Neurofeedback and Affect Regulation Circuitry in Depressed and Healthy Adolescents.

Neurodevelopmental psychopathology seeks to understand higher-order emotion regulation circuitry to develop new therapies for adolescents with depression. Depressed (N = 34) and healthy youth (N = 19) completed neurofeedback (NF) training and exhibited increased bilateral amygdala and hippocampus activity in the region of interest (ROI) analyses by recalling positive autobiographical memories. We tested factors supportive of the engagement of emotion regulation's neural areas during NF (i.e., parental support, medication, and gender effects upon anterior cingulate cortex (ACC) engagement). Whole-brain analyses yielded effects of NF vs. control condition and effects of diagnosis. Youth showed higher amygdala and hippocampus (AMYHIPPO) activity during the NF vs. control condition, particularly in the left hippocampus. ACC's activity was also higher during NF vs. control. Higher average ACC activity was linked to better parental support, absent depression, female gender, and absent medication. Control youth showed higher average AMYHIPPO and ACC activity throughout the task and a faster decline in activity vs. depressed youths. Whole-brain level analyses showed higher activity in the frontotemporal network during the NF vs. control conditions, suggesting targeting their connectivity in future neurofeedback trials.

Self-compassion and neural activity during self-appraisals in depressed and healthy adolescents.

BACKGROUND: Depression is one of the most concerning mental disorders in youth. Because atypical excessive neural activity during self-referential processing is often implicated in depression, identifying psychological factors that link to lower depression and less excessive neural activity during self-referential processing is critical for treatment development. This study examined the relationship between self-compassion - a protective factor of youth depression - and neural activity during self-appraisals, a well-established experimental paradigm for studying self-referential processing, and their associations with depression severity in depressed and healthy youth. METHODS: The sample consisted of 115 youth (79 met the clinical diagnosis of depression; 36 were matched healthy controls) aged from 11 to 17 years (68 females). Self-compassion and depression severity were measured with self-reported scales. In the scanner, participants were asked to judge whether the phrases they heard described them from four perspectives (self, mother, classmate, and best friend). RESULTS: Higher self-compassion was associated with lower PCC/precuneus activity especially during negatively-valenced self-appraisals and explained its association with reduced depression severity. In depressed youth, higher self-compassion was associated with lower superior temporal gyrus/operculum/postcentral gyrus/insula activity especially during positively-valenced self-appraisals. In healthy youth, higher self-compassion was associated with higher activity in these regions. CONCLUSIONS: Self-compassion was associated with less excessive experiential immersion and/or autobiographical memory retrieval during negative self-appraisals. Neural stimulation interventions targeting PCC/precuneus activity during negative self-appraisals combined with behavioral interventions targeting self-compassion could be a promising approach to youth depression treatment.

Medial Prefrontal Cortex Activity to Reward Outcome Moderates the Association Between Victimization Due to Sexual Orientation and Depression in Youth.

BACKGROUND: Sexual minority youth (SMY) are 3 times more likely to experience depression than heterosexual peers. Minority stress theory posits that this association is explained by sexual orientation victimization, which acts as a stressor to impact depression. For those vulnerable to the effects of stress, victimization may worsen depression by altering activity in neural reward systems. This study examines whether neural reward systems moderate the influence of sexual orientation victimization, a common and distressing experience in SMY, on depression. METHODS: A total of 81 participants ages 15 to 22 years (41% SMY, 52% marginalized race) reported sexual orientation victimization, depression severity, and anhedonia severity, and underwent a monetary reward functional magnetic resonance imaging task. Significant activation to reward > neutral outcome (pfamilywise error < .05) was determined within a meta-analytically derived Neurosynth reward mask. A univariate linear model examined the impact of reward activation and identity on victimization-depression relationships. RESULTS: SMY reported higher depression (p < .001), anhedonia (p = .03), and orientation victimization (p < .001) than heterosexual youth. The bilateral ventral striatum, medial prefrontal cortex (mPFC), anterior cingulate cortex, and right orbitofrontal cortex were significantly active to reward. mPFC activation moderated associations between sexual orientation victimization and depression (p = .03), with higher depression severity observed in those with a combination of higher mPFC activation and greater orientation victimization. CONCLUSIONS: Sexual orientation victimization was related to depression but only in the context of higher mPFC activation, a pattern observed in depressed youth. These novel results provide evidence for neural reward sensitivity as a vulnerability factor for depression in SMY, suggesting mechanisms for disparities, and are a first step toward a clinical neuroscience understanding of minority stress in SMY.

Neural Activity Associated with Symptoms Change in Depressed Adolescents following Self-Processing Neurofeedback.

Adolescent depression is prevalent, debilitating, and associated with chronic lifetime mental health disorders. Understanding the neurobiology of depression is critical to developing novel treatments. We tested a neurofeedback protocol targeting emotional regulation and self-processing circuitry and examined brain activity associated with reduced symptom severity, as measured through self-report questionnaires, four hours after neurofeedback. Depressed (n = 34) and healthy (n = 19) adolescents participated in (i) a brief neurofeedback task that involves simultaneously viewing their own happy face, recalling a positive autobiographical memory, and increasing amygdala-hippocampal activity; (ii) a self- vs. other- face recognition task with happy, neutral, and sad facial expressions before and after the neurofeedback. In depressed youth, reduced depression after neurofeedback was associated with increased self-referential and visual areas' activity during neurofeedback, specifically, increased activity in the cuneus, precuneus and parietal lobe. Reduced depression was also associated with increased activation of emotional regulation and cross-modal areas during a self-recognition task. These areas included the cerebellum, middle temporal gyrus, superior temporal gyrus, and supramarginal gyrus. However, decreased rumination was linked to decreased precuneus, angular and temporal gyri activity during neurofeedback. These results tentatively suggest that neurofeedback may induce short-term neurobiological changes in the self-referential and emotional regulation networks associated with reduced symptom severity among depressed adolescents.

Neural substrates of rewarding and punishing self representations in depressed suicide-attempting adolescents.

Adolescence is a period of plasticity in neural substrates underpinning self-processing. Such substrates are worth studying in depressed youth at risks for suicide because altered neurobiology of self-processing might partially explain differences between suicide attempting youth versus youth who contemplate but do not attempt suicide. Understanding altered substrates of self-processing among depressed adolescents with suicide attempts is critical for developing targeted prevention and treatment. Healthy youth (N = 40), youth with depression and low (N = 33) or high suicide ideation (N = 28), and youth with depression and past suicide attempt (N = 28) heard positive or negative self-descriptors during fMRI and evaluated them from their own, their mother's, classmates', and best friend's perspectives. Lower bilateral caudate activity during positive self-processing distinguished suicide attempting adolescents from all other youth. Higher bilateral caudate activity during negatively valenced self-processing tended to distinguish youth with depression. Blunted reward circuitry during positive vs. negative self-related material tended to distinguish suicide attempting youth, reflecting potentially enhanced behavioral preparedness for punishing vs. rewarding self-relevant cues.

Self-compassion and dorsolateral prefrontal cortex activity during sad self-face recognition in depressed adolescents.

BACKGROUND: Given the prevalence of adolescent depression and the modest effects of current treatments, research ought to inform development of effective intervention strategies. Self-compassion is inversely associated with depression, and self-compassion interventions have demonstrated promising effects on reducing depression. However, little is known about the neural mechanisms underlying that relationship. Maladaptive self-processing is a characteristic of depression that contributes to the onset and chronicity of depression. Because our own face is an automatic and direct cue for self-processing, this study investigated whether self-compassion was associated with neural responses during sad v. neutral self-face recognition and explore their relationship with depression severity in depressed adolescents and healthy controls (HCs). METHODS: During functional magnetic resonance imaging, 81 depressed youth and 37 HCs were instructed to identify whether morphed self or other faces with sad, happy, or neutral expressions resembled their own. RESULTS: Self-compassion correlated negatively with activity during sad v. neutral self-face recognition in the dorsal anterior cingulate cortex in the total sample, and in the right posterior cingulate cortex/precuneus in HCs, respectively. In depressed adolescents, higher self-compassion correlated with lower activity during sad v. neutral self-face recognition in the right dorsolateral prefrontal cortex (DLPFC), implying that less cognitive effort might be needed to avoid dwelling on sad self-faces and/or regulate negative affect induced by them. Moreover, higher self-compassion mediated the relationship between lower DLPFC activity and reduced depression severity. CONCLUSIONS: Our findings imply that DLPFC activity might be a biological marker of a successful self-compassion intervention as potential treatment for adolescent depression.

Penalized model-based clustering of fMRI data.

Functional magnetic resonance imaging (fMRI) data have become increasingly available and are useful for describing functional connectivity (FC), the relatedness of neuronal activity in regions of the brain. This FC of the brain provides insight into certain neurodegenerative diseases and psychiatric disorders, and thus is of clinical importance. To help inform physicians regarding patient diagnoses, unsupervised clustering of subjects based on FC is desired, allowing the data to inform us of groupings of patients based on shared features of connectivity. Since heterogeneity in FC is present even between patients within the same group, it is important to allow subject-level differences in connectivity, while still pooling information across patients within each group to describe group-level FC. To this end, we propose a random covariance clustering model (RCCM) to concurrently cluster subjects based on their FC networks, estimate the unique FC networks of each subject, and to infer shared network features. Although current methods exist for estimating FC or clustering subjects using fMRI data, our novel contribution is to cluster or group subjects based on similar FC of the brain while simultaneously providing group- and subject-level FC network estimates. The competitive performance of RCCM relative to other methods is demonstrated through simulations in various settings, achieving both improved clustering of subjects and estimation of FC networks. Utility of the proposed method is demonstrated with application to a resting-state fMRI data set collected on 43 healthy controls and 61 participants diagnosed with schizophrenia.

The impact of child abuse on the neurobiology of self-processing in depressed adolescents.

Child abuse is linked to lifetime psychopathology including abnormal self-processing. Given self-processing maturation in adolescence, we tested duration, presence, and abuse accumulation's impact upon self-processing neurobiology among depressed youth with (N = 54) and without an abuse history (N = 40). Youth evaluated positive and negative self-descriptors across four points of view in the scanner. Regression analyses showed that longer abuse duration (in days) was associated with lower activity in inferior temporal (e.g. insula, fusiform & parahippocampus), striatal, cerebellar and midbrain structures when processing negative self-descriptors with the least activity in youth exposed to 6+ abuse years. Abuse presence vs. absence was linked to higher neural activity. However, youth exposed to a single abuse instance to 3 years of abuse might drive that relative neural hyperactivity. Results support: 1) the toxic stress model of blunted overall neuro-reactivity underpinning emotion, sensorimotor gating, and social cognition during negative stimuli as an adaptation to pervasively toxic environments and 2) the differential impact of acute versus chronic stress upon neurophysiological indices. Finally, child abuse duration might impact these ancillary and higher socioemotional processes differently among depressed youth primarily for negative but not positive self-processing.

Asociación entre los factores del proveedor de salud y el número de atenciones prenatales en las usuarias de un Hospital Peruano / Association Between Health Care Provider Factors And The Number Of Prenatal Visits In Peruvian Hospital Users

Introducción: La atención de la salud materno infantil es una prioridad para los servicios de salud. Objetivo: Identificar la asociación entre los factores del proveedor de salud y el número de atenciones prenatales en las usuarias del Hospital Carlos Lanfranco La Hoz atendidas en el año 2019. Métodos. Estudio cuantitativo, relacional y observacional. Conformaron la muestra 342 usuarias gestantes atendidas de enero a diciembre del 2019, las cuales fueron seleccionadas mediante un muestreo probabilístico sistemático. Para el análisis estadístico se usó una estadística descriptiva mediante la distribución de frecuencias absolutas y relativas y una estadística inferencial mediante el uso de la regresión de Poisson. Resultados: Predominó la edad de 18 a 35 años (74%), el grado de instrucción secundaria (62,9%), el estado civil conviviente (71,1%) y el seguro integral de salud (92,7%). Los factores asociados al número de atenciones prenatales fueron el factor técnico científico-recibir orientación sobre los resultados de análisis en la atención prenatal" (p <0,001; expB=1,2 IC95% 1,10­1,39), y que el médico u obstetra le recomiende medicamentos en su consulta prenatal (p=0,003; expB=1,2 IC95% 1,05­1,27)-: y como factor humano-médico u obstetra la llama por su nombre durante la consulta prenatal (p<0,001; expB=1,5 IC95% 1,19­1,77)-. Conclusión: Existe asociación entre los factores del proveedor de salud y el número de atenciones prenatales en las usuarias del Hospital Carlos Lanfranco La Hoz atendidas en el año 2019.

Introducción: Maternal and child health care is a priority for health services, it is essential that all pregnant women comply with the necessary amount of prenatal care for proper supervision of pregnancy and the detection of possible warning signs or complications in a timely manner. Objective: To identify the association between the health provider factors and the number of prenatal care in the users of the Carlos Lanfranco La Hoz hospital attended in 2019. Methods: quantitative, relational and non-experimental design study. 342 pregnant users attended from January to December 2019, who were selected through a systematic probability sampling. For the statistical analysis, a descriptive statistic was used through the distribution of absolute and relative frequencies and an inferential statistic through the use of Poisson regression. Results: The age from 18 to 35 years (74%) predominated, the degree of secondary instruction (62.9%), the cohabiting marital status (71.1%) and the comprehensive health insurance (92.7%). The factors associated with the number of prenatal care were, as a scientific technical factor, receiving guidance on the results of analysis in prenatal care "(p = 0.000; expB = 1.2 95% CI 1.10­1.39), and the doctor or obstetrician if recommended medications in their prenatal consultation (p = 0.003; expB = 1.2 95% CI 1.05-1.27); As a human factor, the doctor or obstetrician calls her by name during the prenatal visit (p = 0.000; expB = 1.5 95% CI 1.19­1.77). Conclusion: There is an association between the health provider factors and the number of prenatal care in the users of the Carlos Lanfranco La Hoz Hospital attended in 2019.

A random covariance model for bi-level graphical modeling with application to resting-state fMRI data.

We consider a novel problem, bi-level graphical modeling, in which multiple individual graphical models can be considered as variants of a common group-level graphical model and inference of both the group- and individual-level graphical models is of interest. Such a problem arises from many applications, including multi-subject neuro-imaging and genomics data analysis. We propose a novel and efficient statistical method, the random covariance model, to learn the group- and individual-level graphical models simultaneously. The proposed method can be nicely interpreted as a random covariance model that mimics the random effects model for mean structures in linear regression. It accounts for similarity between individual graphical models, identifies group-level connections that are shared by individuals, and simultaneously infers multiple individual-level networks. Compared to existing multiple graphical modeling methods that only focus on individual-level graphical modeling, our model learns the group-level structure underlying the multiple individual graphical models and enjoys computational efficiency that is particularly attractive for practical use. We further define a measure of degrees-of-freedom for the complexity of the model useful for model selection. We demonstrate the asymptotic properties of our method and show its finite-sample performance through simulation studies. Finally, we apply the method to our motivating clinical data, a multi-subject resting-state functional magnetic resonance imaging dataset collected from participants diagnosed with schizophrenia, identifying both individual- and group-level graphical models of functional connectivity.

Amygdala Circuitry During Neurofeedback Training and Symptoms' Change in Adolescents With Varying Depression.

Typical adolescents have increased limbic engagement unchecked by regulatory medial prefrontal cortex (PFC) activity as well as heightened self-focus. The resulting emotion dysregulation and self-focused rumination make adolescents more susceptible to depression and suicide attempts. Heightened self-focus converges with mental illness among depressed adolescents, who deploy exaggerated attention to negative self-relevant stimuli and neglect positive ones as part of depression's phenomenology. This results in rigid negative self-representations during an identity formative period with potential lifetime repercussions. Current empirically supported treatments fail to allay recurrent depression. Evidence-based interventions for illnesses linked to suicide ideation and attempts (e.g., depression) underperform across the lifespan. This could be because current treatments are not successful in altering pervasive negative self-representations and affect dysregulation, which is known to be a risk factor of chronic depression. This study departs from the premise that increasing positive self-processing might be protective against chronic depression particularly during adolescence. The present research is a novel investigation of neurofeedback as a potential treatment alternative for adolescent depression. To enhance positive self-processing, we used the happy self-face as a cue to initiate neurofeedback from the bilateral amygdala and hippocampus and adolescents attempted to upregulate that limbic activity through the recall of positive autobiographical memories. We identified limbic functional circuitry engaged during neurofeedback and links to short-term symptoms' change in depression and rumination. We found that depressed youth showed greater right amygdala to right frontocortical connectivity and lower left amygdala to right frontocortical connectivity compared to healthy controls during neurofeedback vs. control conditions. Depressed youth also showed significant symptom reduction. Connectivity between the right amygdala and frontocortical regions was positively correlated with rumination and depression change, but connectivity between frontocortical regions and the left amygdala was negatively correlated with depression change. The results suggest that depressed youth might engage implicit emotion regulation circuitry while healthy youth recruit explicit emotion regulation circuits during neurofeedback. Our findings support a compensatory approach (i.e., target the right amygdala) during future neurofeedback interventions in depressed youth. Future work ought to include a placebo condition or group.

Neurofeedback and neuroplasticity of visual self-processing in depressed and healthy adolescents: A preliminary study.

Adolescence is a neuroplastic period for self-processing and emotion regulation transformations, that if derailed, are linked to persistent depression. Neural mechanisms of adolescent self-processing and emotion regulation ought to be targeted via new treatments, given moderate effectiveness of current interventions. Thus, we implemented a novel neurofeedback protocol in adolescents to test the engagement of circuits sub-serving self-processing and emotion regulation. METHODS: Depressed (n = 34) and healthy (n = 19) adolescents underwent neurofeedback training using a novel task. They saw their happy face as a cue to recall positive memories and increased displayed amygdala and hippocampus activity. The control condition was counting-backwards while viewing another happy face. A self vs. other face recognition task was administered before and after neurofeedback training. RESULTS: Adolescents showed higher frontotemporal activity during neurofeedback and higher amygdala and hippocampus and hippocampi activity in time series and region of interest analyses respectively. Before neurofeedback there was higher saliency network engagement for self-face recognition, but that network engagement was lower after neurofeedback. Depressed youth exhibited higher fusiform, inferior parietal lobule and cuneus activity during neurofeedback, but controls appeared to increase amygdala and hippocampus activity faster compared to depressed adolescents. CONCLUSIONS: Neurofeedback recruited frontotemporal cortices that support social cognition and emotion regulation. Amygdala and hippocampus engagement via neurofeedback appears to change limbic-frontotemporal networks during self-face recognition. A placebo group or condition and contrasting amygdala and hippocampus, hippocampi or right amygdala versus frontal loci of neurofeedback, e.g. dorsal anterior cingulate cortex, with longer duration of neurofeedback training will elucidate dosage and loci of neurofeedback in adolescents.

Adolescent suicide attempts and ideation are linked to brain function during peer interactions.

Understanding the neural correlates of social interaction among depressed adolescents with suicidal tendencies might help personalize treatment. We tested whether brain function during social interaction is disrupted for depressed adolescents with (1) high suicide ideation and (2) recent attempts. Depressed adolescents with high suicide ideation, including attempters (n = 45;HS) or low suicide ideation (n = 42;LS), and healthy adolescents (n = 39;HC), completed a version of the Cyberball peer interaction task during an fMRI scan. Groups were compared on brain activity during peer exclusion and inclusion versus a non-social condition. During peer exclusion and inclusion, HS youth showed significantly lower activity in precentral and postcentral gyrus, superior temporal gyrus, medial frontal gyrus, insula, and putamen compared to LS youth; and significantly reduced activity in caudate and anterior cingulate cortex compared to HC youth. In a second analysis, suicide attempters (n = 26;SA) were compared to other groups. SA adolescents showed significantly higher activity in ACC and superior and middle frontal gyrus than all other groups. Brain activity was significantly correlated with negative emotionality, social functioning, and cognitive control. Conclusions: Adolescent suicide ideation and attempts were linked to altered neural function during positive and negative peer interactions. We discuss the implications of these findings for suicide prevention efforts.

Amygdala Functional Connectivity During Self-Face Processing in Depressed Adolescents With Recent Suicide Attempt.

OBJECTIVE: Suicide is the second leading cause of death among adolescents; however, objective biomarkers of suicide risk are lacking. Aberrant self-face amygdala activity is associated with suicide ideation, and its connectivity with neural regions that enable self-processing (eg medial prefrontal cortex) may be a suicide risk factor. METHOD: Adolescents (aged 11-17 years; N = 120) were sorted into four groups: healthy controls (HC), depressed individuals with low suicide ideation (LS), depressed individuals with high suicide ideation (HS), and depressed suicide attempters (SA). Youth completed an emotional (Happy, Sad, Neutral) self-face recognition task in the scanner. Bilateral amygdala task-dependent functional connectivity was determined with psychophysiological interaction analysis. Connectivity was compared across groups and within Self versus Other faces across emotions and hemispheres. Voxelwise results were thresholded (p < .005, uncorrected) and corrected for multiple comparisons (p < .05, familywise error). RESULTS: Both HS and SA displayed greater amygdala connectivity with the dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and precuneus, compared to LS, who, in turn, showed greater connectivity than HC. Greater left amygdala-rostral anterior cingulate cortex (rACC) connectivity was observed in SA compared to all other groups, whereas right amygdala-rACC connectivity was greater in HS versus LS and HC. CONCLUSION: Greater connectivity between amygdala and other regions implicated in self-face processing differentiated suicide ideation and suicide attempt groups. A dose-dependent response showed that greater rACC-left amygdala connectivity during self-face processing was associated with a recent suicide attempt, but that a greater rACC-right amygdala connectivity was associated with suicide ideation.

Feeling left out: depressed adolescents may atypically recruit emotional salience and regulation networks during social exclusion.

Depression is associated with negative attention and attribution biases and maladaptive emotion responsivity and regulation, which adversely impact self-evaluations and interpersonal relationships. Using functional magnetic resonance imaging, we investigated the neural substrates of these impairments. We compared neural activity recruited by 126 clinically depressed and healthy adolescents (ages 11-17 years) during social exclusion (Exclusion > Inclusion) using Cyberball. Results revealed significant interaction effects within left anterior insula (AI)/inferior frontal gyrus and left middle temporal gyrus. Insula hyperresponsivity was associated with peer exclusion for depressed adolescents but peer inclusion for healthy adolescents. In additional, healthy adolescents recruited greater lateral temporal activity during peer exclusion. Complementary effect size analyses within independent parcellations offered converging evidence, as well as highlighted medium-to-large effects within subgenual/ventral anterior cingulate cortex and lateral prefrontal, lateral temporal and lateral parietal regions implicated in emotion regulation. Depressogenic neural patterns were associated with negative self-perceptions and negative information processing biases. These findings suggest a neural mechanism underlying cognitive biases in depression, as reflected by emotional hyperresponsivity and maladaptive regulation/reappraisal of negative social evaluative information. This study lends further support for salience and central executive network dysfunction underlying social threat processing, and in particular, highlights the anterior insula as a key region of disturbance in adolescent depression.

The neurobiology of self face recognition among depressed adolescents.

OBJECTIVE: Depression is linked to alterations in both emotion and self-processing. The current study used functional magnetic resonance imaging (fMRI) to assess neural activation in healthy and depressed youth to a novel task that combined emotion processing with self-face recognition. METHODS: An fMRI study involving 81 adolescents (50.6% females; Mage=14.61, SD=1.65) comprised of depressed (DEP, n=43), and healthy controls (HC, n=38). Participants completed a clinical interview and self-report measures during an initial assessment. In the scanner, adolescents completed a face recognition task, viewing emotional (happy, sad, neutral) images of their own face (self) or the face of another youth (other). RESULTS: DEP youth showed higher activity in the cuneus (F=26.29) and post and precentral gyri (F=20.76), across all conditions compared to HC. Sad faces elicited higher posterior cingulate cortex, precuneus (F=10.36) and inferior parietal cortex activity (F=11.0), and self faces elicited higher precuneus, fusiform (F=16.39), insula and putamen (F=16.82) activity in all youth. DEP showed higher middle temporal activity to neutral faces but lower activity to sad faces compared to HC, who showed the opposite pattern (F=12.86). DEP also showed hypoactive mid-temporal limbic activity relative to controls when identifying their self happy face vs. neutral face, yet showed hyperactivity when identifying the other happy face vs. neutral face, and HC showed the opposite pattern (F=10.94). CONCLUSIONS: The neurophysiology of self-face recognition is altered in adolescent depression. Specifically, depression was associated with decreased activity in neural areas that support emotional and associative processing for positive self-faces and increased processing for neutral self-faces. These results suggest that depression in adolescents is associated with hypoactive emotional processing and encoding of positive self-related visual information. This abnormal neural activity at the intersection of reward and self-processing among depressed youth might have long lasting impact in self-formation and future adult self-representations, given that adolescence is a sensitive period for self-development.

The cortisol awakening response and anterior cingulate cortex function in maltreated depressed versus non-maltreated depressed youth.

Symptomatology of depression among children who have (vs. have not) experienced maltreatment is greater in severity, more resistant to conventional treatment, and associated with elevated risk for suicide. Recent evidence implicates perturbations in stress regulatory systems and heightened negative self-appraisals as factors that increase the severity of psychopathology experienced by depressed maltreated (vs. non-maltreated) youth. Likely explanatory mechanisms for these differences are disturbances in the function of the hypothalamic-pituitary axis (HPA) and persistent negative self-referential biases supported by prefrontal cortex function including the dorsal anterior cingulate cortex (dACC). The cortisol awakening response (CAR) and dACC activity during a self-appraisal task were assessed in maltreated and non-maltreated depressed youth. Hierarchical linear models were employed to model the CAR. Maltreatment group, dACC activity during positive and negative self-appraisals as well as other key predictors, were included in the models. Post hoc analyses explored explanations for significant differences. Results indicated that maltreated depressed youth exhibited a higher CAR compared to non-maltreated youth. At low levels of dACC activity during processing of negative self-descriptors maltreated and non-maltreated depressed youth's CAR did not differ. However, at elevated levels of dACC activity during processing of negative self-descriptors maltreated depressed youth exhibited significantly higher CAR compared to non-maltreated depressed youth.

Brain activity and infant attachment history in young men during loss and reward processing.

There is now ample evidence that the quality of early attachment experiences shapes expectations for supportive and responsive care and ultimately serves to scaffold adaptation to the salient tasks of development. Nonetheless, few studies have identified neural mechanisms that might give rise to these associations. Using a moderately large sample of low-income male participants recruited during infancy (N = 171), we studied the predictive significance of attachment insecurity and disorganization at age 18 months (as measured in the Strange Situation Procedure) for patterns of neural activation to reward and loss at age 20 years (assessed during a reward-based task as part of a functional magnetic resonance imaging scan). Results indicated that individuals with a history of insecure attachment showed hyperactivity in (a) reward- and emotion-related (e.g., basal ganglia and amygdala) structures and (b) emotion regulation and self-referential processing (cortical midline structures) in response to positive and negative outcomes (and anticipation of those outcomes). Further, the neural activation of individuals with a history of disorganized attachment suggested that they had greater emotional reactivity in anticipation of reward and employed greater cognitive control when negative outcomes were encountered. Overall, results suggest that the quality of early attachments has lasting impacts on brain function and reward processing.

Ventral Striatum Functional Connectivity during Rewards and Losses and Symptomatology in Depressed Patients.

BACKGROUND: The ventral striatum (VS) and striatal network supports goal motivated behavior. Identifying how depressed patients differ in their striatal network during the processing of emotionally salient events is a step towards uncovering biomarkers for diagnosis and treatment. METHODS: 38 depressed and 30 healthy adults completed a task that examined brain activation to the anticipation and receipt of monetary rewards and losses. Data were collected using a 3T Siemens Trio scanner. Functional connectivity differences were examined with seeds in the Left or Right VS. FC estimates were regressed on specific symptoms. RESULTS: Depressed patients displayed higher functional connectivity between the VS and midline cortical areas during loss versus reward trials. Anhedonia and depressed mood were associated to fairly similar striatal circuits but suicidality was associated to a unique VS-midline structures coupling, while depression severity was linked to higher VS to caudate and precuneus connectivity during loss versus reward trials. CONCLUSIONS: Depression is characterized by excessive VS coupling to cognitive control and associative networks during losses versus rewards. High VS to midline cortical structures coupling may index suicidality.

The neurobiology of self-processing in abused depressed adolescents.

Maltreatment is associated with chronic depression, high negative self-attributions, and lifetime psychopathology. Adolescence is a sensitive period for the formation of self-concept. Identifying neurobiomarkers of self-processing in depressed adolescents with and without maltreatment may parse the effects of trauma and depression on self-development and chronic psychopathology. Depressed adolescents (n = 86) maltreated due to omission (DO, n = 13) or commission (DCM, n = 28) or without maltreatment (DC, n = 45), and HCs (HC, n = 37) appraised positive and negative self-descriptors in the scanner. DCM and DO showed hypoactivity in the dorsal anterior cingulate cortex (dACC) while processing positive versus negative self-descriptors compared to DC youth, who in turn showed reduced dACC recruitment versus HC. HC youth showed the highest activation in the dACC and striatum during positive self-descriptors; these regions showed a linear decline in activity across DC, DO, and DCM. Low dACC activity to positive versus negative self-descriptors was linked to inadequate coregulation of children's emotions by parents. Negative self-cognitions prevalent in DCM and DO adolescents may be perpetuated by activity in the dACC and striatum. Reduced activation of the dACC and striatum for positive self-descriptors, coupled with enhanced activity for negative self-descriptors, may heighten the risk for persistent depression.