Scheme-based benzodiazepine detoxification with oxcarbazepine -- a case report

We attempted to evaluate the tolerability and efficacy of the antiepileptic drug oxcarbazepine in benzodiazepine detoxification, by observing several cases. Detoxification followed a predefined dosage scheme. All patients detoxified with oxcarbazepine completed the withdrawal successfully, without withdrawal symptoms. The administration of oxcarbazepine according to the scheme proved to be tolerable. The dosage was sufficient. Though uncontrolled case observations must be interpreted with caution, oxcarbazepine appears to be a promising drug in inpatient benzodiazepine withdrawal. It should be examined in further randomized placebo-controlled studies including long-term follow-ups.     

Psychiatric and neuropsychological signs and symptoms in patients with fabry disease: literature review

Fabry Disease (FD) is an X-linked lysosomal storage disorder (prevalence about 1 : 100 000) caused by a genetic defect associated with a lack of alpha-galactosidase A (alpha-GAL) enzyme activity. As a consequence, neutral glycosphingolipides can not be cleaved and metabolized, and accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. The most prominent symptoms comprise pain attacks and acroparesthesia, angiokeratoma, corneal opacity, renal and cardiac dysfunction, hypo- and anhidrosis, gastrointestinal symptoms, and cerebrovascular dysfunction with vertigo, headache, and cerebral ischemia. Characteristic symptoms of FD can occur in male and female patients with the same prevalence, while females with FD seem to be less severely affected. The course of untreated illness is progressive with considerable interindividual variability. Since 2001 two enzyme replacement therapies are approved which can possibly stop the disease progress and alleviate symptoms. The very few reports and clinical observations have shown that a very high proportion of FD patients develop neuropsychiatric symptoms. However, accurate data are lacking. Although the pathophysiologic mechanisms are quite unknown, it is surmised that sphingolipid deposits in the endothelium of small cerebral vessels lead to regional cerebral ischemia accompanied by neuropsychiatric symptoms and deficits. Furthermore, patients with FD are chronically distressed by pain attacks and additional somatic and psychological impairment. Frequently, pain attacks are triggered by psychosocial stress. The high interindividual variability can, thus, also be interpreted on the basis of existing stress and coping models. The present paper will review the presently available psychiatric and neuropsychological findings in FD and will discuss difficulties associated with classification and differential diagnosis of psychiatric disorders occurring in patients with FD.     

Clinical features of depressed patients with or without a family history of alcoholism

OBJECTIVE: To compare clinical features of depressed subjects without alcoholism but with a family history of alcoholism to a depressed group without alcoholism and without a family history of alcoholism. METHOD: Clinical and demographic data of 209 depressed subjects without a history of alcoholism in first-degree relatives and 73 depressed individuals with a history of alcoholism in first-degree relatives were compared. Subjects with a personal history of alcoholism were excluded. RESULTS: Depressed subjects with a family history of alcoholism have a significantly higher prevalence of reported childhood physical and sexual abuse and post-traumatic stress disorder (PTSD), make more suicide attempts, and have greater intent to die at the time of their most lethal suicide attempt, compared to depressed subjects without a family history of alcoholism. CONCLUSION: Depressed patients with a family history of alcoholism are at greater risk for suicidal behavior and PTSD and may require more careful management.     

Posttraumatic stress disorder comorbid with major depression: factors mediating the association with suicidal behavior

OBJECTIVE: The purpose of the study was to determine if patients with a history of major depressive episode and comorbid posttraumatic stress disorder (PTSD) have a higher risk for suicide attempt and differ in other measures of suicidal behavior, compared to patients with major depressive episode but no PTSD. In addition, to explore how PTSD comorbidity might increase risk for suicidal behavior in major depressive episode, the authors investigated the relationship between PTSD, cluster B personality disorder, childhood sexual or physical abuse, and aggression/impulsivity. METHOD: The subjects were 230 patients with a lifetime history of major depressive episode; 59 also had lifetime comorbid PTSD. The demographic and clinical characteristics of subjects with and without PTSD were compared. Multivariate analysis was used to examine the relationship between suicidal behavior and lifetime history of PTSD, with adjustment for clinical factors known to be associated with suicidal behavior. RESULTS: Patients with a lifetime history of PTSD were significantly more likely to have made a suicide attempt. The groups did not differ with respect to suicidal ideation or intent, number of attempts made, or maximum lethality of attempts. The PTSD group had higher objective depression, impulsivity, and hostility scores; had a higher rate of comorbid cluster B personality disorder; and were more likely to report a childhood history of abuse. However, cluster B personality disorder was the only independent variable related to lifetime suicide attempts in a multiple regression model. CONCLUSIONS: PTSD is frequently comorbid with major depressive episode, and their co-occurrence enhances the risk for suicidal behavior. A higher rate of comorbid cluster B personality disorder appears to be a salient factor contributing to greater risk for suicidal acts in patients with a history of major depressive episode who also have PTSD, compared to those with major depressive episode alone.     

Correlation of alcohol craving with striatal dopamine synthesis capacity and D2/3 receptor availability: a combined [18F]DOPA and [18F]DMFP PET study in detoxified alcoholic patients

OBJECTIVE: In abstinent alcoholic patients, a low availability of dopamine D2/3 receptors in the ventral striatum and adjacent putamen was associated with a high level of craving for alcohol. Alcohol craving may also depend on presynaptic dysfunction of striatal dopamine production, which may contribute to the risk of relapse. In this study, positron emission tomography (PET) was used to compare dopamine synthesis capacity in the striatum in alcoholic patients and healthy comparison subjects. METHOD: Positron emission tomography (PET) was used to map the net blood-brain clearance of the dopa decarboxylase substrate 6-[18F]fluoro-l-dopa, an index of dopamine synthesis capacity, in the striatum of 12 detoxified male alcoholic patients and 13 age-matched healthy men. The parametric maps were correlated with results of an earlier [18F]desmethoxyfallypride PET study of dopamine D2/3 receptor availability in the same 12 alcoholic patients and in 12 of the healthy volunteers. Alcohol craving was measured with the Alcohol Craving Questionnaire. Patients were followed for 6 months, and alcohol intake was recorded. RESULTS: The magnitude of net blood-brain clearance in the striatum did not differ significantly between detoxified alcoholic patients and the comparison subjects. However, a voxel-wise correlation analysis of net blood-brain clearance in the alcoholic patients linked low levels of dopamine synthesis capacity in the bilateral putamen with high levels of alcohol craving. After normalization of net blood-brain clearance maps to the voxel-wise estimates of dopamine D2/3 receptor availability, there was still a negative correlation with alcohol craving. Alcohol craving at the time of scanning was associated with high level of alcohol intake in the 6-month follow-up period. CONCLUSIONS: Simultaneous assay by PET of pre- and postsynaptic markers of dopamine neurotransmission indicated that a striatal dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk.     

Acute disseminated encephalomyelitis after liver transplantation

BACKGROUND: During the past 10 years, acute disseminated encephalomyelitis has been reported a few times after organ transplantation. OBJECTIVE: To report a case of acute disseminated encephalomyelitis as a complication of liver transplantation. DESIGN: Case report. SETTING: The University of North Carolina Hospital and Medical Center, Chapel Hill.Patient A 49-year-old woman admitted because of acute onset of paresthesias, sensory loss, and weakness after liver transplantation. Acute clinical presentation, results of imaging studies, and comprehensive laboratory evaluation were consistent with acute disseminated encephalomyelitis. INTERVENTIONS: High-dose intravenous corticosteroid therapy followed by maintenance oral dosing. MAIN OUTCOME MEASURES: Clinical and magnetic resonance imaging improvement. RESULTS: Corticosteroid therapy halted clinical progression, with partial resolution of lesions on magnetic resonance images of the brain and spinal cord. CONCLUSIONS: This is, to our knowledge, the first report of acute disseminated encephalomyelitis after liver transplantation. Possible pathogenic mechanisms include a cross-reactive immune response to foreign antigens present within the transplanted organ, or an inflammatory response triggered by viral infection in an immunocompromised host.     

Ganglion cell densities in normal and dark-reared turtle retinas

In dark-reared, neonatal turtle retinas, ganglion cell receptive fields and dendritic trees grow faster than normal. As a result, their areas may become, on average, up to twice as large as in control retinas. This raises the question of whether the coverage factor of dark-reared ganglion cells is larger than normal. Alternatively, dark rearing may lead to smaller-than-normal cell densities by accelerating apoptosis. To test these alternatives, we investigated the effect of light deprivation on densities and soma sizes of turtle retinal ganglion cells. For this purpose, we marked these cells using retrograde labeling of fixed turtle retinas with DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). Control turtles were maintained in a regular 12-h light/dark cycle from hatching until 4 weeks of age, whereas dark-reared turtles were maintained in total darkness for the same period. Ganglion cells in the control and dark-reared retinas were found to be similar in density and soma sizes. These results show that the mean coverage factor of turtle dark-reared ganglion cells is larger than normal.     

Association of the DRD4 exon III polymorphism with smoking in fifteen-year-olds: a mediating role for novelty seeking?

OBJECTIVE: This study was designed to examine the role of DNA variants of the dopamine D4 receptor gene (DRD4) in smoking experimentation in adolescents and to determine the extent to which novelty seeking (NS) could account for a possible effect of DRD4 on tobacco use. METHOD: Participants were from a longitudinal study of an original birth cohort (born 1986-1988) of 384 children from a high-risk community sample. At age 15 years, adolescents completed a self-report questionnaire measuring tobacco consumption and temperament (Junior Temperament and Character Inventory). DNA was taken from 303 participants (144 males, 159 females) and genotyped for the DRD4 exon III polymorphism. RESULTS: DRD4 was associated with smoking status and NS in males but not in females. Males with the seven repeat allele exhibited more smoking involvement (p < .002) and scored higher in NS (p < .002) than males without this allele. In addition, elevated tobacco use was related to a higher level of NS in both males and females (p < .001). Multiple regression analyses revealed that NS mediated the relationship between DRD4 and smoking in males. CONCLUSIONS: These findings highlight the importance of considering the mechanisms underlying the association between genetic factors and tobacco use separately by gender and, possibly, by developmental period.