Plasticity of DNA methylation, functional brain connectivity and efficiency in cognitive remediation for schizophrenia.

Cognitive remediation (CR) is predicated on principles of neuroplasticity, but the actual molecular and neurocircuitry changes underlying cognitive change in individuals with impaired neuroplastic processes is poorly understood. The present study examined epigenetic-neurocircuitry-behavioral outcome measures in schizophrenia, before and after participating in a CR program that targeted higher-order cognitive functions. Outcome measures included DNA methylation of genes central to synaptic plasticity (CpG sites of Reelin promoter and BDNF promoter) from buccal swabs, resting-state functional brain connectivity and topological network efficiency, and global scores of a cognitive battery from 35 inpatients in a rehabilitative ward (18 CR, 17 non-CR) with similar premorbid IQ to 15 healthy controls. Baseline group differences between healthy controls and schizophrenia, group-by-time effects of CR in schizophrenia, and associations between the outcome measures were tested. Baseline functional connectivity abnormalities within the frontal, fronto-temporal and fronto-parietal regions, and trending decreases in global efficiency, but not DNA methylation, were found in schizophrenia; the frontal and fronto-temporal connectivity, and global efficiency correlated with global cognitive performance across all individuals. Notably, CR resulted in differential changes in Reelin promoter CpG methylation levels, altered within-frontal and fronto-temporal functional connectivity, increasing global efficiency and improving cognitive performance in schizophrenia, when compared to non-CR. In the CR inpatients, positive associations between the micro to macro measures: Reelin methylation changes, higher global efficiency and improving global cognitive performance were found. Present findings provide a neurobiological insight into potential CR-led epigenetics-neurocircuitry modifications driving cognitive plasticity.

Correlates of nursing care burden among institutionalized patients with dementia.

ABSTRACTBackground:The stress associated with care of patients with dementia has led to high nursing staff turnover. This study aims to explore patient factors that are related to nursing burden. METHODS: The present study examined nursing care burden related to 55 institutionalized dementia patients using the Modified Nursing Care Assessment Scale (M-NCAS). Cognition was assessed with the Severe Impairment Battery (SIB), activities of daily living (ADLs) were measured with the Alzheimer's Disease Functional Assessment of Change Scale (ADFACS), aggression was measured with the Aggressive Behavior Scale (ABS), and the Charlson Comorbidity Index (CCI) was used to assess medical comorbidity. Finally, the Dementia Cognitive Fluctuation Scale (DCFS) was used to assess the presence and severity of cognitive fluctuations (CFs). Linear regression models were used to assess their relationships with nursing care burden. RESULTS: The mean age of the patients was 90.41 years (SD=2.84) and 89.10% were males. ADFACS total score (B = 0.36, ß = 0.42, p = 0.002) and ABS score (B = 2.933, ß = 0.37, p = 0.002) significantly predicted the M-NCAS Attitude score. ABS score was the only significant predictor of M-NCAS Strain score (B = 2.57, ß = 0.35, p = 0.009). CONCLUSIONS: In the long-term care setting, aggressive behavior plays an important role in both subjective and objective nursing burden, while impaired ADLs increase the objective burden for nursing staff.

The association between cognitive fluctuations and activities of daily living and quality of life among institutionalized patients with dementia.

OBJECTIVE: Cognitive fluctuations (CFs) occur commonly in dementia of all types. While it is generally accepted that CFs can affect the clinical rating of dementia severity and neuropsychological performance, little is known about their impact on patients' activities of daily living (ADLs) and quality of life (QOL). Our study aims to explore the impact of CFs on ADLs and QOL among institutionalized patients with dementia. METHODS: The present study examined the nature and frequency of CFs in 55 institutionalized dementia patients. We used the Dementia Cognitive Fluctuation Scale (DCFS) to assess the presence and severity of CFs. The Alzheimer's Disease Functional Assessment of Change Scale (ADFACS) was used to assess patients' ADLs, and the Quality of Life in Late Stage Dementia scale (QUALID) was used to assess QOL. Linear regression models were used to assess the relationships between CFs, ADLs, and QOL. RESULTS: The mean age of the patients was 90.41 years (SD = 2.84). Their mean Aggressive Behavior Scale score was 1.13 (SD = 1.59), mean Severe Impairment Battery total score was 86.65 (SD = 13.77), and mean DCFS score was 10.07 (SD = 3.04). The mean ADFACS-ADL score was 10.88 (SD = 6.37), mean ADFACS-IADL score was 16.61 (SD = 9.54), and mean QUALID total score was 18.25 (SD = 5.70). DCFS significantly predicted ADFACS-ADL score (R2  = 0.39, ß = 0.30, P = .011) although the relationship between ADFACS-IADL score and DCFS score was not significant (R2  = 0.16, P = .111). DCFS significantly predicted QUALID score (R2  = 0.08, ß = 0.29, P = .033). CONCLUSION: More severe CFs in patients with dementia were significantly associated with impaired ability to engage in ADLs and poorer QOL.

Training eldercare workers in mental healthcare.

INTRODUCTION: A significant proportion of older persons who require support or care services have mental health concerns. There is a need to equip frontline eldercare workers with the necessary skills in caring for older persons with mental illnesses. The Community Psychogeriatric Programme aims to support community eldercare providers with training and consultation. We sought to measure eldercare workers' perceived levels of stress and knowledge about caring for older persons with mental illness before (pre-workshop), immediately after (post-workshop) and three months after (three-month follow-up) they underwent standardised training workshops on dementia and depression. METHODS: Participants who attended two four-hour workshops on dementia and depression were recruited for the study. Their knowledge of topics was evaluated pre-workshop, post-workshop and at three-month follow-up. Perceptions of working with older persons with mental health problems were rated pre-workshop and at three-month follow-up. RESULTS: A total of 71 staff members from various eldercare centres participated in the study, of which 51 (71.8%) were women. At three-month follow-up, there was a significant change in most measures on Ryden's Perception Scale (p < 0.05). There were significant improvements in knowledge scores for dementia and depression (p < 0.001). Knowledge gains after the workshop were maintained at three-month follow-up. CONCLUSION: Training of eldercare workers in mental healthcare is helpful for knowledge improvement and altering perceptions of caring for older persons. With continued support from mental health professionals, such training could contribute to better care for this vulnerable population.

Cognitive Fluctuations and Cognitive Test Performance Among Institutionalized Persons With Dementia.

OBJECTIVE: To examine the nature and frequency of cognitive fluctuations (CFs) among institutionalized persons with dementia. METHOD: A clinical interview and a medical chart review were conducted, and 55 patients were assigned a specific dementia diagnosis. The Severe Impairment Battery (SIB) was administered to assess cognitive function, and the Dementia Cognitive Fluctuation Scale (DCFS) was administered to each patient's primary nurse to determine the presence and severity of CFs. RESULTS: A simple linear regression model was conducted with DCFS as the predictor variable and SIB total score as the dependent variable. The overall model was significant, suggesting that score on the DCFS significantly predicted SIB total score. Additionally, greater severity of CFs predicted poorer performance in the areas of orientation, language, and praxis. CONCLUSIONS: Results suggest that CFs exert a clinically significant influence over patients' cognitive abilities and should be considered as a source of excess disability.

Subtyping Schizophrenia by Treatment Response: Antipsychotic Development and the Central Role of Positive Symptoms.

(Reprinted with permission from The Canadian Journal of Psychiatry 2015; 60(11):515-522).

Subtyping Schizophrenia by Treatment Response: Antipsychotic Development and the Central Role of Positive Symptoms.

We have recently proposed a model for subtyping schizophrenia based on antipsychotic (AP) treatment response. Evidence suggests that APs, both old and new, are comparable in terms of efficacy; however, one AP, clozapine, is uniquely effective in one subgroup of patients (that is, those with treatment-resistant schizophrenia [TRS]). This permits us to subdivide schizophrenia into 3 specific groups: AP responsive, clozapine responsive, and clozapine resistant. Here, we integrate this model with current criteria related to TRS and ultraresistant schizophrenia, the latter referred to in our model as clozapine resistant. We suggest several modifications to existing criteria, in line with current evidence and practice patterns, particularly emphasizing the need to focus on positive symptoms. While APs can favourably impact numerous dimensions related to schizophrenia, it is their effect on positive symptoms that distinguishes them from other psychotropics. Further, it is positive symptoms that are central to AP and clozapine resistance, and it is these people that place the greatest demands on acute and long-term inpatient resources. In moving AP development forward, we advocate specifically focusing on positive symptoms and capitalizing on the evidence we have of 3 subtypes of psychosis (that is, positive symptoms) based on treatment response, implicating 3 distinguishable forms of underlying pathophysiology. Conversely, pooling these groups risks obfuscating potentially identifiable differences. Such a position does not challenge the importance of dopamine D2 receptor blockade, but rather highlights the need to better isolate those other subgroups that require something more or entirely different.

The PSS-SR as a screening tool for PTSD in first-episode psychosis patients.

AIM: We examined the validity of the PTSD Symptom Scale - Self-Report (PSS-SR) as a screening instrument for post-traumatic stress disorder (PTSD) in patients recovering from first-episode psychosis. METHODS: Sixty-one patients from the Early Psychosis Intervention Programme in Singapore completed the PSS-SR questionnaire. The Clinician-Administered PTSD Scale was administered by a blinded interviewer as the 'gold standard' to identify patients with PTSD. The sensitivity, specificity and receiver operating characteristic curve were used to determine the screening performance of the PSS-SR. RESULTS: The score representing the optimal cut-off point for the PSS-SR was 14, with a sensitivity and specificity of 0.83 and 0.71, respectively. The area under the curve was determined to be 0.82 (95% CI: 0.70-0.95). CONCLUSION: These data suggest that the PSS-SR can be a useful screening instrument for PTSD in patients recovering from their first psychotic episode.

Prevalence of post-traumatic stress disorder in first-episode psychosis.

BACKGROUND: Psychosis can be considered one of the most severe stressors that an individual may face. Previous studies have suggested that the traumatic experience of psychotic symptoms and hospitalization may provoke a post-traumatic type reaction. AIM: The aim of this study was to establish the point prevalence of post-traumatic stress disorder (PTSD) among patients recovering from a first-episode of psychosis in Singapore, and to elucidate the factors associated with it. METHODS: Patients from the Early Psychosis Intervention Programme in Singapore, who were recovering from their first psychotic episode, participated in this study. Diagnoses were made using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) - Text Revised Axis I Disorders. The Clinician-Administered PTSD Scale, an interviewer-rated semi-structured interview, was used to diagnose PTSD. RESULTS: Sixty-one patients (30 males, 31 females) were recruited. Twelve (19.7%) patients were diagnosed with PTSD. Hospitalization for treatment, whether compulsory or otherwise, did not increase the rate of PTSD. The Chinese ethnic group had lower risk of developing PTSD (adjusted odds ratio 0.14, P = 0.018). CONCLUSIONS: There was a high prevalence of PTSD in patients recovering from their first psychotic episode. This study raises awareness among clinicians and hopes to promote early recognition and treatment of PTSD so as to potentially improve outcome.