Association between obsessive-compulsive disorder and a variable number of tandem repeats polymorphism in intron 2 of the serotonin transporter gene

BACKGROUND: Pharmacological studies indicate a dysregulation of the serotonergic system in obsessive-compulsive disorder (OCD). A variable number tandem repeats (VNTR) polymorphism with three alleles (Stin2.9, Stin2.10, Stin2.12) has been described in intron 2 of the serotonin transporter (5-HTT) gene. This polymorphism has been associated with unipolar depression, bipolar disorder, schizophrenia, and anxiety disorders including OCD. METHODS: The association between OCD and the polymorphism is examined in 97 OCD patients, 578 psychiatric controls and 406 healthy controls, all Spanish Caucasians. RESULTS: Genotype frequencies for the polymorphism were significantly different in OCD patients, psychiatric patients and controls. There was a significant excess of 12/12 and 12/10 genotypes in OCD patients compared to psychiatric patients and controls. CONCLUSIONS: Our results indicate a possible association between the Stin2.12 allele of the VNTR polymorphism and OCD.     

A biobehavioural model of the night eating syndrome

This paper will propose a biobehavioral mechanism for the Night Eating Syndrome (NES), a disorder characterized by a delayed circadian rhythm of food intake and neuroendocrine function. Food intake consists of at least 25% of daily caloric intake after the evening meal and/or at least two nighttime awakenings with ingestions per week. This will be explored by reviewing neuroimaging of brain serotonin transporters (SERT) and treatment with selective serotonin reuptake inhibitors (SSRIs). SERT binding is elevated in the midbrain of night eaters, causing dysregulation of the circadian rhythm of both food intake and neuroendocrine function. The administration of SSRIs blocks the reuptake of serotonin and restores the circadian rhythm of both food intake and neuroendocrine function. This hypothesis implies that reduction of SERT activity should increase postsynaptic serotonin transmission and relieve NES. This is precisely the effect of SSRIs. NES is a function of elevated SERT, and blocking of SERT with an SSRI resolves NES. This model of NES attests to the validity of the diagnosis of NES and the criteria by which it is identified, and it provides an explanation of the mechanism.     

Sleep changes during long-term treatment of depression with fluvoxamine – a home-based study

Rationale: The effects of antidepressants on sleep in depression have been extensively investigated, although to date there have been relatively few studies of newer drug classes such as specific serotonin reuptake inhibitors (SSRIs). All reported studies on SSRIs have been conducted in patients admitted to sleep laboratories and very few longitudinal studies have continued to measure sleep beyond 5 weeks of treatment. The growing trend towards outpatient and community care has highlighted the need for studies of sleep in depression in a more naturalistic setting, and during longer periods of treatment in line with recommended clinical practice. Objectives: To establish if the changes in sleep architecture and continuity described during early treatment with SSRIs persist after 3 months, to relate these changes to clinical state, and to establish whether home recordings would yield similar results to previous laboratory studies. Methods: We have recorded objective sleep parameters in 12 depressed patients before and during 12-week treatment with an SSRI, fluvoxamine. All the sleep recordings were performed in the patients’ own homes, using the Oxford Medilog system. Results: At 12 weeks, 7/12 patients had responded (HAM-D decreased by >50%). REM latency showed the expected increase early in treatment; this change was less obvious at weeks 3 and 12. Amount of REM sleep was decreased at day 2 and week 3, but returned to baseline by week 12. Slow wave sleep was slightly increased at day 2 and decreased at week 12. Of the sleep continuity measures, the only significant change was in sleep onset latency, which was increased at week 3; the other measures showed non- significant worsening at night 2 and week 3, but most were better than baseline by 12 weeks. Subjective sleep (the three sleep items on the HAM-D) showed a progressive improvement over time, especially in the responders. Conclusions: The effects of the SSRI fluvoxamine on objective sleep measures are in the direction predicted by its pharmacological actions and some persist for at least 12 weeks. In addition subjective appraisal of sleep is strongly affected by mood state. All patients found the home recording procedure acceptable and only minimally disruptive. Received: 5 July 1999 / Final version: 22 November 1999     

Psychotropic medication use and accidents, injuries and cognitive failures

BACKGROUND: Psychotropic medication has the potential to impair psychomotor and cognitive function, and several medications have well documented links to increased accident and injury susceptibility. Those developed more recently have many fewer side effects. However, there is little work examining any association between psychotropic medication use and safety within the context of other demographic, health and lifestyle factors. AIMS: To examine and compare any associations between psychotropic medication use (including benzodiazepines, tricyclics and SSRIs) and accidents, injuries and cognitive failures in a community sample. METHODS: A postal questionnaire survey was conducted among people selected at random from the electoral registers of Cardiff and Merthyr Tydfil. RESULTS: Psychotropic medication use was associated with accidents, injuries and cognitive failures, particularly among those who already had higher levels of other risk factors and/or continuing mental health problems. CONCLUSIONS: The well established associations between accidents and injuries and older psychotropic medications were replicated. SSRIs, however, were relatively safer. The study also highlighted the need to consider any effect of psychotropic medication within the context of both mental health status and other factors.     

Pharmacologic advances in the systemic treatment of itch

Itch is propagated by complex mechanisms located both peripherally and within the central nervous system. For decades, novel treatments of itch have been slow to emerge, with the majority of focus on antagonism of histamine. Recently, with a new understanding of the pathophysiology of itch transmission, new treatment strategies have been elucidated. Opiate receptor antagonists, antidepressants, antiepileptics, and thalidomide are currently available therapeutic options that have benefited many patients with variegated sources of itch. In addition, research focused on the neuromediators of itch transmission has led to the development of novel targets for itch reduction and great potential for future therapies.     

Attributional Style,Hope, and Initial Response to Selective Serotonin Reuptake Inhibitors Youth Psychiatric Inpatients

We investigated the role of attributional style in inpatients’ initial response to treatment, particularly to SSRIs, and explored possible psychological factors implicated in response to SSRIs. One hundred youth psychiatric inpatients completed questionnaires at admission and discharge on attributional style, hopelessness, self-esteem, and depressive symptoms; medication status was recorded. Change in depressive symptoms from admission to discharge varied depending on negative attributional style status and treatment group status. Patients with a relatively positive attributional style and who were on SSRI medicines experienced the largest decreases in depression from admission to discharge, as well as the lowest absolute depression level at discharge. Depression changes were less pronounced in other patients, including those on SSRIs with a negative attributional style. Psychological processes corresponding to these changes appeared to involve increased hope, not enhanced self-esteem. Attributional style may moderate initial SSRI treatment response, an effect that appears to correspond with increased hope.     

Differential effectiveness of newer and older antidepressants appears mediated by an age effect on the phenotypic expression of depression

OBJECTIVE: A possible mechanism whereby the serotonin reuptake inhibitor (SSRI) antidepressants may not (overall) be as effective as the tricyclic (TCA) antidepressants is explored. METHOD: Clinical psychiatrists rated the effectiveness of past antidepressant medications in a clinical panel study of patients with a major depressive disorder, with 200 having previously received a TCA and 219 an SSRI. RESULTS: Analyses indicated decreased SSRI effectiveness with age in those with the melancholic subtype. TCA effectiveness appeared uninfluenced by age and depressive subtype. CONCLUSION: Findings suggest why the broader-based TCAs may be more effective than the SSRIs in implicating age and depressive subtype influences.     

Medical (fluoxetine) and psychological (cognitive-behavioural therapy) treatment for premenstrual dysphoric disorder: a study of treatment processes

OBJECTIVES: To investigate (i) the differential changes in premenstrual symptoms, mood, cognitions, and coping strategies during two treatments [cognitive-behavioural therapy (CBT) and fluoxetine] for premenstrual dysphoric disorder (PMDD) and (ii) the characteristics of those with good vs. poor outcome post treatment and at 1 year follow-up. METHODS: Premenstrual symptoms, mood (Hospital Anxiety and Depression Scale, HADS), causal attributions, and use of cognitive and behavioural coping strategies were examined during 6 months of both treatments. The two treatment groups were then combined and divided on the basis of good vs. poor outcome posttreatment and at 1 year follow-up. Baseline measures were used to predict posttreatment outcome, and baseline and posttreatment measures were examined when attempting to predict outcome at 1 year follow-up. RESULTS: Both treatments were equally effective at the end of 6 months (prospective daily diary measure). Fluoxetine treatment had a more rapid effect and greater impact upon anxiety symptoms, while CBT was associated with increased use of cognitive and behavioural coping strategies and a shift from a biomedical to a biopsychosocial causal attribution of premenstrual symptoms. Depressed mood at baseline assessment was associated with poorer response to both treatments, and learning active behavioural coping strategies was associated with a good outcome at 1 year follow-up. CONCLUSION: These results provide evidence of differential treatment effects of fluoxetine and CBT for PMDD and offer information that will enhance clinical decision-making.     

舍曲林治疗强迫症20例临床分析

目的 探讨舍曲林对强迫症的疗效。方法 应用舍曲林治疗强迫症20例，采用Yale-Brown强迫量表进行评定，并进行临床疗效评定。结果 治疗后Yale-Brown强迫量表评分显著下降，临床疗效评定显示痊愈7例，显著进步7例，进步3例。无效3例。副反应轻微。结论 舍曲林治疗强迫症疗效较好。     

Naltrexone treatment in kleptomanic patients

Kleptomania is an impulse control disorder and that can be treated with the combination of pharmacotherapy and psychotherapy. The most common drug regimens include antidepressants, especially SSRIs and mood stabilizers. However, the low efficacy rates with these drugs urge research for new treatment regimens. Natrexone, an opioid receptor antagonist, which has been used in the treatment of substance abuse and impulse control disorders, may be also useful in the treatment of kleptomania. In this study we report two kleptomanic patients successfully treated with naltrexone. Copyright © 1999 John Wiley & Sons, Ltd.