Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia.

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers.(1) Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs.(2) We examined the association of three polymorphisms in the 5-HT2A receptor gene (HTR2A) with TD susceptibility--T102C(3) and his452tyr(4) in the coding region and A-1438G(5) in the promoter--in matched schizophrenia patients with (n = 59, SCZ-TD-Y) and without TD (n = 62, SCZ-TD-N) and normal control subjects (n = 96). The T102C and the A-1438G polymorphisms are in complete linkage disequilibrium but not his452tyr. There was a significant excess of 102C and -1438G alleles (62.7%) in the SCZ-TD-Y patients compared to SCZ-TD-N patients (41.1%) and controls (45.9%; chi(2) = 12.8, df = 2, P = 0.002; SCZ-TD-Y vs SCZ-TD-N, chi(2) = 11.4, df = 1, P = 0.0008, OR 2.41, 95% CI 1.43-3.99) and of 102CC and -1438GG genotypes (SCZ-TD-Y 42.4%, SCZ-TD-N, 16.1%, controls 20.8%, chi(2) = 13.3, df = 4, P = 0.01). The 102CC and the -1438GG genotypes were associated with significantly higher AIMS trunk dyskinesia scores (F = 3.9; df = 2, 116; P = 0.02) and more incapacitation (F = 5.0; df = 2, 115; P = 0.006). The his452tyr polymorphism showed no association with TD. These findings suggest that the 5-HT2A receptor gene is significantly associated with susceptibility to TD in patients with chronic schizophrenia. Previously reported association of the T102C and A-1438G polymorphisms with schizophrenia(6) may reflect association of a sub-group of patients with a susceptibility to abnormal involuntary movements related to antipsychotic drug exposure.

[Alopecia due to Seroxat therapy].

There are 2 stages of alopecia, anagen and telogen effluvium, both of which may be associated with medication-related alopecia. We describe massive hair loss in a 51-year-old woman during treatment with Seroxat (paroxetine), which remitted after it was discontinued. Pathological mechanisms of drug-associated alopecia are complex and have yet to be fully elucidated.

The prevalence of seborrheic keratoses in people aged 15 to 30 years: is the term senile keratosis redundant?

BACKGROUND: Seborrheic keratoses (SKs) are common skin lesions that have been shown to occur with increasing age, although the age of onset is not well recorded. OBJECTIVE: To determine the prevalence, nature, and distribution of SKs in young people. METHODS: One hundred seventy people aged 15 to 30 years were given a total body examination during which the presence, number, site, and size of SKs were recorded. Biopsy specimens were taken from the first 22 people who had lesions clinically diagnosed as SKs. Data on age, skin type, eye color, and hair color were recorded for all respondents. RESULTS: Forty (23.5%) of 170 respondents had at least one SK, with no significant difference between the sexes. There was an increase in prevalence with age from 15.7% in 15- to 19-year-olds to 32.3% in those aged 25 to 30 years. The size of the SKs also increased with age. A total of 77.5% of SKs were found on the trunk and 22.5% on the limbs, head, and neck. There was no correlation between SKs and any particular hair and eye color or skin type. CONCLUSIONS: These findings confirm that SKs are common lesions in young Australians, appearing in a substantial proportion of people younger than 30 years. The term senile keratosis is no longer appropriate for these lesions.

Pathology quiz. A pigmented skin lesion.

Melanomas can usually be distinguished histologically from benign lesions by the application of accepted criteria of high discriminatory value. Occasionally, the distinction cannot be made with certainty. It is convenient to consider cutaneous melanoma as essentially of one type, with the prognosis being mainly determined by the thickness of the lesion. There is a trend to narrower excision margins with adequacy being judged solely by careful histological assessment. A formula-driven approach should be avoided.

A puzzling rash. Is a skin biopsy a useful diagnostic tool?

The diagnosis of a puzzling skin rash may require the clinician to provide a well taken biopsy specimen with an accompanying detailed description of the rash. The pathologist needs to be cognizant of the clinical manifestation of skin eruptions and to correlate the histopathological findings with the clinical features.

Association between the serotonin 2C receptor gene and tardive dyskinesia in chronic schizophrenia: additive contribution of 5-HT2Cser and DRD3gly alleles to susceptibility.

RATIONALE: Tardive dyskinesia (TD) is a longterm adverse effect of dopamine receptor blockers. The dopamine D3 receptor gene (DRD3) ser9gly polymorphism has been previously associated with susceptibility to TD. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extra-pyramidal effects profile of atypical antipsychotic drugs. OBJECTIVES: To examine the association of a functional polymorphism in the 5-HT2C receptor gene (HT2CR) with TD and the joint contribution of HT2CR and DRD3 to susceptibility. METHODS: Case control association analysis of allele and genotype frequencies among schizophrenia patients with (n=55) and without TD (n=60), matched for antipsychotic drug exposure and other relevant variables, and normal control subjects (n=97). Parametric analyses of the contribution of 5-HT2Cser and DRD3gly alleles to dyskinesia scores. RESULTS: We found a significant excess of 5-HT2Cser alleles in schizophrenia patients with TD (27.2%) compared to patients without TD (14.6%) and normal controls (14.2%; chi2=6.4, df 2, P=0.03) which was due to the female patients (chi2=8.6, df 2, P=0.01). Among the female TD patients there was an excess of cys-ser and ser-ser genotypes (chi2= 11.9, df 4, P=0.02). Analysis of covariance (ANCOVA), controlling for age at first antipsychotic treatment, revealed a significant effect of 5-HT2C genotype on orofacial dyskinesia (OFD) scores (F=3.47, df 2, P=.03). In a stepwise multiple regression analysis, 5-HT2C and DRD3 genotype (5-HT2Cser and DRD3gly allele carriage) respectively contributed 4.2% and 4.7% to the variance in OFD scores. CONCLUSIONS: These findings support a small but significant contribution of the HT2CR and DRD3 to susceptibility to TD, which is additive in nature.

Genotypic association between the dopamine D3 receptor and tardive dyskinesia in chronic schizophrenia.

Dopamine receptor antagonism is a common mechanism underlying the therapeutic efficacy of all classical antipsychotic drugs. It is also thought to underlie the propensity of these agents to induce the movement disorder, tardive dyskinesia (TD), in one fifth of chronically exposed schizophrenia patients. We examined the polymorphic serine to glycine substitution in the first exon of the gene encoding the dopamine D3 receptor (DRD3) inn 53 schizophrenia patients with TD, 63 matched patients with similar antipsychotic exposure but no TD and 117 normal controls. There was a difference in allele frequency that was of borderline significance (P = 0.055), due to an excess of the DRD3gly allele (allele 2) in the schizophrenia patients with TD. The difference in genotype distribution among the groups was highly significant (chi2 = 19.1, d.f. 4, P = 0.0008) due to an excess of the DRD3ser-gly genotype in the schizophrenia patients with TD. The difference between the schizophrenia patients with TD and the controls was highly significant (chi2 = 19.0, d.f. 2, P = 0.00007), even after correction for multiple testing, as was the difference between the combined group of schizophrenia patients and the controls (chi2 = 12.2, d.f. 2, P = 0.002). Comparing the schizophrenia patients with and without TD, genotypes containing the gly allele (DRD3ser-gly and DRD3gly-gly genotypes combined) were significantly associated with dyskinesia (OR = 2.62, 95% CI 1.18-5.59, P = 0.02). DRD3 genotype and age at first antipsychotic treatment contributed significantly to total score on the Abnormal Involuntary Movements Scale (AIMS). The contribution of DRD3 to the variance in AIMS total was 5.2% and the total proportion of the variance accounted for by these two variables together was 11.9%. These results support and extend the report by Steen et al (1997) of an association between DRD3 and TD in schizophrenia patients.

Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior.

OBJECTIVE: The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients. METHOD: Twenty-eight actively psychotic inpatients, aged 20-60 years, who were under treatment with neuroleptic agents were selected for the study. Each was randomly assigned on a double-blind basis to receive either 5 mg i.m. of haloperidol (N=13) or 1 mg i.m. of flunitrazepam (N=15) during an aggressive event. Verbal and physical aggression was measured over time with the Overt Aggression Scale. Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. RESULTS: Both flunitrazepam and haloperidol exhibited acute antiaggressive activity. This beneficial effect, as assessed by the Overt Aggression Scale, was obtained within 30 minutes. CONCLUSIONS: Intramuscular flunitrazepam may serve as a convenient, rapid, safe, and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric settings.

Differences in age and body site distribution of the histological subtypes of basal cell carcinoma. A possible indicator of differing causes.

OBJECTIVE: To assess if there are any significant differences in the sex, anatomical site, and age distribution of patients with different histological subtypes of basal cell carcinoma (BCC). DESIGN: Histopathology reports were analyzed with respect to the subtype of BCC, site of a tumor, and age and sex of a patient. SETTING: Histopathology reports were reviewed from 1 private laboratory that derived its cases from general practitioners, surgeons, and dermatologists. PATIENTS: Patients with BCC (N = 3885) for whom case data were received by the pathology laboratory from January 2, 1991, to June 12, 1991, were included in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Superficial BCCs differed from other subtypes of BCC by occurring more commonly on the trunk and in younger patients. RESULTS: The mean age (56.8 years) of the patients with superficial BCCs was significantly lower than that of the patients with other subtypes of BCC who were examined (P < .001); the mean ages of the patients with these other subtypes were as follows: nodulosuperficial BCC, 62.9 years; nodular BCC, 63.9 years; nodulomorpheic BCC, 66.1 years; and morpheic BCC, 66.0 years. The majority of superficial BCCs occurred on the trunk and limbs (73.3%), while the majority of all other subtypes occurred on the head and neck. CONCLUSIONS: Superficial BCC differs from the other subtypes of BCC in terms of patient age and tumor site, and these findings may reflect differences in the etiology.

Lack of effect of vitamin E on serum creatine phosphokinase in patients with long-term tardive dyskinesia.

Changes in serum creatine phosphokinase have been associated with exacerbation of tardive dyskinesia. Vitamin E, a drug suggested to be effective in the treatment of tardive dyskinesia, has been implicated as a possible cause of increased creatine phosphokinase levels. Ten patients with long-term tardive dyskinesia were treated with vitamin E in a double-blind, placebo-controlled crossover study. Vitamin E blood levels and creatine phosphokinase serum levels were monitored at various phases during the study. There were no significant differences between vitamin E and placebo treated patients in their abilities to affect tardive dyskinesia or to influence creatine phosphokinase levels. These data do not support the hypothesis that administration of vitamin E may alter creatine phosphokinase levels in patients with long-term tardive dyskinesia.

Who removes pigmented skin lesions?

BACKGROUND: Increasing numbers of pigmented skin lesions are being removed because of concern about possible malignancy. OBJECTIVE: Our purpose was to determine the ratio of benign to malignant pigmented tumors removed by different categories of physician and to verify whether any improvement had occurred after 5 years of educational programs. METHODS: All pigmented lesions submitted to a major histopathology service in the years 1989 and 1994 were assessed as to the category of physician who removed the lesion, tumor type, and age and sex of the patient. RESULTS: Dermatologists had the lowest benign/malignant ratio and general practitioners had the highest. General practitioners appeared to have difficulty differentiating both seborrheic keratoses and melanocytic nevi from malignant lesions; the frequency of these benign lesions was highly dependent on the age of the patient. During the 5-year period we observed an improvement among general practitioners in the benign/malignant ratio for melanocytic nevi, but not for seborrheic keratoses. CONCLUSION: There is room for improvement by physicians in differentiating both melanocytic nevi and seborrheic keratoses from melanomas. This is especially true for general practitioners, from whom the public in Australia and in other countries is encouraged to first seek advice about a suspect pigmented lesion.

[Medication group for noncompliant patients in a psychiatric day unit--experiences during a one year period].

A group of noncompliant psychiatric patients was treated on a weekly basis over a 6-month period; 13 started but 3 dropped out. Results indicated greater feeling of security with medication; increased desire to maintain follow-up treatment in the outpatient clinic; greater likelihood of patients accepting their illness; and strong desire to discuss medication-related topics with staff. Our medication group appears to offer a convenient and organized method for addressing issues of psychiatric medication, especially for chronic patients, which we recommend to clinicians in other medical disciplines.

The impact of clinical pharmacy intervention in a psychiatric hospital.

One hundred and nine physician-initiated consultations were directed to a clinical pharmacist over a 1-year period. Two hundred and three (88.2%) recommendations out of 229 were adopted. Major question types included preventive measures, non-response, side-effects and mixed factors. The global effectiveness of pharmacist interventions suggests that 67.9% of patients exhibited a very satisfactory or satisfactory response. While our study suggests that a clinical pharmacist may favourably contribute to the quality of patient care, a control-group study is required to confirm our results.

Antipsychotic drugs and tardive dyskinesia: preliminary results in an adolescent psychiatric ward.

The systematic study of antipsychotic-induced movement disorders in young psychiatric patients is very sparse. We assessed the presence of tardive dyskinesia in an adolescent in-patient psychiatric ward. Eighteen per cent (3/17) exhibited either pronounced or subtle signs of tardive dyskinesia. Our study suggests that young psychiatric patients may develop signs of tardive dyskinesia even though they are exposed to relatively short-term neuroleptic treatment and at dosages that are relatively low. We advocate frequent and systematic monitoring of adolescent patients taking antipsychotic drugs in order to minimize the emergence of this long-term, troublesome complication of neuroleptic drugs.

[Lithium-associated psoriasis].

A number of medications including clonidine, digoxin and beta-blockers have been reported to cause psoriasis. Lithium has also been implicated especially among women. We describe a 45-year-old man who developed diffuse psoriatic lesions 1 year after treatment with lithium was started. Various topical dermatological preparations failed to alleviate the lesions. Several weeks after discontinuation of lithium the psoriasis resolved. We discuss the possible mechanisms for lithium-associated psoriasis and alert clinicians to the possibility of this troublesome side-effect in lithium-treated patients, with or without a family history of psoriasis.

[Lithium-associated alopecia].

A 39-year-old woman who developed alopecia shortly after treatment with lithium carbonate was initiated is described. The alopecia resolved 2 months after lithium was discontinued. Though this side-effect is relatively rare, we suggest that patients getting lithium for short or long term treatment be monitored for it.

Fluvoxamine-associated sexual dysfunction.

OBJECTIVE: To report two cases of sexual dysfunction induced by fluvoxamine, a selective serotonin reuptake inhibitor (SSRI). SETTING: University teaching hospital. PATIENTS: Two depressed patients who developed ejaculation and orgasmic difficulties after initiation of fluvoxamine therapy. DISCUSSION: The literature concerning sexual dysfunction with serotonergic antidepressants is reviewed, and speculated mechanisms for this untoward effect are discussed. CONCLUSIONS: Sexual dysfunction associated with antidepressant drugs, including SSRIs, may be underreported. This troublesome adverse effect may significantly affect patient comfort and compliance. Careful evaluation of sexual function is warranted, prior to and during drug treatment, especially as more serotonergic antidepressant agents become available.

A psychopharmacology education program for psychiatry residents--the role of a clinical pharmacist.

The author describes a psychopharmacology education program administered by a psychiatric clinical pharmacist. The program included biweekly lectures and psychopharmacology review rounds for junior psychiatry residents. This teaching program suggests that a psychiatric clinical pharmacist may favorably contribute to the optimum usage of psychotropic drugs, especially in those residency years when prescribing habits are being formed.

Fluvoxamine-associated manic behavior: a case series.

OBJECTIVE: To report cases of manic-like behavior induced by fluvoxamine, a selective serotonin-reuptake inhibitor; to review pertinent literature; and to encourage replication of our findings in larger patient samples. DESIGN: Description of a case series of fluvoxamine-induced, manic-like behavior. PATIENTS: Eight patients with depression or obsessive features who developed manic-like behavior after initiation of fluvoxamine therapy. RESULTS: Manic symptomatology resolved in all eight patients following dosage reduction or withdrawal of fluvoxamine. Four patients still are maintained on low-dose fluvoxamine without recurrent manic symptoms. CONCLUSIONS: Our case series suggests that fluvoxamine may have the ability to induce or unmask manic behavior in depressed patients. Clinicians are alerted to monitor for this "switching" effect, especially in patients previously or currently treated with neuroleptics or lithium, and in those patients exhibiting characteristics of obsessive-compulsive disorder.