Brain Activation of Patients With Obsessive-Compulsive Disorder During a Mental Rotation Task: A Functional MRI Study.

Functional neuroimaging studies have implicated alterations in frontostriatal and frontoparietal circuits in obsessive-compulsive disorder (OCD) during various tasks. To date, however, brain activation for visuospatial function in conjunction with symptoms in OCD has not been comprehensively evaluated. To elucidate the relationship between neural activity, cognitive function, and obsessive-compulsive symptoms, we investigated regional brain activation during the performance of a visuospatial task in patients with OCD using functional magnetic resonance imaging (fMRI). Seventeen medication-free patients with OCD and 21 age-, sex-, and IQ-matched healthy controls participated in this study. Functional magnetic resonance imaging data were obtained while the subjects performed a mental rotation (MR) task. Brain activation during the task was compared between the two groups using a two-sample t-test. Voxel-wise whole-brain multiple regression analyses were also performed to examine the relationship between obsessive-compulsive symptom severity and neural activity during the task. The two groups did not differ in MR task performance. Both groups also showed similar task-related activation patterns in frontoparietal regions with no significant differences. Activation in the right dorsolateral prefrontal cortex in patients with OCD during the MR task was positively associated with their total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. This study identified the specific brain areas associated with the interaction between symptom severity and visuospatial cognitive function during an MR task in medication-free patients with OCD. These findings may serve as potential neuromodulation targets for OCD treatment.

The effects of selective serotonin reuptake inhibitors on brain functional networks during goal-directed planning in obsessive-compulsive disorder.

Whether brain network connectivity during goal-directed planning in patients with obsessive-compulsive disorder (OCD) is abnormal and restored by treatment with selective serotonin reuptake inhibitors (SSRIs) remains unknown. This study investigated whether the disrupted network connectivity during the Tower of London (ToL) planning task in medication-free OCD patients could be restored by SSRI treatment. Seventeen medication-free OCD patients and 21 matched healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) while performing the ToL task at baseline and again after 16 weeks of SSRI treatment. Internetwork connectivity was compared across the groups and treatment statuses (pretreatment versus posttreatment). At baseline, compared with the HCs, the OCD patients showed lower internetwork connectivity between the dorsal attention network and the default-mode network during the ToL planning task. After 16 weeks of SSRI treatment, the OCD patients showed improved clinical symptoms accompanied by normalized network connectivity, although their improved behavioral performance in the ToL task did not reach that of the HCs. Our findings support the conceptualization of OCD as a network disease characterized by an imbalance between brain networks during goal-directed planning and suggest that internetwork connectivity may serve as an early biomarker of the effects of SSRIs on goal-directed planning.

Validation of the Traumatic Antecedents Questionnaire using item response theory.

BACKGROUND: Traumatic Antecedents Questionnaire (TAQ) is a traumatic experience scale that measures exposure to traumatic events across four age periods. Although the TAQ has good convergent validity with other traumatic scales, the classification of the domains and the psychometric properties of the scale has not been verified. METHODS: A total of 290 young adults completed the TAQ, and 156 participated in the retest. The number of trauma domains was determined using principal component analysis. Rasch model was used for verifying the items that each domain might represent in one common measurement. RESULTS: When scores were transformed as binary a code 0 and 1 from the original 4 categories, 8 domains were established consisting of Domestic violence, Sexual/other rare trauma, Incompetence, Caring family, Accidents to close person, Unstable caring environment, Safe environment, and Lack of sexual/extreme trauma. Most domains had acceptable psychometric properties with a mean-square fit value within the range of 0.7-1.3. The Bland and Altman analysis suggest 98.7% of difference scores between test and retest were within ±2 standard deviations from the mean. TAQ severity showed a significant relationship with the multiplicity score of the Maltreatment and Abuse Chronology of Exposure scale (r = 0.677). CONCLUSIONS: The newly proposed scoring system and 8 domains for the TAQ demonstrated excellent internal consistency, test-retest reliability, and validity. Further studies are needed to develop new items in domains with less than 5 items to improve the psychometric properties of the scale and to create a maltreatment domain that includes bullying items.

Data-driven analysis using multiple self-report questionnaires to identify college students at high risk of depressive disorder.

Depression diagnosis is one of the most important issues in psychiatry. Depression is a complicated mental illness that varies in symptoms and requires patient cooperation. In the present study, we demonstrated a novel data-driven attempt to diagnose depressive disorder based on clinical questionnaires. It includes deep learning, multi-modal representation, and interpretability to overcome the limitations of the data-driven approach in clinical application. We implemented a shared representation model between three different questionnaire forms to represent questionnaire responses in the same latent space. Based on this, we proposed two data-driven diagnostic methods; unsupervised and semi-supervised. We compared them with a cut-off screening method, which is a traditional diagnostic method for depression. The unsupervised method considered more items, relative to the screening method, but showed lower performance because it maximized the difference between groups. In contrast, the semi-supervised method adjusted for bias using information from the screening method and showed higher performance. In addition, we provided the interpretation of diagnosis and statistical analysis of information using local interpretable model-agnostic explanations and ordinal logistic regression. The proposed data-driven framework demonstrated the feasibility of analyzing depressed patients with items directly or indirectly related to depression.

Social noise interferes with learning in a volatile environment.

To learn through feedback, feedback should be reliable. However, if feedback is blurred by irrelevant social information, learning in a volatile environment, which requires fast learning and adaptation, might be disturbed. In this study, we investigated how feedback with social noise interferes with learning in a volatile environment by designing a probabilistic associative learning task in which the association probability changes dynamically, and the outcome was randomly blurred by an emotional face with incongruent valence. Learning in this situation was modelled by HGF-S such that emotionally incongruent feedback induces perceptual uncertainty called social noise. The Bayesian model comparison showed that the HGF-S model explains the subjects' behaviour well, and the simulation showed that social noise interrupts both learning the association probability and the volatility. Furthermore, the learning interruption influenced the subsequent decision. Finally, we found that the individual difference in how the same emotionally incongruent feedback induces social noise in varying degrees was related to the differences in event-related desynchronization induced by happy and sad faces in the right anterior insula, which encodes the degree of emotional feeling. These results advance our understanding of how feedback with emotional interference affects learning.

Verbal Abuse Related to Self-Esteem Damage and Unjust Blame Harms Mental Health and Social Interaction in College Population.

Verbal abuse is an emotional abuse intended to inflict intense humiliation-denigration-fear as perceived by exposed person. Network-based approaches have been applied to explore the integrative-segregated patterns of associations among the psychological features and external stimuli for diverse populations; few studies reported for verbal abuse effects in college population. Self-reporting measurements acquired form 5,616 college students were used for network analyses. Escalating cascades of verbal abuse from differential sources (parents, peers, or supervisors; network 1) and directed associations among verbal abuse severity-psychopathology-social interaction (network 2) were estimated using the directed acyclic graphs. Principal connectors of verbal abuse-psychopathology-social interaction were shown using the graph theory metrics calculated from the intra-individual covariance networks (network 3). Directed propagating patterns of verbal abuse phenomena differed by source (network 1). Severe peer-related verbal abuse affected psychomotor changes and influenced irritability (network 2). Verbal abuse of self-esteem damage and unjust blame served as connectors in the verbal abuse-psychopathology-social interaction; influence of smartphone overuse-related distress was stronger in cases with more severe verbal abuse (network 3). Verbal abuse that damages self-esteem and conveys unjust blame harms mental health and social interaction for college population.

Predicting Suicidal Ideation in College Students with Mental Health Screening Questionnaires.

OBJECTIVE: The present study aimed to identify risk factors for future SI and to predict individual-level risk for future or persistent SI among college students. METHODS: Mental health check-up data collected over 3 years were retrospectively analyzed. Students were categorized as suicidal ideators and non-ideators at baseline. Logistic regression analyses were performed separately for each group, and the predicted probability for each student was calculated. RESULTS: Students likely to exhibit future SI had higher levels of mental health problems, including depression and anxiety, and significant risk factors for future SI included depression, current SI, social phobia, alcohol problems, being female, low self-esteem, and number of close relationships and concerns. Logistic regression models that included current suicide ideators revealed acceptable area under the curve (AUC) values (0.7-0.8) in both the receiver operating characteristic (ROC) and precision recall (PR) curves for predicting future SI. Predictive models with current suicide non-ideators revealed an acceptable level of AUCs only for ROC curves. CONCLUSION: Several factors such as low self-esteem and a focus on short-term rather than long-term outcomes may enhance the prediction of future SI. Because a certain range of SI clearly necessitates clinical attention, further studies differentiating significant from other types of SI are necessary.

Predicting neurocognitive function with hippocampal volumes and DTI metrics in patients with Alzheimer's dementia and mild cognitive impairment.

INTRODUCTION: Cognitive performance in patients with Alzheimer's dementia (AD) and mild cognitive impairment (MCI) has been reported to be related to hippocampal atrophy and microstructural changes in white matter (WM). We aimed to predict the neurocognitive functions of patients with MCI or AD using hippocampal volumes and diffusion tensor imaging (DTI) metrics via partial least squares regression (PLSR). METHODS: A total of 148 elderly female subjects were included: AD (n = 49), MCI (n = 66), and healthy controls (n = 33). Twenty-four hippocampal subfield volumes and the average values for fractional anisotropy (FA) and mean diffusivity (MD) of 48 WM tracts were used as predictors, CERAD-K total scores, scores of CERAD-K 7 cognitive subdomains and K-GDS were used as dependent variables in PLSR. RESULTS: Regarding MCI patients, DTI metrics such as the MD values of the left retrolenticular part of the internal capsule and left fornix (cres)/stria terminalis were significant predictors, while hippocampal subfield volumes, like the left CA1 and hippocampal tail, were main contributors to cognitive function in AD patients, although global FA/MD values were also strong predictors. The 10-fold cross-validation and stricter 300-iteration tests proved that global cognition measured by the CERAD-K total scores and the scores of several CERAD-K subdomains can be reliably predicted using the PLSR models. CONCLUSIONS: Our findings indicate different structural contributions to cognitive function in MCI and AD patients, implying that diffuse WM microstructural changes may precede hippocampal atrophy during the AD neurodegenerative process.

Minnesota Multiphasic Personality Inventory Characteristics of Parricide Offenders with Schizophrenia in Korea.

OBJECTIVE: This study aims to examine the personality characteristics in parricide offenders, by using the Minnesota Multiphasic Personality Inventory (MMPI) test, which is commonly used in clinical medicine. METHODS: A total of 73 parricide offenders with schizophrenia who were admitted to National Forensic Hospital in Gongju city between September 2014 and February 2015, and 104 comparison schizophrenia patients who had been admitted to Dankook University Hospital in Cheonan city the same hospital, completed the Korean version of the MMPI. RESULTS: The parricide offender group showed significantly higher on L, F, Hs, Hy and Pd than the comparison group. The result of the regression analysis indicated that Pd and Si significantly increased the odd ratio of the sexual offender group by 2.77 times and 0.32 times, respectively (p=0.029 and p=0.023). The offenders of parricide may have developed the following characteristics: hypochondriasis, hysteria and psychopathic deviate. CONCLUSION: These results suggested that the psychopatholgy in the offenders of parricide might be different, compared to the control group.

The effects of pharmacological treatment on functional brain connectome in obsessive-compulsive disorder.

BACKGROUND: Previous 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. METHODS: Twenty-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. RESULTS: At 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. CONCLUSIONS: This 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.

The impact of personality traits on ratings of obsessive-compulsive symptoms.

OBJECTIVE: The goal of this study was to evaluate consistencies and discrepancies between clinician-administered and self-report versions of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and to examine relationships between these scales and personality traits. METHODS: A total of 106 patients with obsessive-compulsive disorder (OCD) participated in this study. All participants were assessed with both clinician-administered and self-report versions of the Y-BOCS. The Structured Clinical Interview for DSM-IV Axis II Disorders Personality Questionnaire (SCID-II-PQ) was used to evaluate relationships between personality traits and scores on the Y-BOCS. RESULTS: Scores on the clinician-administered Y-BOCS and its obsession subscale were significantly higher than were those on the self-report version. However, we found no significant differences in compulsion subscale scores. We also found that the discrepancies in the scores on the two versions of the Y-BOCS and its compulsion subscale were significantly positively correlated with scores for narcissistic personality traits on the SCID-II-PQ. Additionally, narcissistic personality traits had a significant effect on the discrepancy in the scores on the two versions of the Y-BOCS and its compulsion subscale in the multiple linear regression analysis. CONCLUSION: This is the first study to elucidate relationships between personality traits and discrepancies between scores on the two versions of the Y-BOCS. Although clinicians tend to rate obsessive symptoms as being more severe than do patients, clinicians may underestimate the degree to which individuals with narcissistic personality traits suffer more from subjective discomfort due to compulsive symptoms. Therefore, the effect of personality traits on symptom severity should be considered in the treatment of OCD.

Altered asymmetry of the anterior cingulate cortex in subjects at genetic high risk for psychosis.

OBJECTIVE: Many studies have reported that patients with schizophrenia often have structural abnormalities of the anterior cingulate cortex (ACC) and that some of these seem to be of genetic origin, therefore predating the onset of illness. The present study aimed to investigate whether these alterations in the ACC are genetic in origin by comparing the morphological patterns of three groups: normal controls, subjects at genetic high risk (GHR) for psychosis, and patients with schizophrenia. The relationships between morphological variations and executive function were also investigated. METHODS: This study examined the magnetic resonance images of cingulate sulcus/paracingulate sulcus (CS/PCS) folding patterns in 222 subjects (103 normal subjects, 30 individuals at GHR, and 89 patients with schizophrenia) and evaluated differences in the morphological and asymmetrical patterns of the ACC among groups. Neurocognitive tests were then performed and differences in cognitive performance were analyzed according to morphological variation. RESULTS: Differences in PCS folding were detected; the control group was significantly more likely than were other groups to show a well-developed left PCS (p=0.009) and leftward asymmetry of the PCS (p<0.001). However, neither GHR subjects (p=0.346) nor patients (p=0.784) showed this leftward asymmetry. No statistically significant differences in CS continuity were observed. A more prominent left PCS (p=0.031) and leftward PCS asymmetry (p=0.030) were both associated with higher scores on the working memory task. CONCLUSION: The results suggest that GHR subjects have distinct neurodevelopmental anomalies that resemble those of patients with schizophrenia even though they do not display any psychotic symptoms. Certain developmental alterations in the ACC, such as the loss of leftward sulcal asymmetry in patients with schizophrenia, might be related to genetic factors. Additionally, this morphological alteration might partly account for the impaired executive function in schizophrenia.

Neural correlate of impulsivity in subjects at ultra-high risk for psychosis.

OBJECTIVE: Impulsivity is one of the most commonly reported behavioral characteristics of patients with schizophrenia. Although there is accumulating evidence regarding behavioral problems in individuals at ultra-high risk (UHR) for psychosis, as yet, no study has reported on impulsivity in this population. The aim of the present study was to assess impulsivity in UHR subjects and to investigate the associated gray matter correlates. METHOD: This study included 32 UHR subjects and 32 age- and gender-matched healthy controls (HCs). The Barratt Impulsiveness Scale version-11 (BIS-11) was employed to assess impulsivity. Differences between the groups in gray matter volume in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex (OFC) were assessed. Then, a correlational analysis between the BIS-11 scores and significant clusters of gray matter volume was conducted in UHR subjects. RESULTS: UHR subjects were more impulsive than HC subjects in terms of attention (t = 3.5187, p<0.01), motor (t = 3.1751, p<0.01), and non-planning (t = 4.4154, p<0.01) scores. The gray matter volume of the ACC was negatively correlated with the motor (r = -0.472, p<0.01) and non-planning (r = -0.354, p = 0.04) scores of the BIS-11 in UHR subjects. CONCLUSION: These results suggest that impulsivity in UHR subjects may reflect altered integrated conflict processing, which likely stems from abnormalities in the ACC, rather than altered reward/punishment processing or executive control.

Impaired body but not face perception in patients with obsessive-compulsive disorder.

BACKGROUND: Empirical evidence involving the processing of social information by patients with obsessive-compulsive disorder (OCD) has been relatively scarce. Our study investigated the perceptual abilities of patients with OCD to recognize human faces and bodies. METHOD: Fifty-four drug-free or drug-naïve patients with OCD and 42 healthy controls performed discrimination tasks consisting of four types of stimuli: two sets of faces that were manipulated with regard to configuration and features, human bodies, and chairs. The stimuli were presented in upright and upside-down orientations. RESULTS: Patients with OCD were significantly less accurate in discriminating pairs of bodily postures implying actions. However, we found no significant differences between patient and control groups in the ability to recognize faces and chairs. The inversion effects for bodies and faces were also comparable between the two groups. CONCLUSIONS: The current findings suggest that patients with OCD experience difficulty in perceiving static forms of bodily postures, but are able to adequately recognize human faces. Our data indicate a selective deficit in the perception of bodily postures in those with OCD and suggest that this deficit is probably not related to the abnormal configurational processing of social objects.

Clinical and neurocognitive profiles of subjects at high risk for psychosis with and without obsessive-compulsive symptoms.

OBJECTIVE: Obsessive-compulsive symptoms (OCS), which are common in psychotic-spectrum illnesses, are of clinical interest because of their association with poor prognosis or cognitive dysfunction. However, few studies on the clinical and neurocognitive implications of OCS in individuals at ultra-high risk for psychosis (UHR) have been conducted. METHOD: Sixty-five UHR subjects [24 with OCS (UHR+OCS), 41 without OCS (UHR-OCS)], and 40 healthy controls were assessed using clinical scales and neurocognitive tests. RESULTS: Those with UHR+OCS showed more severe clinical symptoms and poorer global functioning as compared to both healthy controls and the UHR-OCS group, according to the results of the Global Assessment of Functioning, the Comprehensive Assessment of At-Risk Mental States, and the Positive and Negative Syndrome Scale (total, negative, and general scores). In the neurocognitive domain, those in the UHR-OCS group showed notably greater latency in the Stroop task and more confabulation errors in immediate recall in the Rey-Osterrieth Complex Figure Test compared with those in UHR+OCS group, whose performance levels were similar to those of the healthy control group. CONCLUSIONS: The OCS manifested in UHR individuals was associated with a more severe clinical symptomatic presentation, including lower global functioning and more psychotic symptoms. On the other hand, those with UHR-OCS performed more poorly on some cognitive tests. The features that distinguish the groups can be used for developing prognoses and intervention strategies for the heterogeneous UHR group.

Influence of brain-derived neurotrophic factor and catechol O-methyl transferase polymorphisms on effects of meditation on plasma catecholamines and stress.

Meditation may show differential effects on stress and plasma catecholamines based on genetic polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol O-methyl transferase (COMT). Eighty adults (40 men, 40 women; mean age 26 years) who practiced meditation regularly and 57 healthy control adults (35 men, 22 women; mean age 26 years) participated. Plasma catecholamines (norepinephrine (NE), epinephrine (E), and dopamine (DA)) concentrations were measured, and a modified form of the Stress Response Inventory was administered. The results were analyzed using two-way analysis of covariance (ANCOVA) with control and meditation subjects, gene polymorphism as factors, and meditation duration as the covariate. Two-way ANCOVA showed a significant interaction between control and meditation subjects, and BDNF Val66Met polymorphism on DA/NE+DA/E (p = 0.042) and NE/E+NE/DA (p = 0.046) ratios. A significant interaction was found for control and meditation subjects with COMT Val158Met polymorphism and plasma NE concentrations (p = 0.009). Post hoc ANCOVA in the meditation group, adjusted for meditation duration, showed significantly higher plasma NE concentrations for COMT Met carriers than COMT Val/Val subjects (p = 0.025). Significant differences of stress levels were found between the control and meditation subjects in BDNF Val/Met (p < 0.001) and BDNF Met/Met (p = 0.003), whereas stress levels in the BDNF Val/Val genotype did not differ between the control and meditation groups. This is the first evidence that meditation produces different effects on plasma catecholamines according to BDNF or COMT polymorphisms.

Pharmacotherapy and clinical characteristics of ultra-high-risk for psychosis according to conversion status: a naturalistic observational study.

AIM: To explore the differences in pharmacotherapy and clinical characteristics of individuals at ultra-high-risk (UHR) for psychosis according to the conversion status, we analyzed the data for UHR patients seen at the Seoul Youth Clinic. METHODS: This was a naturalistic observational study. We obtained clinical data, including demographic data, presenting complaint, duration of psychiatric symptoms, diagnosis and scores on clinical rating scales from individual records in the Seoul Youth Clinic. Prescription data were obtained from electronic medical records. RESULTS: As of April 1, 2010, a total of 78 people were registered as being UHR for psychosis in the Seoul Youth Clinic. Patients commonly presented with paranoid ideas and anxiety. On entry to the Seoul Youth Clinic, 81% of the UHR group were diagnosed as having psychiatric disorders according to DSM-IV criteria. Of the 67 individuals who did not drop out of the Seoul Youth Clinic, 14 converted to psychosis. The mean time to conversion was 412 days post baseline examination. The mean duration of psychiatric symptoms before clinic presentation was shorter in the converter group than in the non-converter group. There were no differences in baseline scores on clinical rating scales between the two groups. Antipsychotics were commonly prescribed for UHR patients in the Seoul Youth Clinic, with the converter group exposed to antipsychotics for a longer period and at higher doses than the non-converter group. CONCLUSIONS: In a naturalistic setting, the different pattern of exposure to antipsychotics between the converter and non-converter groups calls attention to the effects of antipsychotics on conversion to psychosis.

Increased white matter integrity in the corpus callosum in subjects with high genetic loading for schizophrenia.

OBJECTIVE: White matter abnormalities in the corpus callosum (CC) of schizophrenia have been reported to predate the illness onset. This study aimed to investigate the effect of genetic predisposition on the white matter integrity of the CC, in subjects at genetically high risk for schizophrenia (GHR) and schizophrenia patients. METHOD: Fractional anisotropy (FA) of the mid-sagittal CC in 22 young GHR, 15 schizophrenia, and 26 control subjects were examined. GHR subjects were defined as non-prodromal individuals who had more than two relatives with schizophrenia within third-degree relatives, one of whom must be a first-degree relative. RESULTS: ANCOVA with age and gender as covariates revealed overall difference of FA in the genu and splenium among the three groups. Post-hoc analysis found significantly increased FA in the genu of GHR subjects compared to controls (corrected p<0.01), whereas schizophrenia patients showed significantly decreased FA in the splenium. CONCLUSION: The white matter change of the CC in young GHR subjects was the opposite of that in schizophrenia. To consider previous reports on FA decrease in the CC in schizophrenia and the impaired frontal functioning in GHR group, the increased FA may be an indicator of compensatory alteration in white matter integrity in young GHR people.

Longitudinal patterns of social functioning and conversion to psychosis in subjects at ultra-high risk.

OBJECTIVE: Impaired social functioning is one of the defining features of patients with schizophrenia and subjects at ultra-high risk (UHR) for psychosis. This prospective study aimed to investigate the course of social dysfunction in UHR subjects and to examine its relationship with later conversion to psychosis. The effect of pharmacotherapy on the course of social dysfunction was also examined. METHOD: A total of 57 UHR subjects and 58 healthy controls participated in this study. The Social Functioning Scale (SFS) was used to assess social functioning of UHR subjects at baseline and at the 1 year follow up. The changes in social functioning of UHR subjects have been examined to compare the social functioning of those who later converted to psychosis ('converters') with those who did not ('non-converters'). The effect of pharmacotherapy on longitudinal change in social functioning was also evaluated. RESULTS: Subjects at UHR for psychosis showed more impaired social functioning at baseline than did healthy controls. Moreover, the course of social dysfunction of the converter and non-converter groups differed during the 1 year follow up period. The converters showed decreases in SFS average (F (1,32) = 7.85, p = 0.009) and interpersonal behaviour (F (1,32) = 10.43, p = 0.003) scores over time, whereas the non-converters showed increased scores. Additionally, we found that pharmacological treatment was associated with increased prosocial activities score (F (1,32) = 4.66, p = 0.038). CONCLUSIONS: We found that the social functioning of converters was impaired before the onset of the psychosis and further declined during the at-risk phase. A series of social functioning indices in the longitudinal course may be helpful in predicting conversion to psychosis in subjects at UHR. Appropriate pharmacotherapy can offer clinical benefits by improving social functioning in UHR individuals.

What is the optimal dose of escitalopram for the treatment of obsessive-compulsive disorder? A naturalistic open-label study.

This study explored the efficacy and tolerability of very high doses (maximum dose of >40 mg/day), high doses (maximum dose of 25-40 mg/day), and standard doses (maximum dose of ≤20 mg/day) of escitalopram (ESC) as an anti-obsessive-compulsive disorder treatment in a naturalistic clinical setting. We reviewed the medical records of all patients with obsessive-compulsive disorder (n=246) who had taken ESC between May 2006 and September 2009, and assigned Clinical Global Impression (CGI) scores, retrospectively. Of the total sample, 24.4, 38.2, and 37.4% patients received very high, high, and standard doses of ESC, and the mean daily maximum doses of ESC were 57.3±12.0 mg, 33.9±5.4 mg, and 13.4±5.8 mg, respectively. The CGI-Severity scores in each group decreased significantly after treatment with ESC, as evidenced by response rates (i.e. CGI-Improvement scores of 1 or 2) of 46.3, 43.2, and 26.2%, respectively. Although some adverse events increased in a dose-dependent manner, most could be managed with an ESC dose adjustment. These results imply that doses less than or equal to 40 mg/day ESC are sufficient for symptomatic improvement with good tolerability for most patients. Very high doses of ESC, on the other hand, can be considered for patients with inadequate therapeutic responses to the administration of 40 mg/day ESC.