Showing papers in "Neuropsychiatric Disease and Treatment in 2012"
TL;DR: It is suggested that a positive CBCL-DESR profile predicts subsequent psychopathology and functional impairments in children with ADHD suggesting that it has the potential to help identifyChildren with ADHD at high risk for compromised outcomes.
Abstract: BACKGROUND: While symptoms of deficient emotional self-regulation (DESR) have been long associated with attention-deficit/hyperactivity disorder (ADHD), there has been limited investigation of this aspect of the clinical picture of the disorder. The main aim of this study was to examine the predictive utility of DESR in moderating the course of ADHD children into adolescence. METHODS: Subjects comprised 177 children with and 204 children without ADHD followed for an average of 4 years (aged 6-18 years at baseline, 54% male). Subjects were assessed with structured diagnostic interviews and measures of psychosocial functioning. DESR was defined by the presence (n = 79) or absence (n = 98) of Child Behavior Checklist (CBCL)-DESR profile (score ≥ 180 Language: en
96 citations
TL;DR: A cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD, which may have implications for neuropsychiatric research and treatment.
Abstract: OBJECTIVE The study aim was to assess the cumulative burden of polymorphisms located within four genetic loci previously associated with posttraumatic stress disorder (PTSD) among outpatients at risk for PTSD. METHODS Diagnostic interviews were completed and DNA samples collected among 412 pain patients to determine if FKBP5 (rs9470080), COMT (rs4680), CHRNA5 (rs16969968), and CRHR1 (rs110402) single nucleotide polymorphisms were cumulatively associated with increased risk for PTSD. RESULTS In bivariate analyses, it was found that a count of specific PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (allele range = 0-6, mean count = 2.92, standard deviation = 1.36) was associated with lifetime (t [409] = 3.430, P = 0.001) and early onset PTSD (t [409] = 4.239, P = 0.000028). In logistic regression, controlling for demographic factors, personality traits, and trauma exposures, this risk allele count remained associated with both lifetime (odds ratio = 1.49, P = 0.00158) and early onset PTSD (odds ratio = 2.36, P = 0.000093). Interaction effects were also detected, whereby individuals with higher risk allele counts and higher trauma exposures had an increased risk of lifetime PTSD (allele count × high trauma, P = 0.026) and early onset PTSD (allele count × high trauma, P = 0.016) in these logistic regressions. Those with no or few risk alleles appeared resilient to PTSD, regardless of exposure history. CONCLUSION A cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD. Level of trauma exposure interacts with risk allele count, such that PTSD is increased in those with higher risk allele counts and higher trauma exposures. Since the single nucleotide polymorphisms studied encompass stress circuitry and addiction biology, these findings may have implications for neuropsychiatric research and treatment.
96 citations
TL;DR: This article proposes a number of recommendations for the treatment of generalized social phobia, based on a systematic literature review and meta-analysis, that include a combination of medication and psychotherapy, along with an assertive clinical management program.
Abstract: This article proposes a number of recommendations for the treatment of generalized social phobia, based on a systematic literature review and meta-analysis. An optimal treatment regimen would include a combination of medication and psychotherapy, along with an assertive clinical management program. For medications, selective serotonin reuptake inhibitors and dual serotonin-norepinephrine reuptake inhibitors are first-line choices based on their efficacy and tolerability profiles. The nonselective monoamine oxidase inhibitor, phenelzine, may be more potent than these two drug classes, but because of its food and drug interaction liabilities, its use should be restricted to patients not responding to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. There are other medication classes with demonstrated efficacy in social phobia (benzodiazepines, antipsychotics, alpha-2-delta ligands), but due to limited published clinical trial data and the potential for dependence and withdrawal issues with benzodiazepines, it is unclear how best to incorporate these drugs into treatment regimens. There are very few clinical trials on the use of combined medications. Cognitive behavior therapy appears to be more effective than other evidence-based psychological techniques, and its effects appear to be more enduring than those of pharmacotherapy. There is some evidence, albeit limited to certain drug classes, that the combination of medication and cognitive behavior therapy may be more effective than either strategy used alone. Generalized social phobia is a chronic disorder, and many patients will require long-term support and treatment.
73 citations
TL;DR: The results suggest the importance of mood assessment in children affected by SRBD and suggest that an apnea-hypopnea index ≥ 3 and an oxygen desaturation index ≥ 1 could be risk factors for development of depressive symptoms.
Abstract: Background
The relationship between sleep and mood regulation is well known, and some reports suggest a key role of sleep-related breathing disorders (SRBD) in the development of the symptomatology of depression, even if no conclusive data are actually found in the clinical literature. The aim of this study was to assess the relationship between SRBD and depressive symptoms in a population of school-aged children.
69 citations
TL;DR: Stepwise linear regression indicated that PPD was significantly predicted by social support, socioeconomic status, feeding of baby, and prior psychiatric problems.
Abstract: Introduction Postpartum depression (PPD) represents a considerable health problem affecting women and their families. The aims of this study were to: (a) compare female patients with PPD to normal controls with regard to some biopsychosocial variables, (b) correlate between the severity of PPD and some clinical and biological variables, and (c) to predict some risk factors for PPD. Method Sixty female patients with PPD were compared with 60 healthy postpartum females (control group). Patient and controls were subjected to: (1) a complete psychiatric and obstetric examination, (2) psychometric studies using the Edinburgh Postnatal Depression Scale, Fahmy and El-Sherbini's Social Classification Scale for Egyptian socioeconomic classification and Horowitz et al's Impact of Event Scale, (3) quantities of thyroid hormone (T3), cortisol hormone, and estrogen were assessed. Results There were high statistical differences between PPD females and controls as regard psychosocial stressors, level of (estradiol, thyroxin [T3], and cortisol), marital status, residence, parity, method of delivery, complicated puerperium, positive history of premenstrual tension syndrome and baby variables (eg, unwelcomed, with a negative attitude of parents toward the baby, underweight, female, artificially feeding, unhealthy baby). While there were moderate statistical differences in attitude toward spouse and social support and mild statistical difference in socioeconomic status between them. Severity of depression is positively highly correlated with onset of depression, psychosocial stress, levels of T3 and cortisol. However, severity of depression is negatively high when correlated with socioeconomic status. Stepwise linear regression indicated that PPD was significantly predicted by social support, socioeconomic status, feeding of baby, and prior psychiatric problems. Conclusion Many factors may lead to development of PPD. These factors include some psychosocial, socioeconomic, obstetric, and hormonal variables. Early detection of these factors could help in prediction of the development of PPD.
69 citations
TL;DR: Factor analysis data showed that the children with migraine seemed to have lower perceptual organization than the children affected by tension-type headache, and a new perspective in understanding of the neuropsychological aspects of young patients affected by headaches is suggested.
Abstract: BACKGROUND The purpose of this study was to assess the cognitive functioning of children affected by headache, pinpointing the differences in intelligence style between subjects affected by migraine without aura and subjects with tension-type headache. METHODS The study population consisted of 147 children (mean age 10.82 ± 2.17 years) with headache, recruited from the Headache Center for Developmental Age, Child and Adolescent Neuropsychiatry Clinic, Second University of Naples. Cognitive profiling was performed using Weschler Intelligence Scale for Children Third Edition throughout the sample. According to the International Classification of Headache Disorders II criteria for pediatric age, subjects were divided into a migraine without aura group (n = 75; 43 boys, 32 girls) and a tension-type headache group (n = 72; 49 boys, 23 girls). The results were compared with the findings obtained from a sample of 137 healthy control subjects recruited from schools in the Campania region, matched for age and gender. RESULTS No difference in full intelligence quotient was found between the groups, but the children with tension-type headache had a lower verbal intelligence quotient and a higher performance intelligence quotient than the healthy controls and children with migraine. Factor analysis data showed that the children with migraine seemed to have lower perceptual organization than the children affected by tension-type headache. CONCLUSION To our knowledge, studies on cognitive functioning in children affected by headache in the interictal phase are scarce, and our results suggest a new perspective in understanding of the neuropsychological aspects of young patients affected by headaches.
59 citations
TL;DR: The results suggest that the administration of atypical antipsychotic drugs for at least 6 months decreased glutamatergic neurotransmissions in the frontal lobe in early-stage first-episode schizophrenia, but there was no difference in frontal-lobe levels between patients and control subjects before administration.
Abstract: Objective
To study the effects of treatment with atypical antipsychotic drugs on brain levels of glutamate plus glutamine in early-stage first-episode schizophrenia.
58 citations
TL;DR: It is concluded that the behavioral phenotype of the 22q13.3 deletion syndrome comprises absent or delayed speech and perseverations with associated autistic-like features, whereas its psychopathological phenotype comprises an atypical bipolar disorder.
Abstract: The 22q13.3 deletion, or Phelan-McDermid syndrome, is characterized by global intellectual disability, generalized hypotonia, severely delayed or absent speech associated with features of autism spectrum disorder, and minor dysmorphisms. Its behavioral phenotype comprises sleep disturbances, communication deficits, and motor perseverations. Data on psychological dysfunctions are so far not available. Previous studies have suggested that the loss of one copy of the gene SH3 and multiple ankyrin repeat domains 3 (SHANK3) is related to the neurobehavioral phenotype. Additional genes proximal to SHANK3 are also likely to play a role in the phenotype of patients with larger deletions. The present paper describes two adult brothers with an identical 2.15 Mb 22qter (22q13.32q13.33) deletion, of whom the youngest was referred for evaluation of recurrent mood changes. In both patients, magnetic resonance imaging of the brain showed hypoplasia of the vermis cerebelli. Extensive clinical examinations led to a final diagnosis of atypical bipolar disorder, of which symptoms fully remitted during treatment with a mood stabilizer. In the older brother, a similar psychopathological picture appeared to be present, although less severe and with a later onset. It is concluded that the behavioral phenotype of the 22q13.3 deletion syndrome comprises absent or delayed speech and perseverations with associated autistic-like features, whereas its psychopathological phenotype comprises an atypical bipolar disorder. The latter may have implications for the treatment regime of the syndrome-related behavioral disturbances.
57 citations
TL;DR: Clinical trials that have evaluated the efficacy of structured, standardized psychotherapeutic and psychopharmacological interventions for PNES are reviewed, finding that cognitive behavioral therapy and augmented psychodynamic interpersonal psychotherapy have evidence of efficacy.
Abstract: Psychogenic nonepileptic seizures (PNES) can significantly affect an individual’s quality of life, the health care system, and even society. The first decade of the new millennium has seen renewed interest in this condition, but etiological understanding and evidence-based treatment availability remain limited. After the diagnosis of PNES is established, the first therapeutic step includes a presentation of the diagnosis that facilitates engagement in treatment. The purpose of this review is to present the current evidence of treatments for PNES published since the year 2000 and to discuss further needs for clinical treatment implementation and research. This article reviews clinical trials that have evaluated the efficacy of structured, standardized psychotherapeutic and psychopharmacological interventions. The primary outcome measure in clinical trials for PNES is event frequency, although it is questionable whether this is the most accurate indicator of functional recovery. Cognitive behavioral therapy has evidence of efficacy, including one pilot randomized, controlled trial where cognitive behavioral therapy was compared with standard medical care. The antidepressant sertraline did not show a significant difference in event frequency change when compared to placebo in a pilot randomized, double-blind, controlled trial, but it did show a significant pre- versus posttreatment decrease in the active arm. Other interventions that have shown efficacy in uncontrolled trials include augmented psychodynamic interpersonal psychotherapy, group psychodynamic psychotherapy, group psychoeducation, and the antidepressant venlafaxine. Larger clinical trials of these promising treatments are necessary, while other psychotherapeutic interventions such as hypnotherapy, mindfulness-based therapies, and eye movement desensitization and reprocessing may deserve exploration. Flexible delivery of treatment that considers the heterogeneous backgrounds of patients is emphasized as necessary for successful outcomes in clinical practice.
53 citations
TL;DR: This investigation confirms the great therapeutic power of ECT and finds that deepTMS seems to be the only therapy that provides a substantial improvement of both depressive symptoms and cognitive performances; nevertheless it is characterized by a poor tolerability.
Abstract: Background: Biological treatments are considered as additional options for the treatment of resistant unipolar depression. Controversial data exist about the efficacy and tolerability of three of the most used somatic treatments: electroconvulsive therapy (ECT), transcranial magnetic stimulation (rTMS), and deep transcranial magnetic stimulation (deepTMS). The aim of this review is to investigate and compare the efficacy and tolerability of these three techniques in drug-free patients with pharmacoresistant unipolar depression. Methods: Three independent reviewers extracted data and assessed the quality of methodological reporting of selected studies. The first outcome was the clinical response to the three different techniques defined as a percentage improvement of Hamilton Depression Rating Scale (HDRS). The second outcome was the evaluation of their neuropsychological effects. The third outcome was the evaluation of the number of remitted patients; remission was defined as an absolute HDRS-24 score of #11 or as an absolute HDRS-17 score of #8. Tolerability was the fourth outcome; it was evaluated by examining the number of dropped-out patients. Results: The comparative evaluation of HDRS percentage variations shows ECT as the most effective method after 4 weeks of therapy; on the other hand, a better efficacy is obtainable by deepTMS after 2 weeks of therapy. DeepTMS is the technique that gives the best improvement of cognitive performances. The percentage of remitted patients obtained with ECT treatment is the same obtained in the deepTMS group. Both techniques have a remitted patients percentage two times larger than the rTMS. DeepTMS shows a tolerability, measured by the number of dropped-out patients, worse than ECT. Conclusion: Our investigation confirms the great therapeutic power of ECT. DeepTMS seems to be the only therapy that provides a substantial improvement of both depressive symptoms and cognitive performances; nevertheless it is characterized by a poor tolerability. rTMS seems to provide a better tolerability for patients, but its therapeutic efficacy is lower. Considering the small therapeutic efficacy of deepTMS in the last 2 weeks of treatment, it could be reasonable to shorten the standard period of deepTMS treatment from 4 to 2 weeks, expecting a reduction
49 citations
TL;DR: A critical overview of AD therapy with donepezil is provided, focusing particularly on the advantages of the transdermal over the oral route of administration, including high selectivity towards acetylcholinesterase inhibition.
Abstract: Alzheimer's disease (AD) is the most common type of senile dementia, characterized by cognitive deficits related to degeneration of cholinergic neurons. The first anti-Alzheimer drugs approved by the Food and Drug Administration were the cholinesterase inhibitors (ChEIs), which are capable of improving cholinergic neurotransmission by inhibiting acetylcholinesterase. The most common ChEIs used to treat cognitive symptoms in mild to moderate AD are rivastigmine, galantamine, and donepezil. In particular, the lattermost drug has been widely used to treat AD patients worldwide because it is significantly less hepatotoxic and better tolerated than its predecessor, tetrahydroaminoacridine. It also demonstrates high selectivity towards acetylcholinesterase inhibition and has a long duration of action. The formulations available for donepezil are immediate release (5 or 10 mg), sustained release (23 mg), and orally disintegrating (5 or 10 mg) tablets, all of which are intended for oral-route administration. Since the oral donepezil therapy is associated with adverse events in the gastrointestinal system and in plasma fluctuations, an alternative route of administration, such as the transdermal one, has been recently attempted. The goal of this paper is to provide a critical overview of AD therapy with donepezil, focusing particularly on the advantages of the transdermal over the oral route of administration.
TL;DR: It is suggested that rTMS has the potential to improve the clinical condition in postpartum depression, while producing marginal gains in social and cognitive function.
Abstract: Background:
This randomized, placebo-controlled, double-blind pilot study evaluated the impact of repetitive transcranial magnetic stimulation (rTMS) on clinical, cognitive, and social performance in women suffering with postpartum depression.
TL;DR: This study describes the application of navigated TMS for motor cortex mapping in patients with a brain tumor located close to the precentral gyrus, and compared TMS mapping with the gold standard mapping with direct cortical electrical stimulation in surgery.
Abstract: Transcranial magnetic stimulation (TMS) is a promising method for both investigation and therapeutic treatment of psychiatric and neurologic disorders and, more recently, for brain mapping. This study describes the application of navigated TMS for motor cortex mapping in patients with a brain tumor located close to the precentral gyrus. Materials and methods: In this prospective study, six patients with low-grade gliomas in or near the precentral gyrus underwent TMS, and their motor responses were correlated to loca- tions in the cortex around the lesion, generating a functional map overlaid on three-dimensional magnetic resonance imaging (MRI) scans of the brain. To determine the accuracy of this new method, we compared TMS mapping with the gold standard mapping with direct cortical elec- trical stimulation in surgery. The same navigation system and TMS-generated map were used during the surgical resection procedure. Results: The motor cortex could be clearly mapped using both methods. The locations corre- sponding to the hand and forearm, found during intraoperative mapping, showed a close spatial relationship to the homotopic areas identified by TMS mapping. The mean distance between TMS and direct cortical electrical stimulation (DES) was 4.16 ± 1.02 mm (range: 2.56-5.27 mm). Conclusion: Preoperative mapping of the motor cortex with navigated TMS prior to brain tumor resection is a useful presurgical planning tool with good accuracy.
TL;DR: In PD, the low Cp concentration and activity in serum and the high iron amounts in the substantia nigra appears to be correlated, which most likely stems from lessened incorporation of copper in the Cp molecule and similar incorporation defects might also apply to other copper enzymes in AD.
Abstract: Ceruloplasmin (Cp) concentration and oxidative activity in serum are lowered in Parkinson’s disease (PD). In most PD patients, iron increases in the substantia nigra in the midbrain. In PD, the low Cp concentration and activity in serum and the high iron amounts in the substantia nigra appears to be correlated. An hereditary background is common in PD and variations in the Cp gene that have been found in PD are associated with high iron levels in the substantia nigra. Variations in Cp synthesis and in the incorporation of copper into the Cp molecule are essential features of PD. In Alzheimer’s disease (AD), the Cp activity in serum is lowered but not the concentration, except in the advanced stages of the disease. Generally, iron is not increased in the AD brain. In the AD brain, iron accumulates in neuritic plaques and in neurofibrillary tangles. There is also increased risk of iron-mediated tissue damage, which may possibly be counteracted by Cp. At the same time, the AD brain is short in copper, which presumably results in the deficient activity of many copper enzymes in the brain, in addition to Cp. Lowered Cp activity in serum most likely stems from lessened incorporation of copper in the Cp molecule and similar incorporation defects might also apply to other copper enzymes in AD.
TL;DR: A review of the Akhawayni’s teachings on sleep paralysis and of descriptions and treatments of sleep paralysis by the Greek, medieval, and Renaissance scholars.
Abstract: Sleep paralysis, a rapid eye movement (REM) parasomnia, is characterized by a period of inability to perform voluntary movements at sleep onset (hypnagogic form) or upon awakening (hypnopompic form).1 During sleep paralysis, although limb, trunk, and head movements typically are not possible, ocular and respiratory movements are intact. The experience is frequently accompanied with panic, enhanced by the inability to speak or breathe.2 Sleep paralysis occurs as an isolated form, in a familial form, and as one of the classic tetrad of narcolepsy symptoms. Apart from therapeutic approaches toward sleep paralysis, controversial reports exist in the literature regarding its early description. Accordingly, the earliest description of sleep paralysis dates back to 1664 by the Dutch physician Isbrand van Diemerbroeck.3 In almost all the earlier descriptions, the word “night-mare” has been used to portray sleep paralysis.4,5
Persia has a long history of medical practice and study. During the Middle Ages, scholars of different religions, such as Muslim, Christian, or Jewish, contributed to the development of Islamic medicine, later influencing the rise of European science during the Renaissance.6 Thanks to the translation and assimilation period (ca 750–900), the Samanid dynasty (819–999) coincided with the appearance of the renowned scholars Muhammad ibn Zakariya al-Razi or Rhazes (ca 865–925), Ali ibn al-Abbas al-Majusi or Haly Abbas (930–994), and Abu-Ali al-Husain ibn Abdollah ibn Sina or Avicenna (981–1037).7 These polymaths were not only responsible for accumulating all the existing information on medicine of the time but adding to this knowledge by their own perceptive observations, trials, and skills. In the era of Arabic language domination in the scientific literature, Hakim Maysari, Abu Mansur Muvaffak Harawi, and Akhawayni Bokhari were three first authors who wrote their treatises in Persian. Hakim Maysari composed medical poems (Danishanameh) in 980. Harawi compiled the Book of the Remedies (Kitab al-Abnyia an Haqaiq al-Adwiya) between 968 and 977. Undoubtedly, the most significant work of the three was that of Akhawayni Bokhari, the Hidayat.6,8,9 Herein, we review the teachings of Akhawayni on sleep paralysis (night-mare) along with a glimpse at those of the Greek, medieval, and Renaissance scholars in this regard. To avoid confusion with the modern use of the term ‘nightmare’ (a long frightening dream waking the dreamer), the term “night-mare,” with a hyphen, is used throughout this paper to designate sleep paralysis.
TL;DR: The complex neuroimmune endocrine and chronobiological alterations found in patients with depression and how these systems interact with each other are summarized and how antidepressant therapy can modify these systems are explained.
Abstract: Antidepressant pharmacotherapy is to date the most often used treatment for depression, but the exact mechanism of action underlying its therapeutic effect is still unclear. Many theories have been put forward to account for depression, as well as antidepressant activity, but none of them is exhaustive. Neuroimmune endocrine impairment is found in depressed patients; high levels of circulating corticosteroids along with hyperactivation of the immune system, high levels of proinflammatory cytokines, low levels of melatonin in plasma and urine, and disentrainment of circadian rhythms have been demonstrated. Moreover, antidepressant treatment seems to correct or at least to interfere with these alterations. In this review, we summarize the complex neuroimmune endocrine and chronobiological alterations found in patients with depression and how these systems interact with each other. We also explain how antidepressant therapy can modify these systems, along with some possible mechanisms of action shown in animal and human models.
TL;DR: The present review aims to summarize the current and evidence-based knowledge on the risk-benefit ratio of both first and second generation neuroleptics in TS.
Abstract: Tourette syndrome (TS) is a neuropsychiatric disorder with typical onset in childhood and characterized by chronic occurrence of motor and vocal tics. The disorder can lead to serious impairments of both quality of life and psychosocial functioning, particularly for those individuals displaying complex tics. In such patients, drug treatment is recommended. The pathophysiology of TS is thought to involve a dysfunction of basal ganglia-related circuits and hyperactive dopaminergic innervations. Congruently, dopamine receptor antagonism of neuroleptics appears to be the most efficacious approach for pharmacological intervention. To assess the efficacy of the different neuroleptics available, a systematic, keyword-related search in PubMed (National Library of Medicine, Washington, DC) was undertaken. Much information on the use of antipsychotics in the treatment of TS is based on older data. Our objective was to give an update and therefore we focused on papers published in the last decade (between 2001 and 2011). Accordingly, the present review aims to summarize the current and evidence-based knowledge on the risk-benefit ratio of both first and second generation neuroleptics in TS.
TL;DR: The results indicate that simvastatin and/or fluoxetine treatment reduces anxiety-like behaviors in the elevated plus-maze and open-field tests and provides an important foundation for future preclinical research.
Abstract: Simvastatin inhibits 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is widely used to control plasma cholesterol levels and prevent cardiovascular disease. However, emerging evidence indicates that the beneficial effects of simvastatin extend to the central nervous system. The effects of simvastatin combined with fluoxetine provide an exciting and potential paradigm to decreased anxiety and depression. Thus, the present paper investigates the possibility of synergistic interactions between simvastatin and fluoxetine in models of anxiety and depression. We investigated the effects of subchronically administered simvastatin (1 or 10 mg/kg/day) combined with fluoxetine (2 or 10 mg/kg) at 24, 5, and 1 hour on adult rats before conducting behavioral tests. The results indicate that simvastatin and/or fluoxetine treatment reduces anxiety-like behaviors in the elevated plus-maze and open-field tests. Our results showed that simvastatin and/or fluoxetine induced a significant increase in the swimming activity during the forced swimming test (antidepressant effect), with a concomitant increase in climbing time in simvastatin-treated animals only (noradrenergic activation). We hypothesize that anxiolytic and antidepressant effects of simvastatin and/or fluoxetine produce their behavioral effects through similar mechanisms and provide an important foundation for future preclinical research.
TL;DR: Davunetide is a novel neuroprotective peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules and is the most advanced drug candidate in this indication.
Abstract: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined distribution. Classically, PSP is diagnosed by symptoms that include progressive gait disturbance, early falls, vertical ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical dementia. There are currently no effective therapies for the treatment of this rapidly degenerating and debilitating disease. Davunetide is a novel neuroprotective peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules. Preclinical activity in models of tauopathy has been translated to clinical studies, demonstrating pharmacologic activity that has supported further development. Davunetide’s efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population.
TL;DR: L-5-hydroxytryptophan (5-HTP) is the immediate precursor of serotonin and may be contraindicated for depression in some of the very patients for whom promoters of 5- HTP advocate its use.
Abstract: L-5-hydroxytryptophan (5-HTP) is the immediate precursor of serotonin. It is readily synthesized into serotonin without biochemical feedback. This nutrient has a large and strong following who advocate exaggerated and inaccurate claims relating to its effectiveness in the treatment of depression and a number of other serotonin-related diseases. These assertions are not supported by the science. Under close examination, 5-HTP may be contraindicated for depression in some of the very patients for whom promoters of 5-HTP advocate its use.
TL;DR: Lurasidone as mentioned in this paper is a new atypical antipsychotic in the benzoisothiazoles class of chemicals, which has much greater affinity for 5-HT(7) subtype receptors than other antipsychotics.
Abstract: Lurasidone is a new atypical antipsychotic in the benzoisothiazoles class of chemicals. Like most second-generation antipsychotics it is a full antagonist at dopamine D(2) and serotonin 5-HT(2A) receptors, and is a partial agonist at 5-HT(1A) receptors, a property shared by some but not all older agents. It has much greater affinity for 5-HT(7) subtype receptors than other atypical antipsychotics. Pharmacokinetic studies showed that lurasidone is reasonably rapidly absorbed, with bioavailability appearing to be increased by food. Lurasidone undergoes extensive metabolism to a number of metabolites, some of which retain pharmacological activities. Metabolism is mainly by CYP3A4, resulting in steady-state concentrations that vary between individuals and are potentially affected by strong inducers and inhibitors of this enzyme. Short-term clinical trials have demonstrated the efficacy of lurasidone in acute schizophrenia, with doses of 40 and 80 mg/day giving significant improvements from baseline in the PANSS and BPRS scores. The most common adverse events are nausea, vomiting, akathisia, dizziness, and sedation, with minimal increases in the risk of developing metabolic syndrome. Lurasidone did not raise the risk of QTc interval prolongation, although additional studies are required. Long-term trials are also needed to assess the risk of new-onset diabetes. Ongoing trials in patients with bipolar disorder are being completed but, again, efficacy and safety have been investigated only in a few short-term clinical trials.
TL;DR: Around 40% of adolescents who self-harmed in the previous year did not seek help, and school nurses were more often consulted by those who did self- Harm, suggesting school-based mental health should screen students at risk of self-harm, and educate school nurses about preventative care.
Abstract: BACKGROUND: The aim of this study was to determine the prevalence of and factors associated with poor help-seeking among adolescents who self-harm and to explore the resources used for help. METHODS: A cross-sectional survey using an anonymous questionnaire was conducted in 47 junior and 30 senior high schools in Japan. Adolescent self-harm was defined as an adolescent who had harmed himself or herself in the previous year, as in previous studies reported in Western countries. Poor help-seeking was defined as not consulting anyone despite reporting current psychological or somatic complaints. Information about sociodemographic and psychological factors possibly associated with help-seeking, such as suicidal thoughts, depression, anxiety, and psychotic-like experiences, was also collected. Regression analyses were performed to examine associated factors. RESULTS: A total of 18,104 students (8620 aged 12-15 years, 9484 aged 15-18 years), accounting for 93% of all students in the relevant student classes, participated in the study. Two hundred and seventy-six (3.3%) junior and 396 (4.3%) senior high school students reported having self-harmed. Of these, 40.6% of adolescents in junior and 37.6% in senior high schools were classified as poor help-seeking. Poor help-seeking with regard to self-harm was significantly more common in those who reported not having consulted anyone about psychological problems (odds ratio 9.2, 95% confidence interval 4.6-18.4 in juniors; odds ratio 9.9, confidence interval 5.5-17.9 in seniors) and in those with current suicidal ideation (odds ratio 2.0, confidence interval 1.0-3.7 in juniors; odds ratio 1.9, confidence interval 1.1-3.4 in seniors). Family members were approached significantly less often as a resource for help by students who self-harmed than by those who did not, and school nurses were more often consulted by those who did self-harm. CONCLUSION: Around 40% of adolescents who self-harmed in the previous year did not seek help. School-based mental health should screen students at risk of self-harm, and educate school nurses about preventative care. Language: en
TL;DR: In this article, the authors conducted a prospective study that included 71 patients in the HD unit with a mean age of 61.9 ± 14.13 years who had undergone HD and 26 healthy control subjects with an average age of 59.3 ± 7.3.
Abstract: Methods: We conducted a prospective study that included 71 patients in the HD unit with a mean age of 61.9 ± 14.13 years who had undergone HD and 26 healthy control subjects with a mean age of 59.3 ± 7.3. Beck’s Depression Inventory and Hamilton Depression Scale assessments were administered. Blood analysis for hematological and biochemical parameters was obtained. Diagnosis was made using the Diagnostic and Statistical Manual of Mental Disorders scale to correlate psychological variables with clinical, hematological, and biochemical parameters. Statistical analysis was carried out using analysis of variance followed by Tukey post-hoc multiple comparison tests. Results: The prevalence of depression was 43.7% in HD patients. Between HD patients and controls, cortisol values were 16.96 ± 0.5476 and 11.96 ± 1.116, respectively (P , 0.0001; 95% confidence intervals [CI]: 2.416–6.825). Between depressed HD patients versus con trol subjects, cortisol values were 16.48 ± 0.72 and 11.96 ± 1.116, respectively (P = 0.0013; 95% CI: 1.878–7.184). Hematological and biochemical parameters were compared between depressed HD and nondepressed patients, but differences between the two groups were found to be insignificant ( P . 0.05). Conclusion: Our HD patients were severely depressed. Studies of glucocorticoid turnover activity such as cortisol, a potent chemical stress hormone, may be used as a model and marker for early diagnosis of depression among HD patients. The strong familial support system in
TL;DR: Upon approval from the Food and Drug Administration and other regulatory authorities, the iontophoretic transdermal delivery of sumatriptan will be a good choice for patients experiencing poor absorption of oral medication often associated with migraine and/or for those with intolerable triptan-related adverse events.
Abstract: Migraine is a chronic, painful, and often disabling primary headache disorder, typically presenting with recurrent attacks that may be accompanied by a variety of neurological, gastrointestinal, and autonomic symptoms. Gastrointestinal symptoms in association with migraine including, nausea, vomiting, and gastroparesis, affect a large proportion of migraine sufferers. These symptoms may result in delays or inconsistencies in the absorption of oral treatments. Hence, the necessity for an innovative, non-invasive, parenteral delivery formulation for quick and effective treatment of migraine attacks is evident. Iontophoresis utilizes minimal amounts of electrical potential to support the fast transfer of ionized medication transdermally and into the general circulation. Two pharmacokinetic clinical trials have shown that iontophoretic delivery of sumatriptan through the skin produces quick and reproducible therapeutic plasma concentrations. A randomized, double-blind, multicenter, phase III study demonstrated superior efficacy versus placebo and excellent tolerability, with no triptan-related adverse events. The proportion of patients that were pain-free at 2 h post-treatment was 18% for the sumatriptan patch vs 9% for placebo (P = 0.0092; number needed to treat = 11.1). Upon approval from the Food and Drug Administration and other regulatory authorities, the iontophoretic transdermal delivery of sumatriptan will be a good choice for patients experiencing poor absorption of oral medication often associated with migraine and/or for those with intolerable triptan-related adverse events.
TL;DR: The known mechanisms of action of botulinum toxin type A are discussed, and the available randomized, placebo-controlled trials that have looked at its efficacy as a migraine preventative are reviewed.
Abstract: OnabotulinumtoxinA, a neurotoxin, has been studied in numerous trials as a novel preventive therapy for migraine headache. The data would support that it may be effective at reducing headache days in patients suffering from chronic migraine (≥15 headache days/month, with eight or more of those migraine headache days). The mechanism by which onabotulinumtoxinA exerts its effects on migraine is not yet understood. It is known to inhibit acetylcholine release at the neuromuscular junction, but this probably does not explain the observed antinociceptive properties noted in preclinical and clinical trials. This review will discuss the known mechanisms of action of botulinum toxin type A, and will review the available randomized, placebo-controlled trials that have looked at its efficacy as a migraine preventative. We also describe the onabotulinumtoxinA injection sites used at our institution.
TL;DR: Activity in brain areas involved in motor control and coordination, including the cerebellum, is altered by administration of a REAC-NPO treatment and this effect is accompanied by an alleviation of functional dysmetria.
Abstract: Purpose
This study assessed changes in functional dysmetria (FD) and in brain activation observable by functional magnetic resonance imaging (fMRI) during a leg flexion-extension motor task following brain stimulation with a single radioelectric asymmetric conveyer (REAC) pulse, according to the precisely defined neuropostural optimization (NPO) protocol.
TL;DR: It was shown that the schizophrenia patients had impaired reward-based learning and that this was independent from their medication status and not related to antipsychotic dose.
Abstract: Although it is known that individuals with schizophrenia demonstrate marked impairment in reinforcement learning, the details of this impairment are not known. The aim of this study was to test the hypothesis that reward-related probability learning is altered in schizophrenia patients. Twenty-five clinically stable schizophrenia patients and 25 age- and gender-matched controls participated in the study. A simple gambling paradigm was used in which five different cues were associated with different reward probabilities (50%, 67%, and 100%). Participants were asked to make their best guess about the reward probability of each cue. Compared with controls, patients had significant impairment in learning contingencies on the basis of reward-related feedback. The correlation analyses revealed that the impairment of patients partially correlated with the severity of negative symptoms as measured on the Positive and Negative Syndrome Scale but that it was not related to antipsychotic dose. In conclusion, the present study showed that the schizophrenia patients had impaired reward-based learning and that this was independent from their medication status.
TL;DR: The long-term tolerability of paliperidone palmitate was generally similar in recently diagnosed schizophrenia subjects and those with more chronic illness, with the exception of some prolactin-related measures.
Abstract: schizophrenia. Methods: Adverse events reported at a $2% margin between subgroups were identified. Relative risks (in the recently diagnosed compared with the chronically ill) and 95% confidence intervals (CI) were determined, and CI not including 1 were considered potentially significant. Results: In both subgroups, the mean monthly dose was 109 mg (69.9 mg eq). Continuous mean exposures were 333.9 ± 271.9 and 308.7 ± 278.3 days in the recently diagnosed and chronic illness subgroups, respectively. Using the criteria outlined in the methods, nasopharyngitis was a potentially significant event reported in more chronically ill than recently diagnosed subjects at months 6, 9, 12, and endpoint (7.2% versus 2.8%; relative risk 0.384; 95% CI 0.163–0.907). Influenza (2.8% versus 0.7%; relative risk 3.9; 95% CI 1.003–15.730) and amenorrhea (3.2% versus 0.9%; relative risk 3.476; 95% CI 1.029–11.744) at endpoint were potentially signifi cant events in more recently diagnosed than chronically ill subjects. Mean weight changes, sedation/somnolence, any extrapyramidal symptom-related or glucose-related events were generally similar between the groups. The mean prolactin level increased in both sexes in both subgroups (changes from baseline of +41.8 ng/mL and +26.5 ng/mL in recently diagnosed and chronic illness females and +12.3 ng/mL and +15.1 ng/mL in recently diagnosed and chronic illness males, respectively), and were higher in females with recently diagnosed illness than in females who were chronically ill (P = 0.0002 at endpoint). Prolactin-related events were reported by 7.9% of recently diagnosed subjects with schizophrenia and 3.5% of those who were chronically ill. Conclusion: The long-term tolerability of paliperidone palmitate was generally similar in recently diagnosed schizophrenia subjects and those with more chronic illness, with the exception of some prolactin-related measures.
TL;DR: A large number of children with speech and language impairment at preschool age had persistent language problems and/or met the criteria for developmental diagnoses other than speech andlanguage impairment at their follow-up as teenagers.
Abstract: Aim: Ten years ago, we published developmental data on a representative group of children (n = 25) with moderate or severe speech and language impairment, who were attending special preschools for ...
TL;DR: As a new option for the treatment of major depressive disorder, vilazodone, due to its unique SPARI mechanism of action, may hold promise for patients who cannot tolerate or have not responded to previous antidepressant monotherapies.
Abstract: BACKGROUND Vilazodone is the latest approved antidepressant available in the United States. Its dual mechanism of action combines the inhibition of serotonin transporters while simultaneously partially agonizing serotonin-1a (5-HT1A) receptors. This combined activity results in serotonin facilitation across the brain's serotonergic pathways, which has been termed by the authors as that of a serotonin partial agonist and reuptake inhibitor, or SPARI. OBJECTIVE The authors to review laboratory, animal model data, and human trial data to synthesize a working theory regarding the mechanism of antidepressant action of this agent and regarding its potential for additional indications. METHODS A MEDLINE and Internet search was conducted and the resultant evidence reviewed. RESULTS Vilazodone has randomized, controlled empirical data which has garnered it an approval for treating major depressive disorder. It combines two well-known pharmacodynamic mechanisms of serotonergic action into a novel agent. Although no head-to-head studies against other antidepressants are published, the efficacy data for vilazodone appears comparable to other known antidepressants, with associated gastrointestinal side effects similar to serotonin selective reuptake inhibitor and serotonin norepinephrine reuptake inhibitor antidepressants, but potentially with a lower incidence of sexual side effects and weight gain. DISCUSSION As a new option for the treatment of major depressive disorder, vilazodone, due to its unique SPARI mechanism of action, may hold promise for patients who cannot tolerate or have not responded to previous antidepressant monotherapies. Additionally, its use may extend to the treatment of other mental health conditions similar to those treated by serotonin selective reuptake inhibitors.