[Show abstract][Hide abstract] ABSTRACT: S100B is a reporter of blood-brain barrier (BBB) integrity which appears in blood when the BBB is breached. Circulating S100B derives from either extracranial sources or release into circulation by normal fluctuations in BBB integrity or pathologic BBB disruption (BBBD). Elevated S100B matches the clinical presence of indices of BBBD (gadolinium enhancement or albumin coefficient). After repeated sub-concussive episodes, serum S100B triggers an antigen-driven production of anti-S100B autoantibodies. We tested the hypothesis that the presence of S100B in extracranial tissue is due to peripheral cellular uptake of serum S100B by antigen presenting cells, which may induce the production of auto antibodies against S100B. To test this hypothesis, we used animal models of seizures, enrolled patients undergoing repeated BBBD, and collected serum samples from epileptic patients. We employed a broad array of techniques, including immunohistochemistry, RNA analysis, tracer injection and serum analysis. mRNA for S100B was segregated to barrier organs (testis, kidney and brain) but S100B protein was detected in immunocompetent cells in spleen, thymus and lymph nodes, in resident immune cells (Langerhans, satellite cells in heart muscle, etc.) and BBB endothelium. Uptake of labeled S100B by rat spleen CD4+ or CD8+ and CD86+ dendritic cells was exacerbated by pilocarpine-induced status epilepticus which is accompanied by BBBD. Clinical seizures were preceded by a surge of serum S100B. In patients undergoing repeated therapeutic BBBD, an autoimmune response against S100B was measured. In addition to its role in the central nervous system and its diagnostic value as a BBBD reporter, S100B may integrate blood-brain barrier disruption to the control of systemic immunity by a mechanism involving the activation of immune cells. We propose a scenario where extravasated S100B may trigger a pathologic autoimmune reaction linking systemic and CNS immune responses.
PLoS ONE 01/2014; 9(7):e101477. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Context: Human and animal studies have suggested an underlying inflammatory mechanism for a variety of neuropsychiatric disorders, including schizophrenia. To date, most available reports focused on adult patients.Objective: We wished to test the hypothesis that the first psychotic episode in youth is associated with inflammation.Patients: We studied patients admitted to a pediatric inpatient psychiatric unit. Patients (n=80) had new-onset psychosis diagnosed using DSM-IV TR criteria for Psychosis NOS, schizophreniform disorder or schizoaffective disorder. Patients were matched for age, race and gender with inpatient controls without psychosis within the same unit (n=66). We also compared these values to normal pediatric hematologic values. To study the role of inflammation in youth with psychosis, we collected serum samples of 28 children presenting with first episode psychosis and compared their serum cytokine and S100B levels to 8 healthy controls.Main Outcome Measures: In this study, we measured serum markers of systemic inflammation.Results: Leukocyte counts revealed a statistically significant increase in absolute monocytes compared to patients without psychosis (0.61±0.282 k/µl vs. 0.496±0.14 k/ml; p<0.01) and lymphocytes (2.51±0.84 k/ml vs. 2.24±0.72 k/ml; p<0.05) in patients with psychosis. All other hematologic values were similar between the groups. In addition, psychosis was characterized by increased serum levels of S100B, a peripheral marker of BBB damage. Several inflammatory mediators (e.g., TNF-α, IL-1β, IL-6Il-5, IL-10, and IFN-γ) were elevated in children with psychosis.Conclusions: These results strongly support a link between systemic inflammation, blood-brain barrier disruption and first episode psychosis in pediatric patients.
Clinical Schizophrenia & Related Psychoses 03/2013;
[Show abstract][Hide abstract] ABSTRACT: Studies have reported an increased risk for suicide in adults with schizophrenia, but limited data on younger populations are available.
We hypothesize that first-episode psychosis is associated with an increased risk of suicidal behavior in adolescents.
A retrospective study was conducted with patients (n=102) diagnosed with psychosis not otherwised specified (NOS), schizophreniform disorder, schizoaffective disorder or schizophrenia within six months prior to admission. A control group consisting of ninety-eight patients with other (nonpsychosis) psychiatric diagnoses admitted to the same unit was matched by age, gender and ethnicity. All patients and controls were administered the Brief Psychiatric Rating Scale-Children version to assess severity of psychiatric symptoms and suicidality, and medical records were used to assess suicidal behavior and possible risk factors.
When compared to controls, patients with psychosis had over twice as many suicide attempts overall (p<0.01). The 32% incidence of suicide attempts reported in this cohort is nearly double what is reported in adults with psychosis. Depressive symptoms were significantly correlated with increased suicide attempts (p<0.05).
There was no significant difference between the number of pediatric psychosis inpatients versus nonpsychotic psychiatric inpatients who attempted suicide. There was, however, a significant difference between the total number of attempts between groups, illustrating that children and adolescents with psychosis are more likely than nonpsychotic psychiatric inpatients to have repeat, or multiple, suicide attempts. Longer duration of untreated psychosis, ADHD and depressive symptoms were found to be the strongest risk factors for patients with psychosis.
Clinical Schizophrenia & Related Psychoses 04/2010; 4(1):34-40.
[Show abstract][Hide abstract] ABSTRACT: Studies have shown that patients suffering from depression or schizophrenia often have immunological alterations that can be detected in the blood. Others reported a possible link between inflammation, a microgliosis and the blood-brain barrier (BBB) in suicidal patients. Serum S100B is a marker of BBB function commonly used to study cerebrovascular wall function.
We measured levels of S100B in serum of 40 adolescents with acute psychosis, 24 adolescents with mood disorders and 20 healthy controls. Patients were diagnosed according to DSM-IV TR criteria. We evaluated suicidal ideation using the suicidality subscale of the Brief Psychiatric Rating Scale for Children (BPRS-C).
Serum S100B levels were significantly higher (p<0.05) and correlated to severity of suicidal ideation in patients with psychosis or mood disorders, independent of psychiatric diagnosis. Patients with a BPRS-C suicidality subscores of 1-4 (low suicidality) had mean serum S100B values +/- SEM of 0.152+/-0.020 ng/mL (n = 34) compared to those with BPRS-C suicidality subscores of 5-7 (high suicidality) with a mean of 0.354+/-0.044 ng/mL (n = 30). This difference was statistically significant (p<0.05).
Our data support the use of S100B as an adjunctive biomarker to assess suicidal risk in patients with mood disorders or schizophrenia.
PLoS ONE 01/2010; 5(6):e11089. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This literature review describes evaluation and treatment of minority youth with ADHD.
A search of databases for reports of ADHD in minority children was conducted.
Interpretation of behavior varies among parents, as does their trust in health care providers and school personnel. Parents desire to avoid stigmatization of their children from diagnostic labels and medications. They may not understand the sequelae of inadequate treatment or fear side effects of treatment. Children respond to stimulant medication but fare better when it is combined with regularly scheduled psychosocial treatment, including education and support for parents. Financial struggles affect access, evaluation, and treatment. Community support is desperately needed to gain parental trust. Creative planning allows health care providers and neighborhood leaders to join in, benefiting the children.
Quality evaluation by a competent provider, careful choice of assessment tools, clear communication with parents, and close follow-up of progress are all needed.
Journal of Attention Disorders 04/2008; 11(5):522-8. · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In addition to being associated with combat, posttraumatic stress disorder (PTSD) also occurs in civilians exposed to severe trauma or serious illness. Manifestations of PTSD are varied and commonly include nonspecific physical symptoms, sleep disturbances, and psychological problems. Treatment with selective serotonin reuptake inhibitors (SSRIs) is usually effective.
Cleveland Clinic Journal of Medicine 03/2006; 73(2):121-2, 125-6, 128-9. · 3.40 Impact Factor