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P#2
: Comings, D.E., & Comings, B.G. (1985). Tourette syndrome: clinical and psychological aspects of 250 cases
ABSTRACT:Tourette syndrome is a common hereditary neuropsychiatric disorder consisting of multiple tics and vocal noises. We summarize here clinical aspects of 250 consecutive cases seen over a period of 3 years. The sex ratio was four males to one female, and the mean age of onset was 6.9 years. Only 10% were Jewish, indicating that it is not more prevalent in Ashkenazi Jews. Only 33% had compulsive swearing (coprolalia), indicating that this is not necessary for the diagnosis. The most frequent initial symptoms were rapid eye-blinking, facial grimacing, and throat-clearing. In this series, it was clear that Tourette syndrome is a psychiatric as well as a neurological disorder. Significant discipline problems and/or problems with anger and violence occurred in 61%, and 54% had attention-deficit disorder with hyperactivity. Some degree of exhibitionism was present in 15.9% of males and 6.1% of females. Obsessive-compulsive behavior was seen in 32%. Other than tics and vocal noises, the most common parental complaints were of short temper and everything being a confrontation. There were no significant clinical differences between familial and sporadic cases. Whenever a child presents with a learning disorder, attention-deficit disorder, or significant discipline or emotional problems, the parents should be questioned about the presence of tics or vocal noises in the patient and other family members. Am.J.Hum.Genet., 37, 435-450.
P#3
: Comings, D.E., & Comings, B.G. (1987). A controlled study of Tourette syndrome. I. Attention-deficit disorder, learning disorders, and school problems
ABSTRACT:Tourette syndrome (TS) is a common, hereditary, neurobehavioral disorder of childhood. To determine the frequency of various behavioral manifestations, we have compared 47 random normal controls to 246 patients with TS, 17 with attention-deficit disorder (ADD), and 15 with ADD secondary to a TS gene (ADD 2(0) TS). All subjects were examined prospectively with a 425-item questionnaire based on the Diagnostic Interview Schedule and the Diagnostic and Statistical Manual of Mental Disorders (DSM III). The TS patients were divided into grade 1 (too mild to treat [17.5%]), grade 2 (requiring treatment [58.9%]), and grade 3 (severe [23.6%]). Patients in all three grades of TS were significantly different from controls for DSM III symptoms of inattention, impulsivity, and hyperactivity. Sixty-two percent of TS patients had ADD, compared with 6.3% of controls; and 48.8% had ADD with hyperactivity (ADDH), compared with 4.2% of controls. In the majority of TS patients, the natural history of the disease was to start with ADDH and 2.4 years later develop motor and vocal tics. Among TS patients, 39% had previously received medication for ADDH or behavior problems, compared with 2% of the controls. Although stimulants can occasionally exacerbate tics, there was no evidence that stimulants cause TS and they are often a valuable adjunct to the treatment of TS. It is estimated that 10%-30% of ADDH is due to or associated with the presence of a TS gene. TS patients had a significantly increased frequency of (1) attending classes for the educationally handicapped, (2) placement in classes for the severely emotionally disturbed, (3) attending any special classes, (4) severe test anxiety, (5) stuttering, (6) letter, number, or word reversal, (7) reading very slowly, and (8) poor retention of material read. A reading-problem score (dyslexia) greater than or equal to 3 was present in 26.8% of TS patients, compared with 4.2% of controls. Number reversal, word reversal, and poor retention were significant even for the TS patients with tics too mild to treat. The multiple ways in which TS impacts school performance, as well as potential remedies, are discussed. Am.J.Hum.Genet., 41, 701-741.
P#4
: Comings, D.E., & Comings, B.G. (1987). A controlled study of Tourette syndrome. II. Conduct.
ABSTRACT:To assess conduct in Tourette syndrome (TS), 47 controls, 246 TS patients, 17 attention-deficit-disorder (ADD), and 15 ADD patients with minor tics or a family history of TS (ADD 2(0) TS) were compared for the following behaviors: running away from home, lying, stealing, starting fires, vandalism, being in trouble with the law, fighting, shouting at parents or peers, attacking others, lack of respect for adults, short temper, hurting animals, feeling full of hate, being unable to stop fighting, and problems with drugs and alcohol. With the exception of running away from home and being in trouble with the law, TS patients were significantly different from controls in all other behaviors. When the components were combined for a total conduct score, only one (2.1%) of the controls had a score greater than 13, and he had TS. By contrast, 35% of the TS patients had scores greater than 13 (P < .0005). The correlation coefficient between the total conduct score and ADD score was .48. Although the presence of ADD was an important factor in determining conduct in TS, other factors such as depression and compulsive behavior also played a contributing role. There was little correlation between the total conduct score and the number of tics. It is estimated that among non-economically disadvantaged children, 10%-30% of conduct disorder may be due to the presence of a TS gene. Am.J.Hum.Genet., 41, 742-760.
P#5
: Comings, D.E., & Comings, B.G. (1987). A controlled study of Tourette syndrome. III. Phobias and panic attacks
ABSTRACT:Comparison was made of the frequency of phobias and panic attacks in normal controls and in patients with Tourette syndrome (TS), attention-deficit disorder (ADD), and ADD secondary to a TS gene. For phobias the most significant difference between controls and TS patients was with respect to fear of public transportation (P = .002), followed by fear of being alone (P = .009), fear of being in a crowd (P = .01), fear of being in water (P = .025), fear of animals (P = .04), fear of public speaking (P = .05), and other fears (P = .05). Only 8.5% of controls had more than three simple phobias and none had more than five, whereas 26% of TS patients had more than three (P = .008) and some had as many as 13. As opposed to 19% of TS patients, none of the controls had phobias that interfered with their life (P = .001). Among female TS patients 55.1% had 3-13 phobias, compared with 8.7% of the female controls (P < .0005). There was no correlation between the ADD score and the number of phobias (r = -.010) and little correlation with the total number of tics (r = .14). Panic attacks were present in 8.3% of the controls and 33% of the TS patients (P = .0008). This frequency increased to 55.2% (P < .0005) for grade 3 (severe) TS patients. None of the controls, 15.9% of all TS patients (P = .002), and 31% of grade 3 TS patients (P < .0005) had more than three panic attacks in 1 wk. Total panic-symptom score (12 possible symptoms) was significantly greater than that in the controls in all grades of TS. The presence or absence of ADD had little effect on the total panic-symptom score, but the presence of ADD resulted in a significantly lower average age at onset of panic attacks (8.8 years) compared with those TS patients without ADD (15.4 years) (P = .03). These observations indicate that phobias and panic attacks are a significant part of the symptomatology of TS and provide the first clear indication that phobias and panic attacks can be due to the presence of a major gene. Am.J.Hum.Genet., 41, 761-781.
P#6
: Comings, D.E., & Comings, B.G. (1987). A controlled study of Tourette syndrome. IV. Obsessions, compulsions, and schizoid behaviors
ABSTRACT:To determine the frequency of obsessive, compulsive, and schizoid behaviors in Tourette syndrome (TS), we prospectively questioned 246 patients with TS, 17 with attention-deficit disorder (ADD), 15 with ADD due to a TS gene, and 47 random controls. The comparative frequency of obsessive, compulsive, and repetitive behaviors--such as obsessive unpleasant thoughts, obsessive silly thoughts, echolalia, palilalia, touching things excessively, touching things a specific number of times, touching others excessively, sexual touching, biting or hurting oneself, head banging, rocking, mimicking others, counting things, and occasional or frequent public exhibitionism--were significantly more common in TS patients than in controls. The frequency of each of these was much higher for grade 3 (severe) TS. Most of these behaviors also occurred significantly more often in individuals with ADD or in individuals with ADD secondary to TS (ADD 2(0) TS). When these features were combined into an obsessive-compulsive score, 45.4% of TS patients had a score of 4-15, whereas 8.5% of controls had a score of 4 or 5. These results indicate that obsessive-compulsive behaviors are an integral part of the expression of the TS gene and can be inherited as an autosomal dominant trait. Schizoid symptoms, such as thinking that people were watching them or plotting against them, were significantly more common in TS patients than in controls. Auditory hallucinations of hearing voices were present in 14.6% of TS patients, compared with 2.1% of controls (P = .02). These symptoms were absent in ADD patients but present in ADD 2(0) TS patients. These voices were often blamed for telling them to do bad things and were frequently identified with the devil. None of the controls had a total schizoid behavior score greater than 3, whereas 10.9% of the TS patients had scores of 4-10 (P = .02). This frequency increased to 20.6% in the grade 3 TS patients. These quantitative results confirm our clinical impression that some TS patients have paranoid ideations, often feel that people are out to get them, and hear voices. Am.J.Hum.Genet., 41, 782-803
P#7
: Comings, B.G., & Comings, D.E. (1987). A controlled study of Tourette syndrome. V. Depression and mania
ABSTRACT:To evaluate the role of depression and mania in Tourette syndrome (TS), we have examined 246 TS patients, 17 attention-deficit disorder (ADD) patients, 15 patients with ADD associated with TS, and 47 controls, using (1) the standardized National Institutes of Mental Health Diagnostic Interview Schedule questions for a life history of major depression and/or mania and (2) a modified Beck depression score for evaluation of depression at the time of the examination. The results were combined into depression, Beck, and mania scores. Among the controls, 2.1% had a depression score greater than 9, and none had a score greater than 10. Among the TS patients, 22.9% had a score greater than 9 and the scores ranged up to the maximum of 18 (P < .0005). None of the pure ADD patients had a score greater than 6, whereas 20% of the ADD-secondary-to-TS (ADD 2(0) TS) patients had scores greater than or equal to 9. Among grade 3 TS patients, 46.6% had scores greater than or equal to 9. There were no differences in the frequency of depression in the TS patients with or without ADD. Comparable results were obtained for the Beck depression score, except that the percent with a score greater than or equal to 8 was higher for the TS patients with ADD (23.7%) than for those without ADD (9.3%). There was a good correlation between the depression score and the Beck score (r = .63), but no correlation between the ADD-with-hyperactivity (ADDH) score and either the depression score (r = .086) or the Beck score (r = .077). Among the controls, none had a mania score greater than or equal to 4, compared with 19.1% of the total TS patients (P ¥= .0005), 11.8% of the ADD patients (P = .002), and 26.6% of the ADD 2(0) TS patients (P = .0005). Although some of the mania questions would be expected to be answered positively by ADDH patients, the correlation coefficient between the ADDH scores and the mania scores was only moderate (r = .29), whereas the correlation with the depression score was much higher (r = .63). There was minimal correlation between the number of tics and either the depression score (r = .267) or the Beck score (r = .193). We conclude that depression and manic-depressive symptoms are common in TS patients and are an integral part of the disorder rather than being secondary to motor or vocal tics. Am.J. Hum.Genet., 41, 804-821
P#8
: Comings, D.E., & Comings, B.G. (1987). A controlled study of Tourette syndrome. VI. Early development, sleep problems, allergies, and handedness
ABSTRACT:Developmental milestones, problems with bladder and bowel control, sleep disturbances, allergies, and handedness were compared in 247 consecutive Tourette syndrome (TS) patients, 17 patients with attention-deficit disorder (ADD), 15 patients with ADD secondary to TS (ADD 2(0) TS), and 47 random controls. There were no significant differences in age of first talking or walking. By contrast, there were significant differences in problems with bladder and bowel control between TS patients and controls, as measured by age of first toilet training, age of last bed-wetting, frequency of enuresis, and age that bowel control was achieved. Sleep problems were pervasive in TS patients, with a significantly increased frequency of sleepwalking, night terrors, trouble getting to sleep, early awakening, and inability to take afternoon naps as a young child. In all diagnostic categories, including mild (grade 1) TS patients, a total sleep-problem score was significantly greater than that in controls. The sleep disorders and other TS symptoms are consistent with TS as a disorder of disinhibition of the limbic system. Allergies and left-handedness have been evoked as contributing to or being associated with ADD and learning disorders. There were no significant differences in the frequency of allergies or left-handedness in TS patients compared with that in controls. We conclude that when there is a clearly defined genetic cause of ADD and learning disorders, it is not associated with an increased frequency of allergies or left-handedness. . Am.J.Hum.Genet., 41, 822-838
P#9
: Comings, D.E. (1987). A controlled study of Tourette syndrome. VII. Summary: a common genetic disorder causing disinhibition of the limbic system
ABSTRACT:Tourette syndrome (TS) is one of the most common genetic disorders affecting man. Approximately one in 100 individuals manifests one or more of the aspects of the TS gene. This series of papers has emphasized that although motor and vocal tics are the hallmark of TS, the complete range of behavioral problems is much broader. This spectrum of behavior can be explained on the basis of the TS gene causing an imbalance of the mesencephalic-mesolimbic dopamine pathways, resulting in disinhibition of the limbic system. Am.J.Hum.Genet., 41 , 839-866.
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