Tae Young Lee

Cognitive functioning in obsessive-compulsive disorder: a meta-analysis

BACKGROUNDnSubstantial empirical evidence has indicated impairment in the cognitive functioning of patients with obsessive-compulsive disorder (OCD) despite inconsistencies. Although several confounding factors have been investigated to explain the conflicting results, the findings remain mixed. This study aimed to investigate cognitive dysfunction in patients with OCD using a meta-analytic approach.nnnMETHODnThe PubMed database was searched between 1980 and October 2012, and reference lists of review papers were examined. A total of 221 studies were identified, of which 88 studies met inclusion criteria. Neuropsychological performance and demographic and clinical variables were extracted from each study.nnnRESULTSnPatients with OCD were significantly impaired in tasks that measured visuospatial memory, executive function, verbal memory and verbal fluency, whereas auditory attention was preserved in these individuals. The largest effect size was found in the ability to recall complex visual stimuli. Overall effect estimates were in the small to medium ranges for executive function, verbal memory and verbal fluency. The effects of potentially confounding factors including educational level, symptom severity, medication status and co-morbid disorders were not significant.nnnCONCLUSIONSnPatients with OCD appear to have wide-ranging cognitive deficits, although their impairment is not so large in general. The different test forms and methods of testing may have influenced the performance of patients with OCD, indicating the need to select carefully the test forms and methods of testing used in future research. The effects of various confounding variables on cognitive functioning need to be investigated further and to be controlled before a definite conclusion can be made.

The crisis of minimal self-awareness in schizophrenia: a meta-analytic review.

Disturbances of the minimal self, characterized by abnormal sense of the body, body ownership and agency have been proposed as the phenomenological phenotype of schizophrenia. However, self-disturbances have not been extensively investigated, in part, due to the subjective nature of such processes, and the associated difficulty of studying these phenomena using empirical methodology. Of 115 potential studies on self-awareness in schizophrenia, a total of 25 studies met the inclusion criteria for the meta-analysis comprising 690 patients with schizophrenia and 979 healthy controls. We calculated Hedges g to obtain a better estimate for the standardized mean difference in small samples. We identified significant basic self-disturbance in schizophrenia, as compared with healthy controls (25 studies, effect size=0.51). Additional comparison of three sub-categories of the sense of body ownership (4 studies, effect size=0.91), the sense of agency (15 studies, effect size=0.49), and self-reported subjective experiences (6 studies, effect size=0.57) also confirmed group differences. The complete set of 25 studies, and the studies in the sub-categories showed the statistical homogeneity of the characteristics. After a correction for potential publication bias using the trim-and-fill method, the main findings for all studies combined remained significant. Overall, patients with schizophrenia showed deficits in the sense of the minimal self, driven by abnormal sense of body ownership and sense of agency. Interestingly, the disturbed sense of agency in schizophrenia suggests an exaggerated self-consciousness rather than a diminished sense of self. Further research that utilizes sophisticated study designs is needed to examine the nature of self-disturbances in schizophrenia.

The Effects of Pharmacological Treatment on Functional Brain Connectome in Obsessive-Compulsive Disorder

BACKGROUNDnPrevious neuroimaging studies of obsessive-compulsive disorder (OCD) have reported both baseline functional alterations and pharmacological changes in localized brain regions and connections; however, the effects of selective serotonin reuptake inhibitor (SSRI) treatment on the whole-brain functional network have not yet been elucidated.nnnMETHODSnTwenty-five drug-free OCD patients underwent resting-state functional magnetic resonance imaging. After 16-weeks, seventeen patients who received SSRI treatment were rescanned. Twenty-three matched healthy control subjects were examined at baseline for comparison, and 21 of them were rescanned after 16 weeks. Topological properties of brain networks (including small-world, efficiency, modularity, and connectivity degree) were analyzed cross-sectionally and longitudinally with graph-theory approach.nnnRESULTSnAt baseline, OCD patients relative to healthy control subjects showed decreased small-world efficiency (including local clustering coefficient, local efficiency, and small-worldness) and functional association between default-mode and frontoparietal modules as well as widespread altered connectivity degrees in many brain areas. We observed clinical improvement in OCD patients after 16 weeks of SSRI treatment, which was accompanied by significantly elevated small-world efficiency, modular organization, and connectivity degree. Improvement of obsessive-compulsive symptoms was significantly correlated with changes in connectivity degree in right ventral frontal cortex in OCD patients after treatment.nnnCONCLUSIONSnThis is first study to use graph-theory approach for investigating valuable biomarkers for the effects of SSRI on neuronal circuitries of OCD patients. Our findings suggest that OCD phenomenology might be the outcome of disrupted optimal balance in the brain networks and that reinstating this balance after SSRI treatment accompanies significant symptom improvement.

Social cognitive functioning in prodromal psychosis: A meta-analysis

BACKGROUNDnThere is substantial evidence regarding a social cognitive deficit in schizophrenia, and it has been suggested to be a trait-marker of this disorder. However, a domain-by-domain analysis of social cognitive deficits in individuals at clinical high risk (CHR) for psychosis has not been performed.nnnMETHODnElectronic databases were searched for studies regarding social cognitive performance in individuals at CHR. The included social cognitive domains, which were classified based on the Social Cognition Psychometric Evaluation (SCOPE) initiative of the National Institute of Mental Health (NIMH), were as follows: theory of mind (ToM), social perception (SP), attributional bias (AB), and emotion processing (EP).nnnRESULTSnTwenty studies that included 1229 individuals at CHR and 825 healthy controls met the inclusion criteria. The overall effect size for social cognition was medium (g=-0.477). The largest effect size was identified for AB (g=-0.708). A medium effect size was identified for EP (g=-0.446) and ToM (g=-0.425), and small effects were identified for SP (g=-0.383).nnnCONCLUSIONnThis is the first quantitative domain-by-domain social cognitive meta-analysis regarding CHR individuals. The present study indicated that individuals at CHR exhibited significant impairments in all domains of social cognition compared with healthy controls, with the largest effect size identified for AB. The identification of social cognitive domains that reflect an increased risk for impending psychosis and of predictors of the conversion to psychosis via a longitudinal follow-up study is required.

Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis

Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography counts representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F= 5.65,P< .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofrontal cortex was significantly reduced compared to both healthy controls (F= 11.86,P< .005) and CHR (F= 6.63,P< .05). Interestingly, CHR exhibited a similar pattern as FEP, albeit with slightly reduced magnitude. Compared to healthy controls, there was a significant decrease (F= 4.16,P< .05) in CHR thalamo-orbitofrontal connectivity. Also, the strength of the thalamo-orbitofrontal connectivity was correlated with the Global Assessment of Functioning score in CHR (r= .35,P< .05). This observed pattern of white matter connectivity disruptions in FEP and in CHR suggests that this pattern of disconnectivity not only highlights the involvement of thalamus but also might be useful as an early biomarker for psychosis.

Symptomatic and functional remission of subjects at clinical high risk for psychosis: A 2-year naturalistic observational study

BACKGROUNDnThe aim of this study was to assess the frequency and predictors of symptomatic and functional remission in individuals at clinical high risk (CHR) for psychosis at 1-2 years of follow-up.nnnMETHODSnHelp-seeking CHR individuals with symptomatic (Scale of Prodromal Symptoms (SOPS) positive scores <3) and functional (Global Assessment of Functioning (GAF) score >60) (CHR-R) remission at 12-24 months were compared to non-remitted individuals (CHR-NR) regarding baseline and treatment characteristics, symptom changes and predictors. Time to full remission was compared with that of symptomatic remission only.nnnRESULTSnOf 73 individuals, 29 (39.7%) achieved full remission; 44 (60.3%) did not. Compared to CHR-NR individuals, CHR-R individuals had lower baseline SOPS positive symptoms (p=0.017), antipsychotic use (p=0.004), antipsychotic chlorpromazine dose equivalents (p=0.001) and anxiolytic use (p=0.004). In survival analyses, the estimated full remission rate was 48.3% (95% confidence interval (CI)=36.2-61.9) and symptomatic remission rate was 67.5% (CI95=55.4-79.2). Time to full remission was longer than time to symptomatic remission (p=0.017). Linear mixed-effect models revealed significantly greater improvements from 6 months onward in CHR-R subjects compared to CHR-NR subjects regarding SOPS positive symptoms (p=0.003), highest SOPS positive symptom (p<0.001) and GAF scores (p=0.004). Examining baseline predictors, time to full remission was significantly longer in patients with higher SOPS positive scores (p=0.017).nnnCONCLUSIONSnMore stringent remission criteria that include functional status in addition to attenuated positive symptom severity should be applied to CHR subjects. Furthermore, more attention should be given to CHR individuals with highly positive prodromal symptoms at baseline.

Altered Fronto-Temporal Functional Connectivity in Individuals at Ultra-High-Risk of Developing Psychosis.

Background The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered. Methods To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl’s gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls. Results Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl’s gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl’s gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (r = .34, p = .03). Conclusions These findings corroborate the fronto-temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis.

Neurocognitive function as a possible marker for remission from clinical high risk for psychosis

BACKGROUNDnRecent studies revealed that nonconverters at clinical high risk (CHR) for psychosis comprise those who later remit from initial CHR state and those who do not remit and continue to have attenuated positive symptoms. CHR subjects who remit symptomatically are comparable to healthy controls for both baseline and longitudinal symptoms. However, the neurocognitive characteristics of this population are still obscure.nnnMETHODSnSeventy-five CHR subjects and 61 healthy controls were recruited, and their neurocognitive functions were assessed. CHR subjects were divided into converter, remitter, and non-remitter groups according to their clinical state during a 12 to 24month follow-up.nnnRESULTSnOnly the remitter group was comparable to healthy controls in terms of baseline neurocognitive functions. We observed that remitters showed better performance at baseline on tasks of attention, immediate/delayed verbal memory, verbal fluency, and immediate visual memory compared with converters. Moreover, we found that performance on semantic fluency was significantly improved in remitters but declined in non-remitters over the 2-year follow-up; however, there was no significant difference between these two groups at baseline.nnnCONCLUSIONnCHR nonconverters who later remit from an initial prodromal state do not show reduced neurocognitive functioning compared with healthy controls at baseline. Therefore, an advanced research diagnostic criterion for a CHR state that considers neurocognitive functions is needed to more precisely predict which patients will develop psychosis.

Factors contributing to the duration of untreated prodromal positive symptoms in individuals at ultra-high risk for psychosis

Individuals at ultra-high risk (UHR) for psychosis experience a considerable delay before appropriate clinical attention is provided. Therefore, we investigated the correlates of this delay by examining clinical, socio-demographic and neuropsychological contributors to the duration of untreated prodromal positive symptoms (DUPP) in them (n=73). The slowly progressive mode of functional decline, defined as a small percentage drop in the Global Assessment of Functioning (GAF) score within the past year, and male gender, explained a considerable portion of the DUPP in the multivariate regression model (F=9.269, p<0.001). Slower functional decline may be correlated with delayed care during the UHR period.

Away from home: the brain of the wandering mind as a model for schizophrenia

BACKGROUNDnThe notion that schizophrenia patients (SZ) sense of being detached from external reality is a core feature of the disorder has existed since the early days of its recognition and is still largely emphasized in first person accounts of SZs; however, its etiology, neurophysiological mechanism, and significance for clinical symptoms are unclear. Mind-wandering is a ubiquitous experience of being detached from reality, the underlying neural mechanism of which closely resembles the brain in a resting-state.nnnMETHODSnThe resting-state functional magnetic resonance imaging data of 33 SZs and 33 matched healthy controls (CNT) were acquired. All subjects answered the mind-wandering subscale of the Imaginal Processing Inventory Questionnaire. Functional connectivity maps were constructed using 82 regions of interest comprising default-mode, salience, and frontoparietal networks.nnnRESULTSnSZs exhibit significantly higher mind-wandering frequency relative to CNT. The elevated mind-wandering frequency in SZs significantly correlated with positive and general symptom severity. The mind-wandering frequency was inversely correlated with connectivity degree in the right ventromedial prefrontal cortex, the brain region involved in self-experience in SZs.nnnCONCLUSIONSnOur results suggest that self-disturbances in SZs can explain SZs disconnection to the external world, leading to the manifestation of positive psychotic symptoms. This study demonstrates strong preliminary evidence that contributes significantly to resolve the complex relationship between self, world, and the brain of SZs, which may lie at the core of psychotic experiences.