Individualized Immunological Data for Precise Classification of OCD Patients
Abstract
:1. Introduction
2. Method
3. Immunological Changes in OCD
3.1. Cytokines
3.2. Antibodies
3.3. White Blood Cells
4. Infections and OCD
4.1. Streptococcal Infection
4.2. Toxoplasma gondii
5. Alternative Treatments for OCD
5.1. Specific Treatment in the PANS/PANDAS Context
5.2. Specific Treatment in the “Classical” OCD Context
6. Conclusions: Future Lines of Research for Etiological Immune Response Factors
6.1. Animal Models
6.2. Microglia
6.3. The Importance of the Attempt to Identify Different OCD Etiologies
Author Contributions
Funding
Conflicts of Interest
References
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Cytokines AND (OCD OR “Obsessive Compulsive Disorder”) | |||
---|---|---|---|
Authors, Date | Subjects | Main Results | Significance |
Jiang C. et al. (2018) [36] Meta-analysis | 435 cases 1073 controls | TNF-α polymorphisms | |
-> G vs. A model: OR = 1.01; 95% CIs = 0.37–2.77; | p = 0.981 | ||
-> GG vs. AA + AG model: OR = 0.93; 95% CIs = 0.37–2.37; | p = 0.879 | ||
-> GG + AG vs. AA model: OR = 0.22; 95% CIs = 0.06–0.73; | p = 0.014 | ||
-> GG vs. AA model: OR = 0.21; 95% CIs = 0.06–0.71; | p = 0.12 | ||
-> AG + AA model: OR = 0.29; 95% CIs = 0.07–1.16; | p = 0.081 | ||
-> GG + AA vs. AG model: OR = 1.17; 95%CIs = 0.55–2.51; | p = 0.683 | ||
Colak Sivri R. et al. (2018) [32] | 44 OCD patients 40 controls | -> OCD log-TNF-α > controls log-TNF-α | p < 0.001 |
-> OCD log-IL-12 < controls log-IL-12 | p = 0.014 | ||
No difference concerning BDNF, TFG-β (tendency of increased level in OCD patients), IL-1β (tendency of decreased level in OCD patients), IL-17, sTNFR1, sTNFR2, CCL3, CCL24 (tendency of increased level in OCD patients), CCL8 | |||
Rodriguez N. et al. (2017) [35] | 102 OCD patients 47 controls | -> Monocytes percentage of OCD patients > controls | |
-> CD16+ monocytes percentage of OCD patients > controls | |||
After LPS stimulation | |||
-> OCD-patients IL-1β > controls IL-1β | p = 0.005 | ||
-> OCD-patients IL-6 > controls IL-6 | p = 0.004 | ||
-> OCD-patients GM-CSF > controls GM-CSF | p = 0.049 | ||
-> OCD-patients TNF-α > controls TNF-α | p = 0.041 | ||
-> OCD-patients IL-8 > controls IL-8 | p = 0.013 | ||
Simsek S. et al. (2016) [33] | 34 OCD patients 34 controls | -> OCD patients IL-17α > controls IL-17α | p = 0.03 |
-> OCD patients TNF-α > controls TNF-α | p = 0.01 | ||
-> OCD patients IL-2 > controls IL-2 | p = 0.02 | ||
No difference for IFNγ, IL-10, IL-6, IL-4 (tendency of increased level in OCD patients) | |||
Rao NP. et al. (2015) [34] | 20 OCD patients 20 controls | -> OCD patients IL-2 > controls IL-2 | p = 0.005 |
-> OCD patients IL-4 > controls IL-4 | p = 0.007 | ||
-> OCD patients IL-6 > controls IL-6 | p = 0.002 | ||
-> OCD patients IL-10 > controls IL-10 | p = 0.006 | ||
-> OCD patients TNF-α > controls TNF-α | p = 0.005 | ||
No difference concerning IFN-γ | |||
Uguz F. et al. (2014) [37] | 7 OCD patients 30 controls | -> cord blood TNF-α of new born infants of women with OCD > cord blood TNF-α of new born infants of control women | p = 0.036 |
Bo Y. et al. (2013) [38] | 241 OCD patients 444 controls | IL-1β-511C/T polymorphism | |
No difference between OCD patients and controls | |||
Zhang X. et al. (2012) [39] | 200 OCD patients 294 controls | MCP-1-2518G/A polymorphism | |
No difference between OCD patients and controls | |||
Liu S. et al. (2012) [40] | 187 OCD patients 281 controls | IL-8-251T/A polymorphism | |
No difference | |||
Gray SM. et al. (2012) [31] Meta-analysis | 169 OCD patients 215 controls | -> Decreased IL-1β in OCD patients | p < 0.01 |
-> Increased IL-6 in adult free-medication OCD patients | p = 0.02 | ||
No difference concerning IL-6 in OCD children | |||
-> Decreased TNF-α in OCD patients without depression | p < 0.001 | ||
No difference in TNF-α when depressed patients are considered | |||
Cappi C. et al. (2012) [22] | 183 OCD patients 249 controls | TNF-α A/G polymorphism | |
-> Association of allele A with OCD (χ2, rs361525) | p = 0.007 | ||
Fontenelle LF. et al. (2012) [23] | 40 OCD patients 40 controls | -> OCD patients CCL3 > controls CCL3 | p = 0.03 |
-> OCD patients CXCL8 > controls CXCL8 | p < 0.001 | ||
-> OCD patients sTNFR1 > controls sTNFR1 | p < 0.001 | ||
-> OCD patients sTNFR2 > controls sTNFR2 | p < 0.01 | ||
No difference between OCD and controls concerning CCL2, CCL11, CCL24 (tendency of increased level in OCD patients), CXCL9, CXCL10 (tendency of decreased level in OCD patients), IL-1ra, TNF-α. | |||
Fluitman SB et al. (2010) [24] | 10 OCD patients 10 controls | During disgust exposure: | |
-> LPS-stimulated TNF-α in OCD patients decreased after disgust exposure | p = 0.07 | ||
LPS-stimulated TNF-α in controls not changed after disgust exposure | |||
-> LPS-stimulated IL-6 in OCD patients decreased after disgust exposure | p = 0.040 | ||
LPS-stimulated IL-6 in control not changed after disgust exposure | |||
Fluitman S. et al. (2010) [25] | 26 OCD patients 52 controls | -> OCD patients LPS-stimulated IL-6 < control LPS-stimulated IL-6 | p = 0.016 |
No difference concerning LPS-stimulated IL-8 and TNF-α | |||
Hounie AG et al. (2008) [26] | 111 OCD patients 250 controls | TNF-α-A/G polymorphism | p = 0.0005 and |
-> Association of the A allele with OCD for 238 G/A and 308 G/A (χ2) | 0.007 respectively | ||
Konuk N. et al. (2007) [27] | 31 OCD patients 31 controls | -> OCD patients TNF-α > control TNF-α | p < 0.001 |
-> OCD patients IL-6 > control IL-6 | p < 0.001 | ||
Denys D. et al. (2004) [28] | 50 OCD patients 25 controls | -> OCD patients LPS stimulated IL-6 > control LPS stimulated IL-6 | p = 0.004 |
-> OCD patients LPS stimulated TNF-α > control LPS stimulated TNF-α | p < 0.001 | ||
-> decreased NK cells activity in OCD patients | p = 0.002 | ||
No difference concerning LPS-stimulated IL-10 | |||
Carpenter LL. et al. (2002) [41] | 26 OCD patients 26 controls | No difference concerning CSF IL-6 level. | |
Monteleone P. et al. (1998) [29] | 14 OCD patients 14 controls | -> OCD patients TNF-α < control TNF-α | p = 0.001 |
No difference concerning IL-6 and IL-1β | |||
Brambilla F. et al. (1997) [30] | 27 OCD patients 27 controls | -> OCD patients IL-1β < control IL-1β | p = 0.0004 |
-> OCD patients TNF-α < control TNF-α | p = 0.0004 | ||
Weizman R. et al. (1996) [20] | 11 OCD patients 11 controls | No difference concerning IL-1β, IL-2, and IL-3-LA production between OCD patients and controls | |
Maes M. et al. (1994) [21] | 19 OCD patients 19 controls | No difference concerning IL-1β, IL-6, sIL-2R, sIL-6R |
Antibody AND (OCD OR “Obsessive Compulsive Disorder”) | |||
---|---|---|---|
Authors, Date | Subjects | Main Results | Significance |
Akaltun I. et al. (2018) [52] | 60 OCD 60 controls | -> Toxoplasma IgG levels related to OCD status | p = 0.001 |
-> IgG positivity individuals: increased risk of OCD: OR = 4.84, 95% CIs = 1.78–13.12 | p = 0.002 | ||
Mataix-Cols D. et al. (2017) [53] | 30082 OCD 472874 patients | -> Augmentation of the risk to develop autoimmune disease: OR = 1.43; 95% CIs = 1.37–1.49 | p < 0.01 |
Flegr J. et al. (2017) [54] | 281 men and 831 women not infected 65 men and 350 women infected with toxoplasma | -> Association between toxoplasma infection and OCD: OR = 2.27, 95% CIs = 1.01–5.09 | p = 0.047 |
Sutterland AL. et al. (2015) [14] Meta-analysis | No information but 2 studies included | -> Association between OCD status and toxoplasma infection: OR = 3.4; 95% CIs = 1.73–6.68 | p = 0.0004 |
Nicolini H. et al. (2015) [55] | 37 PANDAS/OCD or tics patients 12 controls | -> OCD patients anti-enolase > controls anti-enolase | p = 0.035 |
-> OCD patients anti-streptococcal proteins > controls anti-streptococcal proteins | p = 0.05 | ||
No differences concerning anti-neural antibodies. | |||
Singer HS. et al. (2015) [56] | 8 PANDAS/OCD or tics patients 70 controls | No association between clinical exacerbation and anti-tubulin, anti-lysoganglioside GM1, anti D1R, anti D2R titer. | |
Frankovich J. et al. (2015) [57] | 19 PANS/OCD or eating disorder patients 28 non-PANS but OCD or eating disorder patients | No difference concerning comorbidities (anxiety, mood disorder, irritability, suicidality) | |
No difference concerning Ig levels | |||
No difference concerning remitting course, chronic course. | |||
Cox CJ. et al. (2015) [58] | 311 PANDAS/OCD or tics patients 16 controls | -> PANDAS patients anti-D1R patients > controls anti-D1R | p < 0.0001 |
-> PANDAS patients anti-lysoganglioside > controls anti-lysoganglioside | p = 0.0001 | ||
Ebrahimi Taj F. et al. (2015) [59] | 76 OCD/ADHD patients 39 controls | -> OCD/ADHD patients anti-streptolysin O > controls anti-streptolysin O | p < 0.0001 |
-> OCD/ADHD patients anti-streptokinase > controls anti-streptokinase | p < 0.0001 | ||
-> OCD/ADHD patients anti-DNase B > controls anti-DNase B | p < 0.0001 | ||
Murphy TK. et al. (2015) [60] | 43 PANS/OCD patients | infectious triggers: 58% of GAS, 12% of mycoplasma pneumoniae, 37 of upper respiratory infection, 2% of Lyme | |
No differences between patients with tics and without tics concerning anti-DNase B, ASO, Mycoplasma IgM/IgG, Lyme screen, age of onset, CY-BOCS score, Y-GTSS score | |||
Murphy TK. et al. (2012) [61] | 41 PANDAS/OCD or tic patients 68 non-PANDAS but OCD or tic patients | -> PANDAS patients remissions > non-PANDAS patients remissions | p < 0.05 |
-> PANDAS patients dramatic onset > non-PANDAS patients dramatic onset | p < 0.05 | ||
-> PANDAS patients ASO/anti-DNase > non-PANDAS patients ASO/anti-DNaseB | p < 0.0001 | ||
-> remission in PANDAS patients after antibiotic treatment > remission in non-PANDAS after antibiotic treatment | p < 0.01 | ||
Leckman JF et al. (2011) [62] | 31 PANDAS/OCD or tic patients 53 non-PANDAS/OCD or tic patients | No association between clinical exacerbation and new GAS infection. | |
Miman O. et al. (2010) [63] | 42 OCD patients 100 controls | -> OCD patients anti-toxoplasma IgG > controls anti-toxoplasma IgG | p < 0.01 |
Bhattacharyya S. et al. (2009) [48] | 23 OCD patients 23 controls | -> more CSF anti-brain antibody binding to basal ganglia and thalamus for OCD patients than for patients | p < 0.05 |
-> More CSF glutamate and glycine in OCD patients than in controls | p < 0.001 | ||
Gause C. et al. (2009) [64] | 13 OCD only patients 20 PANDAS/OCD patients 23 PANDAS/tic patients 29 controls | No difference concerning ASO titers | |
No difference concerning serum IgG | |||
-> More anti-neural antibodies PANDAS/OCD than in other groups | p < 0.009 | ||
Morer A. et al. (2008) [49] | 32 OCD patients 19 controls | No anti-basal ganglia antibody detected by immunohistochemistry | |
-> Anti-basal ganglia antibodies in OCD patients and no in control detected by immunoscreening | |||
No difference concerning ASO titers | |||
Kirvan CA. et al. (2006) [65] | 16 PANDAS/OCD or tic patients 25 non- | -> lysoganglioside GM1 concentration required to inhibit binding PANDAS sera to GlcNAc (an epitope of GAS carbohydrate) < lysoganglioside GM1 concentration required to inhibit binding non-PANDAS sera to GlcNAc (an epitope of GAS carbohydrate) | p < 0.05 |
PANDAS/OCD or tic or ADHD patients | -> lysoganglioside GM1 = specific inhibitor of PANDAS IgG binding to GlcNAc | ||
-> PANDAS sera induced activation of CaM kinase II more than non-PANDAS sera => PANDAS serum responsible for cell signaling | p = 0.001 | ||
Morer A. et al. (2006) [66] | 18 early onset OCD 21 late onset OCD | -> Child OCD ASO titer > adult OCD ASO titer | p = 0.031 |
No difference for D8/D17 | |||
Singer HS. et al. (2005) [67] | 48 PANDAS (OCD or tic status not informed) patients 43 controls | No median ELISA optical density difference concerning serum antibodies | |
No difference concerning reactivity against pyruvate kinase M1, α-enolase, γ-enolase, aldolase C | |||
Pavone P. et al. (2004) [68] | 22 PANDAS (OCD or tic status no informed) patients 22 GAS uncomplicated infected patients | -> PANDAS anti-basal ganglia antibody > GAS patients anti-basal ganglia antibody | p < 0.001 |
No difference concerning ASO or anti DNase B antibody | |||
Murphy TK. et al. (2004) [69] | 15 OCD or tics patients with large symptom fluctuations 10 OCD or tics patients without large symptom fluctuations | -> positive correlation between OCD severity and ASO titer in patients with large symptom fluctuations | p = 0.0130 |
Luo F. et al. (2004) [70] | 47 OCD or tic patients 19 controls | -> OCD or tic patients percentages of D8/D17 positive cells > controls percentages of D8/D17 positive cells | p = 0.0029 |
Inoff-Germain G. et al. (2003) [71] | 108 positive children for D8/17 marker 132 negative dor D8/17 marker | No association between D8/17 marker status and OCD or tic status | |
Murphy ML. et al. (2002) [72] | 12 PANDAS OCD patients | -> abrupt appearance of OCD symptoms | |
-> elevated anti-DNase B titer | |||
-> mean age at onset = 7 years | |||
Eisen JL. et al. (2001) [73] | 29 OCD patients 26 controls | No difference in D8/D17 marker positivity | |
Murphy TK. et al. (2001) [74] | 32 OCD or tic patients 12 controls | -> OCD/tic patients D8/D17 titers > control D8/17 titers | p = 0.01 |
Peterson BS. et al. (2000) [75] | 105 tic, OCD or ADHD patients 37 controls | No association between OCD or tic disorder and ASO or anti-DNase B titers | No access to p-values |
-> ASO or anti-DNase B titers positively correlated with putamen or globus pallidus volume in OCD patients | |||
Marazziti D. et al. (1999) [76] | 20 OCD patients 20 controls | -> Increased CD8+ lymphocytes in OCD patients | p = 0.002 |
-> decreased CD4+ lymphocytes in OCD patients | p = 0.003 | ||
Chapman F. et al. (1998) [77] | 41 OCD or tic patients 31 controls | -> OCD or tic patients D8/D17 positivity > control D8/D17 positivity | P < 0.0001 |
Khanna S. et al. (1997) [78] | 76 OCD patients 55 controls | -> OCD patients mumps and HSV-I IgG > control mumps and HSV-I IgG | p < 0.05 |
Khanna S. et al. (1997) [79] | 76 OCD patients 30 controls | -> OCD patients measles CSF IgG < control measles CSF IgG | p < 0.001 |
-> OCD patient herpes CSF IgG > control herpes CSF IgG | p < 0.05 | ||
Murphy TK. et al. (1997) [80] | 31 OCD or tic patients 21 controls | -> OCD patients D8/17 positivity > control D8/17 positivity | p < 0.001 |
No difference concerning ASO, anti-DNase B and anti-neural antibodies | |||
Swedo SE. et al. (1997) [81] | 27 PANDAS/OCD or tic patients 24 controls | -> PANDAS/OCD or tic patients D8/D17 positivity > control D8/D17 positivity | p < 0.0001 |
Anti-brain antibody and (OCD OR “obsessive–compulsive disorder”) | |||
Bhattacharyya S. et al. (2009) [48] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Dale RC. et al. (2005) [50] | 50 OCD patients 40 controls with uncomplicated streptococcal infection | -> ABGA level in OCD patients > ABGA level in controls | p < 0.005 |
Pavone P. et al. (2004) [68] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
ABGA and (OCD OR “obsessive–compulsive disorder”) | |||
Pearlman DM. et al. (2014) [51] Meta-analysis | 297 OCD patients 406 controls | -> ABGA seropositivity in OCD patients > ABGA seropositivity in controls | p < 0.0001 |
Dale RC. et al. (2005) [50] | Cf. Anti-brain antibody and (OCD OR “obsessive–compulsive disorder”) |
”White Blood Cells” OR “Total Blood Count” AND (OCD OR “Obsessive Compulsive Disorder”) | |||
---|---|---|---|
Authors, Date | Subjects | Main Results | Significance |
Atmaca M. et al. (2011) [85] | 30 OCD patients 30 controls | -> OCD patients neutrophils < control neutrophils | p < 0.05 |
lymphocyte AND (“obsessive compulsive disorder” OR OCD) | |||
Marazziti D. et al. (2009) [88] | 18 OCD patients | -> CD8+ lymphocytes cells decreased after treatment | p = 0.004 |
-> CD4+ lymphocytes increased after treatment | p = 0.005 | ||
Denys D. et al. (2006) [87] | 42 OCD patients | No effect of paroxetine or venlafaxine on TNF-α, IL-4, IL-6, IL-10, IFN-γ, NK cell activity, monocytes, T-cells, and B-cells percentages | |
Denys D. et al. (2004) [28] | Cf. cytokines AND (OCD OR “obsessive compulsive disorder”) | ||
Marazziti D. et al. (2003) [89] | 10 OCD patients 10 controls | -> OCD patients (3)H-paroxetine-binding density < controls (3)H-paroxetine-binding density | p = 0.0001 |
Eisen JL. et al. (2001) [73] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Murphy TK. et al. (2001) [74] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Marazziti D. et al. (2001) [90] | 10 OCD patients 15 controls | Presence of 5-HT2C and 5-HT2A mRNAs in patients and controls | |
Rocca P. et al. (2000) [91] | 15 OCD patients 10 controls | -> decrease of peripheral benzodiazepine receptor mRNA | p < 0.05 |
Marazziti D. et al. (1999) [76] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Ravindran AV. et al. (1999) [92] | 26 OCD patients 16 controls | -> OCD patients circulating NK cells < control circulating NK cell | p < 0.05 |
No difference concerning B or T cells | |||
No difference in circulating NK cells after treatment. | |||
Chapman F. et al. (1998) [77] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Murphy TK. et al. (1997) [80] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Swedo SE. et al. (1997) [81] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Barber Y et al. (1996) [86] | 7 OCD patients 9 controls | No difference in lymphocytes between OCD patients and OCD | |
No difference in lymphocytes after treatment. | |||
Rocca P. et al. (1991) [93] | 18 OCD patients 50 controls | -> Number of binding sites for peripheral benzodiazepine receptor lower in OCD patients | p < 0.05 |
monocytes AND (“obsessive compulsive disorder” OR OCD) | |||
Rodriguez N et al. (2017) [35] | Cf. cytokines AND (OCD OR “obsessive compulsive disorder”) | ||
Denys D. et al. (2006) [87] | Cf. lymphocyte AND (“obsessive compulsive disorder” OR OCD) | ||
Denys D. et al. (2004) [28] | Cf. lymphocyte AND (“obsessive compulsive disorder” OR OCD) | ||
Weizman R. et al. (1996) [20] | Cf. cytokines AND (OCD OR “obsessive compulsive disorder”) | ||
NK cells” AND (“obsessive compulsive disorder” OR OCD) | |||
Denys D. et al. (2004) [28] | Cf. lymphocyte AND (“obsessive compulsive disorder” OR OCD) | ||
Ravindran V. et al. (1999) [92] | Cf. lymphocyte AND (“obsessive compulsive disorder” OR OCD) |
Infection AND (OCD OR “Obsessive Compulsive Disorder”) | |||
---|---|---|---|
Authors, Date | Subjects | Mains Results | Significance |
Ursoiu F. et al. (2018) [94] | 101 HIV patients | No association between HIV and OCD | |
Akaltun I. et al. (2018) [52] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Flegr J et al. (2017) [54] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Sutterland AL. et al. (2015) [14] Meta-analysis | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Nicolini H. et al. (2015) [55] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Miman O. et al. (2010) [63] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Dale RC. et al. (2004) [95] | 40 patients with post-streptococcal dyskinesias | -> 27.5% of these patients suffered from OCD | |
Giulino L. et al. (2002) [96] | 83 OCD patients | -> OCD patients with upper respiratory infection had more sudden onset than patients without upper respiratory infection | p = 0.02 |
No difference concerning tic or ADHD comorbidity between OCD patients with or without upper respiratory infection. | |||
Lougee L. et al. (2000) [97] | 54 PANDAS/OCD or tic patients 139 first relatives | -> 26% of OCD patients had a relative suffering from OCD | |
lyme AND (“obsessive compulsive disorder” OR OCD) | |||
Johnco C. et al. (2018) [98] | 147 patients with Lyme disease | -> 84% of patients reported obsessive compulsive symptoms | |
-> 90.9% of patients reported gradual onset of symptoms | |||
-> 47% of patients were treated with psychotropic treatment and 76.9% of them presented at least partial improvement | |||
-> 50.9% of patients treated with antibiotics reported at least partial improvement in symptoms | |||
Streptococcus AND (OCD OR “obsessive compulsive disorder”) | |||
Stagi S. et al. (2018) [99] | 179 PANDAS/OCD or tic patients | -> reduced vitamin D in PANDAS patients | p < 0.0001 |
Mataix-Cols D. et al. (2017) [53] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Calaprice D. et al. (2017) [100] | 698 PANS patients | -> age of onset between 7 and 8 years | |
-> 88% of sudden onset | |||
-> 87% of patients presented recurrences | |||
-> 94% of patients presented a history of OCD | |||
-> 71% with motor tics and 57% with vocal tics | |||
Wang HC. et al. (2016) [101] | 2596 patients infected with GAS 25960 controls | -> increased risk of tic disorder in GAS infected patients | No full access |
Nicolini H. et al. (2015) [55] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Frankovich J. et al. (2015) [57] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Ebrahimi Taj F. et al. (2015) [59] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Murphy TK. et al. (2012) [61] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Leckman JF. et al. (2011) [62] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Murphy TK. et al. (2010) [102] | 107 OCD or tic patients | -> 17.8% of patients had mother suffering from autoimmune disease | |
Gause C. et al. (2009) [64] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Kurlan R. et al. (2008) [103] | 40 PANDAS/OCD or tic patients 40 non-PANDAS/OCD or tics | No difference in the number of exacerbations (but a strong tendency for increased exacerbation risk, p = 0.07). | p = 0.002 |
-> more frequent GAS infection associated with exacerbation | |||
Dale RC. et al. (2004) [95] | Cf. infection AND (OCD OR “obsessive compulsive disorder”) | ||
Luo F. et al. (2004) [70] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Pavone P. et al. (2004) [68] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Murphy TK. et al. (2004) [69] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Giulino L. et al. (2002) [96] | Cf. infection AND (OCD OR “obsessive compulsive disorder”) | ||
Murphy TK. et al. (2001) [74] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Lougee L. et al. (2000) [97] | Cf. infection AND (OCD OR “obsessive compulsive disorder”) | ||
Giedd JN. et al. (2000) [104] | 34 PANDAS/OCD or tics 82 controls | -> PANDAS patients mean caudate volume > controls mean caudate volume | p = 0.004 |
-> PANDAS patients mean putamen volume > controls mean putamen volume | p = 0.02 | ||
-> PANDAS patients mean globus pallidus volume > controls mean globus pallidus volume | p = 0.02 | ||
No difference for thalamus and total brain volume | |||
Swedo SE. et al. (1998) [105] | 50 PANDAS patients | -> Mean age at onset: 7.4 years | |
-> tics and OCD: 64%; tics only: 16% and OCD only: 20% | |||
-> ADHD comorbidity: 40%, ODD comorbidity: 40%, MDD comorbidity: 36% | |||
Murphy TK. et al. (1997) [80] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
toxoplasma (OCD OR “obsessive compulsive disorder”) | |||
Akaltun I. et al. (2018) [52] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Flegr J et al. (2017) [54] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Sutterland AL. et al. (2015) [14] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Miman O. et al. (2010) [63] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) |
(PANDAS OR PANS) AND Treatment AND (OCD OR “Obsessive Compulsive Disorder”) | |||
---|---|---|---|
Authors, Date | Subjects | Main Results | Significance |
Leon J. et al. (2018) [118] | 33 PANDAS patients | Follow-up lasted between 2.2 and 4.8 years | |
Initially, all patients treated with antibiotics | |||
During the follow-up period, 45% of patients took psychotropic treatments | |||
At the time of follow-up, 18 patients presented no symptoms, 11 only subclinical symptoms, 3 moderate symptoms, and 1 severe symptom. | |||
Calaprice D. et al. (2018) [120] | 698 PANS patients | 675 patients treated with antibiotics, 437 with anti-inflammatories, 378 with psychotropic treatments | |
52% of “very effective” treatments with antibiotics | |||
NSAIDs were at least “somewhat effective” for 80% of patients | |||
Steroids were at least “somewhat effective” for 72% of patients | |||
IVIG were at least “somewhat effective” for 74% of patients | |||
Brown K. et al. (2017) [121] | 98 PANS patients | -> duration of symptomatic periods treated with steroids < duration of symptomatic periods of non-treated patients | p < 0.001 |
-> shorter symptomatic periods when initially treated with steroids | p < 0.01 | ||
Brown KD. et al. (2017) [126] | 95 PANS patients | -> Symptomatic periods treated with NSAID lasted shorter than non-treated symptomatic periods | p < 0.0001 |
-> the more the duration without treatment is short, the more symptomatic period were short | p = 0.02 | ||
Spartz EJ. et al. (2017) [122] | 159 PANS patients | No clinical data allow to distinguish responders and non-responders to NSAIDs | |
31% of patients with NSAID increases reported improvement in symptoms | |||
35% of patients with NSAID removal reported symptom increases after removal | |||
Murphy TK. et al. (2017) [123] | 31 PANS patients (17 with azithromycin, 14 with placebo) | -> azithromycin group improvement > non-azithromycin group (CGI) | p = 0.003 |
No difference on CY-BOCS | |||
Calaprice D. et al. (2017) [100] | Cf. Streptococcus AND (OCD OR “obsessive compulsive disorder”) | ||
Williams KA. et al. (2016) [124] | 35 PANDAS patients (IVIG group = 17, placebo group = 18) | -> At week 6 (double blind phase): no difference between groups (CY-BOCS) | p < 0.0001 |
-> Improvement after open label IVIG (CY-BOCS) | |||
Nadeau JM. et al. (2015) [127] | 11 PANS patients partially responder to antibiotics | -> Improvement after CBT (CY-BOCS) | p = 0.01 |
Nicolini H. et al. (2015) [55] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Frankovich J. et al. (2015) [57] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Latimer ME. et al. (2015) [128] | 35 PANDAS patients | -> 6 months after therapeutic plasma apheresis: improvement of 65% (local questionnaire) | |
Demesh D. et al. (2015) [129] | 10 PANDAS patients | -> Improvement in symptom intensity after antibiotic treatment (local questionnaire) | p = 0.03 |
-> Improvement in symptom intensity after tonsillectomy (local questionnaire) | p = 0.02 | ||
Ebrahimi Taj F. et al. (2015) [59] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Pavone P. et al. (2014) [130] | 120 PANDAS patients (56 patients with tonsillectomy or adrenotonsillectomy, 64 without) | No difference concerning symptomatology, streptococcal antibodies or anti-neural antibodies (evaluation every two months for 2 years) | |
Murphy TK. et al. (2012) [61] | Cf. antibody AND (OCD OR “obsessive compulsive disorder”) | ||
Bernstein GA. et al. (2010) [131] | 21 PANDAS patients 18 non-PANDAS OCD patients | No difference concerning age at onset of OCD | |
No difference concerning CY-BOCS score | |||
-> PANDAS patients YGTSS score > non-PANDAS patients YGTSS score | p = 0.013 | ||
No difference concerning ASO or anti-DNase B titers | |||
-> In non-PANDAS OCD patients, separation anxiety disorder and social phobia are more frequent | p = 0.02 and 0.047 respectively | ||
Storch EA. et al. (2006) [132] | 7 PANDAS patients | -> CY-BOCS improvement after 3 weeks of CBT | p = 0.018 |
Snider LA. et al. (2005) [133] | 23 PANDAS patients | -> Decrease in number of symptom exacerbations with antibiotic treatment | p < 0.01 |
Garvey MA. et al. (1999) [134] | 37 PANDAS patients (double blind and cross over design) | No difference in symptoms following antibiotic treatment | |
Swedo SE. et al. (1998) [105] | Cf. Streptococcus AND (OCD OR “obsessive compulsive disorder”) | ||
NSAID and (OCD OR “obsessive–compulsive disorder”) | |||
Brown KD. et al. (2017) [126] | Cf. (PANDAS OR PANS) AND treatment AND (OCD OR “obsessive compulsive disorder”) | ||
Spartz EJ. et al. (2017) [122] | Cf. (PANDAS OR PANS) AND treatment AND (OCD OR “obsessive compulsive disorder”) | ||
Shalbafan M. et al. (2015) [135] | 25 OCD patients with celecoxib (+SRI) 25 OCD patients with placebo (+SRI) | -> lower CY-BOCS score at week 10 in celecoxib group than in placebo group | p = 0.047 |
Sayyah M. et al. (2011) [136] | 27 OCD patients with celecoxib (+fluoxetine) 25 OCD patients with placebo (+fluoxetine) | -> lower CY-BOCS score at week 8 in celecoxib group than in placebo group | p = 0.037 |
-> significant effect of time-by-treatment interaction in ANOVA | p = 0.018 | ||
“anti-inflammatory” and (OCD OR “obsessive–compulsive disorder”) | |||
Calaprice D. et al. (2018) [120] | Cf. (PANDAS OR PANS) AND treatment AND (OCD OR “obsessive compulsive disorder”) | ||
Brown K. et al. (2017) [121] | Cf. (PANDAS OR PANS) AND treatment AND (OCD OR “obsessive compulsive disorder”) | ||
Brown KD. et al. (2017) [126] | Cf. (PANDAS OR PANS) AND treatment AND (OCD OR “obsessive compulsive disorder”) | ||
Shalbafan M. et al. (2015) [135] | Cf. NSAID and (OCD OR “obsessive–compulsive disorder”) | ||
Sayyah M. et al. (2011) [136] | Cf. NSAID and (OCD OR “obsessive–compulsive disorder”) | ||
minocycline and (OCD OR “obsessive–compulsive disorder”) | |||
Esalatmanesh et al. (2016) [137] | 47 OCD patients with minocycline (+fluvoxamine) 47 OCD patients with placebo (+fluvoxamine) | -> lower Y-BOCS score at week 10 in minocylcine group than in placebo group | p = 0.008 |
Rodriguez CI. et al. (2010) [138] | 9 OCD patients with minocycline (+SRI) | No effect of minocycline at week 12 | |
N-acetylcysteine and (OCD OR “obsessive–compulsive disorder”) | |||
Ghanizadeh A. et al. (2017) [139] | 18 OCD patients with NAC (+citalopram) 11 OCD patients with placebo (+citalopram) | -> lower Y-BOCS score at week 12 in NAC group than in placebo group | p < 0.02 |
Costa DLC. et al. (2017) [140] | 40 OCD patients randomized in 2 groups: NAC and placebo (no access to the details) | -> No difference between the two groups concerning Y-BOCS scores. | |
Paydary K. et al. (2016) [141] | 23 OCD patients with NAC (+fluvoxamine) 23 OCD patients with placebo (+fluvoxamine) | -> No difference between the two groups concerning Y-BOCS at week 10. | |
Sarris J. et al. (2015) [142] | 22 OCD patients with NAC (+TAU) 22 OCD patients with placebo (+TAU) | -> No difference between the two groups concerning Y-BOCS at week 16. | |
Afshar F. et al. (2012) [143] | 24 OCD patients with NAC (+SRI) 24 OCD patients with placebo (+SRI) | -> lower Y-BOCS score at week 12 in NAC group than in placebo group | p = 0.03 |
Divergent results concerning cytokines (especially IL-6, TNF-α) were found between studies. These discrepancies, therefore, raise the question of different patient populations, with some patients possibly presenting with immunological deficiencies, thus explaining the discrepancies. |
Antibody studies show that autoimmune factors could be specific etiologies in OCD. |
Streptococcus pyogenes is already recognized as possibly leading to OCD through PANS (pediatric acute-onset neuropsychiatric syndrome), as is Toxoplasma gondii. The mechanisms leading to OCD for S. pyognes and T. gondii are still unknown, but autoimmunity seems to be involved. |
According to these different possible immune etiological factors (autoimmunity, infection), some specific treatments were already tested opening the way to individualized specific treatments. An effort to clearly distinguish between the different etiological (including immunological) factors is still necessary in order to develop more effective OCD treatments |
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Lamothe, H.; Baleyte, J.-M.; Smith, P.; Pelissolo, A.; Mallet, L. Individualized Immunological Data for Precise Classification of OCD Patients. Brain Sci. 2018, 8, 149. https://doi.org/10.3390/brainsci8080149
Lamothe H, Baleyte J-M, Smith P, Pelissolo A, Mallet L. Individualized Immunological Data for Precise Classification of OCD Patients. Brain Sciences. 2018; 8(8):149. https://doi.org/10.3390/brainsci8080149
Chicago/Turabian StyleLamothe, Hugues, Jean-Marc Baleyte, Pauline Smith, Antoine Pelissolo, and Luc Mallet. 2018. "Individualized Immunological Data for Precise Classification of OCD Patients" Brain Sciences 8, no. 8: 149. https://doi.org/10.3390/brainsci8080149