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Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex.

OBJECTIVE: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers. METHOD: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function. RESULTS: Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. CONCLUSIONS: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.

Adult↗

The influence of obsessive-compulsive neurosis patients' premorbid personality on obsessive-compulsive symptoms and efficacy of medication.

We conducted a survey with the Lynfield obsessive-compulsive symptom questionnaire (revised version) on 48 obsessive-compulsive neurotic patients as the survey subjects. In the factor analysis five factors of obsessions, were identified: (i) the desire for perfection; (ii) compulsive checking; (iii) washing; (iv) feelings of uncleanliness; and (v) anthropophobia. High correlations were noted between these factors. We also investigated the premorbid personalities of obsessive-compulsive neurotic patients with a multidimensional personality scale and obtained an extroversion dimension and neuroticism dimension. The influence of these premorbid personality dimensions on obsessive-compulsive symptoms became clear; (i) neuroticism is related to the levels of obsession after onset, but not related to compulsive behaviors; and (ii) No differences in premorbid personality dimensions were noted between compulsive checking and compulsive washing behaviors. We also studied whether it was possible to predict the efficacy of pharmacotherapy upon obsessive-compulsive symptoms. It was elucidated that the obsessions of those whose premorbid personalities are emotionally stable and extroversive are susceptible to antidepressants. Based on these results, we discussed the usefulness of premorbid personalities in predicting diversity of obsessive-compulsive symptoms, as well as in prediction the efficacy of medication.

Adolescent↗

Treatment of functional decline in adults with Down syndrome using selective serotonin-reuptake inhibitor drugs.

Alzheimer's disease (AD) is a common cause of functional decline in Down syndrome (DS) adults. Acquired cognitive deficits may be difficult to evaluate in the context of baseline impairments. Behavioral symptoms are also common and may represent the effects of depression, AD, or both. Therefore, the objective of this study was to report a clinical case series of selected adults with DS and behavioral change who responded to treatment with selective serotonin-reuptake inhibitor (SSRI) medication. Six patients, aged 23 to 63 years, 5 women and 1 man, with the clinical diagnosis of DS presented for diagnosis and treatment of functional decline in adult life. Noncognitive symptoms were prominent and included aggression, social withdrawal, and compulsive behaviors. Memory dysfunction was reported in varying degrees. Treatment with SSRI antidepressants was instituted for depressive, apathetic, and compulsive behaviors. Treated patients showed improvement in behaviors as reported by caregivers, and on objective measures, such as workplace productivity. Noncognitive symptoms are a cardinal feature of functional decline in adults with DS and may represent either depression or AD. In some patients, the symptoms respond well to SSRI agents with concomitant improvement in daily function. Treatment trials with SSRIs may, therefore, be warranted in such cases.

Adult↗

Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism.

BACKGROUND: The serotonin transporter (5-HTT) has long been considered likely to play a role in autism. Hyperserotonemia has been consistently found in a proportion of autistic patients, and the use of selective serotonin reuptake inhibitors (SSRIs) can have a positive effect in treating some symptoms of autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion-deletion 5-HTTLPR promoter locus, have been found to modulate its expression and transporter function. METHODS: We examined the transmission of the short or long allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352 families. In addition, we screened five single nucleotide polymorphisms (SNPs) in the 5' region of SLC6A4 previously reported to be positively associated with autism, as well as 4 additional SNPs also in the 5' region. RESULTS: No association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence for association of any of the nine SNPs covering the SLC6A4 gene, or any of their haplotypes, was observed in our study. Using obsessive-compulsive behaviors (OCB), severe OCBs or rigid-compulsive subsets of our cohort gave the same negative results. CONCLUSIONS: SLC6A4 variants do not appear to be significantly involved in the liability to autism.

Autistic Disorder↗

Exposure therapy for phobias and obsessive-compulsive disorders.

When abnormal fears or excessively compulsive behavior begin to rule a person's life, the consequences can be devastating to both patient and family. But three quarters of cooperative patients can be restored to normal functioning through a form of therapy based on exposing the patient continually to the stimuli that evoke symptoms until they can be tolerated and the phobic or compulsive behavior dissipates.

Adult↗

Seizure possibly associated with fluvoxamine.

OBJECTIVE: To inform clinicians of the possibility that seizures due to therapeutic doses of fluvoxamine may not be as rare as previously considered. CASE SUMMARY: A 49-year-old white man with schizoaffective disorder and a past history of seizures secondary to head trauma had been seizure-free for approximately 10 years. Fluvoxamine therapy was begun due to increasing obsessive-compulsive behavior. Despite receiving anticonvulsants for his mood disorder, the patient had a breakthrough seizure. There were no underlying medical conditions that might have induced this seizure. No further seizures occurred after he was placed on a higher dosage of the anticonvulsants. The obsessive-compulsive behavior improved considerably as a result of fluvoxamine treatment. DISCUSSION: The patient presented here developed a seizure with a therapeutic dosage of fluvoxamine; seizures associated with this agent have occurred more often with overdose. Multiple factors such as a prior history of seizures, head trauma, and concurrent treatment with other psychotropic agents are considered in this case report. CONCLUSIONS: Despite the relatively safe and benign adverse effect profile of the selective serotonin-reuptake inhibitors such as fluvoxamine, clinicians should be cautious about seizures as an adverse effect, especially when the patient has even a remote history of seizure or head trauma.

Dose-Response Relationship, Drug↗

Comparison of neuropsychiatric side effects in an observational cohort of efavirenz- and protease inhibitor-treated patients.

PURPOSE: To compare the extent of neuropsychiatric disturbances in two similar groups of HIV-infected patients treated for >4 weeks with either efavirenz (EFV) or protease inhibitors (PIs) as part of their antiretroviral therapy (ART). METHOD: A cross-sectional, questionnaire-based cohort of HIV patients who received two nucleoside reverse transcriptase inhibitors combined with either EFV (n = 75) or one or more PIs (n = 77) for at least 4 weeks and were tolerating therapy. The extent of neuropsychiatric disturbances was evaluated based on self-reported symptoms using the psychological evaluation test SCL-90-R. Treatment duration was broken down into quartiles of 30-198 days, >198-365 days, >365-637 days, and >637 days. RESULTS: In the first 6 months of therapy, significantly higher (worse) scores were seen in 39/75 (52%) of the patients receiving EFV. The EFV-treated group had significantly higher scores for somatization, anxiety, obsessive-compulsive behavior, the Global Severity Index, and the Positive Symptom Distress Index, with trends for higher scores in paranoid ideation and depression symptom subcategories. Over the following 6 to 12 months of therapy, the EFV group scored higher than the PI group in somatization, anxiety, obsessive-compulsive behavior, hostility, depression, the Global Severity Index, and the Positive Symptom Total, but the differences were not significant. After 12 months of therapy, the EFV group had significantly lower scores than the PI group for somatization, interpersonal sensitivity, Global Severity Index, and Positive Symptom Total. CONCLUSION: EFV-induced neuropsychiatric symptoms can last up to 200 days after treatment initiation. However, symptom severity appears to decline over time in EFV-treated patients versus patients treated with a PI-based ART.

Adult↗

[Excessive compulsive buying or "behavioral addiction"? A case study].

Compulsive buying is characterized by repetitive compulsive and excessive misappropriated buying. Labels for this pathological behavior vary and its classification is uncertain. To date, there is no consistent concept for diagnosis and treatment. We present the case of a 36-year old woman with a history of excessive pathological buying. According to the assumption that addiction is a learned behavior, we assume that for the patient compulsive buying as a rewarding behavior has the function of an inadequate stress coping strategy. Therefore, in this case the diagnosis "non-substance-related behavioral addiction" is appropriate. This diagnosis is important for the choice of the therapeutic intervention, which is in accordance to the current therapeutic interventions for substance-related addictions.

Adult↗

Psychologic well-being of surgery residents after inception of the 80-hour workweek: a multi-institutional study.

BACKGROUND: The 80-hour workweek was adopted by US residency programs on July 1, 2003. Our published data from the preceding year indicated significant impairment in psychologic well-being among surgery residents. The purpose of this study was to determine whether psychologic well-being and academic performance of surgery residents improved after inception of the 80-hour workweek. METHODS: A single-blinded survey of general surgery residents (n=130) across 4 US training programs was conducted after July 1, 2003, with the use of validated psychometric surveys (Symptom Checklist-90-R and Perceived Stress Scale) and the American Board of Surgery In-Training Examination; comparison was done with preceding year and societal data. Primary outcomes were "psychologic distress" and "perceived stress." Secondary outcomes were "somatization," "depression," "anxiety," "interpersonal sensitivity," "hostility," "obsessive-compulsive behavior," "phobic anxiety," "paranoid ideation," "psychoticism." and "academic performance." The impact of demographic variables was assessed. RESULTS: Mean psychologic distress improved from the preceding year (P < .01) but remained elevated, compared with societal norms (P < .001). The proportion of residents meeting the criteria for clinical psychologic distress (>or=90th percentile) decreased from 38% before, to 24% after, July 2003. Mean perceived stress remained elevated, compared with norms (P < .0001) without improvement from the preceding year. Overall academic performance was unchanged. Previously elevated secondary psychologic outcomes improved after July 2003 (P < .05), although obsessive-compulsive behavior, depression, interpersonal sensitivity, hostility, and anxiety failed to normalize. Male gender and single status were independent risk factors for psychologic distress. CONCLUSIONS: Inception of the 80-hour workweek is associated with reduced psychologic distress among surgery residents. The perception of stress and academic performance remains unchanged.

Adult↗

Psychological well-being of surgery residents before the 80-hour work week: a multiinstitutional study.

BACKGROUND: Accreditation Council on Graduate Medical Education work-hour restrictions are aimed at improving patient safety and resident well-being. Although surgical trainees will be dramatically affected by these changes, no comprehensive assessment of their well-being has been recently attempted. STUDY DESIGN: A multicenter study of psychological well-being of surgical residents (n = 108) across four US training programs before implementation of the 80-hour work week was performed using two validated surveys (Symptom Checklist-90-R [SCL-90-R] and Perceived Stress Scale [PSS]) during academic year 2002-03. Societal normative populations served as controls. Primary outcomes measures were psychologic distress (SCL-90-R) and perceived stress (PSS). Secondary outcomes measures (SCL-90-R) were somatization, depression, anxiety, interpersonal sensitivity, hostility, obsessive-compulsive behavior, phobic anxiety, paranoid ideation, and psychoticism. The impact of personal variables (age, gender, marital status) and programmatic variables (level of training, laboratory experience, institution) was assessed. RESULTS: Mean psychologic distress was significantly higher in general surgery residents than in the normative population (p < 0.0001), with 38% scoring above the 90th percentile and 72% above the 50th percentile. Mean perceived stress among surgery residents was higher than historic controls (p < 0.0001), with 21% scoring above the 90th percentile and 68% above the 50th percentile. Among secondary outcomes, eight of nine symptom dimensions were significantly higher in surgical residents than in societal controls. In subgroup analyses, male gender was associated with phobic anxiety (p < 0.001) and anxiety (p < 0.05), and junior level of training (PGY 1 to 3) with anxiety (p < 0.05), obsessive-compulsive behavior (p < 0.05), and interpersonal sensitivity (p < 0.05). CONCLUSIONS: More than one-third of general surgery residents meet criteria for clinical psychologic distress. Surgery residents perceive significantly more stress than societal controls. Both personal and programmatic variables likely affect resident well-being and should be considered in assessing the full impact of Accreditation Council on Graduate Medical Education directives and in guiding future restructuring efforts.

Adult↗

Effects of topiramate in adults with Prader-Willi syndrome.

Prader-Willi syndrome is a multisystem neurogenetic obesity disorder with behavioral manifestations, including hyperphagia, compulsive behavior, self-injury, and mild to moderate mental retardation. In an 8-week open-label study, we evaluated adjunctive therapy with the anticonvulsant topiramate in 8 adults with Prader-Willi syndrome. Appetite was measured by a 1-hour access to food four times throughout the study and quantified with a visual analogue scale. Topiramate did not significantly change calories consumed, Body Mass Index, or increase self-reported appetite. In addition, there were no significant changes in compulsions. Surprisingly, topiramate treatment resulted in a clinically significant improvement in the self-injury (i.e., skin-picking) that is characteristic of this syndrome. Potential benefits of topiramate for self-injury should be evaluated further in controlled trials.

Adolescent↗

A controlled study of Tourette syndrome. IV. Obsessions, compulsions, and schizoid behaviors.

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.

Adolescent↗

Obsessive-compulsive disorder in popular magazines.

To examine what the general public is learning about Obsessive-Compulsive Disorder (OCD) through popular magazines, all articles listed in the Reader's Guide to Periodical Literature under the topic headings of "obsessive-compulsive behavior" or "obsessive-compulsive disorder" between 1983 and 1997 were read and rated. Only 31 of the 107 articles under these headings dealt explicitly with OCD, and these were found to be reasonably accurate in their presentations of symptoms, causes, and treatments. Many of the other articles under the target headings, however, focused on incidents of "stalking" of famous people by "obsessed" fans. The implications of the content patterns of these articles for understanding and misunderstanding of OCD are discussed.

Humans↗

The dilemma of Howard Hughes: paradoxical behavior in compulsive disorders.

The history of Howard Hughes illustrates an unusual variant or end state of obsessive-compulsive neurosis in which a germ phobia coincides with the deliberate avoidance of cleaning and neglect of personal hygiene. We have reported on three patients who share similar symptomatology. In these cases, the coincidence of personal filthiness and a germ phobia appear paradoxical.

Adult↗

Self-injurious behavior and serotonin in Prader-Willi syndrome.

Low central nervous system (CNS) serotonin levels have been associated with impulsive, aggressive and self-injurious behavior (SIB). Persons with Prader-Willi Syndrome (PWS) often engage in self-injury by severe compulsive skin picking and gouging and often manifest compulsive eating, hoarding, and explosive outbursts. Some of the compulsive behaviors seen in patients with obsessive-compulsive disorder (OCD) bear similarity to behaviors associated with PWS: Skin picking, trichotillomania, and onychophagia (nail biting). There is abundant evidence that selective serotonin reuptake inhibitors (SSRIs) are effective in treating OCD. Three cases are described in which persons with PWS responded favorably to SSRI treatment. Two persons showed a significant decrease in skin picking. The third case showed a significant decrease in hoarding and explosive outbursts. Strategies are discussed for investigating the possibility of a shared neurochemical basis for the self-injurious, aggressive, and compulsive behaviors in persons with PWS. PWS may provide a relatively homogenous model for the study of skin picking and explosive outbursts among other populations.

Adult↗

Dietary changes, compulsions and sexual behavior in frontotemporal degeneration.

The occurrence of weight gain, sweet and carbohydrate craving, hyposexuality, and compulsions in frontal lobe dementia (FLD) compared to Alzheimer's disease (AD) was evaluated. FLD is a progressive dementia with a high rate of misdiagnosis and therefore better diagnostic criteria for FLD are needed. Fourteen patients meeting research criteria for AD were compared to 14 with suspected FLD. All had cerebral perfusion measured with xenon-133 and imaged with HMPAO using brain-dedicated SPECT. The FLD group showed frontotemporal and AD posterior temporoparietal hypoperfusion. The primary caregivers were queried regarding weight gain, sweet/carbohydrate preference, sexual drive, and compulsions. Differences were compared with Fisher's exact test. The following was found in FLD versus AD: Weight gain in FLD patients amounted to 64% (AD 7%), carbohydrate craving was 79% (vs. 0%) and compulsive behavior 64% (vs. 14%). The differences for these symptoms were statistically significant, whereas for the symptoms increased sexual drive (8 vs. 8%) and reduced sexual drive (54 vs. 23%) no significant difference could be found. In FLD the first symptoms were often dietary changes or hyposexuality. Compulsions were more bizarre and severely disabling in FLD than in AD. Dietary changes, hyposexuality, and disabling compulsions are prominent early symptoms in FLD but not AD. The cause of these symptoms may be due to both frontal and subcortical serotonin loss and dysfunction of the anterior temporal lobes.

Alzheimer Disease↗