RESUMEN
WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The antidepressant effect of ketamine is associated with increased activity in the reward circuitry of the brain and a suppression of circuitry that mediates perceptual processing of negative emotions. The duration of ketamine effect on these brain structures remains to be defined. WHAT THIS ARTICLE TELLS US THAT IS NEW: As expected, ketamine administration led to an improvement in mood and global vigilance. The improvement in mood was accompanied by an increased recruitment of the orbitofrontal cortex, ventral striatum, medial substantial nigra and ventral tegmental area, structures that are part of the reward circuitry.Responses in the mesolimbic structures (amygdala, medial substantial nigra and ventral tegmental area, orbitofrontal cortex) to negative stimuli were decreased after ketamine administration.The data are consistent with the premise that ketamine induces sustained changes in the mesolimbic neural circuits to reset pathological reward and emotional processing. BACKGROUND: Ketamine rapidly improves maladaptive mood states in major depressive disorder, and some of the neural substrates underlying this therapeutic effect have been identified. This study aimed to identify functional changes within neural networks that may underlie the impact of ketamine on both reward and emotional processing in patients with treatment-resistant major depression. METHODS: Ten adult patients with a Montgomery-Åsberg Depression Rating Scale score above 25 were enrolled to receive a single intravenous administration of ketamine (0.5 mg/kg). Patients' performance along with related neural network activations were analyzed in a game-like reward task and in an emotional judgment task using functional magnetic resonance imaging 1 day before and 1 and 7 days after ketamine administration. RESULTS: A significant correlation (R = 0.46, P = 0.03) between the improvement of depression scores and the enhanced reaction time for positive items was found in the game-like reward task 1 day after ketamine administration. This enhanced sensitivity for rewarded items was accompanied by increased activity of reward-related brain regions, including the orbitofrontal cortex, ventral striatum, and the ventral tegmental area, an effect that persisted up to 1 week after ketamine injection. In the emotional judgment task, it was found that ketamine rapidly modified local brain activities in response to emotionally negative, positive, or neutral stimuli in the amygdala, insula, anterior cingulate cortex, and in the ventral tegmental area. CONCLUSIONS: Single bolus ketamine administration rapidly triggers lasting changes in mesolimbic neural networks to improve pathologic reward and emotional processing in patients with major depressive disorder.
Asunto(s)
Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/psicología , Ketamina/administración & dosificación , Sistema Límbico/efectos de los fármacos , Recompensa , Administración Intravenosa , Adulto , Anestésicos Disociativos/administración & dosificación , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Resistente al Tratamiento/diagnóstico por imagen , Femenino , Humanos , Sistema Límbico/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Proyectos PilotoRESUMEN
BACKGROUND: Ketamine has been documented for its rapid antidepressant effects. However, optimal dose and delivery route have not yet been thoroughly investigated. The objectives of this study were to document the safety and test the antidepressant and antisuicidal effects of a single rapid 1-minute injection of ketamine 0.5 mg/kg in treatment-resistant depression (TRD). METHODS: Ten patients with TRD were included in an open, noncontrolled 4-week study and received a rapid intravenous dose of ketamine 0.5 mg/kg. Main outcome measure was the Montgomery-Åsberg Depression Rating Scale and suicidality was assessed using the Scale for Suicide Ideation. RESULTS: Rapid injection of ketamine elicited transient increase of blood pressure and altered states of consciousness in all patients and mild psychotomimetic effects in 4 patients, which all resolved without any intervention. Decrease of depression severity was observed from 40-minute postinjection until day 15. Eight patients became responders within 1 day and all were nonresponders after 4 weeks. The decrease of suicidal ideation was significant until day 7. Analysis indicated that higher severity of depression and anxiety at baseline predicted a larger Montgomery-Åsberg Depression Rating Scale decrease after 4 weeks. CONCLUSIONS: This study suggests that in well-controlled medical settings with adequate monitoring, a single rapid 1-minute injection of ketamine 0.5 mg/kg can be well tolerated and is efficacious in rapidly reducing depression symptoms and suicidal thoughts in outpatients with TRD. These findings are relevant to the practice of general clinical psychiatry and emergency departments were ketamine can have a place in acute management of TRD. Larger studies are necessary to confirm these results.
Asunto(s)
Antidepresivos/farmacología , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Ketamina/farmacología , Evaluación de Resultado en la Atención de Salud , Ideación Suicida , Adulto , Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Femenino , Humanos , Inyecciones Intravenosas , Ketamina/administración & dosificación , Ketamina/efectos adversos , Masculino , Persona de Mediana EdadRESUMEN
Information processing in the medial frontal cortex is often said to be modulated in pathological conditions or by individual traits. This has been observed in neuroimaging and event-related potential studies centered in particular on midcingulate cortex (MCC) functions. This region of the brain is characterized by considerable intersubject morphological variability. Whereas in a subset of hemispheres only a single cingulate sulcus (cgs) is present, a majority of hemispheres exhibit an additional sulcus referred to as the paracingulate sulcus (pcgs). The present functional magnetic resonance imaging study defined the relationship between the local morphology of the cingulate/paracingulate sulcal complex and feedback-related activity. Human subjects performed a trial-and-error learning task in which they had to discover which one of a set of abstract stimuli was the best option. Feedback was provided by means of fruit juice, as in studies with monkeys. A subject-by-subject analysis revealed that the feedback-related activity during exploration was systematically located in the cgs when no pcgs was observed, but in the pcgs when the latter sulcus was present. The activations had the same functional signature when located in either the cgs or in the pcgs, confirming that both regions were homologues. Together, the results show that the location of feedback-related MCC activity can be predicted from morphological features of the cingulate/paracingulate complex.
Asunto(s)
Retroalimentación Fisiológica/fisiología , Giro del Cíngulo/anatomía & histología , Aprendizaje/fisiología , Solución de Problemas/fisiología , Adulto , Mapeo Encefálico , Femenino , Giro del Cíngulo/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND: Recent studies suggest that Posttraumatic Stress Disorder (PTSD) might be associated with dysfunctional reward circuitry. However, further research is needed to understand the key role of the reward system in PTSD symptomatology. METHODS: Twenty participants with PTSD and 21 Trauma-Exposed matched Controls (TECs) completed the Monetary Incentive Delay (MID) task during an MRI session. Reaction times (RTs) and hit rates were recorded. Brain activity was investigated during the anticipation and the outcome of monetary gains and losses. RESULTS: During the anticipation of monetary loss, PTSD participants had higher RTs than TECs. However, the groups did not differ at the neurofunctional level. During successful avoidance of monetary loss, PTSD patients showed higher activation than TECs in the left caudate nucleus. During the anticipation of monetary gains, no differences in RTs were found between groups. PTSD patients had specific activations in the right amygdala, nucleus accumbens, putamen, and middle frontal gyrus (p < 0.05 family-wise error (FWE)-corrected), while TECs had specific activation in the anterior cingulate cortex. When obtaining monetary gains, PTSD patients had specific activation in the caudate nucleus, while TECs had specific activations in the right hypothalamus, subthalamic nucleus, and left inferior frontal gyrus. CONCLUSION: For the first time, functional brain activation during both the anticipation and the outcome of monetary rewards is reported altered in PTSD patients. These alterations might be associated with the complex symptomatology of PTSD.