Correlates of C-reactive protein with neural reward circuitry in adolescents with psychiatric symptoms

Liu, Qi; Simkovic, Sherry; Tao, Annie; Wolchok, Rachel; Alonso, Carmen; Gabbay, Vilma

doi:10.1016/j.bbih.2020.100153

Cited by 14 publications

(29 citation statements)

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“…Clinical cohort. The clinical cohort included 64 adolescents who were reported in a prior fMRI study (Liu et al 2020). Inclusion criteria: presence of psychiatric symptoms either meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (American Psychiatric Association, 1994) diagnostic criteria or subthreshold, based on diagnostic psychiatric assessment (detailed below).…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 99%

“…All participants were psychotropic medication-free. As noted above, 64 adolescents in the clinical cohort (age: 15.17 -2.10 years, 44 female) were previously described in Liu et al (2020). Demographic and clinical data are compiled in Table 1.…”

Section: Participantsmentioning

confidence: 99%

“…However, studies with depressed youth have largely failed to document such an association (Chaiton et al 2010;Khandaker et al 2014;Baumeister et al 2016;Flouri et al 2020;Jha et al 2020), although one group reported a positive association between CRP levels and depression severity in adolescent girls (Tabatabaeizadeh et al 2018). Our group recently carried out an investigation of CRP levels, neural activity during an fMRI reward task, and depression symptomology in a clinical cohort of 64 adolescents with predominantly mood and/or anxiety symptoms (Liu et al 2020). While we found that CRP was associated with brain function during reward, no relationships were found with depression or anxiety symptom severity (Liu et al 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Our group recently carried out an investigation of CRP levels, neural activity during an fMRI reward task, and depression symptomology in a clinical cohort of 64 adolescents with predominantly mood and/or anxiety symptoms (Liu et al 2020). While we found that CRP was associated with brain function during reward, no relationships were found with depression or anxiety symptom severity (Liu et al 2020).…”

Section: Introductionmentioning

confidence: 99%

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Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents

Liu

Simkovic

Alonso

et al. 2021

Journal of Child and Adolescent Psychopharmacology

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Introduction: Increased peripheral inflammation has been consistently documented in both adult and pediatric depression. However, elevated levels of C-reactive protein (CRP), a nonspecific biomarker for inflammation, have been primarily reported in adults; whether CRP plays a similar role in adolescent depression has not been conclusively established. In our prior work, we identified relationships between CRP and reward neurocircuitry in adolescents with psychiatric symptoms (N = 64) but not with depressive symptoms. Extending this work, we sought to examine CRP across the full range of mood and anxiety symptom severity in a larger, clinically diverse cohort of psychotropic medication-free adolescents and healthy controls (HCs). Methods: Subjects were adolescents (N = 127, age: 15.17 -2.19 years, 78 female) with psychiatric symptoms (n = 96, including previous cohort of 64) and HC (n = 31). All completed a semi-structured psychiatric evaluation and dimensional assessments for depression, anxiety, anhedonia, and suicidality. Group-comparison and correlation analyses utilized nonparametric statistics controlled for body mass index, sex, and age at p FWE < 0.05. Results: No group differences were identified in CRP levels between the clinical cohort and HCs. In addition, correlations between CRP and clinical symptomatology were not significant in either the whole sample or the psychiatric group. Conclusions: We found that, unlike in adults, CRP was not associated with depressive symptoms. This suggests that inflammation in pediatric depression is more narrowly delimited at the onset of psychiatric symptoms and may only become systemic with chronicity.

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Section: Inclusion and Exclusion Criteriamentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents

Liu

Simkovic

Alonso

et al. 2021

Journal of Child and Adolescent Psychopharmacology

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“…Rather, neural activation during reward attainment negatively correlated with Factor 2 (eotaxin, IL-12p40, IL-13, IL-15, IL-1α, IL-1Ra, IL-2, IL-5, IL-9, MCP-3, and TNF-β), while neural activity during anticipation negatively correlated with Factor 3 (FGF-2, Flt3-L, fractalkine, GM-CSF, IFN-α2, IFN-γ, IL-3, IL-4, IL-7, IL-17A, MDC, and VEGF). In a related study using the same fMRI task, we recently showed that C-reactive protein (CRP), a marker for generalized inflammation, did not correlate with clinical symptoms yet had specific associations with neural reward function in adolescents (54). Taken together, these results suggest that the effects of inflammation on anhedonia severity in adolescents appear to be subtler than in adults, which we speculate may be related to more robust protective mechanisms in younger ages.…”

Section: Discussionmentioning

confidence: 99%

Clenbuterol Attenuates Immune Reaction to Lipopolysaccharide and Its Relationship to Anhedonia in Adolescents

Nguyen

Kim‐Schulze

Gabbay

2021

Preprint

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While inflammation has been implicated in the manifestation of psychiatric symptoms, the role of immune attenuation via sympathetic modulation in psychopathology remains unclear. Here, this study aimed to assess β2-agonist clenbuterol (CBL) as a promising agent to model adrenergic-induced immune response following ex vivo immune activation with lipopolysaccharide (LPS). Relationships between CBL-modulated cytokine levels and symptom measures were then explored. Adolescents were evaluated with semi-structure interviews and self-reported depression, anxiety, and anhedonia levels. Fasting whole-blood samples were collected and stimulated with LPS in the presence and absence of CBL for 6 hours, with supernatants being subjected to Luminex multiplex assay for 41 cytokines. Cytokine levels between conditions were compared using Bonferroni-corrected nonparametric tests. Exploratory factor analysis reduced 41 cytokines into fewer factors in each experimental condition, and their relationships with psychiatric symptoms were examined with Spearman correlations controlling for age, sex, and BMI. Data from 130 participants (15.25 ± 2.16 years old, 59% female) were analyzed. 10 cytokines were significantly affected by CBL treatment compared to LPS alone. LPS+CBL factor 3 significantly correlated with both anticipatory (rho = -0.39, p = 7.4 × 10-5) and consummatory anhedonia (rho = -0.36, p = 3.3 × 10-4), and these correlations remained significant when controlling additionally for depression. There were no significant associations between immune factors with depression or anxiety severity. Findings support our hypothesis that clenbuterol attenuates inflammatory effects thought to underlie psychiatric conditions in youth. Using a data-driven analytic method, distinctive relationships between CBL-affected cytokines and dimensional anhedonia were reported, further elucidating the role of β2-agonism in adolescent affective symptomatology.

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Clenbuterol attenuates immune reaction to lipopolysaccharide and its relationship to anhedonia in adolescents

Nguyen

Pick

Patel

et al. 2022

Brain, Behavior, and Immunity

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Correlates of C-reactive protein with neural reward circuitry in adolescents with psychiatric symptoms

Cited by 14 publications

References 84 publications

Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents

Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents

Clenbuterol Attenuates Immune Reaction to Lipopolysaccharide and Its Relationship to Anhedonia in Adolescents

Clenbuterol attenuates immune reaction to lipopolysaccharide and its relationship to anhedonia in adolescents

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