RESUMEN
Serotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.
Asunto(s)
Aprendizaje Inverso , Serotonina , Condicionamiento Operante , Humanos , Castigo , Aprendizaje Inverso/fisiología , RecompensaRESUMEN
Converging evidence has linked the anterior mid-cingulate cortex to negative affect, pain and cognitive control. It has previously been proposed that this region uses information about punishment to control aversively motivated actions. Studies on the effects of lesions allow causal inferences about brain function; however, naturally occurring lesions in the anterior mid-cingulate cortex are rare. In two studies we therefore recruited 94 volunteers, comprising 15 patients with treatment-resistant depression who had received bilateral anterior cingulotomy, which consists of lesions made within the anterior mid-cingulate cortex, 20 patients with treatment-resistant depression who had not received surgery and 59 healthy control subjects. Using the Ekman 60 faces paradigm and two Stroop paradigms, we tested the hypothesis that patients who received anterior cingulotomy were impaired in recognizing negative facial affect expressions but not positive or neutral facial expressions, and impaired in Stroop cognitive control, with larger lesions being associated with more impairment. Consistent with this hypothesis, we found that larger volume lesions predicted more impairment in recognizing fear, disgust and anger, and no impairment in recognizing facial expressions of surprise or happiness. However, we found no impairment in recognizing expressions of sadness. Also consistent with the hypothesis, we found that larger volume lesions predicted impaired Stroop cognitive control. Notably, this relationship was only present when anterior mid-cingulate cortex lesion volume was defined as the overlap between cingulotomy lesion volume and Shackman's meta-analysis-derived binary masks for negative affect and cognitive control. Given substantial evidence from healthy subjects that the anterior mid-cingulate cortex is part of a network associated with the experience of negative affect and pain, engaging cognitive control processes for optimizing behaviour in the presence of such stimuli, our findings support the assertion that this region has a causal role in these processes. While the clinical justification for cingulotomy is empirical and not theoretical, it is plausible that lesions within a brain region associated with the subjective experience of negative affect and pain may be therapeutic for patients with otherwise intractable mood, anxiety and pain syndromes.
Asunto(s)
Afecto/fisiología , Cognición/fisiología , Giro del Cíngulo/fisiopatología , Giro del Cíngulo/cirugía , Estudios de Casos y Controles , Trastorno Depresivo Resistente al Tratamiento/diagnóstico por imagen , Trastorno Depresivo Resistente al Tratamiento/patología , Trastorno Depresivo Resistente al Tratamiento/fisiopatología , Trastorno Depresivo Resistente al Tratamiento/cirugía , Expresión Facial , Femenino , Giro del Cíngulo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Test de StroopRESUMEN
Recently, the Council of the UK Royal College of Psychiatrists agreed to use the term 'patient' as the preferred collective noun when referring to people accessing mental health services in its official documentation. Choices regarding terminology have the power to influence those who use such terms and here, David Christmas and Angela Sweeney debate the issue of whether such a decision is appropriate or whether we need to be more careful about the terms we use.
Asunto(s)
Enfermos Mentales , Psiquiatría/normas , Terminología como Asunto , HumanosRESUMEN
Major depressive disorder is characterized by anhedonia, cognitive biases, ruminations, hopelessness and increased anxiety. Blunted responses to rewards have been reported in a number of recent neuroimaging and behavioural studies of major depressive disorder. In contrast, neural responses to aversive events remain an under-studied area. While selective serotonergic reuptake inhibitors are often effective in treating major depressive disorder, their mechanism of action remains unclear. Following a series of animal model investigations of depressive illness and serotonergic function, Deakin and Graeff predicted that brain activity in patients with major depressive disorder is associated with an overactive dorsal raphe nucleus with overactive projections to the amygdala, periaqueductal grey and striatum, and an underactive median raphe nucleus with underactive projections to the hippocampus. Here we describe an instrumental loss-avoidance and win-gain reinforcement learning functional magnetic resonance imaging study with 40 patients with highly treatment-resistant major depressive disorder and never-depressed controls. The dorsal raphe nucleus/ periaqueductal grey region of the midbrain and hippocampus were found to be overactive in major depressive disorder during unsuccessful loss-avoidance although the median raphe nucleus was not found to be underactive. Hippocampal overactivity was due to a failure to deactivate during loss events in comparison to controls, and hippocampal over-activity correlated with depression severity, self-report 'hopelessness' and anxiety. Deakin and Graeff argued that the median raphe nucleus normally acts to inhibit consolidation of aversive memories via the hippocampus and this system is underactive in major depressive disorder, facilitating the development of ruminations, while the dorsal raphe nucleus system is engaged by distal cues predictive of threats and is overactive in major depressive disorder. During win events the striatum was underactive in major depressive disorder. We tested individual patient consistency of these findings using within-study replication. Abnormal hippocampal activity correctly predicted individual patient diagnostic status in 97% (sensitivity 95%, specificity 100%) of subjects, and abnormal striatal activity predicted diagnostic status in 84% (sensitivity 79%, specificity 89%) of subjects. We conclude that the neuroimaging findings were largely consistent with Deaken and Graeff's predictions, abnormally increased hippocampal activity during loss events was an especially consistent abnormality, and brainstem serotonergic nuclei merit further study in depressive illness.
Asunto(s)
Trastorno Depresivo Mayor/patología , Hipocampo/irrigación sanguínea , Refuerzo en Psicología , Adulto , Anciano , Trastorno Depresivo Mayor/tratamiento farmacológico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Mesencéfalo/irrigación sanguínea , Mesencéfalo/patología , Persona de Mediana Edad , Oxígeno/sangre , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Burning mouth syndrome (BMS) is an idiopathic disease characterized by the feeling of burning in the oral cavity. Ten per cent of patients presenting to oral medicine clinics have BMS. Anxiety and depression are common co-morbidities in BMS, but it is not known if they are associated with specific BMS symptoms. OBJECTIVE: In an exploratory analysis, this study examined the association of generalized anxiety and depression with individual BMS symptoms. METHODS: Forty-one patients were recruited from a dental outpatient clinic (30 with BMS and 11 with other oral conditions), evaluating specific BMS symptoms and their intensity. Anxiety and depression symptoms were assessed using a standardized measure (Clinical Interview Schedule-Revised). RESULTS: Taste change (p = 0.007), fear of serious illness (p = 0.011), metallic taste (p = 0.018) and sensation of a film on the gums (p = 0.047) were associated with an excess of psychiatric symptoms. More specifically, metallic taste (coefficient = 0.497, 95% CI = 0.149-0.845; p = 0.006) and sensation of film on gums (coefficient = 0.625, 95% CI = 0.148-1.103; p = 0.012) were associated significantly with higher scores for depressive symptoms; taste change (coefficient = 0.269, 95% CI = 0.077-0.461; p = 0.007), bad breath (coefficient = 0.273, 95% CI = 0.065-0.482; p = 0.012) and fear of serious illness (coefficient = 0.242, 95% CI = 0.036-0.448; p = 0.023) were associated with higher anxiety scores. CONCLUSION: Specific BMS symptoms are associated differentially with generalized anxiety and depression. Dental practitioners should ascertain which BMS symptoms are predominant and be mindful of the association of certain symptoms with anxiety or depression and, where necessary, consider medical consultation.
Asunto(s)
Ansiedad/psicología , Síndrome de Boca Ardiente/psicología , Depresión/psicología , Trastornos de Ansiedad/psicología , Actitud Frente a la Salud , Bruxismo/psicología , Trastorno Depresivo/psicología , Miedo/psicología , Femenino , Enfermedades de las Encías/psicología , Halitosis/psicología , Humanos , Hipoestesia/psicología , Masculino , Persona de Mediana Edad , Parestesia/psicología , Trastornos del Gusto/psicología , Hábitos Linguales/psicología , Xerostomía/psicologíaRESUMEN
BACKGROUND: The evidence base to guide therapeutic choices for patients with chronic and treatment-refractory depression (TRD) remains weak. There is limited comparative information available to guide the choice of intervention for patients with the most severe and disabling forms of illness. OBJECTIVES: The aim of this work was to describe the 12-month clinical outcomes of patients with chronic TRD treated with anterior capsulotomy (ACAPS; n = 5), anterior cingulotomy (ACING; n = 5) or vagus nerve stimulation (VNS; n = 5). METHODS: We performed a retrospective, consecutive, case series comparison. RESULTS: With clinical response defined as a ≥50% reduction from the baseline MADRS score, response rates were 40% for ACAPS, 60% for ACING and 20% for VNS. Adverse effects from all three procedures were relatively mild, consistent with previous reports and, in most cases, transient. Adverse effects from VNS were related to active stimulation, and were modifiable and diminished in severity over time. There were no deaths. CONCLUSIONS: Although based on a small sample, our data represent a unique comparison of ACAPS, ACING and VNS for chronic TRD. The three cohorts were broadly equivalent in terms of baseline clinical characteristics, indices of chronicity, illness severity and estimates of previous failed treatments. ACING and ACAPS, but not VNS, were associated with favourable response rates at 12 months.
Asunto(s)
Trastorno Depresivo Resistente al Tratamiento/terapia , Giro del Cíngulo/cirugía , Psicocirugía/métodos , Estimulación del Nervio Vago , Trastorno Depresivo Resistente al Tratamiento/cirugía , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Cognitive impairment is integral to many neurological illnesses. Specific enhancement of glutamatergic transmission may improve memory and learning. Org 25935 increases the synaptic availability of glycine, an obligate co-agonist with glutamate at N-methyl-D-aspartate receptors. We hypothesised that Org 25935 would acutely improve the learning and memory of healthy volunteers. METHODS: A randomised, double-blind, parallel-group, single-dose study of Org 25935 and placebo was carried out. Thirty-two healthy male volunteers took either 12-mg Org 25935 or matching placebo and were later assessed with the manikin task, digit span and verbal memory tests. Systematic assessments of cardiovascular and adverse events were also taken. RESULTS: There was no effect of Org 25935 on reaction time, number of correct responses or learning (greater or slower improvement over successive tasks) compared with placebo. Org 25935 caused significantly more dizziness and drowsiness compared with placebo; these side effects were mainly mild. CONCLUSIONS: A single dose of Org 25935 does not improve learning or memory in healthy male individuals. However, the drug was well tolerated, and it remains to be seen whether it would have a positive effect on cognition in patient groups with pre-existing cognitive deficits.
Asunto(s)
Cognición/efectos de los fármacos , Memoria/efectos de los fármacos , Inhibidores de la Captación de Neurotransmisores/farmacología , Tetrahidronaftalenos/farmacología , Adolescente , Adulto , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Electrocardiografía , Corazón/efectos de los fármacos , Corazón/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Inhibidores de la Captación de Neurotransmisores/efectos adversos , Inhibidores de la Captación de Neurotransmisores/sangre , Tiempo de Reacción , Análisis y Desempeño de Tareas , Tetrahidronaftalenos/efectos adversos , Tetrahidronaftalenos/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
The role of the adenosine neurochemical system in human cognition is under-studied, despite such receptors being distributed throughout the brain. The aim of this study was to shed light on the role of the adenosine A2A receptors in human cognition using single-dose istradefylline. Twenty healthy male participants, aged 19-49, received 20 mg istradefylline and placebo, in a randomized, double-blind, placebo-controlled cross-over design. Cognition was assessed using computerized cognitive tests, covering both cold (non-emotional) and hot (emotion-laden) domains. Cardiovascular data were recorded serially. Cognitive effects of istradefylline were explored using repeated measures analysis of variance and paired t-tests as appropriate. On the EMOTICOM battery, there was a significant effect of istradefylline versus placebo on the Social Information Preference task (t = 2.50, p = 0.02, d=-0.59), indicating that subjects on istradefylline interpreted social situations more positively. No other significant effects were observed on other cognitive tasks, nor in terms of cardiovascular measures (pulse and blood pressure). De-briefing indicated that blinding was successful, both for participants and the research team. Further exploration of the role of adenosine A2A receptors in emotional processing may be valuable, given that abnormalities in related cognitive functions are implicated in neuropsychiatric disorders. The role of adenosine systems in human cognition requires further clarification, including with different doses of istradefylline and over different schedules of administration.
Asunto(s)
Cognición , Receptor de Adenosina A2A , Humanos , Masculino , Voluntarios Sanos , Método Doble Ciego , Antagonistas del Receptor de Adenosina A2/farmacología , Antagonistas del Receptor de Adenosina A2/uso terapéuticoRESUMEN
(1) Background: Major depressive disorder (MDD) generates a large proportion of global disease burden. Stereotactic radiofrequency ablation (SRA) may be beneficial for selected patients with its most debilitating and refractory forms, but effect size is uncertain. (2) Methods: A systematic literature review and meta-analysis on SRA for MDD was carried out. Patient-level data were extracted from articles reporting validated depression measures (Beck Depression Inventory (BDI), Montgomery-Åsberg Depression Rating Scale (MADRS)), pre- and at least six months post surgery. To accommodate different outcome measures, the standardised mean difference (SMD) between both scores was used as the principal effect size. Data were synthesised using a random-effects model. (3) Results: Five distinct studies were identified, comprising 116 patients (64 included in meta-analysis). Effect size comparing post- vs. pre-operative scores was 1.66 (CI 1.25-2.07). Anterior cingulotomy (two studies, n = 22) and anterior capsulotomy (three studies, n = 42) showed similar effect sizes: 1.51 (CI 0.82-2.20) vs. 1.74 (CI 1.23-2.26). Multiple procedures were performed in 30 of 116 (25.9%) patients. Based on patient-level data, 53% (n = 47) were responders (≥50% improvement), of which 34% reached remission (MADRS ≤ 10 or BDI ≤ 11). BDI mean improvement was 16.7 (44.0%) after a second procedure (n = 19). (4) Conclusions: The results are supportive of the benefit of SRA in selected patients with refractory MDD.
RESUMEN
Motivations shape our behaviour: the promise of reward invigorates, while in the face of punishment, we hold back. Abnormalities of motivational processing are implicated in clinical disorders characterised by excessive habits and loss of top-down control, notably substance and behavioural addictions. Striatal and frontal dopamine have been hypothesised to play complementary roles in the respective generation and control of these motivational biases. However, while dopaminergic interventions have indeed been found to modulate motivational biases, these previous pharmacological studies used regionally non-selective pharmacological agents. Here, we tested the hypothesis that frontal dopamine controls the balance between Pavlovian, bias-driven automated responding and instrumentally learned action values. Specifically, we examined whether selective enhancement of cortical dopamine either (i) enables adaptive suppression of Pavlovian control when biases are maladaptive; or (ii) non-specifically modulates the degree of bias-driven automated responding. Healthy individuals (n = 35) received the catechol-o-methyltransferase (COMT) inhibitor tolcapone in a randomised, double-blind, placebo-controlled cross-over design, and completed a motivational Go NoGo task known to elicit motivational biases. In support of hypothesis (ii), tolcapone globally decreased motivational bias. Specifically, tolcapone improved performance on trials where the bias was unhelpful, but impaired performance in bias-congruent conditions. These results indicate a non-selective role for cortical dopamine in the regulation of motivational processes underpinning top-down control over automated behaviour. The findings have direct relevance to understanding neurobiological mechanisms underpinning addiction and obsessive-compulsive disorders, as well as highlighting a potential trans-diagnostic novel mechanism to address such symptoms.
Asunto(s)
Catecol O-Metiltransferasa , Dopamina , Sesgo , Inhibidores de Catecol O-Metiltransferasa/farmacología , Humanos , Motivación , Tolcapona/farmacologíaRESUMEN
BACKGROUND: There is very limited evidence for the efficacy of any specific therapeutic intervention in chronic, treatment refractory major depression. Thermal anterior capsulotomy (ACAPS) is a rarely performed but established therapeutic procedure for this patient group. While benefit has been claimed, previous ACAPS reports have provided limited information. Detailed prospective reporting of therapeutic effects and side effects is required. OBJECTIVE: To report a prospective study of therapeutic effect, mental status, quality of life, social functioning and neurocognitive functioning in individuals with chronic treatment refractory major depression, treated with ACAPS. METHOD: A prospective case series of 20 patients treated with ACAPS between 1992 and 1999 were reassessed at a mean follow-up of 7.0±3.4 years. Data were collected preoperatively and at long term follow-up. Structural MRI was performed in 14 participants. RESULTS: According to a priori criteria, at long term follow-up, 50% were classified as 'responders' and 40% as 'remitters'. Fifty-five per cent were classified as 'improved'; 35% were 'unchanged'; and 10% had 'deteriorated'. Neurocognitive and personality testing were not significantly different at follow-up. A trend towards improvement in some aspects of executive neuropsychological functioning was observed. Significant adverse effects were infrequent and there were no deaths. CONCLUSIONS: ACAPS may represent an effective intervention for some patients with chronic, disabling, treatment refractory major depression that has failed to respond to other therapeutic approaches. The adverse effect burden within this population was modest, with no evidence of generalised impairment of neurocognitive functioning.
Asunto(s)
Trastorno Depresivo Mayor/cirugía , Cápsula Interna/cirugía , Complicaciones Posoperatorias , Psicocirugía/métodos , Adulto , Trastorno Depresivo Mayor/psicología , Resistencia a Medicamentos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Determinación de la Personalidad , Estudios Prospectivos , Psicocirugía/efectos adversos , Calidad de Vida/psicología , Resultado del TratamientoRESUMEN
Attempted suicide and deliberate self-harm are common and challenging presentations in the emergency department. A proportion of these patients refuse interventions and this presents the clinical, legal, and ethical dilemma as to whether treatment should be provided against their will. Multiple factors influence this decision. It is difficult to foresee the multitude and magnitude of complications that can arise once it has been decided to treat individuals who do not consent. This case illustrates a particularly complex chain of events that occurred after treating someone against their will who presented with self-harm and suicidal ideation. These consequences are contrasted with those of not intervening when similar situations arose with the same patient.
RESUMEN
BACKGROUND: Responding emotionally to danger is critical for survival. Normal functioning also requires flexible alteration of emotional responses when a threat becomes safe. Aberrant threat and safety learning occur in many psychiatric disorders, including posttraumatic stress disorder, obsessive-compulsive disorder, and schizophrenia, in which emotional responses can persist pathologically. While there is evidence that threat and safety learning can be modulated by the serotonin systems, there have been few studies in humans. We addressed a critical clinically relevant question: How does lowering serotonin affect memory retention of conditioned threat and safety memory? METHODS: Forty-seven healthy participants underwent conditioning to two stimuli predictive of threat on day 1. One stimulus but not the other was subsequently presented in an extinction session. Emotional responding was assessed by the skin conductance response. On day 2, we employed acute dietary tryptophan depletion to lower serotonin temporarily, in a double-blind, placebo-controlled, randomized between-groups design. We then tested for the retention of conditioned threat and extinction memory. We also measured self-reported intolerance of uncertainty, known to modulate threat memory expression. RESULTS: The expression of emotional memory was attenuated in participants who had undergone tryptophan depletion. Individuals who were more intolerant of uncertainty showed even greater attenuation of emotion following depletion. CONCLUSIONS: These results support the view that serotonin is involved in predicting aversive outcomes and refine our understanding of the role of serotonin in the persistence of emotional responsivity, with implications for individual differences in vulnerability to psychopathology.
Asunto(s)
Extinción Psicológica , Triptófano , Condicionamiento Clásico , Humanos , Aprendizaje , IncertidumbreRESUMEN
Serotonin is involved in a wide range of mental capacities essential for navigating the social world, including emotion and impulse control. Much recent work on serotonin and social functioning has focused on decision-making. Here we investigated the influence of serotonin on human emotional reactions to social conflict. We used a novel computerised task that required mentally simulating social situations involving unjust harm and found that depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-enhanced emotional responses to the scenarios in a large sample of healthy volunteers (n = 73), and interacted with individual differences in trait personality to produce distinctive human emotions. Whereas guilt was preferentially elevated in highly empathic participants, annoyance was potentiated in those high in trait psychopathy, with medium to large effect sizes. Our findings show how individual differences in personality, when combined with fluctuations of serotonin, may produce diverse emotional phenotypes. This has implications for understanding vulnerability to psychopathology, determining who may be more sensitive to serotonin-modulating treatments, and casts new light on the functions of serotonin in emotional processing.
Asunto(s)
Emociones , Individualidad , Personalidad , Serotonina , Método Doble Ciego , Empatía , Voluntarios Sanos , Humanos , TriptófanoRESUMEN
Objectives: Face-to-face healthcare, including psychiatric provision, must continue despite reduced interpersonal contact during the COVID-19 (SARS-CoV-2 coronavirus) pandemic. Community-based services might use domiciliary visits, consultations in healthcare settings, or remote consultations. Services might also alter direct contact between clinicians. We examined the effects of appointment types and clinician-clinician encounters upon infection rates. Design: Computer simulation. Methods: We modelled a COVID-19-like disease in a hypothetical community healthcare team, their patients, and patients' household contacts (family). In one condition, clinicians met patients and briefly met family (e.g., home visit or collateral history). In another, patients attended alone (e.g., clinic visit), segregated from each other. In another, face-to-face contact was eliminated (e.g., videoconferencing). We also varied clinician-clinician contact; baseline and ongoing "external" infection rates; whether overt symptoms reduced transmission risk behaviourally (e.g., via personal protective equipment, PPE); and household clustering. Results: Service organisation had minimal effects on whole-population infection under our assumptions but materially affected clinician infection. Appointment type and inter-clinician contact had greater effects at low external infection rates and without a behavioural symptom response. Clustering magnified the effect of appointment type. We discuss infection control and other factors affecting appointment choice and team organisation. Conclusions: Distancing between clinicians can have significant effects on team infection. Loss of clinicians to infection likely has an adverse impact on care, not modelled here. Appointments must account for clinical necessity as well as infection control. Interventions to reduce transmission risk can synergize, arguing for maximal distancing and behavioural measures (e.g., PPE) consistent with safe care.
RESUMEN
One of the major goals of antidepressant treatment is a sustained response and remission of depressive symptoms. Some of the previous studies of vagus nerve stimulation (VNS) have suggested antidepressant effects. Our naturalistic study assessed the efficacy and the safety of VNS in 74 European patients with therapy-resistant major depressive disorder. Psychometric measures were obtained after 3, 12, and 24 months of VNS. Mixed-model repeated-measures analysis of variance revealed a significant reduction (P < or = 0.05) at all the 3 time points in the 28-item Hamilton Rating Scale for Depression (HRSD28) score, the primary outcome measure. After 2 years, 53.1% (26/49) of the patients fulfilled the response criteria (> or =50% reduction in the HRSD28 scores from baseline) and 38.9% (19/49) fulfilled the remission criteria (HRSD28 scores < or = 10). The proportion of patients who fulfilled the remission criteria remained constant as the duration of VNS treatment increased. Voice alteration, cough, and pain were the most frequently reported adverse effects. Two patients committed suicide during the study; no other deaths were reported. No statistically significant differences were seen in the number of concomitant antidepressant medications. The results of this 2-year open-label trial suggest a clinical response and a comparatively benign adverse effect profile among patients with treatment-resistant depression.
Asunto(s)
Trastorno Depresivo Mayor/psicología , Trastorno Depresivo Mayor/terapia , Estimulación del Nervio Vago/métodos , Adulto , Anciano , Estudios de Cohortes , Terapia por Estimulación Eléctrica/métodos , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
The involvement of serotonin in responses to negative feedback is well established. Acute serotonin reuptake inhibition has enhanced sensitivity to negative feedback (SNF), modelled by behaviour in probabilistic reversal learning (PRL) paradigms. Whilst experiments employing acute tryptophan depletion (ATD) in humans, to reduce serotonin synthesis, have shown no clear effect on SNF, sample sizes have been small. We studied a large sample of healthy volunteers, male and female, and found ATD had no effect on core behavioural measures in PRL. These results indicate that ATD effects can differ from other manipulations of serotonin expected to have a parallel or opposing action.
Asunto(s)
Aprendizaje Inverso/fisiología , Serotonina/metabolismo , Triptófano/metabolismo , Retroalimentación , Femenino , Humanos , Masculino , Tamaño de la MuestraRESUMEN
BACKGROUND: Early worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking. AIMS: To review systematically all evidence relating to jitteriness/anxiety syndrome to identify: constituent symptoms; medications implicated; disorders in which it was reported; incidence; time course; management strategies; relationship of this syndrome to therapeutic response; distinction between syndrome and akathisia; relationship between syndrome and suicide; and genetic predispositions. METHOD: A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome. RESULTS: Of 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome. CONCLUSIONS: Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.
Asunto(s)
Acatisia Inducida por Medicamentos , Antidepresivos/efectos adversos , Trastornos de Ansiedad/tratamiento farmacológico , Ansiedad/inducido químicamente , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Suicidio , Antidepresivos/uso terapéutico , Relación Dosis-Respuesta a Droga , Predisposición Genética a la Enfermedad , Humanos , Factores de Riesgo , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Síndrome , Factores de Tiempo , Negativa del Paciente al TratamientoAsunto(s)
Ansiedad/terapia , Depresión/terapia , Epilepsias Parciales/psicología , Fototerapia/métodos , Femenino , Humanos , MasculinoRESUMEN
Four patients that had received an anterior cingulotomy (ACING) and five patients that had received both an ACING and an anterior capsulotomy (ACAPS) as an intervention for chronic, treatment refractory depression were presented with a series of dynamic emotional stimuli and invited to identify the emotion portrayed. Their performance was compared with that of a group of non-surgically treated patients with major depression (n=17) and with a group of matched, never-depressed controls (n=22). At the time of testing, four of the nine neurosurgery patients had recovered from their depressive episode, whereas five remained depressed. Analysis of emotion recognition accuracy revealed no significant differences between depressed and non-depressed neurosurgically treated patients. Similarly, no significant differences were observed between the patients treated with ACING alone and those treated with both ACING and ACAPS. Comparison of the emotion recognition accuracy of the neurosurgically treated patients and the depressed and healthy control groups revealed that the surgically treated patients exhibited a general impairment in their recognition accuracy compared to healthy controls. Regression analysis revealed that participants' emotion recognition accuracy was predicted by the number of errors they made on the Stroop colour-naming task. It is plausible that the observed deficit in emotion recognition accuracy was a consequence of impaired attentional control, which may have been a result of the surgical lesions to the anterior cingulate cortex.