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1.
Psychiatr Prax ; 47(1): 22-28, 2020 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-31910457

RESUMEN

INTRODUCTION: Over the last decade, methamphetamine use has spread rapidly in Europe, leading to a significant medical shortfall in many regions. To date, there are no standardized German-language therapy programs for qualified detoxification and motivation treatment. We have developed a therapy manual ("CrystalClean") over 15 therapy modules, which was evaluated in the present pilot study with regard to feasibility and acceptability. METHODS: Observational study with systematic interviews over 3 months on 31 patients with methamphetamine dependence. RESULTS: Acceptability of most modules was rated as high by both patients and therapists. In addition, the manual was considered to be well feasible in inpatient daily routine. However, contact terminations frequently occurred when switching to outpatient treatment. CONCLUSION: Results from our study point to a high acceptance of the manual for the accompaniment of qualified detoxification and motivation treatment in patients with methamphetamine dependence. Feasibility in the clinical setting can be improved by reducing the number of modules to the 12 best evaluated and by increasing the frequency of therapies.


Asunto(s)
Lenguaje , Metanfetamina , Trastornos Relacionados con Opioides/rehabilitación , Trastornos Relacionados con Sustancias/rehabilitación , Europa (Continente) , Estudios de Factibilidad , Alemania , Humanos , Motivación , Aceptación de la Atención de Salud , Proyectos Piloto , Traducción
2.
Addict Biol ; 25(2): e12866, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31859437

RESUMEN

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.

3.
Int J Bipolar Disord ; 7(1): 23, 2019 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-31680193

RESUMEN

BACKGROUND: Despite various pharmacological and psychological treatment interventions, bipolar disorders rank among the leading causes of global disease burden. Group psychoeducation has been demonstrated an effective add-on to pharmacotherapy, but it may be difficult to implement in practice depending on the clinical setting and available human resources. METHODS: Multicenter, rater-blind, randomized controlled trial to investigate the efficacy of a new intervention program consisting of an initial 6-week psychoeducation protocol plus a subsequent structured daily computer-based self-charting program (ChronoRecord) over 54 weeks in remitted patients with bipolar disorders. The control condition included non-structured group sessions followed by daily computer-based self-reports (unstructured like a diary). Both groups received treatment-as-usual. RESULTS: Over 2 years, 41 mood episodes occurred in the experimental group (n = 39) compared to 27 in the control group (n = 34), without reaching statistical significance. Time to recurrence did not significantly differ between the experimental and control group (25% relapsed after 112 and 273 days, respectively). There were no significant group-by-time interactions in mood symptoms, quality of life, self-efficacy expectations or perceived involvement in care. CONCLUSIONS: Six weekly psychoeducational group sessions followed by daily self-monitoring via ChronoRecord for 54 weeks may not be superior to non-structured group meetings followed by unstructured self-reporting. Other psychotherapeutic interventions may be needed to optimize the treatment of patients with bipolar disorders, especially for those at later disease stages. Trial registration Retrospectively registered at German Clinical Trials Register on May 24, 2019; DRKS00017319.

4.
Int J Bipolar Disord ; 7(1): 21, 2019 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-31583561

RESUMEN

BACKGROUND: Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. METHODS: Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). RESULTS: Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). CONCLUSIONS: This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012-Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839.

5.
J Clin Med ; 8(8)2019 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-31344831

RESUMEN

Individuals with substance use disorders (SUDs) have to cope with drug-related cues and contexts which can affect instrumental drug seeking, as shown with Pavlovian-to-instrumental transfer (PIT) tasks among humans and animals. Our review addresses two potential mechanisms that may contribute to habitual or even compulsive drug seeking and taking. One mechanism is represented by Pavlovian and PIT effects on drug intake. The other is a shift from goal-directed to habitual drug intake, which can be accessed via model-based versus model-free decision-making in respective learning tasks. We discuss the impact of these learning mechanisms on drug consumption. First, we describe how Pavlovian and instrumental learning mechanisms interact in drug addiction. Secondly, we address the effects of acute and chronic stress exposure on behavioral and neural PIT effects in alcohol use disorder (AUD). Thirdly, we discuss how these learning mechanisms and their respective neurobiological correlates can contribute to losing versus regaining control over drug intake. Utilizing mobile technology (mobile applications on smartphones including games that measure learning mechanisms, activity bracelets), computational models, and real-world data may help to better identify patients with a high relapse risk and to offer targeted behavioral and pharmacotherapeutic interventions for vulnerable patients.

6.
Pharmacopsychiatry ; 52(3): 117-125, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29986372

RESUMEN

In spite of multiple new treatment options, chronic and treatment refractory courses still are a major challenge in the treatment of depression. Providing algorithm-guided antidepressant treatments is considered an important strategy to optimize treatment delivery and avoid or overcome treatment-resistant courses of major depressive disorder (MDD). The clinical benefits of algorithms in the treatment of inpatients with MDD have been investigated in large-scale, randomized controlled trials. Results showed that a stepwise treatment regimen (algorithm) with critical decision points at the end of each treatment step based on standardized and systematic measurements of response and an algorithm-guided decision-making process increases the chances of achieving remission and optimizes prescription behaviors for antidepressants. In conclusion, research in MDD revealed that systematic and structured treatment procedures, the diligent assessment of response at critical decision points, and timely dose and treatment type adjustments make the substantial difference in treatment outcomes between algorithm-guided treatment and treatment as usual.


Asunto(s)
Algoritmos , Antidepresivos/uso terapéutico , Análisis Costo-Beneficio , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/economía , Humanos , Resultado del Tratamiento
7.
J Affect Disord ; 238: 213-217, 2018 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-29886201

RESUMEN

BACKGROUND: To investigate long-term effects of adjunctive prophylactic treatment with supraphysiologic doses of levothyroxine (L-T4) on cardiovascular tolerability in 23 patients with treatment-refractory mood disorders. METHODS: Starting point for a comprehensive cardiovascular assessment in patients was the indication for long-term maintenance treatment with L-T4 (mean dose 463 mcg/day). Prospective longitudinal assessment of the cardiovascular risk profile included in addition to a physical examination and blood pressure measurement, several technical investigations: resting electrocardiogram, transthoracic echocardiogram, cardiac stress test, and holter electrocardiogram. Statistical analysis was performed by linear mixed effects models (LMM) for evaluation of longitudinal changes in various heart measures. RESULTS: During the mean observational period of 20.4 months none of the heart measures reached statistical significance in change over time. None of the assessed cardiac parameters of each single patient was in a range predictive for cardiac dysfunction. LIMITATIONS: Small sample size, no technical cardiac investigations prior to L-T4 initiation, no patient control group with mood disorders who did not receive L-T4. CONCLUSIONS: Results of this study indicated no increased risk for cardiovascular disorders during treatment with supraphysiologic L-T4 doses in patients with refractory mood disorders.


Asunto(s)
Antidepresivos/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Trastornos del Humor/tratamiento farmacológico , Tiroxina/sangre , Adulto , Afecto/efectos de los fármacos , Antidepresivos/efectos adversos , Relación Dosis-Respuesta a Droga , Electrocardiografía , Femenino , Humanos , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Estudios Prospectivos
8.
Int J Bipolar Disord ; 6(1): 10, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29713845

RESUMEN

BACKGROUND: Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics. METHODS: Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity. RESULTS: There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049). CONCLUSION: Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.

9.
Int J Bipolar Disord ; 3(1): 29, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26033382

RESUMEN

BACKGROUND: Dietary supplements are taken by about half of Americans. Knowledge of dietary supplement use is important because they may interact with prescription drugs or other supplements, cause adverse reactions including psychiatric symptoms, or contain inherently toxic ingredients or contaminants. This study explores the use of dietary supplements by patients with bipolar disorder in the US. METHODS: Data were obtained from an ongoing, naturalistic study of patients with bipolar disorder who received pharmacological treatment as usual. The patients self-reported their daily mood, sleep, and medications taken, including all drugs prescribed for bipolar disorder or that the patient felt impacted their mood. These included other prescribed drugs, over-the-counter drugs and dietary supplements. Drugs that received premarketing approval from the FDA were not included as dietary supplements. Patient demographics and daily medication use were characterized. RESULTS: Data were available from 348 patients in the US who returned a mean 249.5 days of data. In addition to prescribed psychiatric drugs, 101 of the 348 patients (29 %) used a dietary supplement for at least 7 days and 69 (20 %) used a supplement long term (for at least 50 % of days). Of the 101 supplement users, 72 (71.3 %) took one supplement daily. The 101 patients tried over 40 different supplements, and the long-term users took 19 different supplements. The most commonly taken supplements for both groups were fish oil, B vitamins, melatonin, and multivitamins. Patients using supplements were more likely to be white (p < 0.001), older (p = 0.009), and ill for more years (p = 0.025). CONCLUSIONS: Many patients with bipolar disorder use dietary supplements in addition to prescribed drugs. Physicians should obtain detailed information about all dietary supplements taken by patients with bipolar disorder.

10.
Dev Cogn Neurosci ; 14: 23-31, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26093849

RESUMEN

Appropriate reactions toward emotional stimuli depend on the distribution of prefrontal attentional resources. In mid-adolescence, prefrontal top-down control systems are less engaged, while subcortical bottom-up emotional systems are more engaged. We used functional magnetic resonance imaging to follow the neural development of attentional distribution, i.e. attending versus ignoring emotional stimuli, in adolescence. 144 healthy adolescents were studied longitudinally at age 14 and 16 while performing a perceptual discrimination task. Participants viewed two pairs of stimuli--one emotional, one abstract--and reported on one pair whether the items were the same or different, while ignoring the other pair. Hence, two experimental conditions were created: "attending emotion/ignoring abstract" and "ignoring emotion/attending abstract". Emotional valence varied between negative, positive, and neutral. Across conditions, reaction times and error rates decreased and activation in the anterior cingulate and inferior frontal gyrus increased from age 14 to 16. In contrast, subcortical regions showed no developmental effect. Activation of the anterior insula increased across ages for attending positive and ignoring negative emotions. Results suggest an ongoing development of prefrontal top-down resources elicited by emotional attention from age 14 to 16 while activity of subcortical regions representing bottom-up processing remains stable.


Asunto(s)
Atención/fisiología , Cognición/fisiología , Emociones/fisiología , Adolescente , Desarrollo del Adolescente , Envejecimiento/psicología , Amígdala del Cerebelo/crecimiento & desarrollo , Amígdala del Cerebelo/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa , Corteza Prefrontal/crecimiento & desarrollo , Corteza Prefrontal/fisiología , Psicología del Adolescente , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología
11.
Psychoneuroendocrinology ; 46: 88-99, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24882161

RESUMEN

Venepuncture procedures are frequently employed to continuously monitor humoral stress markers. As such procedures are conceived as "potent psychological and physiological stressors", there is a need to determine whether venepuncture procedures themselves elicit cortisol responses and if so, how to deal with them appropriately. In order to assess the rate of cortisol responses to venepuncture, we conducted a literature review, which suggested that venepuncture procedures induce cortisol responses with a probability of approximately 30%. By utilizing Bayesian analysis, this result was integrated with the cortisol data of 18 healthy men who were exposed to a venepuncture procedure twice (time lag: 1 week). The currently observed response rate of 47% differed substantially from the earlier findings, which we attribute to a self-selective sampling of participants. In addition, participants showing a response to the first venepuncture were highly likely to also show a response to the second one. In this regard, we discuss the presumed conditioning of cortisol responses to venepuncture procedures. To prevent the superposition of venepuncture-induced cortisol responses and responses induced by target stressors, we propose a time- and selection-based strategy: cortisol samples taken about 110min after venepuncture should be virtually adjusted for its superimposing effects. Furthermore, previous experiences of venepuncture were highly predictive for cortisol responsiveness. This association could be utilized in further studies to identify participants who will probably show a cortisol response to venepuncture.


Asunto(s)
Hidrocortisona/sangre , Personalidad , Flebotomía/psicología , Estrés Psicológico/sangre , Estrés Psicológico/psicología , Adolescente , Adulto , Depresión/psicología , Miedo/psicología , Humanos , Masculino , Adulto Joven
12.
J Am Acad Child Adolesc Psychiatry ; 53(5): 559-68.e6, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24745955

RESUMEN

OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies have identified increased amygdala responses to negative stimuli as a risk marker of depression in adults, and as a state marker of depression in adults and adolescents. Hyperreactivity of the amygdala has been linked to negatively biased emotional processing in depression. However, no study has elucidated whether similar amygdala perturbations can be found in healthy mid-adolescents with familial liability for depression. We hypothesized that healthy 14-year-olds with relatives with depression would demonstrate increased amygdala responses to negative stimuli, as compared with their peers with no family history of mental disorders. METHOD: We investigated a community-based sample of 164 typically developing 14-year-olds without record of past or current mental disorders. Of these individuals, 28 fulfilled criteria for family history of depression, and 136 served as controls. Groups did not differ with regard to cognitive ability, depressive symptomatology, and anxiety. During fMRI they performed a perceptual discrimination task in which visual target and distractor stimuli varied systematically with regard to emotional valence. RESULTS: Both a hypothesis-driven region-of-interest analysis and a whole-brain analysis of variance revealed that negative distractors elicited greater amygdala activation in adolescents with a family history of depression compared to controls. Amygdala responses also differed during the processing of negative target stimuli, but effects were reversed. CONCLUSION: Our study demonstrates that familial liability for depression is associated with correlates of negatively biased emotional processing in healthy adolescents. Amygdala perturbations during the processing of negative stimuli might reflect an early and subtle risk marker for depression.


Asunto(s)
Amígdala del Cerebelo/fisiopatología , Trastorno Depresivo/genética , Trastorno Depresivo/fisiopatología , Predisposición Genética a la Enfermedad/genética , Imagen por Resonancia Magnética , Adolescente , Nivel de Alerta/fisiología , Atención/fisiología , Trastorno Depresivo/psicología , Emociones/fisiología , Femenino , Humanos , Masculino , Reconocimiento Visual de Modelos/fisiología
13.
Hum Psychopharmacol ; 29(4): 384-7, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24710917

RESUMEN

OBJECTIVE: We studied whether suppressed secretion of the orexigenic peptide ghrelin might be involved in the anorexigenic effects of nicotine. METHODS: Fifty healthy non-smokers chewed gums containing 2 mg nicotine, or no nicotine in a double-blind randomised crossover design in two independent studies. RESULTS: Plasma nonacylated ghrelin was not significantly affected by nicotine after 30 and 60 min. Increased blood pressure and decreased appetite ratings confirmed a biological nicotine effect. CONCLUSIONS: These results do not support a key role of peripheral ghrelin secretion in weight changes related to smoking or smoking cessation, but do not rule out that central nervous system ghrelin is involved.


Asunto(s)
Apetito/efectos de los fármacos , Apetito/fisiología , Ghrelina/sangre , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Goma de Mascar , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Autoinforme , Factores de Tiempo , Adulto Joven
14.
CNS Drugs ; 28(4): 331-42, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24590663

RESUMEN

The high rate of non-responders to initial treatment with antidepressants requires subsequent treatment strategies such as augmentation of antidepressants. Clinical guidelines recommend lithium augmentation as a first-line treatment strategy for non-responding depressed patients. The objectives of this review were to discuss the current place of lithium augmentation in the management of treatment-resistant depression and to review novel findings concerning lithium's mechanisms of action. We conducted a comprehensive and critical review of randomized, placebo-controlled trials, controlled and naturalistic comparator studies, and continuation-phase and discontinuation studies of lithium augmentation in major depression. The outcomes of interest were efficacy, factors allowing outcome prediction and results from preclinical studies investigating molecular mechanisms of lithium action. Substantial efficacy of lithium augmentation in the acute treatment of major depression has been demonstrated in more than 30 open-label studies and 10 placebo-controlled trials. In a meta-analysis addressing the efficacy of lithium in 10 randomized, controlled trials, it had a significant positive effect versus placebo, with an odds ratio of 3.11 corresponding to a number-needed-to-treat (NNT) of 5 and a mean response rate of 41.2% (versus 14.4% in the placebo group). The main limitations of these studies were the relatively small numbers of study participants and the fact that most studies included augmentation of tricyclic antidepressants, which are not in widespread use anymore. Evidence from continuation-phase studies is sparse but suggests that lithium augmentation should be maintained in the lithium-antidepressant combination for at least 1 year to prevent early relapses. Concerning outcome prediction, single studies have reported associations of better outcome rates with more severe depressive symptomatology, significant weight loss, psychomotor retardation, a history of more than three major depressive episodes and a family history of major depression. Additionally, one study suggested a predictive role of the -50T/C single nucleotide polymorphism of the glycogen synthase kinase 3 beta (GSK3B) gene in the probability of response to lithium augmentation. With regard to novel mechanisms of action, GABAergic, neurotrophic and genetic effects might explain the effects of lithium augmentation. In conclusion, augmentation of antidepressants with lithium remains a first-line, evidence-based management option for patients with major depression who have not responded adequately to antidepressants. While the mechanisms of action are currently widely studied, further clinical research on the role of lithium potentiation of the current generation of antidepressants is warranted to reinforce its role as a gold-standard treatment for patients who respond inadequately to antidepressants.


Asunto(s)
Antidepresivos/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Manejo de la Enfermedad , Carbonato de Litio/administración & dosificación , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos
15.
Biol Psychiatry ; 76(9): 698-707, 2014 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-24560581

RESUMEN

BACKGROUND: A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. METHODS: We measured inhibitory control in 50 young adults with a stop-signal task during functional magnetic resonance imaging. In a single-blind placebo-controlled cross-over design, all participants performed the stop-signal task once under alcohol with a breath alcohol concentration of .6 g/kg and once under placebo. In addition, alcohol consumption was assessed with a free-access alcohol self-administration paradigm in the same participants. RESULTS: Inhibitory control was robustly decreased under alcohol compared with placebo, indicated by longer stop-signal reaction times. On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. CONCLUSIONS: We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans, which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control might enhance alcohol consumption in young adults, which might promote future alcohol problems.


Asunto(s)
Depresores del Sistema Nervioso Central/efectos adversos , Etanol/efectos adversos , Lóbulo Frontal/efectos de los fármacos , Lóbulo Temporal/efectos de los fármacos , Adolescente , Alcoholes/metabolismo , Conducta de Elección/efectos de los fármacos , Estudios Cruzados , Femenino , Lóbulo Frontal/irrigación sanguínea , Humanos , Procesamiento de Imagen Asistida por Computador , Estudios Longitudinales , Masculino , Oxígeno/sangre , Autoadministración , Método Simple Ciego , Fumar/psicología , Trastornos Relacionados con Sustancias/psicología , Lóbulo Temporal/irrigación sanguínea , Factores de Tiempo , Adulto Joven
16.
J Cereb Blood Flow Metab ; 34(3): 472-9, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24398943

RESUMEN

While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6 g/kg followed by a steady exposure of 100 minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tolerance effect is not observable on the time scale of 2 hours. Larger studies are needed to investigate the origin and the consequences of the effect, as well as the correlates of inter-subject variations.


Asunto(s)
Consumo de Bebidas Alcohólicas/fisiopatología , Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Etanol/farmacología , Adolescente , Adulto , Factores de Edad , Consumo de Bebidas Alcohólicas/sangre , Consumo de Bebidas Alcohólicas/metabolismo , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Pruebas Respiratorias , Estudios Cruzados , Interpretación Estadística de Datos , Etanol/administración & dosificación , Etanol/sangre , Etanol/farmacocinética , Femenino , Humanos , Infusiones Intravenosas , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Factores Sexuales , Método Simple Ciego , Marcadores de Spin , Factores de Tiempo , Adulto Joven
17.
Bipolar Disord ; 16(1): 58-71, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24245529

RESUMEN

OBJECTIVES: Thyroid hormones play a critical role in the functioning of the adult brain, and thyroid diseases impair both mood and cognition. This paper reviews gender differences in thyroid system function that are relevant to the diagnosis and treatment of bipolar disorder. METHODS: The study comprised a comprehensive literature review of gender differences in thyroid disease that are pertinent to mood disorders. RESULTS: The prevalence of thyroid disease was found to be much higher in females than males, and to increase with age. The most commonly detected abnormality was subclinical hypothyroidism, which was found to occur in up to 20% of postmenopausal women. Females also had higher rates of thyroid autoimmunity. Individuals at risk for thyroid disease, such as adult females, may have had less ability to compensate for additional challenges to thyroid metabolism, including lithium treatment. Thyroid abnormalities were associated with a poorer response to standard treatments for mood disorders. Females with treatment-resistant mood disorders may have responded better than males to adjunctive therapy with thyroid hormones. CONCLUSIONS: Disturbances of thyroid system function, which occur commonly in females, may complicate the diagnosis and treatment of mood disorders. In particular, this is clinically relevant during lithium treatment because lithium may impair vital thyroid metabolic pathways secondary to its anti-thyroid activity.


Asunto(s)
Trastorno Bipolar/diagnóstico , Trastorno Bipolar/terapia , Caracteres Sexuales , Glándula Tiroides/fisiología , Femenino , Humanos , Masculino
18.
J Clin Psychiatry ; 75(2): 162-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24345793

RESUMEN

OBJECTIVE: Suboptimal availability of circulating thyroid hormones may contribute to the high rate of treatment failures in bipolar disorder. This study tested the efficacy of adjunctive treatment with supraphysiologic doses of levothyroxine in patients with bipolar depression and the hypothesis that women would display a better outcome compared to men. METHOD: The aims of this multicenter, 6-week, double-blind, randomized, placebo-controlled fixed-dose (300 µg/d) trial conducted from 2004 to 2009 were to assess efficacy and tolerability of levothyroxine adjunctive to continuing treatment with mood stabilizer and/or antidepressant medication for patients with bipolar I or II disorder, currently depressed (DSM-IV), and to investigate gender differences in treatment response. The primary efficacy variable was mean change in Hamilton Depression Rating Scale (HDRS) score. RESULTS: Of 74 patients enrolled in the study, 62 (35 with bipolar I; mean age = 44.9 years) were randomized. Mean change in HDRS score from randomization to week 6 was larger in the levothyroxine group compared to the placebo group, with a 2.7-point difference (decline of -7.8 [38.3%] vs -5.1 [25.5%]; last-observation-carried-forward analysis). The course of HDRS scores over time from randomization to week 6 was significantly different between groups at week 4 (P = .046) but not at the end of the placebo-controlled phase (P = .198). The secondary analysis of women (n = 32) revealed a significant difference between groups in mean change in HDRS score (-16.6% placebo vs -42.4% levothyroxine, P = .018). A mixed-effects model for repeated-measures analysis showed a significant between-group difference in HDRS score (6.8, P = .012) for women. High thyroid-stimulating hormone levels, indicating suboptimal levels of circulating thyroid hormones, were predictive for positive treatment outcome in women treated with levothyroxine in a linear regression model (F3 = 3.47; P = .05). DISCUSSION: This trial demonstrated that patients treated with levothyroxine did numerically better than those treated with placebo; however, the study failed to detect a statistically significant difference between the 2 groups in the primary outcome measure due to a high placebo response rate. Previous findings that women show better improvement in depression scores with levothyroxine compared to men were confirmed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01528839.


Asunto(s)
Trastorno Bipolar/tratamiento farmacológico , Tiroxina/biosíntesis , Tiroxina/farmacología , Adulto , Antidepresivos/uso terapéutico , Antimaníacos/uso terapéutico , Antipsicóticos/uso terapéutico , Trastorno Bipolar/metabolismo , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Efecto Placebo , Factores Sexuales , Tiroxina/administración & dosificación , Tiroxina/sangre , Resultado del Tratamiento
19.
J Nerv Ment Dis ; 201(1): 76-9, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23274301

RESUMEN

Courses of Parkinson's disease (PD) that are complicated by weight loss result in poorer overall treatment outcome and lower quality of life. To determine the contribution of depression, which has not yet been specified in the etiology of weight loss in PD, symptomatology and anamnesis from 215 outpatients diagnosed with PD were assessed using a comprehensive battery of neuropsychiatric scales. A percentage of 31 comorbid depressed patients and a comparison with a control population allowed an accurate characterization of effect sizes, sex differences, and patterns of the contribution of comorbid depression to weight loss. Our study showed that comorbid depression had a clinically relevant effect concerning reduced body mass index in male (0.3; Hedges' g) but not in female PD patients. Although some possible confounders are not controlled here, our results support the need of monitoring depressive symptoms in the courses of PD, particularly in male patients.


Asunto(s)
Trastorno Depresivo/fisiopatología , Enfermedad de Parkinson/fisiopatología , Pérdida de Peso/fisiología , Anciano , Índice de Masa Corporal , Estudios de Cohortes , Comorbilidad , Trastorno Depresivo/epidemiología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Enfermedad de Parkinson/epidemiología , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Factores Sexuales
20.
Addict Biol ; 18(5): 855-62, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22974271

RESUMEN

Ghrelin figures prominently in the regulation of appetite in normal-weighed individuals. The apparent failure of this mechanism in eating disorders and the connection to addictive behavior in general demand a deeper understanding of the endogenous central-nervous processes related to ghrelin. Thus, we investigated processing of pictures showing palatable food after overnight fasting and following a standardized caloric intake (i.e. a 75-g oral glucose tolerance test) using functional magnetic resonance imaging and correlated it with blood plasma levels of ghrelin. Twenty-six healthy female and male volunteers viewed food and control pictures in a block design and rated their appetite after each block. Fasting levels of ghrelin correlated positively with food-cue reactivity in a bilateral network of visual processing-, reward- and taste-related regions, including limbic and paralimbic regions. Notably, among those regions were the hypothalamus and the midbrain where ghrelin receptors are densely concentrated. In addition, high fasting ghrelin levels were associated with stronger increases of subjective appetite during the food-cue-reactivity task. In conclusion, brain activation and subjective appetite ratings suggest that ghrelin elevates the hedonic effects of food pictures. Thereby, fasting ghrelin levels may generally enhance subjective craving when confronted with reward cues.


Asunto(s)
Apetito/fisiología , Encéfalo/fisiología , Alimentos , Ghrelina/sangre , Hambre/fisiología , Adulto , Animales , Señales (Psicología) , Ayuno/sangre , Femenino , Neuroimagen Funcional/métodos , Ghrelina/fisiología , Prueba de Tolerancia a la Glucosa , Humanos , Procesamiento de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa/métodos , Recompensa , Roedores , Estadística como Asunto , Factores de Tiempo , Adulto Joven
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