symptoms of depression. Interventions specifically targeted at affect regulation and recognition of emotional state could promote emotional well-being in schizophrenia patients.

Inhibit yourself and understand the other: neural basis of distinct processes underlying Theory of Mind.

Taking the perspective of somebody else (Theory of Mind; ToM) is an essential human ability depending on a large cerebral network comprising prefrontal and temporo-parietal regions. Recently, ToM was suggested to consist of two processes: (1) self-perspective inhibition and (2) belief reasoning. Moreover, it has been hypothesized that self-perspective inhibition may build upon basic motor response inhibition. This study tested both hypotheses for the first time using functional Magnetic Resonance Imaging (fMRI), through administering both a ToM and a stop-signal paradigm in the same subjects. Both self-perspective and motor response inhibition yielded bilateral inferior frontal gyrus (IFG) activation, suggesting a common inhibitory mechanism, while belief reasoning was mediated by the superior temporal gyrus (STG) and temporo-parietal junction (TPJ). Thus, we provide neurobiological evidence for a subdivision of ToM into self-perspective inhibition and belief reasoning. Furthermore, evidence for partially shared neural mechanisms for inhibition in complex social situations and basic motor response inhibition was found.

Insight in Psychosis: Relationship With Neurocognition, Social Cognition and Clinical Symptoms Depends on Phase of Illness

Reduced insight has been reported in a majority of patients with a psychotic disorder. Most studies have focused on associations with neurocognition, neglecting relations with social cognition. Two hundred seventy patients with nonaffective psychosis participated in this study, which was part of the GROUP (Genetic Risk and OUtcome of Psychosis)-project. Linear regression analyses were performed to investigate the predictive value of composite measures of neurocognition, social cognition, and clinical symptoms. The moderating effect of phase of illness was also investigated. Insight was measured with a composite measure, based on the insight item on the Positive And Negative Syndrome Scale (PANSS) and the Birchwood Insight Scale (BIS). Insight on the BIS and the PANSS correlated significantly (r = .406). All independent variables correlated with the insight composite measure. The additional effect of social cognition and clinical symptoms were both significant. Phase of illness was a moderating variable: In patients with recent-onset psychosis (ROP), none of the independent variables explained variance. In patients with multiple episode or chronic psychosis, both social cognition and clinical symptoms had additional effects and explained insight, along with neurocognition, together explaining 20% of the variance. These findings indicate that multiple factors are associated with insight in psychosis. Specifically, associations of insight with social cognitive and clinical symptom measures were observed, over and above a contribution of neurocognition. This supports theories that imply a role for deficient emotion recognition and mentalizing in reduced insight. Further studies need to investigate insight in ROP into more detail.

Not on speaking terms: hallucinations and structural network disconnectivity in schizophrenia

Auditory verbal hallucinations (AVH) in schizophrenia have previously been associated with functional deficiencies in language networks, specifically with functional disconnectivity in fronto-temporal connections in the left hemisphere and in interhemispheric connections between frontal regions. Here, we investigate whether AVH are accompanied by white matter abnormalities in tracts connecting the frontal, parietal and temporal lobes, also engaged during language tasks. We combined diffusion tensor imaging with tract-based spatial statistics and found white matter abnormalities in patients with schizophrenia as compared with healthy controls. The patients showed reduced fractional anisotropy bilaterally: in the anterior thalamic radiation (ATR), body of the corpus callosum (forceps minor), cingulum, temporal part of the superior longitudinal fasciculus (SLF) and a small area in the inferior fronto-occipital fasciculus (IFOF); and in the right hemisphere: in the visual cortex, forceps major, body of the corpus callosum (posterior parts) and inferior parietal cortex. Compared to patients without current hallucinations, patients with hallucinations revealed decreased fractional anisotropy in the left IFOF, uncinate fasciculus, arcuate fasciculus with SLF, corpus callosum (posterior parts–forceps major), cingulate, corticospinal tract and ATR. The severity of hallucinations correlated negatively with white matter integrity in tracts connecting the left frontal lobe with temporal regions (uncinate fasciculus, IFOF, cingulum, arcuate fasciculus anterior and long part and superior long fasciculus frontal part) and in interhemispheric connections (anterior corona radiata). These findings support the hypothesis that hallucinations in schizophrenia are accompanied by a complex pattern of white matter alterations that negatively affect the language, emotion and attention/perception networks.

Reduced Connectivity in the Self-Processing Network of Schizophrenia Patients with Poor Insight

Lack of insight (unawareness of illness) is a common and clinically relevant feature of schizophrenia. Reduced levels of self-referential processing have been proposed as a mechanism underlying poor insight. The default mode network (DMN) has been implicated as a key node in the circuit for self-referential processing. We hypothesized that during resting state the DMN network would show decreased connectivity in schizophrenia patients with poor insight compared to patients with good insight. Patients with schizophrenia were recruited from mental health care centers in the north of the Netherlands and categorized in groups having good insight (n = 25) or poor insight (n = 19). All subjects underwent a resting state fMRI scan. A healthy control group (n = 30) was used as a reference. Functional connectivity of the anterior and posterior part of the DMN, identified using Independent Component Analysis, was compared between groups. Patients with poor insight showed lower connectivity of the ACC within the anterior DMN component and precuneus within the posterior DMN component compared to patients with good insight. Connectivity between the anterior and posterior part of the DMN was lower in patients than controls, and qualitatively different between the good and poor insight patient groups. As predicted, subjects with poor insight in psychosis showed decreased connectivity in DMN regions implicated in self-referential processing, although this concerned only part of the network. This finding is compatible with theories implying a role of reduced self-referential processing as a mechanism contributing to poor insight.

Voxel-based gray and white matter morphometry correlates of hallucinations in schizophrenia: The superior temporal gyrus does not stand alone

Introduction Auditory verbal hallucinations (AVH) in schizophrenia (SZ) have been proposed to result from abnormal local, interregional and interhemispheric integration of brain signals in regions involved in language production and perception. This abnormal functional integration may find its base in morphological abnormalities. Structurally, AVHs have been frequently linked to abnormal morphology of the superior temporal gyrus (STG), but only a few studies investigated the relation of hallucination presence with both whole-brain gray matter (GM) and white matter (WM) morphometry. Methods Using a unified voxel-based morphometry–DARTEL approach, we investigated correlates of AVH presence in 51 schizophrenia patients (20 non-hallucinating [SZ −], 31 hallucinating [SZ +]), and included 51 age and sex matched healthy participants. Effects are reported at p < .05 FWE corrected. Results Patients showed lower GM volume of the left STG than controls, irrespective of AVH presence. In addition, SZ + showed lower GM volume of the left inferior frontal and right parahippocampal gyrus, and higher WM volume of the left postcentral and superior parietal lobule than controls. Finally, volume of the putamen was lower in SZ + compared to SZ −. No effects on corpus callosum morphometry were observed. Delusion severity, general positive and negative symptomatology illness duration, and medication status could not explain the results. Discussion Results suggest that STG GM abnormalities underlie the general susceptibility to experience psychotic symptoms and that additional abnormalities in a network of medial temporal, ventrolateral, putaminal, and parietal regions related to verbal memory and speech production may specifically increase the likelihood of experiencing AVH. Future studies should clarify the meaning of morphometry abnormalities for functional interregional communication.

Neural correlates of emotion regulation in patients with schizophrenia and non-affected siblings.

Background Patients with schizophrenia often experience problems regulating their emotions. Non-affected relatives show similar difficulties, although to a lesser extent, and the neural basis of such difficulties remains to be elucidated. In the current paper we investigated whether schizophrenia patients, non-affected siblings and healthy controls (HC) exhibit differences in brain activation during emotion regulation. Methods All subjects (n = 20 per group) performed an emotion regulation task while they were in an fMRI scanner. The task contained two experimental conditions for the down-regulation of emotions (reappraise and suppress), in which IAPS pictures were used to generate a negative affect. We also assessed whether the groups differed in emotion regulation strategies used in daily life by means of the emotion regulation questionnaire (ERQ). Results Though the overall negative affect was higher for patients as well as for siblings compared to HC for all conditions, all groups reported decreased negative affect after both regulation conditions. Nonetheless, neuroimaging results showed hypoactivation relative to HC in VLPFC, insula, middle temporal gyrus, caudate and thalamus for patients when reappraising negative pictures. In siblings, the same pattern was evident as in patients, but only in cortical areas. Conclusions Given that all groups performed similarly on the emotion regulation task, but differed in overall negative affect ratings and brain activation, our findings suggest reduced levels of emotion regulation processing in neural circuits in patients with schizophrenia. Notably, this also holds for siblings, albeit to a lesser extent, indicating that it may be part and parcel of a vulnerability for psychosis.

Insight in bipolar disorder: associations with cognitive and emotional processing and illness characteristics

van der Werf‐Eldering MJ, van der Meer L, Burger H, Holthausen EAE, Nolen WA, Aleman A. Insight in bipolar disorder: associations with cognitive and emotional processing and illness characteristics.
Bipolar Disord 2011: 13: 343–354.

Insight and Psychosis: Functional and Anatomical Brain Connectivity and Self-Reflection in Schizophrenia

Impaired insight into illness, associated with worse treatment outcome, is common in schizophrenia. Insight has been related to the self‐reflective processing, centred on the medial frontal cortex. We hypothesized that anatomical and functional routes to and from the ventromedial prefrontal cortex (vmPFC) would differ in patients according to their degree of impaired insight. Forty‐five schizophrenia patients and 19 healthy subjects performed a self‐reflection task during fMRI, and underwent diffusion tensor imaging. Using dynamic causal modelling we observed increased effective connectivity from the posterior cingulate cortex (PCC), inferior parietal lobule (IPL), and dorsal mPFC (dmPFC) towards the vmPFC with poorer insight and decrease from vmPFC to the IPL. Stronger connectivity from the PCC to vmPFC during judgment of traits related to self was associated with poorer insight. We found small‐scale significant changes in white matter integrity associated with clinical insight. Self‐reflection may be influenced by synaptic changes that lead to the observed alterations in functional connectivity accompanied by the small‐scale but measurable alterations in anatomical connections. Our findings may point to a neural compensatory response to an impairment of connectivity between self‐processing regions. Similarly, the observed hyper‐connectivity might be a primary deficit linked to inefficiency in the component cognitive processes that lead to impaired insight. We suggest that the stronger cognitive demands placed on patients with poor insight is reflected in increased effective connectivity during the task in this study. Hum Brain Mapp 36:4859–4868, 2015.