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This study examined the efficacy and acceptability of a hybrid, clinician-guided internet-based Cognitive Behavioural Therapy (iCBT) programme for outpatients with depression in a psychiatric hospital in Singapore. Fifty three participants were randomly assigned to a treatment or wait-list control group before they underwent a cross-over of conditions. Treatment consisted of a 4-week iCBT with three face-to-face sessions. 60.9% of participants who received treatment completed all six modules. Intention-to-treat analysis showed treatment was associated with significant reductions in symptoms of depression, anxiety and psychological distress but not in functional impairment, while the control condition was not associated with changes in any measures. These reductions had moderate to large effect sizes (ESs) for symptoms of depression and anxiety, and moderate ES for psychological distress. The between-group difference in depression score had a moderate ES. There was a significant between-group treatment effect in depressive symptoms, but not in the other measures. Treatment gains were maintained at 3-month follow-up. Most of the participants were highly satisfied with the programme, with 90 percent stating they would recommend it. This is the first RCT to provide preliminary evidence for the efficacy and acceptability of iCBT for depression in Singapore.
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Relational aggression such as social rejection is common within school peer groups. Converging evidence suggests that adolescent females are particularly sensitive to social rejection. We used a novel fMRI adaptation of the Cyberball social rejection paradigm to investigate the neural response to social rejection in 19 mid-adolescent (aged 14-16) and 16 adult female participants. Across all participants, social exclusion (relative to inclusion) elicited a response in bilateral medial prefrontal cortex (mPFC) extending into ventral and subgenual anterior cingulate cortex and medial orbitofrontal cortex; and the left ventrolateral PFC (vlPFC); regions that have been associated in previous studies with social evaluation, negative affective processing, and affect regulation respectively. However, the exclusion-related response in right vlPFC, a region associated in previous studies with the regulation of rejection-related distress, was attenuated in adolescents. Within mPFC, greater activation during exclusion vs. inclusion was associated with greater self-reported susceptibility to peer influence in adolescents but not in adults. This suggests that the brain's response to experimentally-induced social rejection relates to adolescent behaviour in real-world social interactions. We speculate about the potential implications of these findings for educational settings. In particular, functional development of affective circuitry during adolescence may influence social interaction within the school peer group.
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Desarrollo del Adolescente/fisiología , Mapeo Encefálico , Encéfalo/fisiología , Psicología del Adolescente , Rechazo en Psicología , Adolescente , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Relaciones Interpersonales , Imagen por Resonancia Magnética , Neurociencias , Grupo Paritario , Instituciones AcadémicasRESUMEN
Recent genetic studies have implicated a number of candidate genes in the pathogenesis of Autism Spectrum Disorder (ASD). Polymorphisms of CNTNAP2 (contactin-associated like protein-2), a member of the neurexin family, have already been implicated as a susceptibility gene for autism by at least 3 separate studies. We investigated variation in white and grey matter morphology using structural MRI and diffusion tensor imaging. We compared volumetric differences in white and grey matter and fractional anisotropy values in control subjects characterised by genotype at rs7794745, a single nucleotide polymorphism in CNTNAP2. Homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation. Thus a risk allele for autism results in significant cerebral morphological variation, despite the absence of overt symptoms or behavioural abnormalities. The results are consistent with accumulating evidence of CNTNAP2's function in neuronal development. The finding suggests the possibility that the heterogeneous manifestations of ASD can be aetiologically characterised into distinct subtypes through genetic-morphological analysis.
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Cerebelo/patología , Trastornos Generalizados del Desarrollo Infantil/genética , Trastornos Generalizados del Desarrollo Infantil/fisiopatología , Lóbulo Frontal/patología , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Lóbulo Occipital/patología , Anisotropía , Niño , Endofenotipos , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Vías Nerviosas/patología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido SimpleRESUMEN
Genetic variation at the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with altered amygdala reactivity and lack of prefrontal regulatory control. Similar regions mediate decision-making biases driven by contextual cues and ambiguity, for example the "framing effect." We hypothesized that individuals hemozygous for the short (s) allele at the 5-HTTLPR would be more susceptible to framing. Participants, selected as homozygous for either the long (la) or s allele, performed a decision-making task where they made choices between receiving an amount of money for certain and taking a gamble. A strong bias was evident toward choosing the certain option when the option was phrased in terms of gains and toward gambling when the decision was phrased in terms of losses (the frame effect). Critically, this bias was significantly greater in the ss group compared with the lala group. In simultaneously acquired functional magnetic resonance imaging data, the ss group showed greater amygdala during choices made in accord, compared with those made counter to the frame, an effect not seen in the lala group. These differences were also mirrored by differences in anterior cingulate-amygdala coupling between the genotype groups during decision making. Specifically, lala participants showed increased coupling during choices made counter to, relative to those made in accord with, the frame, with no such effect evident in ss participants. These data suggest that genetically mediated differences in prefrontal-amygdala interactions underpin interindividual differences in economic decision making.
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Amígdala del Cerebelo/fisiología , Sesgo , Mapeo Encefálico , Toma de Decisiones/fisiología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adulto , Amígdala del Cerebelo/irrigación sanguínea , Análisis de Varianza , Femenino , Genotipo , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Oxígeno/sangre , Personalidad/genética , Psicofísica , Tiempo de Reacción/genética , Análisis de Regresión , Proteínas de Transporte de Serotonina en la Membrana Plasmática/fisiología , Adulto JovenRESUMEN
A polymorphism in the human serotonin transporter (5-HTT) gene is implicated in susceptibility to anxiety and depression and in enhanced emotion-induced activation in the amygdala. A role for 5-HTT polymorphism in the emotional modulation of human episodic memory has yet to be demonstrated. Here, we demonstrate that whereas emotional memory for aversive events per se is not influenced by 5-HTT polymorphism, an emotion-induced retrograde amnesia is expressed solely in the presence of the short allele. The findings indicate a critical role for the serotonin system in emotion-mediated memory disruption.
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Amnesia Retrógrada/etiología , Amnesia Retrógrada/genética , Emociones , Polimorfismo Genético/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
The goal of this study was to examine the efficacy of liver-targeted gene delivery by chitosan-DNA nanoparticles through retrograde intrabiliary infusion (RII). The transfection efficiency of chitosan-DNA nanoparticles, as compared with PEI-DNA nanoparticles or naked DNA, was evaluated in Wistar rats by infusion into the common bile duct, portal vein, or tail vein. Chitosan-DNA nanoparticles administrated through the portal vein or tail vein did not produce detectable luciferase expression. In contrast, rats that received chitosan-DNA nanoparticles showed more than 500 times higher luciferase expression in the liver 3 days after RII; and transgene expression levels decreased gradually over 14 days. Luciferase expression in the kidney, lung, spleen, and heart was negligible compared with that in the liver. RII of chitosan-DNA nanoparticles did not yield significant toxicity and damage to the liver and biliary tree as evidenced by liver function analysis and histopathological examination. Luciferase expression by RII of PEI-DNA nanoparticles was 17-fold lower than that of chitosan-DNA nanoparticles on day 3, but it increased slightly over time. These results suggest that RII is a promising routine to achieve liver-targeted gene delivery by non-viral nanoparticles; and both gene carrier characteristics and mode of administration significantly influence gene delivery efficiency.