Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder.

Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We explored the relationship between fasting plasma proline levels and COMT Val(158)Met genotype on symptoms (positive, negative and total) in schizophrenia patients. In an exploratory study we also examined symptom change in patients with bipolar disorder. There was a significant interaction between peripheral proline and COMT on negative symptoms in schizophrenia (P<0.0001, n=95). In COMT Val/Val patients, high proline was associated with low Scale for the Assessment of Negative Symptom (SANS) scores. In contrast, high proline was associated with high SANS scores in patients carrying a Met allele. The relationship between proline and COMT also appears to modify negative symptoms across psychiatric illness. In bipolar disorder, a significant interaction was also observed on negative-symptom change (P=0.007, n=43). Negative symptoms are intractable and largely unaddressed by current medications. These data indicate a significant interaction between peripheral proline and COMT genotype, influencing negative symptoms in schizophrenia and bipolar disorder. That high proline has converse effects on symptoms by COMT genotype, may have implications for therapeutic decisions.

Dyskinesias differentiate autistic disorder from catatonia.

Autistic disorder and catatonia are neuropsychiatric syndromes defined by impairments in social interaction, communication, and restricted, stereotypical motor routines. Assessments of children with these disorders are typically restricted in scope by the patients' limited ability to comprehend directions. The authors performed systematic assessments of dyskinesias on six prepubertal boys with autistic disorder and mental retardation and on one adolescent male with catatonia to determine if this type of information could be routinely obtained. The boys with autistic disorder had more stereotypies and tics, a greater degree of akathisia and hyperactivity, and more compulsions than the adolescent with catatonia. Catatonia was associated with catalepsy and dystonic postures. The authors conclude that the diagnostic accuracy and specificity of neuropsychiatric syndromes may be enhanced by the systematic assessment of the dyskinesias associated with each condition.

A review of the literature and a preliminary study of family compliance in a developmental disabilities clinic.

To investigate the compliance of family members with the treatment recommended for patients, three child and adolescent psychiatrists assessed the charts of all active outpatients in a developmental disabilities clinic in the psychiatric department of a tertiary care municipal hospital utilizing a Family Compliance Checklist, a survey form for chart review, in October, 1993 (n = 40), and in April, 1994 (n = 41). Almost no clients missed appointments over a 6-mo. period. Only one family refused to permit the use of medication. Three families refused to make appointments. The majority of the patients were Hispanic and almost half were Roman Catholic. We conclude that most families of patients in a developmental disabilities clinic comply with recommended treatment plans including scheduled appointments and prescribed medications.

Dyskinesias subside off all medication in a boy with autistic disorder and severe mental retardation.

A boy with autistic disorder and severe mental retardation developed severe dyskinesias, including objective akathisia (probable) and tics, a month after discontinuation of at least two years of treatment with drugs block dopamine receptors. These dyskinesias greatly subsided during a 17-wk. open-label nonblind clinical trial of clomipramine, and returned transiently when the parents abruptly discontinued clomipramine. However, the dyskinesias gradually subsided during two and a half years of follow-up with the boy being off all medication. A few stereotypies remain. We believe this suggests the hypothesis that movement disorders, such as withdrawal and tardive akathisia and tics, occurring in boys with autistic disorder treated with dopamine receptor-blocking drugs may subside months or years after discontinuation of the agents and that clomipramine may facilitate this process. We also hypothesize that some boys with autistic disorder and mental retardation exhibit fewer movement disorders, fewer psychiatric symptoms, and better over-all functioning after they have received no dopamine receptor-blocking drugs for several months, and this improvement continues years after the medication has ceased.

Clinical assessment of self-injurious behavior.

The Timed Self-injurious Behavior Scale is an observational scale rating the frequency of 16 types of self-injurious behaviors during each 10-sec. interval of a 10-min. observation period. Advantages of the scale are utilization of direct observation and independence from the variable recollection of symptoms by subjects and care givers. 19 videotaped sessions of a subject who exhibited eight types of self-injurious behaviors were rated with the scale independently by three raters. Eighty percent and better agreement was found for the four specific forms of those behaviors exhibited by the subject sufficiently frequently, self biting, head punching, head slapping, and hair removal.