Cerebrospinal fluid neural cell adhesion molecule levels and their correlation with clinical variables in patients with schizophrenia, bipolar disorder, and major depressive disorder

Hidese, Shinsuke; Hattori, Kotaro; Sasayama, Daimei; Miyakawa, Tomoko; Matsumura, Ryo; Yokota, Yukio; Ishida, Ikki; Matsuo, Junko; Noda, Takamasa; Yoshida, Sumiko; Teraishi, Toshiya; Hori, Hiroaki; Ota, Miho; Kunugi, Hiroshi

doi:10.1016/j.pnpbp.2017.02.016

Cited by 21 publications

(32 citation statements)

References 47 publications

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“…The latter form is found in the cerebrospinal fluid (CSF). 5 Previous studies have suggested that NCAM and sNCAM participate in cell adhesion, cell guidance, synaptic plasticity, 6,7 nerve growth, 8 and myelin formation and reformation. 9,10 Similar observations have also been made in MS 11 A number of studies have shown lower levels of sNCAM in MS patients than in healthy controls (HC).…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid NCAM levels are modulated by disease‐modifying therapies

et al. 2019

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Background: Little is known about what leads to recovery between relapses in multiple sclerosis (MS), particularly following treatment. In the past, it has been demonstrated that soluble neural cell adhesion molecule (sNCAM), a putative biomarker of neuroplasticity, increased following steroid treatment in the Cerebrospinal fluid (CSF) of MS subjects undergoing acute relapses. Taking this a step further, we have evaluated the effect of disease-modifying treatment (DMTs) on CSF sNCAM levels in various subtypes of MS. Methods: We measured CSF sNCAM levels at baseline and after 12-24 months of DMT in 69 patients, 49 relapsing-remitting MS (RRMS), 20 progressive MS(PMS), and 24 healthy controls (HC) using an in-house ELISA. Of this, 31 patients had received natalizumab, 17 mitoxantrone, and 21 fingolimod. Changes in disability were measured using EDSS and disease severity by MSSS. In conjunction, CSF NfL levels were also measured. Results: At baseline, the mean sNCAM level was 268.7 ng/mL (SD: 109 ng/mL) in MS patients compared with 340.6 ng/ml (SD: 139 ng/mL) in HC, and PMS had significantly lower sNCAM (239.2 ng/mL, SD: 123.0, P = 0.019) compared to RRMS (269.4, SD: 127.4, P = 0.043). After natalizumab and mitoxantrone treatments, we observed an increase in mean sNCAM. However, in the fingolimod-treated group, mean sNCAM decreased. There was no correlation found with EDSS or MSSS, or NfL levels as a whole.Conclusions: Cerebrospinal fluid sNCAM levels were found to be lower in MS than in HC and the lowest sNCAM levels were found in PMS. Following natalizumab and mitoxantrone treatments, we observed an elevation in sNCAM levels, an effect that was not observed following fingolimod treatment. These changes, however, did not appear to correlate with disability in the short-term or NfL levels. K E Y W O R D S Cerebrospinal fluid (CSF), Disease-modifying therapies (DMTs), EDSS, Multiple sclerosis (MS), Soluble neural cell adhesion molecule (sNCAM) | 423 AXELSSON Et AL. How to cite this article: Axelsson M, Dubuisson N, Novakova L, et al. Cerebrospinal fluid NCAM levels are modulated by disease-modifying therapies. Acta Neurol Scand.

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Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid NCAM levels are modulated by disease‐modifying therapies

et al. 2019

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“…Among inflammatory biomarkers only N-CAM was investigated more than once. Thus, N-CAM levels were increased in a small older study with uneven gender distribution (19) and decreased in a large, recent, age and gender-matched study (25). Highly statistically significant differences were found, but not replicated regarding interleukin (IL)1β, IL6 (21), IL8 (22), monocytes chemoattractant protein 1 (23) and, chittinase-3-like protein 1 (23).…”

Section: Inflammationmentioning

confidence: 90%

“…In case control studies it is obviously important that the segregation of the groups is strict in order to avoid systematic errors. Diagnosis of bipolar disorder was thorough across the studies: DSM III (19,24,30), DSM IV (4,5,15,18,(21)(22)(23)(24)(25)28,30,32,33,35,37,41,42), specified by Research Diagnostic Criteria (44) (13,16,26,(29)(30)(31)34,36,38,40,43). Besides information on BD, demographical information, other clinical parameters as duration of illness, duration of current affective state, smoking have been reported in newer studies and may influence findings.…”

Section: ) Diagnosismentioning

confidence: 99%

“…George In a total of 15 studies the patients with BD were drug free at the time of the lumbar puncture (12)(13)(14)(15)(16)24,26,27,29,31,34,36,(38)(39)(40) and statistically significant differences were found regarding cortisol (26), pregnonolone (31) and, somatostatin (40). In the remaining 19 studies the patients received medication at the time of the lumbar puncture (4,5,(17)(18)(19)(20)(21)(22)(23)25,28,30,32,33,35,37,(41)(42)(43).…”

Section: ) Gendermentioning

confidence: 99%

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Biomarkers in cerebrospinal fluid of patients with bipolar disorder versus healthy individuals: A systematic review

Knorr

Simonsen

Zetterberg

et al. 2019

European Neuropsychopharmacology

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Background: The pathophysiological processes of bipolar disorder (BD) may be detectable by the use of cerebrospinal fluid (CSF) biomarkers. Biomarkers for BD may in time assist with diagnosis, prediction of disease course, or identification of response outcome to treatments. Explorative biomarkers have been proposed in many studies but no CSF biomarkers are integrated into routine clinical practice.Aim: We aimed for the first time to review studies of CSF biomarkers in patients with BD compared to healthy control individuals (HC). We investigated the effect of diagnosis, age, gender, clinical state, medication, technical characteristics of tests, fasting state and, cognitive function if applicable.Method: We did a systematic review according to the PRISMA Statement based on comprehensive database searches for studies on cerebrospinal biomarkers in patients with bipolar disorder versus HC. Risk of bias was systematically assessed.Results: The search strategy identified X studies of which thirty-four fulfilled the inclusion criteria.A total of 117 unique biomarkers were investigated. Forty biomarkers showed statistically significant differences between BD and HC. Eleven biomarkers were evaluated in more than one study. Only the findings of elevated homovanillic acid and 5-hydroxy-indoleacetic acid were replicated across studies. Most studies had a cross sectional design and were influenced by risk of bias mainly due to small sample size, lack of data on mood state at the time of the CSF puncture and not considering potential confounders including age, gender, diagnoses, BMI, life style factors such as smoking, and psychotropic medication.Conclusion: Specific monoamine CSF biomarkers may be related to the pathophysiology of BD.Future studies must aim at increasing the level of evidence by validating the positive findings in prospective studies with stringent methodology. limits; English language and human, using the following search terms both as keywords and as text words: Cerebrospinal fluid AND bipolar disorder. In addition reference lists of relevant studies were searched by hand. Study selection and data collection processStudy titles and abstracts identified by the initial search were screened by UK. Subsequent retrieval of full text articles or other additional information, assessment for eligibility and data extraction was performed independently by two researchers; UK and AHS. Disagreements were resolved by discussion with LVK.The association between cognitive function in BD and various CSF markers has been sporadically investigated (4-7), but these data were not included in this review. Data itemsA data sheet was constructed and the following data was extracted: Study identification, age, gender, duration of illness, BD subtype, symptom severity, duration of current affective state, medication use, smoking, alcohol use, BMI, exercise or physical activity, biomarker concentration in CSF, measurement method, blinding of analysts, time of day and fasting state at lumbar puncture.In comparisons between BD pati...

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“…NCAM-knockout mice display an abnormal brain structure as well as learning and behavioral abnormalities (Brandewiede et al, 2014;Bukalo et al, 2004;Stork et al, 1999;Wood et al, 1998). Moreover, single nucleotide polymorphisms in the NCAM gene and/or abnormal polysialylation or proteolysis of NCAM protein alter NCAM function in neurodevelopmental, neuropsychiatric, and neurodegenerative disorders in humans (Brennaman and Maness, 2010;Hidese et al, 2017;Purcell et al, 2001;Wang et al, 2012), suggesting a crucial role of NCAM in cortical development. NCAM plays a role in regulation of neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

NCAM regulates temporal specification of neural progenitor cells via profilin2 during corticogenesis

Huang

Yuan

et al. 2019

Journal of Cell Biology

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The development of cerebral cortex requires spatially and temporally orchestrated proliferation, migration, and differentiation of neural progenitor cells (NPCs). The molecular mechanisms underlying cortical development are, however, not fully understood. The neural cell adhesion molecule (NCAM) has been suggested to play a role in corticogenesis. Here we show that NCAM is dynamically expressed in the developing cortex. NCAM expression in NPCs is highest in the neurogenic period and declines during the gliogenic period. In mice bearing an NPC-specific NCAM deletion, proliferation of NPCs is reduced, and production of cortical neurons is delayed, while formation of cortical glia is advanced. Mechanistically, NCAM enhances actin polymerization in NPCs by interacting with actin-associated protein profilin2. NCAM-dependent regulation of NPCs is blocked by mutations in the profilin2 binding site. Thus, NCAM plays an essential role in NPC proliferation and fate decision during cortical development by regulating profilin2-dependent actin polymerization.

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Cerebrospinal fluid neural cell adhesion molecule levels and their correlation with clinical variables in patients with schizophrenia, bipolar disorder, and major depressive disorder

Cited by 21 publications

References 47 publications

Cerebrospinal fluid NCAM levels are modulated by disease‐modifying therapies

Cerebrospinal fluid NCAM levels are modulated by disease‐modifying therapies

Biomarkers in cerebrospinal fluid of patients with bipolar disorder versus healthy individuals: A systematic review

NCAM regulates temporal specification of neural progenitor cells via profilin2 during corticogenesis

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