Associations among psychosis, mood, anxiety, and posttraumatic stress symptoms: A network analysis.

The associations among psychotic experiences (i.e., hallucinations and delusions), trauma exposure, and posttraumatic stress symptoms are complex and multidirectional. Using network analysis to understand how psychotic experiences and symptoms of posttraumatic stress disorder (PTSD) relate to one another may identify new interventional targets to treat comorbidity and its underlying pathological processes. This study aimed to use network analysis to examine the associations among psychotic experiences; negative symptoms of psychosis; and symptoms of PTSD, anxiety, and depression. In this population-based cohort study, 4,472 participants (36.7% male) were assessed for psychotic experiences, negative symptoms of psychosis, PTSD, anxiety, and depression at age 23 (M = 23.86 years, SD = 0.520) or 24 years (M = 24.03, SD = 0.848). Associations among symptoms were assessed via network analysis. Exploratory graph analysis identified three clusters of densely connected symptoms within the overall network: psychotic experiences; PTSD symptoms; and depressive and anxiety symptoms and negative symptoms of psychosis. Psychotic experiences had the strongest associations with other symptoms in the network, and symptoms of anxiety played a key role in bridging psychotic experiences, symptoms of PTSD, and depressive symptoms. Consistent with the stress reactivity and affective models for psychotic experiences, the results suggest that symptoms of anxiety and emotional distress (e.g., hyperarousal, panic) may have a key role in the development and maintenance of psychotic experiences and symptoms of PTSD. Targeting these symptoms may ameliorate symptom burden transdiagnostically.

Support needs and barriers to accessing support: Baseline results of a mixed-methods national survey of people bereaved during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is a mass bereavement event which has profoundly disrupted grief experiences. Understanding support needs and access to support among people bereaved at this time is crucial to ensuring appropriate bereavement support infrastructure. AIM: To investigate grief experiences, support needs and use of formal and informal bereavement support among people bereaved during the pandemic. DESIGN: Baseline results from a longitudinal survey. Support needs and experiences of accessing support are reported using descriptive statistics and thematic analysis of free-text data. SETTING/PARTICIPANTS: 711 adults bereaved in the UK between March and December 2020, recruited via media, social media, national associations and community/charitable organisations. RESULTS: High-level needs for emotional support were identified. Most participants had not sought support from bereavement services (59%, n = 422) or their General-Practitioner (60%, n = 428). Of participants who had sought such support, over half experienced difficulties accessing bereavement services (56%, n = 149)/General-Practitioner support (52%, n = 135). About 51% reported high/severe vulnerability in grief; among these, 74% were not accessing bereavement or mental-health services. Barriers included limited availability, lack of appropriate support, discomfort asking for help and not knowing how to access services. About 39% (n = 279) experienced difficulties getting support from family/friends, including relational challenges, little face-to-face contact and disrupted collective mourning. The perceived uniqueness of pandemic bereavement and wider societal strains exacerbated their isolation. CONCLUSIONS: People bereaved during the pandemic have high levels of support needs alongside difficulties accessing support. We recommend increased provision and tailoring of bereavement services, improved information on support options and social/educational initiatives to bolster informal support and ameliorate isolation.

Disturbed Sleep Connects Symptoms of Posttraumatic Stress Disorder and Somatization: A Network Analysis Approach.

Posttraumatic stress disorder (PTSD) and physical health problems, particularly somatic symptom disorder, are highly comorbid. Studies have only examined this co-occurrence at the disorder level rather than assessing the associations between specific symptoms. Using network analysis to identify symptoms that act as bridges between these disorders may allow for the development of interventions to specifically target this comorbidity. We examined the association between somatization and PTSD symptoms via network analysis. This included 349 trauma-exposed individuals recruited through the National Centre for Mental Health PTSD cohort who completed the Clinician-Administered PTSD Scale for DSM-5 and the Patient Health Questionnaire-15. A total of 215 (61.6%) individuals met the DSM-5 diagnostic criteria for PTSD. An exploratory graph analysis identified four clusters of densely connected symptoms within the overall network: PTSD, chronic pain, gastrointestinal issues, and more general somatic complaints. Sleep difficulties played a key role in bridging PTSD and somatic symptoms. Our network analysis demonstrates the distinct nature of PTSD and somatization symptoms, with this association connected by disturbed sleep.

Searching for information about stem cells online in an age of artificial intelligence: How should the stem cell community respond?

Patients and their families routinely use the Internet to learn about stem cell research. What they find, is increasingly influenced by ongoing changes in how information is filtered and presented online. This article reflects on recent developments in generative artificial intelligence and how the stem cell community should respond.

Mindfulness increases recall of self-threatening information.

Previous research has suggested that we tend to show impaired memory for self-threatening information, an effect known as mnemic neglect. Mnemic neglect is believed to be due to shallow processing or inhibition of self-threatening information. Mnemic neglect, however, could also be an example of experiential avoidance and mindfulness training has been demonstrated to counteract experiential avoidance. The current study was designed to negate experiential avoidance on a memory task via mindfulness training and attempt to increase recall of self-threatening information. Participants were exposed to a short intervention, either mindfulness or unfocused attention, before being instructed to read and later recall self-referent behaviors. The findings indicated that recall of self-threatening and other self-referent information was increased following the mindfulness but not unfocused attention intervention. The utility of mindfulness as a strategy for negating the experiential avoidance normally associated with self-threatening information and increasing memory performance are discussed.

Factors associated with the outcomes of a novel virtual reality therapy for military veterans with PTSD: Theory development using a mixed methods analysis.

BACKGROUND: Multi-modular motion-assisted memory desensitization and reconsolidation therapy (3MDR) is a new psychological intervention for people with post-traumatic stress disorder (PTSD). 3MDR is immersive, delivered in a virtual reality environment, and emphasises engagement, recollection and reprocessing. OBJECTIVE: Through a theory-driven examination of data relating to 10 out of 42 UK military veterans taking part in a trial of 3MDR, the principal objective was to explore the complex interrelationships between people, interventions and context and to investigate how factors within these domains interacted in specific outcome typologies. METHOD: Quantitative and qualitative data relating to 10 trial participants were derived from: researcher-assessed and self-report clinical measures; interviews; physiological recordings; words describing thoughts and feelings during therapy; and subjective unit of distress scores. Using a convergent mixed methods approach, data were tabulated using a person, intervention and context model. Participant summaries were grouped into outcome typologies, followed by an analysis of data convergence and divergence within each and an interpretation of identified patterns. RESULTS: Three outcome response typologies were identified: dramatic improvement, moderate improvement and minimal improvement. Within the person domain, factors associated with outcomes included walking capacity, commitment and ability to complete therapy, and levels of subjective distress. Within the intervention domain, factors associated with outcomes related to image selection and use, therapeutic alliance and orientations towards the tailoring of sessions. Within the context domain, factors associated with outcomes included reactions to the therapy environment. The patterning of secondary outcomes broadly corresponded with primary outcomes within each typology. Alongside patterned data differentiating aspects of the person, intervention and context domains, within the three response typologies data also existed where no obvious patterning was detected. CONCLUSIONS: The model developed here may have novel value in evaluating a range of personalised interventions, but further work is needed before confident assertions can be made of who is likely to benefit from 3MDR specifically.

Increased structural connectivity in high schizotypy.

The link between brain structural connectivity and schizotypy was explored in two healthy participant cohorts, collected at two different neuroimaging centres, comprising 140 and 115 participants, respectively. The participants completed the Schizotypal Personality Questionnaire (SPQ), through which their schizotypy scores were calculated. Diffusion-MRI data were used to perform tractography and to generate the structural brain networks of the participants. The edges of the networks were weighted with the inverse radial diffusivity. Graph theoretical metrics of the default mode, sensorimotor, visual, and auditory subnetworks were derived and their correlation coefficients with the schizotypy scores were calculated. To the best of our knowledge, this is the first time that graph theoretical measures of structural brain networks are investigated in relation to schizotypy. A positive correlation was found between the schizotypy score and the mean node degree and mean clustering coefficient of the sensorimotor and the default mode subnetworks. The nodes driving these correlations were the right postcentral gyrus, the left paracentral lobule, the right superior frontal gyrus, the left parahippocampal gyrus, and the bilateral precuneus, that is, nodes that exhibit compromised functional connectivity in schizophrenia. Implications for schizophrenia and schizotypy are discussed.

'It was brutal. It still is': a qualitative analysis of the challenges of bereavement during the COVID-19 pandemic reported in two national surveys.

Background: The COVID-19 pandemic has been a devastating, mass bereavement event characterised by high levels of disruption to end-of-life, grieving and coping processes. Quantitative evidence is emerging on the effects of the pandemic on grief outcomes, but rich qualitative evidence on the lived experiences of people bereaved during these times is lacking. Methods: We analysed qualitative data from two independent UK-wide online surveys to describe the experiences of 881 people bereaved during the pandemic. We analysed the data in two phases, conducting an inductive thematic analysis and then applying Stroebe and Schut's Dual Process Model (DPM) and concepts of loss-oriented and restoration-oriented coping (1999; 2010) as an analytic lens to further contextualise and interpret the data. Results: We identified six main themes: troubled deaths; mourning, memorialisation and death administration; mass bereavement, the media and the ongoing threat of the pandemic; grieving and coping; work and employment; and support from the health and social care system. Examples of loss-oriented stressors included being unable to visit and say goodbye at the end of life and restricted funeral and memorialisation practices. Associated reactions were feelings of guilt, anger, and problems accepting the death and beginning to grieve. Examples of restoration-oriented stressors and reactions were severely curtailed support-systems and social/recreational activities, which impacted people's ability to cope. Conclusion: Study results demonstrate the exceptionally difficult sets of experiences associated with pandemic bereavement, and the utility of the DPM for conceptualising these additional challenges and their impacts on grieving. Our analysis builds and expands on previous use of the DPM in explicating the impact of the pandemic on bereavement. We make recommendations for statutory, private and third sector organisations for improving the experiences of people bereaved during and following this and future pandemics.

The psychophysiological response during post-traumatic stress disorder treatment with modular motion-assisted memory desensitisation and reconsolidation (3MDR).

Background: Psychophysiological changes are part of post-traumatic stress disorder (PTSD) symptomatology and can signal emotional engagement during psychological treatment. Objectives: The aim of this study was to explore psychophysiological responses during multi-modular motion-assisted memory desensitization and reconsolidation (3MDR) therapy. Increased self-reported distress, substantially increased heart rate (HR) and breathing rate (BR) were expected at the start of therapy and predicted to improve over time. Since physical exercise demands during therapy were low, any large HR or BR responses were considered part of the psychophysiological response. Methods: This study used pooled data collected during a randomized controlled trial of 3MDR, which demonstrated significant improvement as measured by the Clinician Administered PTSD Scale. Whilst attending therapy, HR and BR data, subjective units of distress (SUD) score and phrases to describe feelings whilst exposed to trauma-related images were collected continuously from 37 UK male military veterans with PTSD. Results: HR and BR were significantly increased throughout all sessions (p < .01 for both). Whilst HR was raised slightly remaining on average below 100 beats/minute, BR was increased substantially with average values between 40 and 50 breaths/minute. SUD scores were very high during therapy which concurred with the many negative feelings experienced during therapy sessions. Across the course of the treatment, SUD scores (p < .01) and negative feelings were reduced (p < .001), and positive feelings have increased (p < .01) significantly, reflecting improvements in clinicians assessed PTSD symptoms. Across therapy sessions, HR (p = .888) and BR (p = .466) responses did not change. Conclusions: The strong psychophysiological response alongside high levels of self-reported distress and negative feelings is interpreted as high emotional engagement during therapy. A novel finding was the very significant BR increase throughout recorded sessions. Future PTSD research should include BR response to therapy and explore breathing control as a treatment target.

Antecedentes: Los cambios psicofisiológicos son parte de la sintomatología del trastorno de estrés postraumático (TEPT) y pueden indicar un compromiso emocional durante el tratamiento psicológico.Objetivos: El objetivo de este estudio fue explorar las respuestas psicofisiológicas durante la terapia multimodular de desensibilización y reconsolidación de la memoria asistida por movimiento (3MDR). Se esperaba un aumento de la angustia autoinformada, un aumento sustancial de la frecuencia cardíaca (FC) y la frecuencia respiratoria (FR) al inicio de la terapia y se predijo que mejoraría con el tiempo. Dado que las demandas del ejercicio físico durante la terapia fueron bajas, cualquier respuesta grande de FC o FR se consideró parte de la respuesta psicofisiológica.Métodos: Este estudio utilizó datos agrupados recopilados durante un ensayo controlado aleatorio de 3MDR, que demostró una mejora significativa según lo medido por la Entrevista de TEPT Administrada por el Médico. Mientras asistían a la terapia, se recopilaron continuamente datos de FC y FR, puntuación de las unidades subjetivas de angustia (SUD en su sigla en inglés), y frases para describir los sentimientos mientras estaban expuestos a imágenes relacionadas con el trauma; de 37 veteranos militares masculinos del Reino Unido con TEPT.Resultados: FC y FR aumentaron significativamente a lo largo de todas las sesiones (p < .01 para ambas). Mientras que la FC se elevó ligeramente permaneciendo en promedio por debajo de 100 latidos por minuto, la FR aumentó sustancialmente con valores promedio entre 40 y 50 respiraciones por minuto. Los puntajes de SUD fueron muy altos durante la terapia, lo que coincidió con los muchos sentimientos negativos experimentados durante las sesiones de terapia. A lo largo del tratamiento, las puntuaciones SUD (p < .01) y los sentimientos negativos se redujeron (p < .001), y los sentimientos positivos aumentaron (p < .01) de manera significativa, lo que refleja mejoras en los síntomas de TEPT evaluados por el médico. A lo largo de las sesiones de terapia, las respuestas de FC (p = .888) y FR (p = .466) no cambiaron.Conclusiones: La fuerte respuesta psicofisiológica junto con los altos niveles de angustia autoinformada y sentimientos negativos se interpreta como un alto compromiso emocional durante la terapia. Un hallazgo novedoso fue el aumento muy significativo de FR durante las sesiones grabadas. La investigación futura del TEPT debería incluir la respuesta de la FR a la terapia y explorar el control de la respiración como un objetivo del tratamiento.

The reconsolidation using rewind study (RETURN): trial protocol.

Background: An increasing body of research highlights reconsolidation-based therapies as emerging treatments for post-traumatic stress disorder (PTSD). The Rewind Technique is a non-pharmacological reconsolidation-based therapy with promising early results, which now requires evaluation through an RCT. Objectives: This is a preliminary efficacy RCT to determine if the Rewind Technique is likely to be a good candidate to test against usual care in a future pragmatic efficacy RCT. Methods: 40 participants will be randomised to receive either the Rewind Technique immediately, or after an 8 week wait. The primary outcome will be PTSD symptom severity as measured by the Clinician-Administered PTSD Scale for DSM5 (CAPS-5) at 8 and 16 weeks post-randomisation. Secondary outcome measures include the PTSD Checklist (PCL-5), International Trauma Questionnaire (ITQ), Patient Health Questionnaire (PHQ-9), the General Anxiety Disorder-7 (GAD-7), Insomnia Severity Index, the Euro-Qol-5D (EQ5D-5 L), the prominence of re-experiencing specific symptoms (CAPS-5) and an intervention acceptability questionnaire to measure tolerability of the intervention. Conclusions: This study will be the first RCT to assess the Rewind Technique. Using a cross-over methodology we hope to rigorously assess the efficacy and tolerability of Rewind using pragmatic inclusion criteria. Potential challenges include participant recruitment and retention. Trial registration: ISRCTN91345822.

Antecedentes: Un creciente cuerpo de investigación destaca las terapias basadas en la reconsolidación como tratamientos emergentes para el trastorno de estrés postraumático (TEPT). La Técnica de Rebobinado es una terapia no farmacológica basada en la reconsolidación con resultados tempranos prometedores, que ahora requiere evaluación a través de un ECA.Objetivos: Este es un ECA preliminar de eficacia para determinar si es probable que la técnica de rebobinado sea una candidata adecuada para probar en comparación con el cuidado habitual en un futuro ECA de eficacia pragmática.Método: 40 participantes serán asignados al azar para recibir la técnica de rebobinado inmediatamente o después de una espera de 8 semanas. El resultado primario será la gravedad de los síntomas del TEPT según lo medido por la Escala de TEPT administrada por el médico para DSM5 (CAPS-5 en su sigla en inglés) a las 8 y 16 semanas posteriores a la aleatorización. Las medidas de resultados secundarios incluyen la Lista de Verificación de TEPT (PCL-5 en su sigla en inglés), el Cuestionario Internacional de Trauma (ITQ en su sigla en inglés), el Cuestionario de Salud del Paciente (PHQ-9 en su sigla en inglés), el Trastorno de Ansiedad General-7 (GAD-7 en su sigla en inglés), el Índice de Gravedad del Insomnio, el Euro-Qol- 5D (EQ5D-5L en su sigla en inglés), la prominencia de re-experimentar los síntomas específicos (CAPS-5) y un cuestionario de aceptabilidad de la intervención para medir la tolerabilidad de la intervención.Conclusiones: Este estudio será el primer ECA para evaluar la Técnica de Rebobinado. Utilizando una metodología cruzada, esperamos evaluar rigurosamente la eficacia y tolerabilidad del Rebobinado utilizando criterios de inclusión pragmáticos. Los desafíos potenciales incluyen el reclutamiento y la retención de los participantes.Registro de prueba: ISRCTN91345822.

A systematic review of factors associated with outcome of psychological treatments for post-traumatic stress disorder.

OBJECTIVE: Psychological interventions for post-traumatic stress disorder (PTSD) are not always effective and can leave some individuals with enduring symptoms. Little is known about factors that are associated with better or worse treatment outcome. Our objective was to address this gap. METHOD: We undertook a systematic review following Cochrane Collaboration Guidelines. We included 126 randomized controlled trials (RCTs) of psychological interventions for PTSD and examined factors that were associated with treatment outcome, in terms of severity of PTSD symptoms post-treatment, and recovery or remission. RESULTS: Associations were neither consistent nor strong. Two factors were associated with smaller reductions in severity of PTSD symptoms post-treatment: comorbid diagnosis of depression, and higher PTSD symptom severity at baseline assessment. Higher education, adherence to homework and experience of a more recent trauma were associated with better treatment outcome. CONCLUSION: Identifying and understanding why certain factors are associated with treatment outcome is vital to determine which individuals are most likely to benefit from particular treatments and to develop more effective treatments in the future. There is an urgent need for consistent and standardized reporting of factors associated with treatment outcome in all clinical trials.

Objetivo: Las intervenciones psicológicas para el trastorno de estrés postraumático (TEPT) no son siempre efectivas y pueden dejar a algunos individuos con síntomas permanentes. Se sabe poco acerca de los factores que se han asociado con mejores o peores resultados del tratamiento. Nuestro objetivo fue abordar este vacío.Método: Llevamos a cabo una revisión sistemática siguiendo las Pautas de Colaboración de Cochrane. Incluimos 126 ensayos controlados aleatorizados (RCTs por sus siglas en ingles) de intervenciones psicológicas para TEPT y examinamos los factores que estuvieron asociados con el resultado del tratamiento, en términos de severidad de síntomas de TEPT postratamiento, y recuperación o remisión.Resultados: Las asociaciones no fueron ni consistentes ni fuertes. Dos factores se asociaron con reducciones más pequeñas en la severidad de síntomas de TEPT postratamiento: el diagnóstico comórbido de depresión y mayor severidad de los síntomas de TEPT en la evaluación inicial. Los niveles de educación más alta, la adherencia a las tareas y la experiencia de un trauma más reciente se asociaron con mejores resultados del tratamiento.Conclusión: La identificación y comprensión de por qué ciertos factores se asociaron con los resultados del tratamiento es vital para determinar qué individuos se podrían beneficiar de determinados tratamientos y desarrollar en el futuro, tratamientos más efectivos. Existe una necesidad imperiosa de un reporte consistente y estandarizado de los factores asociados con los resultados de los tratamientos en todos los estudios clínicos.

Acceptability of internet-based cognitive behavioural therapy (i-CBT) for post-traumatic stress disorder (PTSD): a systematic review.

Background: Internet-delivered Cognitive Behavioural Therapy (i-CBT) offers potential as an alternative, accessible, clinically and cost-effective treatment for post-traumatic stress disorder (PTSD), but little is known about its acceptability. Objective: To review the available evidence to understand the acceptability of i-CBT for PTSD. Method: We undertook a mixed-methods systematic review according to Cochrane Collaboration Guidelines, of randomised controlled trials (RCTs) of i-CBT for adults with PTSD. We examined included studies for measures of acceptability, and possible proxy indicators of acceptability, including dropout rates, which were meta-analysed as risk ratios (RRs). Results: Ten studies with 720 participants were included. We found i-CBT to be acceptable according to specific acceptability measures, and suggestions for acceptability according to some proxy measures of i-CBT programme usage. There was, however, evidence of greater dropout from i-CBT than waitlist (RR 1.39, CI 1.03-1.88; 8 studies; participants = 585) and no evidence of a difference in dropout between i-CBT and i-non-CBT (RR 2.14, CI 0.97-4.73; participants = 132; 2 studies). Conclusion: i-CBT appears a potentially acceptable intervention for adults with PTSD. We identified clinical and research questions, including the status of proxy indicators, and call for standardised, consistent treatment acceptability measurement.

Antecedentes: La terapia cognitivo conductual entregada a través de internet (i-TCC) ofrece potencial como un tratamiento alternativo accesible, clínicamente eficaz y costo-efectivo para el trastorno de Estrés Postraumático (TEPT), pero se conoce poco acerca de su aceptabilidad.Objetivo: Revisar la evidencia disponible para comprender la aceptabilidad de i-TCC para TEPT.Método: Realizamos una revisión sistemática de métodos mixtos de acuerdo a las Guías de la Colaboración Cochrane, de estudios aleatorizados controlados (RCT por sus sigla en inglés) de i-TCC para adultos con TEPT. Examinamos los estudios incluídos buscando medidas de aceptabilidad, y posibles indicadores indirectos de aceptabilidad, incluyendo tasas de abandono, los que fueron meta-analizados como Riesgo Relativo (RR).Resultados: Diez estudios con 720 participantes fueron incluídos. Encontramos que i-TCC era aceptable de acuerdo a medidas específicas de aceptabilidad y sugerencias de su aceptabilidad de acuerdo a algunas medidas indirectas del uso del programa de i-TCC. Hubo, sin embargo, evidencia de un mayor abandono desde i-TCC que Lista de Espera (RR 1.39, IC 1.03-1.88; 8 estudios, participantes = 585) y no hubo diferencia en abandono entre i-TCC y otras intervenciones a través de internet no TCC (RR 2.14, IC 0.97-4.73; participantes = 132; 2 estudios).Conclusión: i-TCC aparece como una intervención potencialmente aceptable para adultos con TEPT. Identificamos preguntas clínicas y de investigación, incluyendo el estado de los indicadores indirectos, y la necesidad de medidas de aceptabilidad estandarizadas y consistentes.

Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer's disease.

We studied resting-state oscillatory connectivity using magnetoencephalography in healthy young humans (N = 183) genotyped for APOE-ɛ4, the greatest genetic risk for Alzheimer's disease (AD). Connectivity across frequencies, but most prevalent in alpha/beta, was increased in APOE-ɛ4 in a set of mostly right-hemisphere connections, including lateral parietal and precuneus regions of the Default Mode Network. Similar regions also demonstrated hyperactivity, but only in gamma (40-160 Hz). In a separate study of AD patients, hypoconnectivity was seen in an extended bilateral network that partially overlapped with the hyperconnected regions seen in young APOE-ɛ4 carriers. Using machine-learning, AD patients could be distinguished from elderly controls with reasonable sensitivity and specificity, while young APOE-e4 carriers could also be distinguished from their controls with above chance performance. These results support theories of initial hyperconnectivity driving eventual profound disconnection in AD and suggest that this is present decades before the onset of AD symptomology.

Targeting the affective brain-a randomized controlled trial of real-time fMRI neurofeedback in patients with depression.

Functional magnetic resonance imaging neurofeedback (fMRI-NF) training of areas involved in emotion processing can reduce depressive symptoms by over 40% on the Hamilton Depression Rating Scale (HDRS). However, it remains unclear if this efficacy is specific to feedback from emotion-regulating regions. We tested in a single-blind, randomized, controlled trial if upregulation of emotion areas (NFE) yields superior efficacy compared to upregulation of a control region activated by visual scenes (NFS). Forty-three moderately to severely depressed medicated patients were randomly assigned to five sessions augmentation treatment of either NFE or NFS training. At primary outcome (week 12) no significant group mean HDRS difference was found (B = -0.415 [95% CI -4.847 to 4.016], p = 0.848) for the 32 completers (16 per group). However, across groups depressive symptoms decreased by 43%, and 38% of patients remitted. These improvements lasted until follow-up (week 18). Both groups upregulated target regions to a similar extent. Further, clinical improvement was correlated with an increase in self-efficacy scores. However, the interpretation of clinical improvements remains limited due to lack of a sham-control group. We thus surveyed effects reported for accepted augmentation therapies in depression. Data indicated that our findings exceed expected regression to the mean and placebo effects that have been reported for drug trials and other sham-controlled high-technology interventions. Taken together, we suggest that the experience of successful self-regulation during fMRI-NF training may be therapeutic. We conclude that if fMRI-NF is effective for depression, self-regulation training of higher visual areas may provide an effective alternative.