Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (21 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2023)
There is mounting evidence that the social determinants of psychosis operate via a long and circuitous route. Here, we comment on the striking findings from a recent study by Ku et al., that area-level social environmental factors yield social disability and increased risk for schizophrenia through intervening variables and over a long time course. We discuss the relevance of animal models of social isolation to understand how environmental factors interrelate with individual-level mechanisms. We also discuss treatment implications, including the search for novel psychopharmacological treatments for reduced social motivation, and the need for a comprehensive prediction and prevention model.
    Cover page: Understanding the Causal Pathway of Social Determinants of Psychosis: The Role of Social Functioning, Relevance of Animal Models, and Implications for Treatment.
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2013)

    Current classification systems of mental illness characterize bipolar disorder (BD) and schizophrenia (SCZ) as discrete diagnostic categories, presupposing distinct presentation, etiology, and treatment, despite mounting evidence of epidemiological and genetic overlap between the two and in a way that does not fully reflect increasing knowledge of underlying biological mechanisms or pathogenesis. To further elucidate the nature of phenotypic overlap versus differentiation between the two, emotion perception and regulation deficits were examined via a task of affect recognition during fMRI. Data were collected at the Karolinska Institute in Sweden; demographically matched participants were recruited based on national medical records data in line with study protocol approved by Karolinska and UCLA IRB. Behaviorally, patients with SCZ (n=41) and BD (n=38) demonstrated similar impairment in affect labeling relative to controls (n=64); however, SCZ patients showed greater deficits during affect matching and the two groups showed differences in corresponding patterns of neural activation. During affect matching, whole-brain voxel-wise BOLD signal analysis indicated both patient groups showed hypoactivation relative to controls in putative social cognitive network regions but the specific regions differed by group, such that BD patients showed hypoactivation of posterior cingulate/precuneus, whereas SCZ patients showed hypoactivity in right amygdala/hippocampus. In addition, the SCZ group demonstrated failure of fronto-limbic circuitry to modulate ventral face and emotion processing regions during affect labeling; they showed hyperactivation of fusiform gyrus, inferior occipital cortex, and posterior superior and middle temporal gyrus and did not show negative functional connectivity between these regions as shown in controls and BD patients through PPI analysis. SCZ patients also showed aberrant positive cortico-cortical connectivity in frontal regions versus BD patients, suggestive of compensatory recruitment of additional frontal regions. The current study thus adds new and novel evidence to the ongoing debate regarding the utility of categorical classification of disease, demonstrating underlying disparateness in neurophysiology related to specific aspects of the socio-emotional domain and lending at least partial validation to the current diagnostic distinction. Implications for treatment considerations are also discussed.

      Cover page: Beyond the Kraepelinian Dichotomy: Investigation into Neural Phenotypes of Schizophrenia and Bipolar Disorder
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2019)
      Individuals with schizophrenia and bipolar disorder show alterations in functional neural connectivity during rest. However, resting-state network (RSN) disruptions have not been systematically compared between the two disorders. Further, the impact of RSN disruptions on social cognition, a key determinant of functional outcome, has not been studied. Forty-eight individuals with schizophrenia, 46 with bipolar disorder, and 48 healthy controls completed resting-state functional magnetic resonance imaging. An atlas-based approach was used to examine functional connectivity within nine RSNs across the cortex. RSN connectivity was assessed via nonparametric permutation testing, and associations with performance on emotion perception, mentalizing, and emotion management tasks were examined. Group differences were observed in the medial and lateral visual networks and the sensorimotor network. Individuals with schizophrenia demonstrated reduced connectivity relative to healthy controls in all three networks. Individuals with bipolar disorder demonstrated reduced connectivity relative to controls in the medial visual network and connectivity within this network was significantly positively correlated with emotion management. In healthy controls, connectivity within the medial and lateral visual networks positively correlated with mentalizing. No significant correlations were found for either visual network in schizophrenia. Results highlight the role of altered early visual processing in social cognitive deficits in both schizophrenia and bipolar disorder. However, individuals with bipolar disorder appear to compensate for disrupted visual network connectivity on social cognitive tasks, whereas those with schizophrenia do not. The current study adds clarity on the neurophysiology underlying social cognitive deficits that result in impaired functioning in serious mental illness.
        Cover page: Linking resting-state networks and social cognition in schizophrenia and bipolar disorder.
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2017)
        Patients with schizophrenia show specific abnormalities in visual perception, and patients with bipolar disorder may have related perceptual deficits. During tasks that highlight perceptual dysfunction, patients with schizophrenia show abnormal activity in visual brain areas, including the lateral occipital complex (LOC) and early retinotopic cortex. It is unclear whether the anatomical structure of those visual areas is atypical in schizophrenia and bipolar disorder. In members of those two patient groups and healthy controls, we localized LOC and early retinotopic cortex individually for each participant using functional magnetic resonance imaging (MRI), then measured the thickness of those regions of interest using structural MRI scans. In both regions, patients with schizophrenia had the thinnest cortex, controls had the thickest cortex, and bipolar patients had intermediate cortical thickness. A control region, motor cortex, did not show this pattern of group differences. The thickness of each visual region of interest was significantly correlated with performance on a visual object masking task, but only in schizophrenia patients. These findings suggest an anatomical substrate for visual processing abnormalities that have been found with both neural and behavioral measures in schizophrenia and other severe mental illnesses.
          Cover page: Cortical Thickness of Functionally Defined Visual Areas in Schizophrenia and Bipolar Disorder.
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2022)
          Several studies of reward processing in schizophrenia have shown reduced sensitivity to positive, but not negative, outcomes although inconsistencies have been reported. In addition, few studies have investigated whether patients show a relative deficit to social versus nonsocial rewards, whether deficits occur across the spectrum of psychosis, or whether deficits relate to negative symptoms and functioning. This study examined probabilistic implicit learning via two visually distinctive slot machines for social and nonsocial rewards in 101 outpatients with diverse psychotic disorders and 48 community controls. The task consisted of two trial types: positive (optimal to choose a positive vs. neutral machine) and negative (optimal to choose a neutral vs. negative machine), with two reward conditions: social (faces) and nonsocial (money) reward conditions. A significant group X trial type interaction indicated that controls performed better on positive than negative trials, whereas patients showed the opposite pattern of better performance on negative than positive trials. In addition, both groups performed better for social than nonsocial stimuli, despite lower overall task performance in patients. Within patients, worse performance on negative trials showed significant, small-to-moderate correlations with motivation and pleasure-related negative symptoms and social functioning. The current findings suggest reward processing disturbances, particularly decreased sensitivity to positive outcomes, extend beyond schizophrenia to a broader spectrum of psychotic disorders and relate to important clinical outcomes.
            Cover page: Aberrant reward processing to positive versus negative outcomes across psychotic disorders.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2019)

            Background

            Human beings find social stimuli rewarding, which is thought to facilitate efficient social functioning. Although reward processing has been extensively studied in schizophrenia, a few studies have examined neural processes specifically involved in social reward processing. This study examined neural sensitivity to social and nonsocial rewards in schizophrenia.

            Methods

            Twenty-seven patients with schizophrenia and 25 community controls completed a One-Armed Bandit Task, an implicit reinforcement learning task, in the scanner. There were 2 conditions with an identical trial structure, one with social rewards and the other with nonsocial rewards. The data were analyzed using a region of interest (ROI) approach, focusing on the ventral striatum, ventromedial prefrontal cortex, and anterior cingulate cortex.

            Results

            Across all 3 ROIs, patients showed reduced activation for social rewards compared to controls. However, the 2 groups showed comparable levels of activation for nonsocial rewards. Within the patient group, levels of neural activation in these ROIs during the social reward condition were associated with better performance.

            Conclusions

            This study found reduced neural sensitivity in patients with schizophrenia in key reward-processing regions for social but not for nonsocial rewards. These findings suggest a relatively specific social reward-processing deficit in schizophrenia during an implicit reinforcement learning task.
              Cover page: Reduced Neural Sensitivity to Social vs Nonsocial Reward in Schizophrenia.
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2022)
              Event-related potential (ERP) studies of motivated attention in schizophrenia typically show intact sensitivity to affective vs. non-affective images depicting diverse types of content. However, it is not known whether this ERP pattern: 1) extends to images that solely depict social content, (2) applies across a broad sample with diverse psychotic disorders, and (3) relates to self-reported trait social anhedonia. We examined late positive potential (LPP) amplitudes to images involving people that were normatively pleasant (affiliative), unpleasant (threatening), or neutral in 97 stable outpatients with various psychotic disorders and 38 healthy controls. Both groups showed enhanced LPP to pleasant and unpleasant vs. neutral images to a similar degree, despite lower overall LPP in patients. Within the patients, there were no significant LPP differences among subgroups (schizophrenia vs. other psychotic disorders; affective vs. non-affective psychosis) for the valence effect (pleasant/unpleasant vs. neutral). Higher social anhedonia showed a small, significant relation to lower LPP to pleasant images across all groups. These findings suggest intact motivated attention to social images extends across psychotic disorder subgroups. Dimensional transdiagnostic analyses revealed a modest association between self-reported trait social anhedonia and an LPP index of neural sensitivity to pleasant affiliative images.
                Cover page: Intact differentiation of responses to socially-relevant emotional stimuli across psychotic disorders: An event-related potential (ERP) study.
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2019)
                Social cognitive skills training interventions for psychotic disorders have shown improvement in social cognitive performance tasks, but little was known about brain-based biomarkers linked to treatment effects. In this pilot study, we examined whether social cognitive skills training could modulate extrinsic and intrinsic functional connectivity in psychosis using functional magnetic resonance imaging (fMRI). Twenty-six chronic outpatients with psychotic disorders were recruited from either a Social Cognitive Skills Training (SCST) or an activity- and time-matched control intervention. At baseline and the end of intervention (12 weeks), participants completed two social cognitive tasks: a Facial Affect Matching task and a Mental State Attribution Task, as well as resting-state fMRI (rs-fMRI). Extrinsic functional connectivity was assessed using psychophysiological interaction (PPI) with amygdala and temporo-parietal junction as a seed region for the Facial Affect Matching Task and the Mental State Attribution task, respectively. Intrinsic functional connectivity was assessed with independent component analysis on rs-fMRI, with a focus on the default mode network (DMN). During the Facial Affect Matching task, we observed stronger PPI connectivity in the SCST group after intervention (compared to baseline), but no treatment-related change in the Control group. Neither group showed treatment-related changes in PPI connectivity during the Mental State Attribution task. During rs-fMRI, we found treatment-related changes in the DMN in the SCST group, but not in Control group. This study found that social cognitive skills training modulated both extrinsic and intrinsic functional connectivity in individuals with psychotic disorders after a 12-week intervention. These findings suggest treatment-related changes in functional connectivity as a potential brain-based biomarker of social cognitive skills training.
                  Cover page: fMRI biomarkers of social cognitive skills training in psychosis: Extrinsic and intrinsic functional connectivity
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2017)
                  Individuals with schizophrenia demonstrate difficulties in attending to important stimuli (e.g., targets) and ignoring distractors (e.g., non-targets). We used a visual oddball task during fMRI to examine functional connectivity within and between the ventral and dorsal attention networks to determine the relative contribution of each network to detection of rare visual targets in schizophrenia. The sample comprised 25 schizophrenia patients and 27 healthy controls. Psychophysiological interaction analysis was used to examine whole-brain functional connectivity in response to targets. We used the right temporo parietal junction (TPJ) as the seed region for the ventral network and the right medial intraparietal sulcus (IPS) as the seed region for the dorsal network. We found that connectivity between right IPS and right anterior insula (AI; a component of the ventral network) was significantly greater in controls than patients. Expected patterns of within- and between-network connectivity for right TPJ were observed in controls, and not significantly different in patients. These findings indicate functional connectivity deficits between the dorsal and ventral attention networks in schizophrenia that may create problems in processing relevant versus irrelevant stimuli. Understanding the nature of network disruptions underlying cognitive deficits of schizophrenia may help shed light on the pathophysiology of this disorder.
                    Cover page: Functional connectivity when detecting rare visual targets in schizophrenia
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2018)
                    Social perceptual deficits in schizophrenia are well established. Recent work suggests that the ability to extract social information from bodily cues is reduced in patients. However, little is known about the neurobiological mechanisms underlying this deficit. In the current study, 20 schizophrenia patients and 16 controls completed two tasks using point-light animations during fMRI: a basic biological motion task and an emotion in biological motion task. The basic biological motion task was used to localize activity in posterior superior temporal sulcus (pSTS), a critical region for biological motion perception. During the emotion in biological motion task, participants viewed brief videos depicting happiness, fear, anger, or neutral emotions and were asked to decide which emotion was portrayed. Activity in pSTS and amygdala was interrogated during this task. Results indicated that patients showed overall reduced activation compared to controls in pSTS and at a trend level in amygdala across emotions, despite similar task performance. Further, a functional connectivity analysis revealed that controls, but not patients, showed significant positive connectivity between pSTS and left frontal regions as well as bilateral angular gyrus during the emotion in biological motion task. These findings indicate that schizophrenia patients show aberrant neural activity and functional connectivity when extracting complex social information from simple motion stimuli, which may contribute to social perception deficits in this disorder.
                      Cover page: Aberrant patterns of neural activity when perceiving emotion from biological motion in schizophrenia.
                      Top