Appropriate screening tools are required to accurately detect complex post traumatic stress disorder (CPTSD). This systematic review aimed to assess and compare measurement tools. A literature search ...using key words 'complex post traumatic stress disorder', 'PTSD', and 'assessment' was undertaken on Embase and PsychINFO during February 2022 by two reviewers. Inclusion criteria included full text papers between 2002-2022 which evaluated CPTSD using assessment tools. Exclusion criteria included reviews, editorials, meta-analyses, or conference abstracts. Twenty-two papers met selection criteria. Thirteen studies used the International Trauma Questionnaire (ITQ). Two studies each evaluated CPTSD with the International Trauma Interview (ITI) or Symptoms of Trauma Scale (SOTS). The Developmental Trauma Inventory (DTI), Cameron Complex Trauma Interview (CCTI), Complex PTSD Item Set additional to the Clinician Administered PTSD Scale (COPISAC), Complex Trauma Questionnaire (ComplexTQ), and Scale 8 of the Minnesota Multiphasic Personality Inventory Scale (MMPI) were used by a single study each. The ITQ was the most thoroughly investigated, validated across different populations, and is a convenient questionnaire for screening within the clinical setting. Where self-report measures are inappropriate, the ITI, SOTS, and COPISAC are interview tools which detect CPTSD. However, they require further validation and should be used alongside clinical history and examination.
Objectives: Vitamin D deficiency is associated with worse physical and mental health outcomes. Low vitamin D levels are more common among people who experience mental health issues. This is ...particularly vital due to the outdoor restrictions which arose from the COVID-19 pandemic. This systematic review assessed vitamin D deficiency and insufficiency among psychiatric inpatients.
Methods: A literature search was performed using the key words 'vitamin D', 'mental health', 'mental illness' and 'inpatient' and articles were selected by two independent reviewers. Eighteen studies were identified as eligible according to inclusion and exclusion criteria.
Results: Vitamin D deficiency (29 − 96%) and insufficiency (20 − 63%) were common among psychiatric inpatients. Over half of the studies recommended or advised consideration of vitamin D level screening among psychiatric inpatients, while nine recommended consideration of vitamin D supplementation.
Conclusions: Screening for vitamin D deficiency during psychiatric admission may be clinically indicated and improve patient wellbeing and outcomes.
Key points
Low vitamin D levels are very common among people admitted to inpatient mental health services.
Vitamin D level screening upon inpatient psychiatric admission is warranted to optimise general health outcomes.
Vitamin D supplementation should be considered among inpatients with vitamin D deficiency or insufficiency.
Background
It is common for patients presenting with neuropsychiatric symptoms to endure significant diagnostic odyssey. Neurofilament light chain (NfL) has shown promise in being able to ...differentiate between neurodegenerative and psychiatric disorders. This study aimed to assess the clinical utility of NfL in avoiding misdiagnosis.
Method
In this retrospective study, we conducted file review of patients assessed at Neuropsychiatry, Royal Melbourne Hospital between 2009 to 2020. We included all patients (n = 212) who had a CSF NfL level at their baseline assessment. Investigators blinded to NfL levels extracted clinical information including diagnoses from the initial and follow‐up assessments using documentation available. In addition, we collected follow‐up data from external services where available. Initial and follow‐up/final diagnoses were categorised as neurodegenerative disorder (ND), psychiatric disorder (PSY), mild cognitive impairment (MCI), unclear, and not‐neurodegenerative (Not‐ND). Not‐ND were individuals who did not meet the diagnosis for PSY or MCI, and did not have worsening symptoms. Based on our previous findings, we defined an NfL>582pg/mL as a positive test result for ND.
Result
So far, we have collected information from 135 patients. Of these, 14/89 (16%) patients initially diagnosed with ND were re‐diagnosed as PSY or Not‐ND. 2/30 (7%) patients initially diagnosed with PSY were re‐diagnosed as having ND. Including MCI and unclear, 32/135 (24%) had a delayed diagnosis, which could have been reduced to 14% based on baseline CSF NfL predicting ND or Not‐ND/MC/PSY. Data analysis is ongoing and full results will be presented at the conference.
Conclusion
Baseline CSF NfL could have aided clinicians in a real‐world clinical setting, to reduce misdiagnosis, and increase diagnostic accuracy from 76% to 86%. An elevated level could prompt assertive investigations for neurological and neurodegenerative causes. Conversely, a low NfL, could reassure against a neurodegenerative disorder, preventing unnecessary assessments. Timely and accurate diagnosis will improve outcomes and precision care for patients and families.
Objective:
Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary ...psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models.
Methods:
Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models).
Results:
Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS.
Conclusions:
This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
Introduction
Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and ...total‐tau (t‐tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders.
Methods
Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt‐Jakob registry (Creutzfeldt‐Jakob disease CJD and rapidly progressive dementias/atypically rapid variants of common ND, RapidND).
Results
A total of 498 participants were included: 197 ND, 67 PSY, 161 CJD, 48 RapidND, and 20 controls. NfL was elevated in ND compared to PSY and controls, with highest levels in CJD and RapidND. NfL distinguished ND from PSY with 95%/78% positive/negative predictive value, 92%/87% sensitivity/specificity, 91% accuracy. NfL outperformed t‐tau in most real‐life clinical diagnostic dilemma scenarios, except distinguishing CJD from RapidND.
Discussion
We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.
Background
Patients presenting with neuropsychiatric symptoms often face significant diagnostic odyssey. Our recent research (Eratne et al, ANZJP, 2020) found neurofilament light (NfL) differentiated ...between neurodegenerative and psychiatric disorders, with high accuracy. Yet the clinical utility of NfL, as to whether it can aid clinicians in avoiding misdiagnosis in a real‐world clinical setting, is unknown. Our primary aim was to measure the rates of diagnostic change in patients with neuropsychiatric symptoms assessed at a tertiary multidisciplinary service, and determine whether baseline cerebrospinal (CSF) NfL level could have prevented misdiagnoses, by predicting the final diagnosis after follow up.
Methods
We conducted a retrospective file review of patients assessed at an Australian neuropsychiatry and young‐onset dementia service between 2009‐2020. NfL levels were measured from CSF collected at their baseline assessment. Blinded investigators (MK, HD, DE) extracted clinical data including diagnoses from discharge summaries and outpatient letters from the initial assessment and re‐assessment. Baseline and final diagnoses were categorised as neurodegenerative disorder ND, or, other non‐neurodegenerative conditions including primary psychiatric disorder Other/PPD. We also obtained follow‐up information on patients that were subsequently seen at external services where available.
Results
From a preliminary analysis of those with follow‐up information for at least a year (N=32), six patients’ diagnostic categories (19%) were revised (ND to Other/PPD=5; Other/PPD to ND=1). In all six cases (figure 2), baseline CSF NfL levels, using our previously established cut‐off, would have predicted the final revised diagnosis.
As this study is underway, findings for over 200 patients will be presented for the Conference.
Conclusions
In a real‐world tertiary clinical setting, baseline CSF NfL would have accurately predicted diagnostic change, showing promise to aid clinicians assessing patients with neuropsychiatric symptoms, and reduce misdiagnosis. An elevated level could help exclude primary psychiatric provisional or differential diagnoses, and prompt assertive investigations for neurological and neurodegenerative causes. Conversely, a low NfL, could reassure against a neurodegenerative disorder, preventing unnecessary assessments. Timely and accurate diagnosis will reduce uncertainty, enable early care planning, reduce patient and carer burden, thus improving outcomes and the diagnostic odyssey faced by patients and families.
Background
Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non‐neurodegenerative ‘non‐progressor’, ‘phenocopy’ mimics of frontal lobe dysfunction, can be one of the most ...challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay.
Method
Cerebrospinal fluid (CSF) NfL, amyloid beta 1‐42 (AB42), total and phosphorylated tau (T‐tau, P‐tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow up information, patients were categorised as Progressors. Non‐Progressors were subtyped in to Phenocopy Non‐Progressors (non‐neurological/neurodegenerative final diagnosis), and Static Non‐Progressors (static deficits, not fully explained by non‐neurological/neurodegenerative causes).
Result
Forty‐three patients were included: 20 Progressors, 23 Non‐Progressors (15 Phenocopy, 8 Static), 20 controls. NfL concentrations were lower in Non‐Progressors (Non‐Progressors Mean, M=554pg/mL, 95%CI:461, 675, Phenocopy Non‐Progressors M=459pg/mL, 95%CI:385, 539, Static Non‐Progressors M=730pg/mL, 95%CI:516, 940), compared to bvFTD Progressors (M=2397pg/mL, 95%CI:1607, 3332). NfL distinguished Progressors from Non‐Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Static Non‐Progressors tended to have higher T‐tau and P‐tau levels compared to Phenocopy Non‐Progressors.
Conclusion
This study demonstrated strong diagnostic utility of CSF NfL in distinguishing bvFTD from phenocopy non‐progressor variants, at baseline, with high accuracy, in a real‐world clinical setting. This has important clinical implications to improve outcomes for patients and clinicians facing this challenging clinical dilemma, as well as for healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non‐progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL.
Background
Accurate, timely diagnosis of neuropsychiatric symptoms, in particular distinguishing primary psychiatric from neurological disorders and in younger people, can be challenging. ...Neurofilament light (NfL) and other blood biomarkers have shown promise to reduce the diagnostic odyssey and improve outcomes. The MiND Study in investigating the diagnostic utility of NfL and other markers, to distinguish neurological/neurodegenerative from psychiatric disorders, to lead to a widely available, routine screening blood test.
Methods
We assessed NfL, p‐tau181 and GFAP in broad cohorts, including: patients assessed for neurocognitive/psychiatric symptoms at Neuropsychiatry and other services, in a wide range of disorders including Alzheimer disease, frontotemporal dementia, schizophrenia, bipolar disorder, depression, functional neurological disorders, Niemann‐Pick Type C, epilepsy.
Results
Updates on the The MiND Study progress and findings that NfL differentiated diverse neurodegenerative from psychiatric disorders, with 90+% accuracy, from over 500 patients/participants, will be presented, with real patient and family stories to demonstrate the challenges and potential clinical impact of The MiND Study. Plasma P‐tau181 levels distinguished Alzheimer disease (mainly younger sporadic), from non‐Alzheimer. As recruitment, sample analysis, data collection is ongoing, the most up to date results including GFAP, cognitive and neuroimaging markers, will be presented.
Conclusions
NfL shows great promise as a diagnostic screening blood test, akin to a “CRP for the brain”. Plasma p‐tau181 shows strong diagnostic utility in younger‐onset Alzheimer disease. NfL could dramatically alter clinical care of patients with neuropsychiatric and neurological symptoms, improving outcomes for patients, their families, the healthcare system, and clinical trials, facilitating precision medicine algorithmic diagnostics incorporating other biomarkers and clinical/cognitive markers, for real‐world clinical settings.
Background
Accurate, timely diagnosis of neurodegenerative disorders, in particular distinguishing primary psychiatric from neurological disorders and in younger people, can be challenging. There is ...a need for biomarkers to reduce the diagnostic odyssey and improve outcomes. Neurofilament light (NfL) has shown promise as a diagnostic biomarker in a wide range of disorders. Our Markers in Neuropsychiatric Disorders (MiND) Study builds on our pilot (Eratne et al, ANZJP, 2020), to explore the diagnostic and broader utility of plasma and cerebrospinal fluid (CSF) NfL and other novel markers such as phosphorylated tau 181 (p‐tau181), in a broad range of psychiatric and neurodegenerative/neurological disorders, with a view of translation into routine clinical practice.
Methods
We assessed plasma and/or CSF NfL and p‐tau181 concentrations in broad cohorts, including: patients assessed for neurocognitive/psychiatric symptoms at Neuropsychiatry and Melbourne Young‐Onset Dementia services and other services, in a wide range of disorders including Alzheimer disease, frontotemporal dementia, schizophrenia, bipolar disorder, depression, Niemann‐Pick Type C, epilepsy, functional neurological disorders. The most recent primary consensus diagnosis informed by established diagnostic criteria was categorised: primary psychiatric disorder (PPD), neurodegenerative/neurological disorder (ND), or healthy controls (HC).
Results
Findings from over 500 patients/participants will be presented, which indicate that CSF and plasma NfL levels are significantly elevated in a broad range of ND compared to a broad range of PPD, and HC, and bvFTD progressors from phenocopy syndromes, differentiating with areas under the curve of >0.90, sensitivity and specificity >90%. Plasma P‐tau181 levels distinguished Alzheimer disease (mainly younger sporadic), compared to other neurodegenerative disorders, with AUC 0.90, 90% sensitivity and specificity. As recruitment, sample analysis, data collection is ongoing, the most up to date results will be presented.
Conclusions
NfL shows great promise as a diagnostic test to assist with the common, challenging diagnostic dilemma of distinguishing neurodegenerative from non‐neurodegenerative and primary psychiatric disorders. Plasma p‐tau181 shows strong diagnostic utility in younger‐onset Alzheimer disease. A significantly elevated NfL in someone with a psychiatric diagnosis should prompt consideration of neurodegenerative differentials. Plasma NfL could dramatically alter clinical care of patients with neuropsychiatric and neurological symptoms, improving outcomes for patients, their families, the healthcare system, and clinical trials.
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