[SSRI and SNRI treatment in children and adolescents. Current views of the benefits and risks]. / SSRI- und SNRI-Behandlung im Kindes- und Jugendalter. Aktuelle Informationen zum Nutzen-Risiko-Verhältnis.

The risk of suicidal thoughts and behaviours in the treatment of depressive children and adolescents with selective serotonin reuptake inhibitors (SSRI) and selective noradrenalin reuptake inhibitors (SNRI) is slightly but significantly elevated. These treatments in underage patients with anxiety or obsessive-compulsive disorders are however not related to a higher risk of suicidality. Effect sizes of SSRI/SNRI treatment in children and adolescents are medium to high in anxiety disorders (0.69), medium in obsessive-compulsive disorders (0.48), and low in depressive disorders (0.25). Nevertheless, the benefit:risk ratio is still positive in all three disorders.

A 2-year prospective study of bone metabolism and bone mineral density in adolescents with anorexia nervosa.

Osteopenia and osteoporosis are complications of adolescent anorexia nervosa (AN) and may result in a permanent deficit of bone mass in adulthood. It is still unclear if a complete catch-up in bone mineral density (BMD) is possible after weight rehabilitation in AN. METHODS. We investigated bone formation (bAP, PICP), bone resorption (CTX) and BMD (lumbar spine, femoral neck) along with endocrinological parameters in 19 girls with AN (14.4 +/- 1.6 years) and in 19 healthy controls for 2 years after inpatient re-feeding. RESULTS. Re-feeding normalised bone formation activity in patients. The pattern of bone turnover in patients after 2 years was similar to the pattern healthy controls had shown 2 years before. BMD of patients was significantly lower than in controls and did not change throughout the entire study. CONCLUSIONS. Weight rehabilitation leads to prolonged normalization of bone turnover in adolescent AN. Since we could not observe a "catch up" effect in BMD of girls with AN in a 2-year follow-up, BMD of these patients needs to be carefully monitored until adulthood to detect early osteoporosis.

Weight gain associated with clozapine, olanzapine and risperidone in children and adolescents.

The study was aimed at the evaluation of weight gain associated with atypical antipsychotics and its clinical risk factors in children and adolescents. Weight and body mass index (BMI) of initially hospitalised patients treated with clozapine (n = 15), olanzapine (n = 15), and risperidone (n = 15) were prospectively monitored on a weekly basis for the first 6 weeks. Different clinical risk factors were tested for their association with weight gain in the three groups. All three groups experienced significant weight gain between baseline and endpoint (p < 0.0001). For all weight measures, planned comparisons were all significant between olanzapine vs. clozapine and risperidone, respectively. Average weight gain was significantly higher for the olanzapine group (mean = 4.6 kg, SD = 1.9) than for the risperidone (mean = 2.8 kg, SD = 1.3) and clozapine (mean = 2.5 kg, SD = 2.9) groups. Olanzapine and risperidone, but not clozapine, caused a disproportionately higher weight gain in children and adolescents in comparison to adults.

The role of leptin in anorexia nervosa: clinical implications.

Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with this eating disorder are related to the low leptin levels, which are characteristic of acute AN. Weight gain in AN patients can induce relative hyperleptinaemia in comparison to controls matched for body mass index; circulating leptin concentrations in AN patients thus transverse from subnormal to supranormal levels within a few weeks. We review findings on leptin secretion in AN and focus on implications, particularly for the hypothalamus-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Undoubtedly, the elucidation of leptin's function as a trigger of diverse neuroendocrine adaptations to a restricted energy intake has substantially advanced our knowledge of the pathogenesis of distinct symptoms of AN, including amenorrhoea that represents one of the four diagnostic criteria. The fact that hypoleptinaemia can induce hyperactivity in a rat model for AN has led to a series of studies in AN patients, which support the notion that application of leptin to severely hyperactive patients might prove beneficial.

Oculomotor inhibition in children with and without attention-deficit hyperactivity disorder (ADHD).

The aim of the present study was to distinguish between a general deficit in oculomotor control and a deficit restricted to inhibitory functions in children with attention deficit hyperactivity disorder (ADHD). In addition, we were interested in differentiating between a general inhibition deficit and deficient subfunctions of inhibition. We used a prosaccade task to measure general oculomotor abilities in 22 children with ADHD and in age- and gender-matched healthy controls. A fixation, an antisaccade and a countermanding saccade task were used to measure specific aspects of oculomotor inhibition. Two major results were obtained: First, our prosaccade task suggests similar saccadic response preparation and saccadic accuracy in the ADHD compared to the control children. Secondly, the fixation and the countermanding saccade task indicate deficits on measures of oculomotor inhibition in the ADHD group. While patients were specifically impaired in stopping an already initiated response or in suppressing exploratory saccades in a novel situation, inhibition of a prepotent response was not deficient. Our data thus indicate an underlying impairment in cognitive inhibition in ADHD that has been associated with prefrontal lobe functions. More specifically, as the anterior cingulate gyrus has been associated with the countermanding saccade task and group differences were most pronounced in this paradigm our data are in line with imaging data stressing the importance of this cortical structure in the pathophysiology of ADHD.

Depression, anxiety, and obsessionality in long-term recovered patients with adolescent-onset anorexia nervosa.

Anorexia nervosa (AN) is frequently associated with symptoms of depression, anxiety, and obsessive-compulsive behavior which also develop secondary to semistarvation. It is less certain if these symptoms persist after recovery. A few studies have already reported on high prevalence rates of anxious, depressive, and obsessive features in long-term recovered patients with AN, but several of these so called "long-term" recovered patients had only maintained weight restoration for six to twelve months. The aim of this study was to determine whether depressive, anxious, and obsessive-compulsive symptoms persist in truly long-term recovered patients (BMI 20.3+/-2.5 kg/m(2)) who no longer had any eating disorder symptoms (including weight phobia) for at least 3 years. Seventeen subjects of an AN sample (n=39) previously described in a 10-year follow-up met our strict criteria of at least 3 years of complete recovery of AN. In comparison to 39 age-, sex-, and occupation-matched healthy subjects without a history of psychiatric or eating disorder, long-term recovered patients had higher levels of depressive (p=0.002), anxious (p=0.006), and obsessive-compulsive (p=0.015) features but did not differ with regard to psychiatric morbidity and psychosocial adaptation. In conclusion, depressive, anxious, and obsessive-compulsive symptoms may be personality traits in subjects with former adolescent anorexia nervosa.

A retrospective study of SSRI treatment in adolescent anorexia nervosa: insufficient evidence for efficacy.

Although selective-serotonin-reuptake-inhibitors (SSRI) have been of limited efficacy in the treatment of eating disorder psychopathology and comorbid symptoms of malnourished patients with anorexia nervosa (AN), there is recent data suggesting that SSRI may play a role in preventing relapse among weight-restored patients. Though some previous studies included patients in late adolescence, the vast majority of investigated subjects have been adults. The aim of our retrospective study was to assess the effects of SSRI treatment in partially weight-restored children and adolescents with AN. Thirty two females with AN (mean 14.5+/-1.4 years) were investigated three times during inpatient treatment and at 3- and 6-month follow-up for BMI, eating disorder psychopathology, depressive symptomology, and obsessive-compulsive symptomology. Medication history during inpatient and outpatient treatment was reconstructed at the 6-month follow-up. Nineteen patients received SSRI treatment, while 13 subjects were non-medicated. In comparison to the non-SSRI group, the SSRI group had similar BMI and obsessive-compulsive scores, but higher levels of core eating disorder psychopathology and depressive symptoms at the start of medication. Rates of re-admissions were similar in both groups (SSRI group: 36%, non-SSRI group: 31%, Phi: p=0.72). Repeated measures ANOVA revealed no significant group with time interactions for BMI-SDS (p=0.84), core eating disorder symptoms (ANIS, p=0.79), depression (DIKJ, p=0.75), and obsessive-compulsive (CY-BOCS, p=0.40) scores indicating minimal or no effects of SSRI medication on the course of these variables. In conclusion, our results challenge the efficacy of SSRI medication in the treatment of eating disorder psychopathology as well as depressive and obsessive-compulsive comorbidity in adolescent AN. Clinicians should be chary in prescribing SSRI in adolescent AN unless randomized controlled trials have proofed the benefit of these drugs.

Verbal memory and aspects of attentional control in children and adolescents with anxiety disorders or depressive disorders.

BACKGROUND: The aim was to examine basic performance on attention and memory tasks in treatment-naive children and adolescents with anxiety disorder or depressive disorder and in healthy subjects under drug-free conditions. METHODS: Basic neurocognitive performance on attention and verbal memory tasks was examined in children and adolescents with emotional disorders, between 6 and 17 years of age. A total of 34 children with an anxiety disorder, 31 children with a depressive disorder, and 33 healthy controls were assessed with a comprehensive neuropsychological test battery. All children were treatment-naive at the time of testing. Five different computerised attention tasks and the Rey Auditory-Verbal Learning Test were administered. RESULTS: A significant effect of diagnosis was found for verbal memory but not for attention. LIMITATIONS: The large age range and inclusion of different diagnoses resulted in rather inhomogeneous groups. CONCLUSION: The present study provided evidence for an undisturbed attentional performance in both patient groups and a dissociation in memory functioning between anxious and depressed children. Memory impairment was found to be specifically associated with childhood depression.

Congenital duplication of the thumb.

Duplication or polydactyly of the thumb is among the most common congenital deformities that involve the hand. The purpose of this presentation is to review the Mayo Clinic experience with thumb duplication and to present preferred operative procedures to achieve the best clinical outcome and esthetic appearance for the hand. We propose that a combination or "best of parts", utilizing the components of both duplicates with retention of the ulnar duplicate as the base for reconstruction will provide the most functional clinical result. A clinical grading system and analysis of results from our personal experience during two different time frames provides the scientific support for our conclusions that combination procedures are preferred to simple excisions or to central joining of parts as in the Bilhaut-Cloquet procedure.

High serum leptin levels subsequent to weight gain predict renewed weight loss in patients with anorexia nervosa.

It has repeatedly been shown that high serum leptin levels at target weight ensue from therapeutically induced weight gain in patients with anorexia nervosa (AN). It was hypothesized that elevated leptin levels may be an important factor underlying the difficulties of maintaining the target-weight in AN patients after re-feeding. The aim of this study was to examine if serum leptin levels at discharge from inpatient treatment predict renewed weight loss within 2 months after discharge and upon a 1 yr follow-up. Univariate variance analysis (ANOVA) revealed that 60% (cor. R2=0.60, P=0.002) of the variance in the BMI standard deviation score (BMI-SDS) 2 months after discharge was explained by the model consisting of the independent variables lg10 leptin levels at discharge (P=0.019) and at admission (P=0.069) and BMI-SDS at admission (P=0.002) and delta BMI between admission and discharge (P=0.047). Similarly, 60% (cor. R2=0.60, P=0.005) of the variance in BMI-SDS 1 yr after discharge was explained by lg10 leptin levels at discharge (P=0.046) and at admission (P=0.052) and BMI-SDS at admission (P=0.008) and 2 months after discharge (P=0.007) and delta BMI between admission and discharge (P=0.933). Patients with a poor outcome after 1 yr (n=9, ANCOVA, group: descriptive P=0.041), but not recovered patients (n=9, P=0.649), had lg10 leptin levels at discharge higher than those of controls when adjusted for BMI and % body fat at discharge. In conclusion, high serum leptin levels at discharge from inpatient treatment may indicate a risk for renewed weight loss and an unfavorable 1 yr outcome in AN.

Overweight and obesity in children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Epidemiological studies suggest that adiposity in children may be associated with a reduced level of physical activity. Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are physically hyperactive as of early childhood and have been shown to exhibit higher levels of motor activity than normal. The aim of our study was to assess if the prevalence of overweight and obesity is lower in a population of boys with ADHD in comparison with the German healthy male reference population of the same age. DESIGN: Patients were investigated from 1999 until 2001 upon referral to the inpatient and outpatient unit of the Department of Child and Adolescent Psychiatry of the University of Aachen. SUBJECTS: A total of 97 male patients (mean age 10+/-2 y) with a diagnosis of ADHD according the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), who were free of potentially orexigenic medication and who had no further comorbid diagnosis apart from conduct disorder. MEASUREMENTS: BMI standard deviation scores (BMI-SDS) were calculated and compared to age-adapted reference value of the German population. RESULTS: Patients' mean BMI-SDS was significantly higher than the age-adapted reference values of the German population (P=0.038). Our sample included significantly more subjects than expected with a BMI > or =90th percentile (19.6%, P<0.001) and > or =97th percentile (7.2%, P=0.007). CONCLUSION: Surprisingly, being 'hyperactive' in the sense of the DSM-IV diagnosis of ADHD does not prevent the development or persistence of overweight and obesity in children. The examination of these children might be a helpful approach in the investigation of the relationship between obesity and its contributing psychological and behavioural factors.

The effect of therapeutically induced weight gain on plasma leptin levels in patients with anorexia nervosa.

Previously it was shown that hyperleptinemia ensues from the therapeutically induced weight gain in patients with anorexia nervosa (AN). However, not all studies have been able to confirm this finding. To further investigate leptin secretion during weight gain in AN and potential functional implications serum leptin levels, body mass index (BMI),% body fat, fT3, fT4 and TSH of 18 adolescent AN patients (BMI at admission: 14.4+/-1.2) were examined four times during 11 weeks of re-feeding and compared to 18 weight stable controls. Additionally, serum leptin levels, BMI and % body fat were determined in patients reaching target weight after 11-20 weeks (mean 14.3+/-3) of inpatient re-feeding. At admission patients showed lower lg10 leptin levels (P=0.000) and BMI (P=0.000) than controls. At target weight patients still had significantly lower BMI (P=0.000) and% body fat (P=0.000) than controls but lg10 leptin levels of patients were higher than those of controls when adjusted for BMI and% body fat (ANCOVA, group P=0.038). In patients, correlation coefficients between lg10 leptin levels and BMI increments increased during the 11 weeks of re-feeding. BMI,% body fat and fT3 levels were not significantly correlated to lg10 leptin levels in week 11, however, 53% of the variance of leptin levels (corrected R(2)=0.53, P=0.001) was explained by BMI increments between weeks 7 and 11 (P=0.001) and lg10 leptin level at admission (P=0.002). In conclusion, we confirmed weight gain induced hyperleptinemia in AN. Further research is required to assess if this phenomenon contributes to renewed weight loss.

Reproductive function during weight gain in anorexia nervosa. Leptin represents a metabolic gate to gonadotropin secretion.

The adipocyte hormone leptin plays an important part in the reproductive function and in energy homeostasis. Only single studies have addressed the relationship between leptin and the hypothalamus-pituitary-gonadal axis (HPG) in anorexia nervosa (AN). In the present study 18 female adolescents with AN were investigated during weight gain. Leptin, LH, FSH, fT3, BMI and body composition were measured in the 1(st), 3(rd), 7(th) and 11(th) week of inpatient treatment. 18 eumenorrheic age- and gender-matched controls were examined once during the early follicular phase of their menstrual cycle. Our results demonstrate a critical leptin level of 1.2 ng/ml for an increase of FSH and confirmed a leptin threshold level of 1.85 ng/ml for LH. It may be concluded that leptin represents a metabolic gate to gonadotropin secretion. Once this is exceeded other biological mechanisms seem to be important for the complete recovery of the reproductive function and the resumption of menses.

[Personality disorders and psychiatric comorbidity in obsessive-compulsive disorder and anorexia nervosa]. / Persönlichkeitsstörungen und psychiatrische Komorbidität im Verlauf der Zwangsstörung und der Anorexia nervosa. Vergleich zweier 10-Jahres-Katamnesen.

The aim of this prospective longitudinal study was to examine the course of adolescent anorexia nervosa and obsessive-compulsive disorder (OCD) (fulfilling DSM-III-R criteria) to compare psychiatric comorbidity and personality disorders of both groups. Because anorexia nervosa patients are mainly female, we compared them only with female OCD patients. Ten years after discharge the whole sample (32 female patients; 100%) of a group of 39 (32 female; 7 male) anorexia nervosa patients could be reexamined personally. 25 (61%) female patients of a group of 116 patients (41 female; 75 male) with obsessive-compulsive disorder were also reexamined. The anorexia nervosa patients were interviewed using the Structured Interview for Anorexia and Bulimia nervosa (SIAB [39]) to assess eating disorder symptomatology. To examine comorbid psychiatric disorders we used the Composite International Diagnostic Interview, WHO [44] and SCID-II [45] for personality disorders. One fourth of the patients with anorexia nervosa (AN) and 20% of the patients with obsessive-compulsive disorder had a personality disorder according to DSM-III-R. Most of them were "Cluster C"-personality disorders (AN: 28%; OCD: 20%). In the group of the female OCD patients 8% schizoid, 4% schizotype and 12% paranoid personality disorders were observed. The most prevalent psychiatric disorders were anxiety (AN: 28%; OCD: 20%) and affective disorders (AN: 16%; OCD: 16%). Our results support the view that in the course of anorexia nervosa and in obsessive-compulsive disorder there is a high prevalence of psychiatric comorbidity and "Cluster C"-personality disorders according to DSM-III-R. These results might confirm a model of a high vulnerability of the serotonergic neurotransmitter system in patients with anorexia nervosa or OCD.

Is knee joint proprioception worse in the arthritic knee versus the unaffected knee in unilateral knee osteoarthritis?

OBJECTIVE: Neuromuscular joint protection requires proprioceptive input and motor output. Impairment of proprioception in knee osteoarthritis (OA) may contribute to, and/or result from, the disease. If this impairment was exclusively a local result of OA, a between-knee difference would be expected in patients with unilateral OA (UOA). To explore causal directions, 2 hypotheses were tested: 1) proprioception is worse in UOA patients versus elderly controls; 2) proprioception is worse in the arthritic knee versus the unaffected knee in UOA patients. METHODS: Twenty-eight UOA patients (Kellgren-Lawrence grade > or =2 in 1 knee and <2 in the other knee) and 29 elderly controls were enrolled. The unaffected knee of each UOA patient and both knees of the elderly controls were required to meet symptom, examination, and radiographic criteria. Proprioception (detection threshold of joint displacement after slow, passive, automated knee motion), body mass index, pain, functional status, range of motion, and laxity were measured. RESULTS: UOA patients had worse proprioception than did elderly controls, in either knee. A between-knee difference was not found in UOA patients. CONCLUSION: Impaired proprioception is not exclusively a local result of disease in knee OA. The relative importance of impaired proprioception in the development and progression of knee OA will require longitudinal study.