A Southeast Asia Consensus on the Definition and Management of Treatment-Resistant Depression.

Introduction: Despite the abundance of literature on treatment-resistant depression (TRD), there is no universally accepted definition of TRD and available treatment pathways for the management of TRD vary across the Southeast Asia (SEA) region, highlighting the need for a uniform definition and treatment principles to optimize the management TRD in SEA. Methods: Following a thematic literature review and pre-meeting survey, a SEA expert panel comprising 13 psychiatrists with clinical experience in managing patients with TRD convened and utilized the RAND/UCLA Appropriateness Method to develop consensus-based recommendations on the appropriate definition of TRD and principles for its management. Results: The expert panel agreed that "pharmacotherapy-resistant depression" (PRD) is a more suitable term for TRD and defined it as "failure of two drug treatments of adequate doses, for 4-8 weeks duration with adequate adherence, during a major depressive episode". A stepwise treatment approach should be employed for the management of PRD - treatment strategies can include maximizing dose, switching to a different class, and augmenting or combining treatments. Non-pharmacological treatments, such as electroconvulsive therapy and repetitive transcranial magnetic stimulation, are also appropriate options for patients with PRD. Conclusion: These consensus recommendations on the operational definition of PRD and treatment principles for its management can be adapted to local contexts in the SEA countries but should not replace clinical judgement. Individual circumstances and benefit-risk balance should be carefully considered while determining the most appropriate treatment option for patients with PRD.

A Southeast Asian expert consensus on the management of major depressive disorder with suicidal behavior in adults under 65 years of age.

BACKGROUND: The high prevalence of suicidal behavior among individuals with major depressive disorder (MDD) in Southeast Asia (SEA) underscores the need for optimized management to address depressive symptoms, reduce suicide risk and prevent suicide in these individuals. Given the lack of clear guideline recommendations for assessing and managing these patients, regional consensus-based recommendations which take into account diverse local contexts across SEA may provide useful guidance for clinical practice. METHODS: A narrative literature review and pre-meeting survey were conducted prior to the consensus meeting of an SEA expert panel comprising 13 psychiatrists with clinical experience in managing patients with MDD with suicidal behavior. Utilizing the RAND/UCLA Appropriateness Method, the expert panel developed consensus-based recommendations on the assessment and treatment of adult patients with MDD with suicidal behavior under 65 years. RESULTS: Screening of adult patients under 65 years with MDD for suicide risk using both a validated assessment tool and clinical interview is recommended. An improved suicide risk stratification - incorporating both severity and temporality, or using a prevention-focused risk formulation - should be considered. For a patient with an MDD episode with low risk of suicide, use of antidepressant monotherapy, and psychotherapy in combination with pharmacological treatment are both recommended approaches. For a patient with an MDD episode with high risk of suicide, or imminent risk of suicide requiring rapid clinical response, or for a patient who had received adequate AD but still reported suicidal behavior, recommended treatment strategies include antidepressant augmentation, combination use of psychotherapy or electroconvulsive therapy with pharmacological treatment, and inpatient care. Suicide-specific psychosocial interventions are important for suicide prevention and should also be part of the management of patients with MDD with suicidal behavior. CONCLUSIONS: There are still unmet needs in the assessment of suicide risk and availability of treatment options that can deliver rapid response in patients with MDD with suicidal behavior. These consensus recommendations on the management of adult patients with MDD with suicidal behavior under 65 years may serve as a useful guidance in diverse clinical practices across the SEA region. Clinical judgment based on careful consideration of individual circumstances of each patient remains key to determining the most appropriate treatment option.

Health Action Process Approach (HAPA) as a Framework to Understand Compliance Issues With Health Protocols Among People Undergoing Isolation at Emergency Hospital for COVID-19 Wisma Atlet Kemayoran and RSCM Kiara Ultimate Jakarta Indonesia.

Introduction: This study aims to identify the psychosocial determinants and examine the mediation mechanisms of the compliance with COVID-19 health protocols among people undergoing isolation in health facilities that specifically treat COVID-19 cases in Jakarta, Indonesia. Methods: This is a cross-sectional study which used socio-cognitive approach, known as the Health Action Process Approach (HAPA), to understand the complexity of issues related to compliance with health protocols. A total of 1,584 subjects participated in this study, including 865 men and 719 women over the age of 18 years old during the data collection period (October 19-26, 2020). The data were collected using questionnaire that was developed by a team of experts from the Faculty of Medicine, Universitas Indonesia-Dr. Cipto Mangunkusumo General Hospital, and survivors. The data that has been collected were then analyzed using Structural Equation Modeling, a multivariate data analysis technique. Results: The final research model in this study fulfills the criteria for a good model fit. This study found that individuals who have strong self-efficacy regarding their ability to implement behaviors and overcome obstacles will have stronger intent to comply in the future. The study also found that stronger intent will lead to stronger planning, and planning was found mediating intention and compliance with health protocols. Conclusion: This research model is comprehensive and useful in understanding compliance with health protocols among people undergoing isolation in health facilities for COVID-19 (Wisma Atlet and RSCM Kiara Ultimate). Having intent (related to the risk perception, outcome expectancies, and self-efficacy) and having a plan can positively influence the behavior of people undergoing isolation, resulting in better compliance to health protocols. The understanding gained from this study can be used to improve strategies related to compliance with health protocols against COVID-19 in the communities.

The level of tumour necrosis factor-alpha and its relationship to the cognitive function of Malayan-Mongoloid patients with schizophrenia.

Aim Schizophrenia is a mental disorder and one of the suspected causes is cytokines. One of them is tumour necrosis factor-alpha (TNF-α). Cytokines have the potential to affect cognitive function. The study aimed to find a correlation of TNF-α level with the Mini-Mental State Examination (MMSE) score in patients with schizophrenia (PwS), and comparing the level of TNF-α levels between PwS and healthy controls. Methods We conducted a cross-sectional analytic study and the study designs were correlation and comparative analysis, i.e. using a Mann-Whitney U test. A total number of 100 subjects were collected, and they were divided into two groups of PwS and control group, respectively. Results The results found that most of the PwS subjects were 39 men (78.0%), while the control group were 28 men (56.%). The differences in TNF-α levels between PwS and control groups were found to be significant p<0.001, there was no significant correlation between TNF-α level and the score of MMSE of the PwS with p = 0.938, with a very weak correlation that was r = -0.011, and a negative correlation direction. Conclusion There was a significant difference between TNF-α level of PwS and control group, i.e. PwS group had lower TNF-α level compared to the control group. The TNF-α level of PwS group had a very weak effect on the cause of cognitive dysfunction in PwS group, yet the higher level of it could reduce MMSE score in PwS group.

Decision Tree Clinical Algorithm for Screening of Mild Cognitive Impairment in the Elderly in Primary Health Care: Development, Test of Accuracy, and Time-Effectiveness Analysis.

Mild cognitive impairment (MCI) is predicted to be a common cognitive impairment in primary health care. Early detection and appropriate management of MCI can slow the rate of deterioration in cognitive deficits. The current methods for early detection of MCI have not been satisfactory for some doctors in primary health care. Therefore, an easy, fast, accurate and reliable method for screening of MCI in primary health care is needed. This study intends to develop a decision tree clinical algorithm based on a combination of simple neurological physical examination and brief cognitive assessment for distinguishing elderly with MCI from normal elderly in primary health care. This is a diagnostic study, comparative analysis in elderly with normal cognition and those presenting with MCI. We enrolled 212 elderly people aged 60.04-79.92 years old. Multivariate statistical analysis showed that the existence of subjective memory complaints, history of lack of physical exercise, abnormal verbal semantic fluency, and poor one-leg balance were found to be predictors of MCI diagnosis (p ≤ 0.001; p = 0.036; p ≤ 0.001; p = 0.013). The decision trees clinical algorithm, which is a combination of these variables, has a fairly good accuracy in distinguishing elderly with MCI from normal elderly (accuracy = 89.62%; sensitivity = 71.05%; specificity = 100%; positive predictive value = 100%; negative predictive value = 86.08%; negative likelihood ratio = 0.29; and time effectiveness ratio = 3.03). These results suggest that the decision tree clinical algorithm can be used for screening of MCI in the elderly in primary health care.

Rates and Risk Factors for Suicide Ideas among Schizophrenia Patients in Indonesia.

BACKGROUND: Schizophrenia is associated with a high rate of suicide. AIM: Our study was aimed to identify the rates of suicide ideas in patients with schizophrenia as well as the risk factors associated with suicide ideas. METHODS: As many as 1130 subjects were evaluated using the Indonesian version of Diagnosis Interview for Psychosis (DIP) to establish the diagnosis of schizophrenia. Subjects aged 18-65 years. The risk factors were socio-demographic data, mental disorder history in the family, clinical symptoms and clinical course of schizophrenia. Risk factors that have the strongest correlation with suicide ideas were analysed using multivariate logistic regression analysis. RESULTS: About 6.1% of subjects reported suicide ideas in their life. The age of disease onset (p = 0.006), family history of schizophrenia (p = 0.013), poor concentration (p = 0.032), loss of enjoyment (p = 0.000), guilty feeling (p = 0.000), family history of mental illness (p = 0.000), nihilistic delusion (p = 0.001) and alcohol abuse (p = 0.000) were significantly associated with suicide ideas. CONCLUSION: Suicide idea is quite common in people with schizophrenia. Evaluation and management of risk factors associated with suicide ideas should be performed to prevent suicide attempts or death. Suicide ideas and risk factors can become clinical parameters in the instrument of suicide prevention.

Cognitive complaints and predictors of perceived cognitive dysfunction in adults with major depressive disorder: Findings from the Cognitive Dysfunction in Asians with Depression (CogDAD) study.

BACKGROUND: Several studies have described the presence of perceived cognitive dysfunction amongst Asian patients with major depressive disorder (MDD). To date, no study has been conducted investigating the predictors of perceived cognitive dysfunction amongst Asian MDD patients. METHODS: This was a post-hoc analysis of the Cognitive Dysfunction in Asian patients with Depression (CogDAD) study. Descriptive statistics were used to describe the most common cognitive complaints by patients. Univariate and multivariate analyses were performed to determine variables associated with perceived cognitive dysfunction (Perceived Deficit Questionnaire-Depression, PDQ-D). RESULTS: The CogDAD study population is comprised of MDD patients with mild-to-moderate depression (Patient Health Questionnaire 9-item [PHQ-9]: 11.3 ±â€¯6.9) who reported perceived cognitive dysfunction (PDQ-D = 22.6 ±â€¯16.2). The most common cognitive complaints were: mind drifting (42.3%), trouble making decision (39.6%) and trouble concentrating (38.0%). Predictors of perceived cognitive dysfunction were: being Southeast Asians (vs. Taiwanese) (p < 0.001), current episode longer than 8 weeks (vs. 1-8 weeks) (p < 0.05), the presence of disability (vs. no disability) (p < 0.05), younger age (p < 0.01), and higher PHQ-9 total scores (p < 0.001). LIMITATIONS: The causal relationship between predictive variables and PDQ-D could not be tested due to the cross-sectional nature of the study. Furthermore, a neuropsychological test was not included in the CogDAD study and use of concomitant medications, including anti-depressants, could have impacted patient's perceived cognitive ability. CONCLUSIONS: The present study results suggest a potential role for subjective cognitive assessment in patients with MDD who are young, with long durations of depression or severe depression.

Cardiopulmonary Bypass Alone Does Not Cause Postoperative Cognitive Dysfunction Following Open Heart Surgery.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is commonly observed following cardiac surgery. The utilization of cardiopulmonary bypass (CPB) is associated with many possible mechanisms to cause POCD. However, there is no evidence confirming that CPB alone is the cause of POCD. OBJECTIVES: The current study aimed at evaluating several factors suspected to cause POCD following cardiac surgery in Cipto Mangunkusumo Hospital, Jakarta, Indonesia. METHODS: The current prospective cohort study was conducted on 54 patients who were candidates for cardiac surgery. The assessment of memory, attention, and executive functions was performed by neuropsychological tests, before and after the surgery. Cognitive decline was defined as a 20% decrease in cognitive function in at least one of the tests. Inclusion criteria were adults spokeing Bahasa Indonesia fluently, literate, and giving consent to participate in the study. The analyzed risk factors included age, diabetes, educational level, duration of aortic cross clamp, and duration of cardio-pulmonary bypass. RESULTS: POCD occured in 40.7% of subjects that underwent cardiac surgery using cardiopulmonary bypass. Age was the only influential factor through bivariate test and logistic regression analysis (P = 0.001). The current study conducted a logistic regression test on age variable; the obtained result indicated an increasing trend of POCD in accordance with age group. CONCLUSIONS: Durations of CPB, cross clamp, diabetes, and educational level were not the main risks of POCD. Old age was a significant predictor to POCD.

Recommendations for the optimal care of patients with recent-onset psychosis in the Asia-Pacific region.

Providing optimal care to patients with recent-onset psychosis can improve outcomes and reduce relapse. However, there is a lack of consistency of the implementation of guidelines for such patients across the Asia-Pacific region. We determined a pragmatic set of recommendations for use on a day-to-day basis to help provide optimal care at this crucial stage of illness. The recommendations were developed over a series of meetings by an international faculty of 15 experts from the Asia-Pacific region, Europe, and South Africa. A structured search of the PubMed database was conducted. This was further developed based on the faculty's clinical experience and knowledge of the literature into 10 key aspects of optimal care for patients during the first five years of a diagnosis of a psychotic disorder, with particular relevance to the Asia-Pacific region. Several common principles emerged: adherence to antipsychotic medications is crucial; substance abuse, psychiatric and medical comorbidities should be addressed; psychosocial interventions play a pivotal role; and family members can play a vital role in overall patient care. By following these recommendations, clinicians may improve outcomes for patients with recent-onset psychosis.

Enhancing Diagnostic Accuracy of aMCI in the Elderly: Combination of Olfactory Test, Pupillary Response Test, BDNF Plasma Level, and APOE Genotype.

Background. Amnestic Mild Cognitive Impairment (aMCI) often progresses to Alzheimer's disease. There are clinical markers and biomarkers to identify the degenerative process in the brain. Objectives. To obtain the diagnostic values of olfactory test, pupillary response to tropicamide 0.01%, BDNF plasma level, and APOE ε 4 in diagnosing aMCI. Methods. Cross-sectional, comparative analysis. Results. There were 109 subjects enrolled (aMCI: 51, normal cognition: 58) with age 64 ± 5.54 years. For diagnosing aMCI, cut-off point for the olfactory score was <7 out of 10 and >22% for pupil dilatation response. Low BDNF plasma level was related significantly with olfactory deficits and aMCI (P < 0.05). Four of five subjects with homozygote e4 presented with multiple-domain aMCI. This group displayed the lowest means of olfactory score and the highest means of pupillary hypersensitivity response (P < 0.0001). Combination of olfactory deficit and pupillary hypersensitivity response in detection of aMCI was beneficial with Sp 91% and PPV 87%. In conjunction with clinical markers, BDNF plasma level and presence of APOE e4+ improved Sp and PPV. Conclusions. Combination of olfactory test and pupillary response test was useful as diagnostic tool in aMCI. In conjunction with clinical markers, low level of BDNF plasma and presence of APOE e4 improved the diagnostic value.

Association of rs1344706 in the ZNF804A gene with schizophrenia in a case/control sample from Indonesia.

BACKGROUND: Association of rs1344706 in the ZNF804A gene (2q32.1) with schizophrenia was first reported in a genome wide scan conducted in a sample of 479 cases and replicated in 6666 cases. Subsequently, evidence by replication was obtained in several samples with European- and Asian ancestral background. METHODS: We report ascertainment, clinical characterization, quality control, and determination of ancestral background of a case control sample from Indonesia, comprising 1067 cases and 1111 ancestry matched controls. Genotyping was performed using a fluorescence-based allelic discrimination assay (TaqMan SNP genotyping assay) and a newly designed PCR-RFLP assay for confirmation of rs1344706 genotypes. RESULTS: We confirmed association of the T-allele of rs1344706 with schizophrenia in a newly ascertained sample from Indonesia with Southeast Asian ancestral background (P=0.019, OR=1.155, 95%, CI 1.025-1.301). In addition, we studied several SNPs in the vicinity of rs1344706, for which nominally significant results had been reported. None of the association P values of the additional SNPs exceeded that of rs1344706. CONCLUSION: We provide additional evidence for association of the ZNF804A gene with schizophrenia. We conclude that rs1344706 or a yet unknown polymorphism in linkage disequilibrium is also involved in conferring susceptibility to schizophrenia in samples with different (Asian) ancestral backgrounds.

A family-based association study of DNA sequence variants in GRM7 with schizophrenia in an Indonesian population.

We previously reported genome-wide significant linkage to chromosome 3p in a sib-pair family sample from Indonesia. A promising candidate gene within the linked region is the metabotropic glutamate receptor subtype 7 (GRM7), involved in glutamatergic neurotransmission. We genotyped 18 single nucleotide polymorphisms in GRM7 in the sample of 124 Indonesian sib-pair families that had provided the significant linkage finding. Transmission disequilibrium analysis revealed nominally significant transmission distortion of rs17031835 in intron 1 of GRM7 (p=0.004, before correction for multiple testing), along with haplotypes containing rs17031835. No other single marker was found to be significantly associated with schizophrenia in our sample. The results from our study provide support for the idea that glutamatergic neurotransmission and specifically the GRM7 gene might be relevant to the development of schizophrenia. Further studies supporting this finding are warranted.