Background Increased systemic cytokine levels, modulators of the immune system, have been repeatedly documented in adult and adolescent major depressive disorder (MDD). This preliminary study extends this work to test the role of cytokines in suicidal symptomatology in adolescent MDD. Hypotheses were that acutely suicidal depressed adolescents would have: (1) increased plasma levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, and (2) a proinflammatory/antiinflammatory cytokine imbalance (indexed by plasma IFN-γ/IL-4), compared to nonsuicidal depressed adolescents and healthy controls. Methods Twelve suicidal adolescents with MDD (7 females [58%]; 5 medication-free/naïve), 18 nonsuicidal adolescents with MDD (12 females [67%]; 8 medication-free/naïve), and 15 controls (8 females [53%]) were enrolled. MDD had to be of at least 6 weeks duration, with a minimum severity score of 40 on the Children's Depression Rating Scale–Revised. Plasma cytokines were examined using enzyme-linked immunosorbent assays. Nonparametric tests were used to compare subject groups. Results Unexpectedly, suicidal adolescents with MDD had significantly decreased plasma TNF-α concentrations compared to nonsuicidal adolescents with MDD (1.33 ± 2.95 pg/mL versus 30.9 ± 110.9 pg/mL; p = 0.03). IFN-γ was increased in both suicidal and nonsuicidal adolescents with MDD compared to controls (2.14 ± 6.22 and 4.20 ± 14.48 versus 0.37 ± 0.64; p < 0.02, p = 0.005). Findings remained evident when controlled for age and gender. Conclusions Our preliminary findings suggest that immune system dysregulation may be associated with suicidal symptomatology in adolescent MDD. These findings should be replicated in larger samples with medication-free adolescents.

Background Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro-inflammatory cytokines via induction of the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM-MDD adolescents, adolescents with M-MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3-hydroxyanthranilic acid (3-HAA, neurotoxin) and 3-HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites. Methods Subjects were 20 adolescents with M-MDD, 30 adolescents with NonM-MDD, and 22 healthy adolescents. MDD episode duration had to be ≥ 6 weeks and Children’s Depression Rating Scale-Revised (CDRS-R) scores were ≥ 36. Blood samples were collected at AM after an overnight fast and analyzed using high-performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS-R scores. Analyses were repeated excluding medicated patients. Fisher’s protected least significant difference was used for multiple comparisons. Results As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M-MDD compared to NonM-MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M-MDD group between KYN and 3-HAA/KYN and CDRS-R. Conclusions Findings support the notion that adolescent M-MDD may represent a biologically distinct clinical syndrome.

Background-While immune system dysregulation has been postulated to play a role in Tourette's disorder (TD), most research has focused on the hypothesis of an autoimmune process similar to rheumatic fever. This study examined the potential role of cytokines, modulators of the immune system. We hypothesized that children with TD would have increased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β and IL-6, and decreased IL-2. We also explored whether comorbid obsessive compulsive disorder (OCD) had an effect on the cytokine profile of TD patients.Method-Thirty-two children and adolescents with TD (27 males, ages 7-18 years), 17 with comorbid OCD (14 males), and 16 healthy comparison subjects (7 males, ages 9-19), were enrolled. Plasma cytokines were examined using an enzyme-linked immunosorbent assay. The MannWhitney and binary logistic regression tests were used to compare the groups.Results-Only patients with comorbid OCD (TD+OCD; n = 17) had significantly elevated IL-12 plasma levels compared to controls (2.73 ± 5.12 pg/ml vs. 0.55 ± 0.88 pg/ml, rank statistic = 222.5; p<0.04). IL-2 was significantly higher in the TD+OCD subgroup compared to the non-OCD TD subgroup (0.74 ± 0.29 pg/ml vs. 0.49 ± 0.24 pg/ml, rank statistics = 108.5; p<0.03). There were no other significant cytokine differences between groups.Conclusions-Findings suggest a role for IL-12 and IL-2 in TD, and that the TD+OCD subgroup may involve different neuroimmunological functions than the TD−OCD subgroup. Larger studies with medication-free patients should follow.

The empirical basis for understanding disclosure in clinical supervision is limited. Research has indicated that a majority of psychology trainees engage in concealment or distortion of clinical and nonclinical material despite expectations of transparency. This article explores the risks and benefits of disclosure by examining two experiences from my doctoral training. In Case Illustration 1, I describe working with a teenage boy, with a history of caregiver abandonment, and disclosing to my supervisor a desire to shift the therapeutic approach. I examine how my disclosure impacted our supervisory alliance and the patient's treatment outcome. In Case Illustration 2, I describe how a supervisor's personal disclosure facilitated my understanding of countertransference and intersubjectivity. I conclude by offering suggestions on how disclosure can strengthen alliance and felt security in supervision.

Learning about potential threats in the environment is indispensable for survival. Deficits in threat learning constitute a key dimension of multiple brain disorders, which include posttraumatic stress disorder and anxiety disorder. While human brain imaging studies have highlighted a reliable engagement of the anterior insular cortex (AIC) in threat learning, its precise role remains elusive partly due to the lack of animal studies that can address causality and mechanistic questions. Filling in this gap, the present mouse study proposes a novel AICmediated mechanism underlying the association of temporally discontiguous stimuli during threat learning. We identified that activity of AIC layer 5 (L5) pyramidal neurons is required for associating temporally discontiguous stimuli, specifically during a time interval between them. Notably, the AIC is not required for associating temporally contiguous stimuli during threat learning. The AIC not only sends the essential information, via its L5 pyramidal neurons, to the basolateral amygdala (BLA) during the time interval, but also receives from the BLA. We also identified a modulatory role of AIC dopamine D1 receptor (D1R)-mediated dopamine signaling in associating temporally discontiguous stimuli during the time interval.