Isidora Ljuri

Predictors of response to cognitive remediation in service recipients with severe mental illness.

Objective: Cognitive challenges are prominent features of individuals diagnosed with schizophrenia, impairing occupational, social, and economic functioning. These challenges are predictive of social and work outcomes. Cognitive remediation has been shown to be effective in improving both cognitive and social functions. However, cognitive remediation does not produce improvement in all participants. We investigated demographic, neurocognitive, and psychopathological predictors associated with improvement following cognitive remediation interventions in service recipients with severe mental illnesses. Method: One hundred thirty-seven adult participants with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) were enrolled in 12-week cognitive remediation programs. Assessments of demographic and illness variables, together with baseline and end point assessment of psychopathology (Positive and Negative Syndrome Scale [PANSS]), neurocognition (Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] Consensus Cognitive Battery [MCBB]), and social functions (Personal and Social Performance Scale [PSP]) were conducted. Change in cognitive domains was calculated using the reliable change index. Logistic regression analysis was used to assess predictors of cognitive improvement after the intervention. Results: Sixty-two percent of participants improved on at least 1 of the MCCB domains. Higher baseline speed of processing, attention or vigilance, and working memory predicted a positive response to cognitive remediation. Younger age, higher education level, shorter length of stay, and lower PANSS Negative and Disorganized factors were additional predictors. Conclusions and Implications for Practice: Our results indicate the clinical usefulness of cognitive remediation and identified a pattern of clinical and cognitive predictors of good response to the intervention. Identification of these predictive factors by clinicians may enhance the outcome and aid in the development of individualized rehabilitative cognitive remediation treatment plans.

Does social cognition training augment response to computer-assisted cognitive remediation for schizophrenia?

OBJECTIVES Cognitive remediation therapy (CRT) has shown significant improvement in cognition in schizophrenia. However, effect sizes of CRT have been reported to be modest raising the issue how to augment the effects of CRT on neurocognition and social cognition. Our aim was to examine whether the addition of computerized social cognition training would enhance the effects on neurocognition and social cognition as compared to CRT alone. METHODS This is a 12-week, parallel group trial of 131 in- and out-patients with schizophrenia randomized to CRT (COGPACK or Brain Fitness) with computerized social cognition training (MRIGE), or CRT alone for 36 sessions. Participants were assessed at baseline and after 12 weeks of treatment. Assessments included neurocognition, social cognition, psychopathology, and functioning. RESULTS The combined intervention, CRT + MRIGE, showed greater improvements in the MCCB indices of Visual Learning, Working Memory, Reasoning and Problem-Solving, and the neurocognitive composite score compared to CRT alone (Bonferroni adjusted p = 0.004, p = 0.005, p = 0.01, respectively), as did social cognition measures (Bonferroni adjusted p = 0.006, p = 0.005, respectively). CONCLUSIONS Supplementing CRT with computerized social cognition training produced greater benefits in neurocognition, including visual learning, memory, executive functions, and social cognition relative to cognitive training alone. These findings favoring the combined training may be contributed to both the greater overall amount of cognitive practice, as well as the specific cognitive functions engaged by the social cognition training.

T43. TRANSCRANIAL DIRECT-CURRENT STIMULATION (TDCS) IN PATIENTS WITH ULTRA-TREATMENT-REFRACTORY AUDITORY HALLUCINATIONS

Abstract Background Transcranial direct-current stimulation (tDCS), a noninvasive neurostimulation treatment, has been reported to show improvements in treatment-resistant auditory hallucinations in patients with schizophrenia. tDCS administered over a limited number of sessions effectively produced lasting attenuation of auditory hallucinations in otherwise stable outpatients. It has also been shown that tDCS may be a useful intervention for ameliorating cognitive deficits in patients with chronic schizophrenia. The purpose of this study was to test tDCS for auditory hallucinations in ultra-treatment resistant schizophrenia to assess if this form of neurostimulation can alleviate treatment-refractory auditory hallucination symptoms up to 4 weeks after the final treatment. In addition, we also wanted to examine the effects of tDCS on cognitive functions. Methods 28 inpatients with DSM-V schizophrenia and long-standing treatment resistance and persistent auditory verbal hallucinations were recruited. Each individual participated in behavioral assessments at baseline, endpoint and follow-up [PANSS and Auditory Hallucinations Rating Scale (AHRS) and MCCB cognitive battery] and were randomized to receive active vs. sham tDCS treatments. For active treatment, patients had the inhibitory (cathodal) tDCS electrode placed over left auditory cortex relative to an excitatory (anodal) electrode placed over frontal cortex on the right side. tDCS treatments took place for 20 min twice daily for 5 consecutive days. Assessment batteries were repeated following the 4 weeks of treatment. The Chattanooga, dual channel CHA-1335 stimulator with two 7 × 5 cm (35 cm2) sponge electrodes soaked in a saline solution (0.9% NaCl) was used for the delivery of 2 mA current. Results A total of 28 subjects were enrolled (tDCS, n = 13; Control, n = 15). 20 subjects completed the trial. 3 subjects dropped out of the active tDCS treatment group, while 4 subjects did not complete the control treatment due to early discharge from the hospital. Most subjects were male (tDCS n = 10, 76.9%; Control n = 6, 40.0%). Length of present psychiatric admission ranged from 1–25 months, with a mode of 2 months (n = 12) and average of 2.9 months. Participating inpatients were on clozapine, haloperidol, paliperidone depot, fluphenazine decanoate, paliperidone, olanzapine, and risperidone as primary medications. Repeated Measures ANOVA showed a significant difference for the auditory hallucination total score, frequency and number of voices over time (p < 0.05) with greater reduction in scores observed for the tDCS group. Improvements were maintained after 4 weeks. There was no significant change over time observed for the PANSS positive symptoms or total score, or for the PANSS Hallucinatory Behavior item score. When assessing cognitive functioning, only Working Memory change was significant (p = 0.048) between the tDCS and the Control group with the tDCS group showing significant improvement in T-Score as compared to the Control group. Discussion Subjects who received tDCS treatment showed a significant reduction in the frequency, number of voices, and total scores of their auditory hallucination. Additionally, subjects in the tDCS group showed significant improvement in the Working Memory. Our results indicate that patients who have been ultra-resistant to antipsychotic treatments and who received tDCS treatment presented with robust diminution of their auditory hallucinations. We conclude that tDCS seems to be effective not only for ambulatory, higher functioning patients, but also for much lower functioning patients with medication-refractory auditory verbal hallucinations.

F143. PREDICTORS OF RELAPSE: PATIENT, DISEASE, COGNITIVE, AND FUNCTIONAL CHARACTERISTICS WITH COMT GENE VAL158MET POLYMORPHISM IN A 2-YEAR FOLLOW-UP

Abstract Background Schizophrenia is a severe and chronic mental illness characterized by continual relapses that may require hospitalization, changes in medications, arrests, emergency room hospitalizations, self-harm or suicidal behavior. Research has shown that costs associated with treatment received following relapse may constitute the largest share of treatment costs psychiatric illnesses. Although, demographic and clinical characteristics associated with relapse have been examined in previous research, information about potential predictors of relapse are limited. The aim of this study was to evaluate the effect of patient and disease characteristics, cognitive, functioning, and COMT gene polymorphism (rs4680) on relapse during 2-year following completion of an inpatient rehabilitation and cognitive treatment. Methods Data were taken from a COMT genotype and response to cognitive remediation study of schizophrenia in the United States conducted between 07/2005 and 10/2015 for inpatients with schizophrenia who were also participating in psychiatric rehabilitation. Patients with and without relapse 2 years following completion of the study were compared on clinical, demographic, cognitive, functional and COMT genotype characteristics. The COMT gene rs4680 polymorphism was genotyped using a DNA sequence detection system. Relapse or events identified as treatment failures include: arrest, psychiatric re-hospitalization, suicide, discontinuation of antipsychotic treatment due to inadequate efficacy, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to safety or tolerability, or increase in the level of psychiatric services. Baseline (end of study, start of 2-year follow-up) predictors of subsequent relapse were also assessed. Univariate Analsyis and Cox’s regression was used to examine the effect of potential predictors on outcome. Results Of 140 subjects with eligible data, 91 (65.00%) relapsed during the 2-year follow-up period. Patients who relapsed were younger (< 45 years), higher number of previous hospitalizations, shorter chronicity of illness (< 10 years), PANSS baseline score of >4 on the core PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content), higher negative symptom factor, substance use, PSP score of < 60 and lower MCCB composite T score (> 2 SD below the mean). Univariate analysis shows that COMT rs4680 gene variants were different between relapse and stable groups. The COMT rs4680 gene had an interaction with PANSS baseline core item scores and MCCB composite score. Number of previous antipsychotic trials did not predict relapse. Discussion There is a high relapse rate within 2 years in chronic schizophrenia. Behavioral symptoms, aided by genetic and environmental factors common to this population (homelessness, unemployment, and social isolation) frequently lead to treatment failure. Knowing potential triggers of relapse can help in developing resources for this population to reduce treatment failures and associated costs.

F63. COGNITIVE CORRELATES OF THE NEGATIVE SYMPTOMS EXPRESSIVE AND EXPERIENTIAL DEFICIT FACTORS IN PSYCHOSIS

Abstract Background Primary negative symptoms of schizophrenia contribute heavily to functional disability. Treatment of these symptoms continues to be a major unmet need, even when positive symptoms are controlled. Recent factor analyses of negative symptoms using the PANSS and other symptom assessments in patients with schizophrenia have identified two factors of negative symptoms: expressive and experiential deficits. These two factors most likely have very different clinical, neurocognitive and neurobiological correlates. This study examines the clinical and cognitive correlates associated with expressive and experiential deficits in a large cohort of patients with psychosis before and after computerized cognitive remediation. Methods This is a secondary data analysis of subjects enrolled in a cognitive remediation program for 12 weeks. One hundred fifty-one subjects age 18 - 55 with a DSM IV-TR diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder were enrolled. Assessments of demographic, psychopathology (PANSS), cognition (MCBB), and daily living skills (UPSA-Brief) were conducted at baseline and endpoint. Exploratory (EFA) and confirmatory (CFA) factor analyses of PANSS items as well as Pearson’s correlations between factors, demographics, MCCB, and UPSA-Brief scores were examined at baseline and endpoint. Results EFA baseline PANSS data resulted in the five-factor model of the PANSS with seven items attributed to the Negative Symptom Factor (NSF; N1, blunted affect; N2, emotional withdrawal; N3, poor rapport; N4, passive social withdrawal; N6, lack of spontaneity and flow of conversation; G7, motor retardation; and G16, active social avoidance). CFA of the NSF revealed a two-factor model consisting of an Expressive Deficit (N1, N3, N6, G7), and an Experiential Deficit (N2, N4, and G16). Difference tests comparing the one-factor and two-factor models found that the two-factor model exhibited significantly better fit than the one-factor model (χ2 = 67.117, df = 1, p ≤ 0.001; CFI = 0.92; Tucker–Lewis index TLI = 0.91; root mean square error of approximation RMSEA = 0.040; and Goodness of Fit index GFI = 0.93). There were significant correlations between the Expressive Deficit factor score and cognition: TMT- A (r=-0.259, p=0.001), BACS Symbol coding (r=-0.287, p=0.001), Category Fluency (r=-0.342, p=0.001), Hopkins Verbal Learning Test – revised (HTLV-R) (r=-0.236, p=0.05), Letter Number Sequencing (r=-0.256, P=0.001), and NAB Mazes (r=-0.409, p=0.001). The Expressive Deficit factor was also significantly correlated with the neurocognitive domains of Processing Speed (r=-0.352, p=0.001) and Reasoning/Problem Solving (r=-0.338, p=0.001). There were no significant correlations between either factor and UPSA-Brief or the MCCB cognitive composite. There were no significant correlations for change from baseline to endpoint in negative symptoms. Discussion Our results support the negative symptom two-factor model of Expressive Deficit and Experiential Deficit domains. Only the Expressive Deficit factor was associated with baseline deficits in Working Memory, Processing Speed, Reasoning/Problem Solving and Verbal Learning. The association of the Expressive Deficit factor with significant cognitive impairments supports a more profound neurobiological dysfunction in contrast to the Experiential Deficit factor and may represent an important treatment challenge. The relevance of these findings for the treatment of negative symptoms in schizophrenia will be discussed.

Transcranial Direct-Current Stimulation in Ultra-Treatment-Resistant Schizophrenia

BACKGROUND Transcranial direct-current stimulation (tDCS), a non-invasive neurostimulation treatment, has been reported in a number of sham-controlled studies to show significant improvements in treatment-resistant auditory hallucinations in schizophrenia patients, primarily in ambulatory and higher-functioning patients, but little is known of the effects of tDCS on hospitalized, low-functioning inpatients. OBJECTIVE/HYPOTHESIS The purpose of this study was to examine the efficacy and safety of tDCS for auditory hallucinations in hospitalized ultra-treatment-resistant schizophrenia (TRS) and to evaluate the effects of tDCS on cognitive functions. We hypothesized that treatment non-response reported in previous tDCS studies may have been due to the insufficient duration of direct-current stimulation. METHODS Inpatient participants with DSM-V schizophrenia, long-standing treatment-resistance, and auditory verbal hallucinations (AVH) participated in this 4-week sham-controlled, randomized trial. Assessments included the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) at baseline and endpoint (at the end of Week 4), and the Auditory Hallucinations Rating Scale (AHRS) administered at baseline, endpoint, and weekly throughout the study. Participants were randomized to receive active vs. sham tDCS treatments twice daily for 4 weeks. RESULTS Twenty-eight participants were enrolled (tDCS, n = 15; control, n = 13) and 21 participants completed all 4 weeks of the trial. Results showed a significant reduction for the auditory hallucination total score (p ≤ 0.05). We found a 21.9% decrease in AHRS Total Score for the tDCS group and a 12.6% decrease in AHRS Total Score for the control group. Significant reductions in frequency, number of voices over time, length of auditory hallucinations, and overall psychopathology were also observed for the tDCS group. When assessing cognitive functioning, only Working Memory showed improvement for the tDCS group. CONCLUSION Although there was only a small improvement noted in auditory hallucination scores for the tDCS group, this improvement was meaningful when compared to no standard treatment of the control group. While this makes the interpretation of clinical significance debatable, it does confirm that tDCS combined with pharmacological intervention can provide clinical gains over pharmacological intervention alone. Therefore, tDCS treatment appears to be effective not only for ambulatory, higher-functioning patients, but also for patients with ultra-treatment-resistant schizophrenia.

The relationship of cognitive improvement after cognitive remediation with social functioning in patients with schizophrenia and severe cognitive deficits

BACKGROUND This study aims to examine the effects of change in neurocognition on functional outcomes and to examine predictors of change in social functions following a 12-week course of cognitive remediation in patients with schizophrenia and schizoaffective disorder with severe cognitive impairments. METHOD Level of social functioning was assessed using a performance based measure of functional capacity (PSP) in patients prior to and after the completion of 12-week cognitive remediation treatment (CRT). Participants completed a neuropsychological battery (MCCB-MATRICS) and clinical measures at both time points. RESULTS 63 subjects with a mean age of 41.4 (SD=12.2) and with 12.2years of education (SD=2.4) were enrolled. There were significant improvements in overall PSP score from baseline to endpoint (p=0.021) as well as in PSP domain A (socially useful activities) (p≤0.001), domain B (personal and social relationships) (p=0.009), and domain D (disturbing and aggressive behaviors) (p=0.003). There was a significant improvement in the composite MCCB score (p=0.020) and the Working Memory (p<0.046). Stepwise logistic regression yielded a significant association for baseline Visual Learning (Wald=6.537, p=0.011, OR=1.195), Speed of Processing (Wald=4.112, p=0.043, OR=0.850) and level of PANSS positive symptoms (Wald=4.087, p=0.043, OR=0.739) with PSP overall improvement. CONCLUSIONS Faster speed of processing, better visual and verbal learning and less prominent positive symptoms were associated with greater functional improvement after a systematic cognitive intervention within a rehabilitative setting.