IU Indianapolis ScholarWorks :: Browsing by Subject "schizophrenia"

Browsing by Subject "schizophrenia"

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An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7
(Elsevier, 2016-07) Gass, Natalia; Weber-Fahr, Wolfgang; Sartorius, Alexander; Becker, Robert; Didriksen, Michael; Stensbøl, Tine Bryan; Bastlund, Jesper Frank; Meyer-Lindenberg, Andreas; Schwarz, Adam J.; Department of Radiology and Imaging Sciences, IU School of Medicine
The 15q13.3 microdeletion copy number variation is strongly associated with schizophrenia and epilepsy. The CHRNA7 gene, encoding nicotinic acetylcholine alpha 7 receptors (nAChA7Rs), is hypothesized to be one of the main genes in this deletion causing the neuropsychiatric phenotype. Here we used a recently developed 15q13.3 microdeletion mouse model to explore whether an established schizophrenia-associated connectivity phenotype is replicated in a murine model, and whether positive modulation of nAChA7 receptor might pharmacologically normalize the connectivity patterns. Resting-state fMRI data were acquired from male mice carrying a hemizygous 15q13.3 microdeletion (N=9) and from wild-type mice (N=9). To study the connectivity profile of 15q13.3 mice and test the effect of nAChA7 positive allosteric modulation, the 15q13.3 mice underwent two imaging sessions, one week apart, receiving a single intraperitoneal injection of either 15 mg/kg Lu AF58801 or saline. The control group comprised wild-type mice treated with saline. We performed seed-based functional connectivity analysis to delineate aberrant connectivity patterns associated with the deletion (15q13.3 mice (saline treatment) versus wild-type mice (saline treatment)) and their modulation by Lu AF58801 (15q13.3 mice (Lu AF58801 treatment) versus 15q13.3 mice (saline treatment)). Compared to wild-type mice, 15q13.3 mice evidenced a predominant hyperconnectivity pattern. The main effect of Lu AF58801 was a normalization of elevated functional connectivity between prefrontal and frontal, hippocampal, striatal, thalamic and auditory regions. The strongest effects were observed in brain regions expressing nAChA7Rs, namely hippocampus, cerebral cortex and thalamus. These effects may underlie the antiepileptic, pro-cognitive and auditory gating deficit-reversal effects of nAChA7R stimulation.
Advocacy in Mental Health Social Interactions on Public Social Media
(2022-02) Cornet, Victor P.; Holden, Richard J.; Bolchini, Davide; Brady, Erin; Mohler, George; Hong, Michin; Lee, Sangwon
Health advocacy is a social phenomenon in which individuals and collectives attempt to raise awareness and change opinions and policies about health-related causes. Mental health advocacy is health advocacy to advance treatment, rights, and recognition of people living with a mental health condition. The Internet is reshaping how mental health advocacy is performed on a global scale, by facilitating and broadening the reach of advocacy activities, but also giving more room for opposing mental health advocacy. Another factor contributing to mental health advocacy lies in the cultural underpinnings of mental health in different societies; East Asian countries like South Korea have higher stigma attached to mental health compared to Western countries like the US. This study examines interactions about schizophrenia, a specific mental health diagnosis, on public social media (Facebook, Instagram, and Twitter) in two different languages, English and Korean, to determine how mental health advocacy and its opposition are expressed on social media. After delineation of a set of keywords for retrieval of content about schizophrenia, three months’ worth of social media posts were collected; a subset of these posts was then analyzed qualitatively using constant comparing with a proposed model describing online mental heath advocacy based on existing literature. Various expressions of light mental health advocacy, such as sharing facts about schizophrenia, and strong advocacy, showcasing offline engagement, were found in English posts; many of these expressions were however absent from the analyzed Korean posts that heavily featured jokes, insults, and criticisms. These findings were used to train machine learning classifiers to detect advocacy and counter-advocacy. The classifiers confirmed the predominance of counter-advocacy in Korean posts compared to important advocacy prevalence in English posts. These findings informed culturally sensitive recommendations for social media uses by mental health advocates and implications for international social media studies in human-computer interaction.
Affective Empathy in Schizophrenia: A Meta-Analysis
(Elsevier, 2016-08) Bonfils, Kelsey A.; Lysaker, Paul H.; Minor, Kyle S.; Salyers, Michelle P.; Department of Psychiatry, IU School of Medicine
Background Affective empathy, or the emotional response one has to the experiences or emotional states of others, contributes to relationship-maintaining behaviors and is key in fostering social connections, yet no work has synthesized the body of literature for people with schizophrenia. The aim of the present meta-analysis was to determine the extent to which those diagnosed with schizophrenia experience deficits in affective empathy. Methods A literature search was conducted of studies examining empathy. Data were analyzed using a random effects meta-analytic model with Hedges' g standardized mean difference effect size. Results Individuals with schizophrenia exhibited significant, medium deficits in affective empathy (k = 37). Measurement type moderated the affective empathy deficit such that performance-based measures showed larger schizophrenia group deficits than self-report measures. Conclusion Consistent, significant deficits in affective empathy were found comparing people with schizophrenia to healthy controls, especially when using performance-based assessments. The medium effect suggests an important role for empathy in the realm of social cognitive research, and points to the need for further investigation of measurement techniques and associations with functional outcomes.
Antipsychotic Efficacy of KarXT (Xanomeline−Trospium): Post Hoc Analysis of Positive and Negative Syndrome Scale Categorical Response Rates, Time Course of Response, and Symptom Domains of Response in a Phase 2 Study
(Physicians Postgraduate Press, 2022-05-11) Weiden, Peter J.; Breier, Alan; Kavanagh, Sarah; Miller, Andrew C.; Brannan, Stephen K.; Paul, Steven M.; Psychiatry, School of Medicine
Objective: To evaluate Positive and Negative Syndrome Scale (PANSS) categorical response rates, time course of response, and symptom subdomains of response with the combination oral agent KarXT (xanomeline-trospium) in the treatment of schizophrenia. Methods: Post hoc analysis was conducted for EMERGENT-1 (NCT03697252), a 5-week, inpatient, placebo-controlled, phase 2 study of acute psychosis in patients who met DSM-5 criteria for schizophrenia. The EMERGENT-1 study was conducted between September 2018 and August 2019. Categorical thresholds of response used were PANSS total score reductions of ≥ 20%, ≥ 30%, ≥ 40%, and ≥ 50% between baseline and study end. Number needed to treat (NNT) for each categorical threshold was calculated. The proportion of KarXT- and placebo-treated patients achieving each response threshold at weeks 2, 4, and 5 was assessed. Marder 5-factor analysis of PANSS assessed response with KarXT across symptom domains. Results: A total of 83 patients in the KarXT group and 87 patients in the placebo group were included in the modified intent-to-treat analysis. Response rates with KarXT ranged from 59.0% for a ≥ 20% threshold to 15.7% for a ≥ 50% threshold. All response rates with KarXT were significantly higher than in the placebo arm (P < .05), with NNTs ranging from 3 (≥ 20% improvement) to 11 (≥ 50% improvement). KarXT was associated with a significantly higher response rate relative to placebo as early as 2 weeks for ≥ 20% (P = .0001) and ≥ 30% (P = .0022) thresholds and at 4 weeks for the ≥ 40% (P = .0049) and ≥ 50% (P = .0041) thresholds. Each of the Marder 5 factors showed significant differences favoring KarXT over placebo (P < .05) by 2 weeks and continuing through week 5 (endpoint Cohen d effect sizes, 0.48-0.66). Conclusions: KarXT provided clinically meaningful responder rates on PANSS total score compared with placebo at each response threshold, providing further support of the successful primary and secondary endpoints. Response was demonstrated as early as 2 weeks relative to placebo. KarXT demonstrated improvements vs placebo in all 5 factors (positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility, and anxiety/depression). Trial Registration: ClinicalTrials.gov identifier: NCT03697252.
Clinical and Psychological Correlates of Two Domains of Hopelessness in Schizophrenia
(2008-12) Lysaker, Paul H.; Salyers, Michelle P.; Tsai, Jack; Spurrier, Linda Yorkman; Davis, Louanne W.
Hopelessness is a widely observed barrier to recovery from schizophrenia spectrum disorders. Yet little is known about how clinical, social, and psychological factors independently affect hope. Additionally, the relationships that exist between these factors and different kinds of hope are unclear. To explore both issues, we correlated two aspects of hope, expectations of the future and agency, with stigma, clinical symptoms, anxiety, and coping preferences in 143 persons with a schizophrenia spectrum disorder. Multiple regressions revealed that hope for the future was predicted by lesser alienation, lesser preference for ignoring stressors, and lesser emotional discomfort and negative symptoms, accounting for 43% of the variance. A greater sense of agency was linked to lesser endorsement of mental illness stereotypes, fewer negative symptoms, lesser social phobia, and lesser preference for ignoring stressors, accounting for 44% of the variance. Implications for research and interventions are discussed.
Compared to high and low cannabis use, moderate use is associated with fewer cognitive deficits in psychosis
(Elsevier, 2016-12) Martin, Ashley M. Schnakenberg; Bonfils, Kelsey A.; Davis, Beshaun J.; Smith, Elizabeth A.; Schuder, Kelly; Lysaker, Paul H.; Department of Psychiatry, IU School of Medicine
Literature on the relationship of cannabis use and cognition in schizophrenia provides the paradoxical view that cannabis use is sometimes linked with less severe impairment in neurocognition. This paper explored the possibility that this is a reflection of a dose related response between lifetime cannabis use and two forms of cognition, neurocognition and metacognition, in schizophrenia. It was hypothesized that three groups of patients could be differentiated, those with (1) little to no cannabis use with poor levels of cognition, (2) moderate cannabis use and relatively better levels of cognition and (3) high cannabis use with relatively poorer levels of cognition. Sixty-six adults with schizophrenia completed assessments of neurocognition, metacognition and months of lifetime cannabis use. A k-means cluster analysis yielded three distinct groups based on these assessments. The clusters included: (1) low cannabis/poor cognition (n = 34); (2) heavy cannabis/moderately impaired cognition (n = 10); and (3) moderate cannabis/higher cognition (n = 22). Consistent with our hypothesis, participants with high and moderate lifetime cannabis use had lesser impairment of neurocognition and metacognition compared to low lifetime cannabis use. Participants with moderate lifetime cannabis use also had lesser impairment of metacognition compared to low and heavy use. These findings suggest that a dose related relationship exists between cannabis use and cognition. Results could be due to an influence of pre-existing cognitive level on likelihood of lifetime cannabis use, or to an interaction between use and cognitive function.
Contrasting metacognitive profiles and their association with negative symptoms in groups with schizophrenia, early psychosis and depression in a Russian sample
(Elsevier, 2020-09) Lysaker, Paul H.; Chernov, Nikita; Moiseeva, Tatyana; Sozinova, Marta; Dmitryeva, Nadezhda; Alyoshin, Vitaliy; Faith, Laura A.; Karpenko, Olga; Kostyuk, Georgiy; Psychiatry, School of Medicine
Research has suggested that negative symptoms in psychotic disorders may be in part fueled by deficits in metacognition or the ability to form integrated ideas about oneself and others. One limitation of this work is that it has largely come from North America and Western Europe. To further the literature, we assessed symptoms using the Positive and Negative Syndrome Scale and Metacognition using the Metacognitive Assessment Scale - Abbreviated in a sample of outpatients with prolonged schizophrenia (n = 41), early episode psychosis (n = 37) and major depression (n = 30) gathered in Moscow, Russia. Verbal memory was assessed for use as a potential covariate. ANOVA revealed the two groups with psychosis had significantly poorer metacognitive function in terms of self-reflectivity and awareness of the other, than the group with depression. In both psychosis groups negative symptoms were more robustly related to metacognition than other forms of symptoms after controlling for neurocognition. Results support the possibility that metacognitive deficits are a psychological factor which cross culturally contributes to negative symptoms and point to metacognition as a potentially important target for intervention.
Contrasting Metacognitive, Social Cognitive and Alexithymia Profiles in Adults with Borderline Personality Disorder, Schizophrenia and Substance Use Disorder
(Elsevier, 2017-11) Lysaker, Paul H.; George, Sunita; Chaudoin-Patzoldt, Kelly A.; Pec, Ondrej; Bob, Petr; Leonhardt, Bethany L.; Vohs, Jenifer L.; James, Alison V.; Wickett, Amanda; Buck, Kelly D.; Dimaggio, Giancarlo; Department of Psychiatry, School of Medicine
Deficits in the ability to recognize and think about mental states are broadly understood to be a root cause of dysfunction in Borderline Personality Disorder (PD). This study compared the magnitude of those deficits relative to other forms of serious mental illness or psychiatric conditions. Assessments were performed using the metacognition assessment scale-abbreviated (MAS-A), emotion recognition using the Bell Lysaker Emotion Recognition Test and alexithymia using the Toronto Alexithymia Scale among adults with schizophrenia (n = 65), Borderline PD (n = 34) and Substance Use disorder without psychosis or significant Borderline traits (n = 32). ANCOVA controlling for age revealed the Borderline PD group had significantly greater levels of metacognitive capacity on the MAS-A than the schizophrenia group and significantly lower levels of metacognitive capacity than the Substance Use group. Multiple comparisons revealed the Borderline PD group had significantly higher self-reflectivity and awareness of the other's mind than the schizophrenia group but lesser mastery and decentration on the MAS-A than substance use group, after controlling for self-report of psychopathology and overall number of PD traits. The Borderline PD and Schizophrenia group had significantly higher levels of alexithymia than the substance use group. No differences were found for emotion recognition. Results suggest metacognitive functioning is differentially affected in different mental disorders.
Convergent Functional Genomics of Schizophrenia: From Comprehensive Understanding to Genetic Risk Prediction
(Office of the Vice Chancellor for Research, 2012-04-13) Ayalew, M.; Le-Niculescu, H.; Levey, D.F.; Jain, N.; Changala, B.; Patel, S.D.; Winiger, E.; Breier, A.; Shekhar, A.; Amdur, R.; Koller, D.; Nurnberger, J.I.; Corvin, A.; Geyer, M.; Tsuang, M.T.; Salomon, D.; Schork, N.; Fanous, A.H.; O’ Donovan, M.C.; Niculescu, A.B.
We have used a translational convergent functional genomics (CFG) approach to identify and prioritize genes involved in schizophrenia, by gene-level integration of genome-wide association study (GWAS) data with other genetic and gene expression studies in humans and animal models. Using this polyevidence scoring and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1, NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1, GRIA1, GRN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination, cell adhesion, glutamate receptor signaling, G-protein coupled receptor signaling and cAMP- mediated signaling as key to pathophysiology and as targets for therapeutic intervention. Overall, the data is consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability. In addition, we show how the top candidate genes identified by CFG can be used to generate a genetic risk prediction score (GRPS) to aid schizophrenia diagnostics, with predictive ability in independent cohorts. The GRPS also differentiates classic age of onset schizophrenia from early onset and late-onset disease. We also show, in three independent cohorts, two European-American (EA) and one African-American (AA), increasing overlap, reproducibility and consistency of findings from SNPs to genes, then genes prioritized by CFG, and ultimately at the level of biological pathways and mechanisms. Lastly, we compared our top candidate genes for schizophrenia from this analysis with top candidate genes for bipolar disorder and anxiety disorders from previous CFG analyses conducted by us, as well as findings from the fields of autism and Alzheimer. Overall, our work maps the genomic and biological landscape for schizophrenia, providing leads towards a better understanding of illness, diagnostics, and therapeutics. It also reveals the significant genetic overlap with other major psychiatric disorder domains, suggesting the need for improved nosology.
Coping with Positive and Negative Symptoms of Schizophrenia
(2010-08) Rollins, Angela L.; Bond, Gary R.; Lysaker, Paul H.; McGrew, John H.; Salyers, Michelle P.
Objective: Although coping with positive symptoms of schizophrenia has been studied widely, few studies have examined coping with negative symptoms. This study compares the appraisal of stressfulness and coping patterns in response to positive and negative symptoms experienced by clients with schizophrenia attending a community mental health center. Methods: Clients were interviewed to assess symptom severity, appraisal of symptom stressfulness, and coping strategies used for selected symptoms rated as severe and reported as stressful. Open-ended responses from clients regarding coping strategies were coded according to an a priori coding scheme. Results: Clients reported negative symptoms as less stressful, and they used fewer coping strategies in response than they did for positive symptoms. Clients used some types of coping more than others: behavioral more than cognitive, nonsocial more than social, emotion-focused more than problem-focused, and avoidant more than nonavoidant. Conclusions: Clients more often report positive symptoms as stressful compared with negative symptoms, though negative symptoms are still reported as stressful to a certain degree, indicating a need to improve our ability to help clients cope with negative symptoms. Clients are less likely to use coping strategies to counteract negative symptoms compared with positive symptoms. Implications are discussed for developing interventions tailored to promoting awareness of and ways of coping with negative symptoms.

Browsing by Subject "schizophrenia"

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