Suk Kyoon An

To discard or not to discard: the neural basis of hoarding symptoms in obsessive-compulsive disorder

Preliminary neuroimaging studies suggest that patients with the ‘compulsive hoarding syndrome’ may be a neurobiologically distinct variant of obsessive-compulsive disorder (OCD) but further research is needed. A total of 29 OCD patients (13 with and 16 without prominent hoarding symptoms) and 21 healthy controls of both sexes participated in two functional magnetic resonance imaging experiments consisting of the provocation of hoarding-related and symptom-unrelated (aversive control) anxiety. In response to the hoarding-related (but not symptom-unrelated) anxiety provocation, OCD patients with prominent hoarding symptoms showed greater activation in bilateral anterior ventromedial prefrontal cortex (VMPFC) than patients without hoarding symptoms and healthy controls. In the entire patient group (n=29), provoked anxiety was positively correlated with activation in a frontolimbic network that included the anterior VMPFC, medial temporal structures, thalamus and sensorimotor cortex. Negative correlations were observed in the left dorsal anterior cingulate gyrus, bilateral temporal cortex, bilateral dorsolateral/medial prefrontal regions, basal ganglia and parieto-occipital regions. These results were independent from the effects of age, sex, level of education, state anxiety, depression, comorbidity and use of medication. The findings are consistent with the animal and lesion literature and several landmark clinical features of compulsive hoarding, particularly decision-making difficulties. Whether the results are generalizable to hoarders who do not meet criteria for OCD remains to be investigated.

Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification

IMPORTANCE Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown. OBJECTIVE To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-). DATA SOURCES Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles. STUDY SELECTION We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-. DATA EXTRACTION AND SYNTHESIS Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test. MAIN OUTCOMES AND MEASURES The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up. RESULTS Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too few BS or BS and UHR studies to allow robust conclusions. CONCLUSIONS AND RELEVANCE There is meta-analytical evidence that BLIPS represents separate risk subgroup compared with the APS. The GRD subgroup is infrequent and not associated with an increased risk of psychosis. Future studies are advised to stratify their findings across these different subgroups. The CHR guidelines should be updated to reflect these differences.

ATTRIBUTION BIAS IN ULTRA-HIGH RISK FOR PSYCHOSIS AND FIRST-EPISODE SCHIZOPHRENIA

BACKGROUND Attribution style bias, such as a greater tendency to perceive hostility, has been reported to be associated with paranoia in multi-episode, chronic schizophrenia patients. The aim of this study was to investigate whether young, first-episode schizophrenia patients exhibited a perceived hostility bias and if this bias was correlated with persecutory symptoms. This study also explored whether this attribution bias, associated with paranoid tendencies, also emerged in participants at ultra-high risk (UHR) for psychosis. METHODS Thirty-nine normal controls, 24 UHR participants, and 20 young, first-episode schizophrenia patients were asked to complete the Ambiguous Intentions Hostility Questionnaire (AIHQ) and other psychosocial measures. The AIHQ, specifically developed for paranoia, is a self-report questionnaire about negative outcomes that varied intentionality (i.e., intentional, accidental, and ambiguous intentions). The perceived hostility, composite blame, and aggression bias scores were calculated, in this study, from the ambiguous situations. RESULTS First-episode patients with schizophrenia were found to have a perceived hostility bias, which was associated with persecutory symptoms. The UHR participants also showed an attribution bias for perceiving hostility and blaming others, and this attribution bias was linked to the paranoia process. CONCLUSIONS These findings suggest that a biased attribution style linked with paranoid symptoms may not only be present in first-episode psychotic patients but may already have evolved prior to the onset of frank psychotic symptoms. A biased attribution style may play a pivotal role in the persecutory process during the prodromal phase as well as a patients first schizophrenic episode.

Individual differences in disgust sensitivity modulate neural responses to aversive/disgusting stimuli

Little is known about how individual differences in trait disgust sensitivity modulate the neural responses to disgusting stimuli in the brain. Thirty‐seven adult healthy volunteers completed the Disgust Scale (DS) and viewed alternating blocks of disgusting and neutral pictures from the International Affective Picture System while undergoing fMRI scanning. DS scores correlated positively with activations in brain regions previously associated with disgust (anterior insula, ventrolateral prefrontal cortex–temporal pole, putamen–globus pallidus, dorsal anterior cingulate, and visual cortex) and negatively with brain regions involved in the regulation of emotions (dorsolateral and rostral prefrontal cortices). The results were not confounded by biological sex, anxiety or depression scores, which were statistically controlled for. Disgust sensitivity, a behavioral trait that is normally distributed in the general population, predicts the magnitude of the individual’s neural responses to a broad range of disgusting stimuli. The results have implications for disgust‐related psychiatric disorders.

Neural Responses to Facial Expressions of Disgust but not Fear are Modulated by Washing Symptoms in OCD

BACKGROUND Washing symptoms in Obsessive-Compulsive Disorder (OCD) are associated with increased trait sensitivity to disgust. This study explored neural systems underlying sensitivity to symptom-unrelated disgust and fear in OCD using functional neuroimaging. METHODS Seventeen OCD subjects and 19 controls viewed facial expressions of disgust and fear (versus neutral) presented just above the level of conscious awareness in a backward masking paradigm. RESULTS The OCD group showed greater activation than controls in the left ventrolateral prefrontal cortex, but reduced activation in the thalamus, to facial expressions of disgust. There were no between-group differences in response to fear. Further analysis using a median-split to divide OCD subjects into high and low washers suggested that the enhanced ventrolateral prefrontal cortex response was being driven by predominantly female OCD subjects with high washing symptoms. These subjects also reported higher levels of trait sensitivity to disgust. CONCLUSIONS These findings are consistent with previous reports of increased response to symptom-relevant and generally disgusting stimuli in neural regions associated with disgust and autonomic response processing in OCD patients with prominent washing symptoms. Together, these findings point to increased sensitivity to disgust stimuli as a component of the pathophysiology of the washing/contamination symptom dimension of OCD.

Increased P3 amplitudes induced by alcohol-related pictures in patients with alcohol dependence.

BACKGROUND Alcohol craving, a key element in alcohol dependence, is recognized as being a kind of motivational or emotional state. It is meaningful in research and clinical practice involving alcohol dependence to explore ways of measuring alcohol craving. The aim of this study was to measure the P3 event-related potentials induced by alcohol-related pictures in patients with alcohol dependence; these potentials are considered to constitute a neuronal correlate of alcohol craving. METHODS On the basis of our previous study, six alcohol-related pictures and six neutral pictures were chosen as the visual stimuli. Each set of stimuli consisted of alcohol-related or neutral pictures as the target stimuli and same-sized checkerboards as the nontarget stimuli. The stimuli were presented by using the oddball paradigm for 300 msec, with an interstimulus interval of 1000 msec, in 12 controls and 16 abstinent patients with alcohol dependence. Each electroencephalography session consisted of three blocks: a practice block, a neutral block, and an alcohol-craving block. RESULTS The amplitudes of P3 elicited by the alcohol-related pictures were significantly larger than those elicited by the neutral pictures in the patients with alcohol dependence, whereas there was no significant difference according to the stimuli in the P3 amplitudes of controls. Repeated-measures ANOVA on the amplitudes of P3 revealed that there was a significant interaction effect of block by subject group. CONCLUSIONS These results suggest that event-related potentials can be used as a neuronal correlate of alcohol craving in alcohol-dependent patients. Future investigations will be needed to assess the frequency of relapse in the patients included in this study, to elucidate the meaning of the observed results with regard to the therapeutic outcomes.

Reduced P3 amplitudes by negative facial emotional photographs in schizophrenia

Event-related potentials (ERPs), mostly P3, were measured in 20 schizophrenia and 20 healthy control subjects, in order to determine whether patients with schizophrenia have greater impairment in the processing of negative emotions. Study subjects were instructed to feel and respond to rare targets of facial photographs placed between frequent nontarget checkerboards. We found that P3 amplitudes associated with negative emotional photographs, in normal controls, were significantly larger than those of positive stimuli. Unlike the controls, in patients with schizophrenia, P3 amplitudes generated by negative emotional targets were significantly smaller than those of positive stimuli. We conclude that schizophrenia patients might be neurophysiologically different from healthy controls in terms of the manner in which they process facial emotion. Our findings are in line with previous neurobehavioral studies, in which patients with schizophrenia showed greater impairment in the recognition of negative emotions.

Structural Brain Alterations in Individuals at Ultra-high Risk for Psychosis: A Review of Magnetic Resonance Imaging Studies and Future Directions

Individuals at ultra-high-risk (UHR) for psychosis have become a major focus for research designed to explore markers for early detection of and clinical intervention in schizophrenia. In particular, structural magnetic resonance imaging studies in UHR individuals have provided important insight into the neurobiological basis of psychosis and have shown the brain changes associated with clinical risk factors. In this review, we describe the structural brain abnormalities in magnetic resonance images in UHR individuals. The current accumulated data demonstrate that abnormalities in the prefrontal and temporal cortex and anterior cingulate cortex occur before illness onset. These regions are compatible with the regions of structural deficits found in schizophrenia and first-episode patients. In addition, the burgeoning evidence suggests that such structural abnormalities are potential markers for the transition to psychosis. However, most findings to date are limited because they are from cross-sectional rather than longitudinal studies. Recently, researchers have emphasized neurodevelopmental considerations with respect to brain structural alterations in UHR individuals. Future studies should be conducted to characterize the differences in the brain developmental trajectory between UHR individuals and healthy controls using a longitudinal design. These new studies should contribute to early detection and management as well as provide more predictive markers of later psychosis.

Genetic fuzzy classifier for sleep stage identification

Soft-computing techniques are commonly used to detect medical phenomena and help with clinical diagnoses and treatment. In this work, we propose a design for a computerized sleep scoring method, which is based on a fuzzy classifier and a genetic algorithm (GA). We design the fuzzy classifier based on the GA using a single electroencephalogram (EEG) signal that detects differences in spectral features. Polysomnography was performed on four healthy young adults (males with a mean age of 27.5 years). The sleep classifier was designed using a sleep record and tested on the sleep records of the subjects. Our results show that the genetic fuzzy classifier (GFC) agreed with visual sleep staging approximately 84.6% of the time in detection of wakefulness (WA), shallow sleep (SS), deep sleep (DS), and rapid eye movement (REM) stages.

Alteration of brain metabolites in young alcoholics without structural changes

Using proton magnetic resonance spectroscopy and magnetic resonance imaging, we investigated concentrations of various brain metabolites, including glutamate, and measured brain volumes and neuropsychological performances in 13 recently abstinent young alcoholic men compared with 18 controls. No differences were found in volumetric variables between groups (intracranial volume, white matter, grey matter, anterior cingulate, insula, hippocampus, and amygdala). For the anterior cingulate, choline and creatine levels in the patient group were significantly lower than controls, and the glutamate to creatine ratio was significantly increased. These were correlated with altered short-term memory functions. Thus, neurochemical changes can occur even in the brains of young alcoholic men lacking brain atrophy.