Faculty Bibliography

The FDA (February 3, 2005) issued a black box warning that all antidepressants increase the risk of suicidal thinking and behavior in children and adolescents that must be cited in all advertising as well as included in the package insert. Following this, there was a sharp decrease in antidepressant prescriptions for children with uncertain public health impact. The current black box does not claim that these medications increase the risk of completed suicides, although this is the clear implication of the term 'suicidality'. The interpretation by the press is unequivocal that lethal outcomes prompted this action. This review concludes the following: (1) Since no suicide occurred in clinical trials of approximately 4400 children, the analyses relied upon 'suicidality' as a surrogate. (2) The classification of adverse events by the Columbia group necessarily relied on inferences, because the available evidence was not prospectively collected for this purpose. (3) The data analysis relied on a composite variable labeled 'suicidality', an unvalidated, inappropriate surrogate. Specific criticisms of analytic procedures and inferences are presented. The failure of the FDA's post-marketing surveillance system is reviewed. The data necessary for objective evaluations of possible post-marketing harm cannot be gathered by the current process. Proper prospective post-marketing surveillance by linked computerized medical records is a crucial issue that deserves major public and political attention and prompt action.

OBJECTIVE: A previous laboratory-based study found elevated cortisol levels in anxious children susceptible to CO(2)-induced panic, but the effects of parent diagnosis were not considered. The current home-based study tested the hypothesis that parental panic disorder and offspring response to CO(2) are associated with elevated cortisol levels in juvenile offspring. METHOD: A total of 131 offspring (ages 9-19) of parents with panic disorder, major depression, and no mental disorder underwent CO(2) inhalation. Parent and child diagnoses were assessed. Salivary cortisol was assayed before and after CO(2) inhalation. RESULTS: Neither parents with panic disorder, parents with major depression, or offspring anxiety predicted offspring cortisol levels. Independent of parent and child diagnoses, anxiety response to CO(2) predicted elevated cortisol levels in offspring. CONCLUSIONS: As in adults, anxiety response to CO(2) in juveniles is associated with elevated cortisol levels, but elevated cortisol levels are not related to parent or child diagnoses

This study examines the relationship between urban parents'/caregivers' previous experiences obtaining mental health care for their children and their perceptions of barriers to their children's use of services in the future. Assessments of prior treatment outcome and aspects of relationships with former providers were linked to endorsements of doubt about the utility of treatment as a potential barrier to the children's use of services in the future and the number of barriers parents endorsed. Implications for urban child mental health service delivery are drawn.

A multi-site study of 351 children with Autism Spectrum Disorders (ASD) and 31 typically developing children used caregiver interviews to describe the children's early acquisition and loss of social-communication milestones. For the majority of children with ASD who had experienced a regression, pre-loss development was clearly atypical. Children who had lost skills also showed slightly poorer outcomes in verbal IQ and social reciprocity, a later mean age of onset of autistic symptoms, and more gastrointestinal symptoms than children with ASD and no regression. There was no evidence that onset of autistic symptoms or of regression was related to measles-mumps-rubella vaccination. The implications of these findings for the existence of a 'regressive phenotype' of ASD are discussed

A multicenter study of 308 children with Autism Spectrum Disorder (ASD) was conducted through the Collaborative Programs of Excellence in Autism (CPEA), sponsored by the National Institute of Child Health and Human Development, to compare the family history of autoimmune disorders in children with ASD with and without a history of regression. A history of regression was determined from the results of the Autism Diagnostic Interview-Revised (ADI-R). Family history of autoimmune disorders was obtained by telephone interview. Regression was significantly associated with a family history of autoimmune disorders (adjusted OR=1.89; 95% CI: 1.17, 3.10). The only specific autoimmune disorder found to be associated with regression was autoimmune thyroid disease (adjusted OR=2.09; 95% CI: 1.28, 3.41)

Previous studies have suggested that children with autism spectrum disorders (ASD) may have different medical histories than nonspectrum children in several areas: their reactions to vaccinations, number of ear infections, chronic gastrointestinal problems, and use of antibiotics. Furthermore, some studies have found associations between regressive autism and gastrointestinal (GI) symptoms. The present study analyzes the medical records from birth to the age of 2 years of 99 children (24 typically developing; 75 with ASD, of whom 29 had parent-reported regression). Data were coded in the following areas: frequency and purpose of pediatrician visits, frequency and type of illnesses and medications, type and chronicity of GI complaints, date of vaccinations, growth data, and whether the pediatrician noted behaviors indicative of an ASD before the age of 2 years. Children with ASD were found to have significantly more ear infections than the typically developing children as well as to use significantly more antibiotics. Typically developing children had significantly more illness-related fevers. There was a nonsignificant trend toward the ASD group having more chronic gastrointestinal problems. There were no significant differences between the groups for the age of vaccination or for number of pediatrician visits. Finally, pediatricians noted symptoms of onset of possible autism, including language delay, for 44 of the 75 children with ASD and 2 of the 24 typical children. Results are discussed in terms of needs for future research

Deficit schizophrenia (DS) is considered a distinct subtype within the diagnosis of schizophrenia. While the common assumption is that DS represents a single, cohesive domain of psychopathology, the factorial structure of DS has not been investigated. We assessed 52 individuals with DSM-IV diagnoses of schizophrenia with DS. A principal component analysis (PCA) was conducted on the symptoms of the Schedule for the Deficit Syndrome. The PCA resulted in 2 distinct factors explaining 73.8% of the variance. Factor 1 (avolition) is made up of symptoms of curbing of interests, diminished sense of purpose, and diminished social drive. Factor 2 (emotional expression) is made up of symptoms of restricted affect, diminished emotional range, and poverty of speech. The results indicate that DS is best characterized by these 2 factors. The great majority of participants (86%) displayed DS symptoms from both factors. On average, participants had 4.19 (S.D. = 1.39) symptoms that were primary, enduring, and at least moderate in severity. The mean severity of symptoms was 2.25 (S.D. = 1.06). We discuss possible links between the obtained factors and putative neurobiological mechanisms, as well as directions for future research

Schizophrenia, which has both genetic and environmental causes, is associated with persistent symptoms and severe functional disability. The illness lies dormant during the premorbid phase and begins to express itself during adolescence or early adulthood. Clinical progression and deterioration reaches a plateau in which the patient is said to be in the chronic phase of illness and at which point restoration of prior functioning is unlikely. The severe deficits associated with schizophrenia are often the result of progression of illness due to lack of appropriate treatment. However, recent advances in neuropsychiatry have led to very early identification of individuals at risk for psychosis, even during the prodromal stage when psychosis has not yet manifested clinically. While research has demonstrated that the efficacy of antipsychotics is limited when used during the chronic phase of illness, these medications can effectively control symptoms and prevent progression of illness when used during the early stages of illness. The evidence of neural degeneration in the pathophysiology of schizophrenic illness suggests that there may be treatment opportunities through neural protection. Neuroprotection, which refers to treatment that helps maintain central nervous system functionality in response to neurobiologic stress, may be responsible for prevention of disease progression and deterioration. In this monograph, Jeffrey L. Lieberman, MD, introduces the phases of schizophrenic illness in relation to the concepts of progression and deterioration. Next, Dolores Malaspina, MD, reviews the neurodevelopmental and neurodegenerative components of schizophrenia. Finally, L. Fredrik Jarskog, MD, focuses on the neuroprotective aspects of therapeutic interventions in schizophrenia

The Experience Sampling Method (ESM) is an ecologically valid, time-sampling of self-reports developed to study the dynamic process of person-environment interactions. ESM with digital wristwatch and booklets (paper-based ESM; ESMp) has been used extensively to study schizophrenia. The present study is designed to test the feasibility and validity of using Computerized ESM (ESMc) among individuals with schizophrenia. ESMc is advantageous in allowing for recording of precise time-stamps of responses. We used PDAs ('Personal Digital Assistant'; Palm handheld computers) to collect data on momentary psychotic symptoms, mood, and thoughts over a one day period among 10 hospitalized schizophrenia patients and 10 healthy controls. ESMc was equally acceptable to both groups, with similar ratings of comfort carrying the PDAs and operating them, interference with daily activities, as well as response rates. The schizophrenia patients reported significantly higher ratings of auditory and visual hallucinations, suspiciousness, sense of unreality, lack of thought control, fear of losing control, difficulty expressing thoughts, as well as depression/sadness, loneliness and less cheerfulness. Significant inverse relationships were found among both groups between ratings of feeling cheerful and being stressed, irritated, and sad/depressed. Among the schizophrenia subjects, the correlation between ratings of suspiciousness on ESMc and Scale for Assessment of Positive Symptoms (SAPS) approached significance, as well as the link between suspiciousness and stress. Our results support the feasibility and validity of using ESMc for assessment of momentary psychotic symptoms, mood, and experiences among individuals with schizophrenia. The authors discuss the potential applications of combining ESMc with ambulatory physiological measures

Schizophrenia, which has both genetic and environmental causes, is associated with persistent symptoms and severe functional disability. The illness lies dormant during the premorbid phase and begins to express itself during adolescence or early adulthood. Clinical progression and deterioration reaches a plateau in which the patient is said to be in the chronic phase of illness and at which point restoration of prior functioning is unlikely. The severe deficits associated with schizophrenia are often the result of progression of illness due to lack of appropriate treatment. However, recent advances in neuropsychiatry have led to very early identification of individuals at risk for psychosis, even during the prodromal stage when psychosis has not yet manifested clinically. While research has demonstrated that the efficacy of antipsychotics is limited when used during the chronic phase of illness, these medications can effectively control symptoms and prevent progression of illness when used during the early stages of illness. The evidence of neural degeneration in the pathophysiology of schizophrenic illness suggests that there may be treatment opportunities through neural protection. Neuroprotection, which refers to treatment that helps maintain central nervous system functionality in response to neurobiologic stress, may be responsible for prevention of disease progression and deterioration. In this monograph, Jeffrey L. Lieberman, MD, introduces the phases of schizophrenic illness in relation to the concepts of progression and deterioration. Next, Dolores Malaspina, MD, reviews the neurodevelopmental and neurodegenerative components of schizophrenia. Finally, L. Fredrik Jarskog, MD, focuses on the neuroprotective aspects of therapeutic interventions in schizophrenia. (journal abstract)