Very early interventions in psychotic disorders.

It is well accepted that most serious psychiatric conditions begin in adolescence and are characterized by initial symptoms that predate the full manifestation of illness. This early period often consists of nonspecific symptoms, making accurate detection difficult. Classification as "prodromal" is only possible retrospectively, after a patient has developed positive psychotic symptoms. To monitor these patients prospectively, we must identify and follow patients who are at risk for psychosis, understanding that this group may also include false positives who do not go on to develop psychotic illness. Improving detection of at-risk individuals gives us an opportunity to intervene earlier in the course of the disorder, creating a window of opportunity to improve outcome and decrease overall burden of illness.

An investigation of prepulse inhibition in pediatric bipolar disorder.

OBJECTIVES: Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, have been noted in psychopathologies including schizophrenia and adult bipolar disorder (BPD). Sensorimotor gating deficits may contribute to the emotional and behavioral dysregulation characteristic of pediatric BPD. The current study investigated possible PPI deficits in children with BPD. METHODS: Sixteen children with BPD (medicated, euthymic and non-psychotic) were compared with 13 control subjects on the magnitude of startle habituation, startle-alone response, and inhibition of startle following a 60 or 120-ms prepulse. RESULTS: Both groups displayed startle inhibition by a prepulse, with no significant between-group differences on the magnitude of inhibition after the 60- or 120-ms prepulse. In addition, there were no between-group differences on habituation or baseline startle response. PPI level was not significantly correlated with mood symptoms and did not differ based on comorbid attention deficit hyperactivity disorder. CONCLUSIONS: A lack of PPI deficits in our pediatric bipolar sample contrasts with previous results in adult bipolar and schizophrenic samples. These negative results may reflect the fact that our sample was medicated and was neither acutely manic nor psychotic. Deficits in sensorimotor gating may not be implicated in the emotional and behavioral dysregulation in pediatric BPD.

Using affect-modulated startle to study phenotypes of pediatric bipolar disorder.

OBJECTIVES: Affective neuroscience research that investigates core symptoms of pediatric bipolar disorder (PBD) may be effective in differentiating PBD phenotypes. The current study used affect-modulated startle to examine potential differences in reactivity to emotional stimuli (reward and punishment) in narrow and broad phenotype PBD and controls. METHODS: Thirty children meeting DSM-IV bipolar disorder criteria (i.e. narrow phenotype PBD with defined manic episodes with elevated/expansive mood), 19 children meeting criteria for severe mood dysregulation (i.e. broad phenotype with chronic irritability, hyper-reactivity, and hyperarousal), and 19 controls completed a lottery startle paradigm involving reward (money) and punishment (loud noise). Startle probes were presented during anticipation of the emotional stimulus, immediately following the presentation of the stimulus, or during return to baseline following the stimulus. RESULTS: By self-report, patients and controls found the putative punishment to be preferable to the neutral condition. In the reward condition, patient samples reported greater arousal than did controls, but no between-group differences were found on the magnitude of startle response during the reward, punishment, or neutral conditions. CONCLUSIONS: The failure to find differences in affect-modulated startle between control children and those with narrow or broad PBD phenotypes speaks to the methodological challenges associated with studying reward mechanisms in PBD. Alternative paradigms that focus on different aspects of reward mechanisms are discussed.

Defining clinical phenotypes of juvenile mania.

OBJECTIVE: The authors suggest criteria for a range of narrow to broad phenotypes of bipolar disorder in children, differentiated according to the characteristics of the manic or hypomanic episodes, and present methods for validation of the criteria. METHOD: Relevant literature describing bipolar disorder in both children and adults was reviewed critically, and the input of experts was sought. RESULTS: Areas of controversy include whether the diagnosis of bipolar disorder should require clearly demarcated affective episodes and, if so, of what duration, and whether specific hallmark symptoms of mania should be required for the diagnosis. The authors suggest a phenotypic system of juvenile mania consisting of a narrow phenotype, two intermediate phenotypes, and a broad phenotype. The narrow phenotype is exhibited by patients who meet the full DSM-IV diagnostic criteria for hypomania or mania, including the duration criterion, and also have hallmark symptoms of elevated mood or grandiosity. The intermediate phenotypes include 1) hypomania or mania not otherwise specified, in which the patient has clear episodes and hallmark symptoms, but the episodes are between 1 and 3 days in duration, and 2) irritable hypomania or mania, in which the patient has demarcated episodes with irritable, but not elevated, mood. The broad phenotype is exhibited by patients who have a chronic, nonepisodic illness that does not include the hallmark symptoms of mania but shares with the narrower phenotypes the symptoms of severe irritability and hyperarousal. CONCLUSIONS: The presence of distinct episodes and hallmark symptoms can be used to differentiate clinical phenotypes of juvenile mania. The utility and validity of this system can be tested in subsequent research.

Medication use in children and adolescents treated in the community for bipolar disorder.

We assessed the use of mood stabilizers, stimulants, antipsychotic medication, and selective serotonin reuptake inhibitors in children being treated in the community for bipolar disorder (BPD). One hundred eleven patients were screened via parent phone interview for possible inclusion in a phenomenological study of BPD. Data were obtained on the patients' medication trials and side effects. The results of the study indicated that children and adolescents who carry a diagnosis of BPD are treated with a mean of 3.40 +/- 1.48 medications and have had a mean of 6.32 +/- 3.67 trials of psychotropic medication in the past. Ninety-eight percent have had a trial of a mood stabilizer or anticonvulsant, with the most common being valproate (79%), lithium (51%), and gabapentin (29%).

Clinical correlates of episodicity in juvenile mania.

OBJECTIVE: Researchers debate whether the diagnostic criteria for mania should differ between children and adults. Specifically, although the Diagnostic and Statistical Manual of Mental Disorders (fourth edition; DSM-IV) requires episodic mood changes, children commonly are diagnosed as manic on the basis of chronic irritability. In this preliminary study, children carrying a diagnosis of bipolar disorder (BPD) in the community were classified as having either episodic or chronic symptoms. We hypothesized that the episodic group would be more likely to have a history of psychosis and a parental history of BPD, whereas the chronic group would be more likely to have conduct disorder. METHODS: Parents of children carrying the BPD diagnosis were interviewed on the telephone to obtain psychiatric and family histories. Children were considered episodic (n = 34) if they had a history of one or more DSM-IV manic/hypomanic episodes meeting full duration criteria and chronic (n = 53) if they had no discernable episodes. RESULTS: The episodic group was more likely to have had psychosis, parental history of BPD, and to have experienced each manic symptom except for irritability and psychomotor agitation. Children in the episodic group were also more likely to have had a depressive episode meeting full DSM-IV criteria and were more likely to have made a suicide attempt. Children in the chronic group were not more likely to meet criteria for conduct disorder but were more likely to exhibit violence toward others. CONCLUSIONS: These preliminary data indicate that, among children being treated for BPD in the community, those with discrete episodes of mania may be more likely to have a lifetime history of psychosis and a parental history of BPD. The latter hypothesis should be tested in a sample where relatives are interviewed directly.

Affective neuroscience and the study of normal and abnormal emotion regulation.

Affective neuroscience allows investigators to study the biologic basis of psychologic phenomena such as emotion and mood. Understanding the components of emotion, valence, and arousal and their physiologic correlates is the starting point for studies that quantify emotional and physiologic reactions. This information could provide insight into the biologic foundations of numerous psychiatric conditions. Understanding the normal development of emotions and regulation of emotion will provide new avenues of research into the complex problem of severe mood disorders.