Opponent intrinsic brain network connectivity profiles associated with posttraumatic fear and dysphoria symptoms in trauma-exposed refugees.

OBJECTIVE: Resting-state functional magnetic resonance imaging (rsfMRI) studies report functional alterations in the connectivity between intrinsic brain networks in posttraumatic stress disorder (PTSD), but PTSD heterogeneity is rarely considered. Evidence points to fear (e.g., reexperiencing) and dysphoria (e.g., withdrawal) symptom factors as important in PTSD presentations, including relating to variable emotion dysregulation patterns. This study, therefore, tested how fear and dysphoria posttraumatic symptoms were differentially associated with core network connectivity and emotion dysregulation behaviors in a large group of trauma-exposed refugees. METHOD: A final sample of 77 trauma-exposed participants completed a rsfMRI scan. Independent component analysis identified active networks and functional network connectivity (FNC) between networks was assessed. Fear and dysphoria posttraumatic symptoms were partially correlated with FNCs, and linear regression models examined relationships with self-reported difficulties in emotion regulation. RESULTS: Twenty-three active networks were identified, eight being in the networks of interest (p < .05 false discovery rate-corrected). Fear and dysphoria symptoms were specifically related to connectivity patterns between two subnetworks of the default mode network (DMN). Fear symptoms were negatively associated with anterior dorsomedial DMN (admDMN) and temporoparietal DMN (tpDMN) connectivity; whereas dysphoria symptoms were positively associated with admDMN-tpDMN connectivity. Additionally, admDMN-tpDMN connectivity was positively predicted by goal-directed emotion dysregulation but negatively predicted by poor emotional clarity. CONCLUSIONS: Fear and dysphoria posttraumatic symptoms showed opponent associations with admDMN and tpDMN connectivity, potentially reflecting patterns of under- and overemotion dysregulation associated with these symptom profiles respectively. Findings highlight the importance of considering posttraumatic heterogeneity when constructing neural models of PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Refugee visa insecurity disrupts the brain's default mode network.

BACKGROUND: Research has largely focused on the psychological consequences of refugee trauma exposure, but refugees living with visa insecurity face an uncertain future that also adversely affects psychological functioning and self-determination. OBJECTIVE: This study aimed to examine how refugee visa insecurity affects the functional brain. METHOD: We measured resting state brain activity via fMRI in 47 refugees with insecure visas (i.e. temporary visa status) and 52 refugees with secure visas (i.e. permanent visa status) residing in Australia, matched on key demographic, trauma exposure and psychopathology. Data analysis comprised independent components analysis to identify active networks and dynamic functional causal modelling tested visa security group differences in network connectivity. RESULTS: We found that visa insecurity specifically affected sub-systems within the default mode network (DMN) - an intrinsic network subserving self-referential processes and mental simulations about the future. The insecure visa group showed less spectral power in the low frequency band in the anterior ventromedial DMN, and reduced activity in the posterior frontal DMN, compared to the secure visa group. Using functional dynamic causal modelling, we observed positive coupling between the anterior and posterior midline DMN hubs in the secure visa group, while the insecure visa group displayed negative coupling that correlated with self-reported fear of future deportation. CONCLUSIONS: Living with visa-related uncertainty appears to undermine synchrony between anterior-posterior midline components of the DMN responsible for governing the construction of the self and making mental representations of the future. This could represent a neural signature of refugee visa insecurity, which is marked by a perception of living in limbo and a truncated sense of the future.

Refugee visa insecurity disrupts default mode network (DMN) connectivity ­ a core network that supports the internal construction of the self.Refugees living with insecure visa status showed decreased connectivity in the DMN and more negative coupling between midline anterior­posterior hubs of the DMN, compared to refugees living with secure visas.Diminished DMN connectivity may represent a neural basis for the psychological effects of refugee visa insecurity, which is associated with prolonged uncertainty regarding the future self and increased risk for psychological distress.

Significant age by childhood trauma interactions on grey matter volumes: A whole brain VBM analysis.

BACKGROUND: Childhood trauma is deleterious to long term brain development. The changes are variable, and depend on gender, age and the nature of the trauma. In this exploratory analysis, we investigated the effects of exposure to emotional trauma on grey matter (GM) volumes in adolescent females. METHODS: We explored GM volumes in non-clinical females aged 12-17 years who had been exposed to either higher (HET; N = 75) or minimal (MET; N = 127) emotional trauma. High-resolution T1-weighted structural images were analysed with an optimised FSL-VBM protocol. The General Linear Model was run on HET versus MET with continuous age as an interaction. Mean GM volumes were extracted from significant corrected age interaction statistical maps and scrutinised with SPSS®. RESULTS: We observed greater HET*age than MET*age interactions (corrected p-value = 0.0002), in 4 separate bilateral cortical regions associated with mood disorders. Scrutiny of these regions showed significant GM volume enlargements in the early adolescent HET group (p = 0.017) and reductions in the late adolescent HET group (p < 0.0001). Notably, there were no differences in middle adolescence (p > 0.05). LIMITATIONS: Causality cannot be inferred from this cross-sectional study and the onset of trauma cannot be determined using retrospective measures. CONCLUSIONS: Whilst GM volumes diminish from early adolescence onwards, our results show that HET impacts this brain development, perhaps first via unstable adaptative mechanisms, followed by maladaptive processes in late adolescence. This suggests that compromises of emotional and cognitive self-regulation in mood disorders may underpin the structural abnormalities observed across multiple brain regions in these teenage girls.

Eating disorder features in bipolar disorder: clinical implications.

BACKGROUND: Bipolar disorder (BD) is associated with elevated rates of eating disorders (EDs), but the nature and impact of specific ED features are unclear. AIMS: This study sought to identify which ED features are common in BD, and whether these relate to quality of life (QoL) impairment and body mass index (BMI). METHOD: A clinical sample of 73 adults with BD completed self-report measures of health, ED features, emotion regulation ability, impulsivity, and QoL. RESULTS: Binge eating (45%), excessive dietary restriction (39%), overvaluation of weight/shape (51%), purging (16%) and driven exercise (27%) were common, and associated with a poorer clinical picture, including poorer QoL and poorer emotion regulation. Furthermore, regular binge eating episodes explained a significant proportion of variance in QoL impairment after controlling for other significant predictors. The best predictors of BMI were number of medical conditions, impulsivity and positive beliefs about binge eating. CONCLUSIONS: ED features that may not meet criteria for a fully diagnosable ED - particularly overvaluation of weight/shape and binge eating - warrant greater attention, as they may still significantly worsen QoL. Future research should focus on modifying existing psychological interventions to better target ED features among individuals with BD and thereby improve clinical outcomes.

An fMRI examination of the neural basis of suicide attempts: The role of mentalizing in the context of mood.

OBJECTIVES: Facial emotion recognition (FER) deficits in depressed mood disorder patients contribute to suicidality. Prior research shows that intrinsic brain activity patterns are altered by attempting suicide. Therefore, we investigated in depressed patients whether differences in FER contribute to their clinical symptoms of suicide. METHODS: Neural activity in response to an FER task was compared across three groups: healthy controls (HCs, N = 66), suicide non-attempter (SNA, N = 50), suicide attempter (SA, N = 25). Modulation of brain networks by the task and functional connectivity (FC) within (using spatial map, spectral power) and between (using functional network connectivity; FNC) were examined. The contribution of these differences to suicidal symptoms in each group was also examined. RESULTS: Patient groups displayed impaired FC both within and between networks but differed in nature and networks involved. They also showed differential modulation of networks by task, such that compared with both HC and SNA, SA displayed impaired FC within the default-mode network (DMN) and also its task modulation. In the SA group, FC within the DMN and FNC between two lateral prefrontal networks, and its interaction with the basal ganglia network contributed significantly to the clinical symptoms of suicide. CONCLUSIONS: This study affirms differences between SA and SNA brain activity patterns and suggests that suicidal activity probably emanates via different mechanisms in these patient groups. Perhaps, over-attribution of emotion impairs one's self-referential thought processes and coupled with diminished emotional control this makes depressed individuals vulnerable to suicide.

Torture exposure and the functional brain: investigating disruptions to intrinsic network connectivity using resting state fMRI.

Torture has profound psychological and physiological consequences for survivors. While some brain structures and functions appear altered in torture survivors, it is unclear how torture exposure influences functional connectivity within and between core intrinsic brain networks. In this study, 37 torture survivors (TS) and 62 non-torture survivors (NTS) participated in a resting-state fMRI scan. Data-driven independent components analysis identified active intrinsic networks. Group differences in functional connectivity in the default mode network (DMN), salience network (SN) and central executive network (CEN) of the triple network model, as well any prefrontal network, were examined while controlling for PTSD symptoms and exposure to other potentially traumatic events. The analysis identified 25 networks; eight comprised our networks of interest. Within-network group differences were observed in the left CEN (lCEN), where the TS group showed less spectral power in the low-frequency band. Differential internetwork dynamic connectivity patterns were observed, where the TS group showed stronger positive coupling between the lCEN and anterior dorsomedial and ventromedial DMN, and stronger negative coupling between a lateral frontal network and the lCEN and anterior dorsomedial DMN (when contrasted with the NTS group). Group differences were not attributed to torture severity or dissociative symptoms. Torture survivors showed disrupted dynamic functional connectivity between a laterally-aligned lCEN that serves top-down control functions over external processes and the midline DMN that underpins internal self-referential processes, which may be an adaptive response to mitigate the worst effects of the torture experience. This study provides a critical step in mapping the neural signature of torture exposure to guide treatment development and selection.

Activating the attachment system modulates neural responses to threat in refugees with PTSD.

Social attachment systems are disrupted for refugees through trauma and forced displacement. This study tested how the attachment system mitigates neural responses to threat in refugees with posttraumatic stress disorder (PTSD). Refugees with PTSD (N = 28) and refugee trauma-exposed controls (N = 22) viewed threat-related stimuli primed by attachment cues during a functional magnetic resonance imaging scan. Group differences and the moderating effects of avoidant or anxious attachment style and grief related to separation from family on brain activity and connectivity patterns were examined. Separation grief was associated with increased amygdala but decreased ventromedial prefrontal cortical (VMPFC) activity to the attachment prime and decreased VMPFC and hippocampal activity to attachment primed threat in the PTSD (vs trauma-exposed control) group. Avoidant attachment style was connected with increased dorsal frontoparietal attention regional activity to attachment prime cues in the PTSD group. Anxious attachment style was associated with reduced left amygdala connectivity with left medial prefrontal regions to attachment primed threat in the PTSD group. Separation grief appears to reduce attachment buffering of threat reactivity in refugees with PTSD, while avoidant and anxious attachment style modulated attentional and prefrontal regulatory mechanisms in PTSD, respectively. Considering social attachments in refugees could be important to post-trauma recovery, based within changes in key emotion regulation brain systems.

Irritability and mood symptoms in adolescent girls: Trait anxiety and emotion dysregulation as mediators.

BACKGROUND: Irritability is a common symptom in youth that is thought to be predictive of mood disorders. Its effects on mood are likely to be age-dependent, with direct and indirect mediators. We assessed age-related effects and mediators of irritability in adolescent girls with subthreshold depressive and manic symptoms. METHODS: We analysed the irritability item from the Mood Disorder Questionnaire in 3 cohorts of girls aged 12-18years (N=229); 12-13years (N=82); 14-15years (N=68); and 16-18years (N=79). They also completed mood, anxiety and emotion regulation questionnaires. MANOVA, correlations and bootstrapped mediation analyses were performed with SPSS®v25 and Hayes Processv3.5®. RESULTS: Overall, irritable girls had higher depressive and manic symptoms, trait anxiety and emotion dysregulation than those who were not irritable. Significantly higher rates of irritability were observed in mid-adolescents (aged 14-15years; p = 0.001). Notably, irritability exerted effects on depressive symptoms via trait anxiety, non-acceptance of emotions and dysregulation in emotion clarity throughout adolescence. However, irritability directly exerted effects on manic symptoms in mid-adolescence but in older adolescents, their relationship was indirect via impulse control dysregulation. LIMITATIONS: The cross-sectional design and non-clinical sample limit generalisability of our findings. CONCLUSIONS: Irritability is involved in subthreshold depressive symptoms, via trait anxiety and perceptual emotion dysregulation. On the other hand, irritability is directly and indirectly associated with subthreshold manic symptoms via dysregulated impulse control depending on age. Therefore, screening for irritability, trait anxiety and emotion dysregulation throughout adolescence may facilitate the early detection of subthreshold depressive and manic symptoms, and the implementation of preventive strategies.

"The Food Matches the Mood": Experiences of Eating Disorders in Bipolar Disorder.

Approximately 33% of those with bipolar disorder (BD) have a comorbid eating disorder (ED). However, the trajectory of these conditions has received little research attention. Nine participants who met criteria for BD and an ED participated in qualitative interviews exploring experiences of illness onset, the interaction of these conditions, and service provision. Almost all participants in the sample reported minimal to no screening of ED problems, despite their health professionals' frequent discussion of obesity. Findings suggested that ED features were diverse and evolved over time. Mania and depression were connected to ED features such as overeating and restricting, but this differed between and within participants. Most participants disclosed historic trauma which they considered central to their mental health concerns. This clinical group appears to be underserviced. Clinicians and researchers should routinely screen for ED features when treating and diagnosing BD to inform their physical and mental health interventions.

The impact of torture on interpersonal threat and reward neurocircuitry.

OBJECTIVE: Torture adversely influences emotional functioning, but the neurophysiological mechanisms underpinning its impact are unknown. This study examined how torture exposure affects the neural substrates of interpersonal threat and reward processing. METHODS: Male refugees with (N = 31) and without (N = 27) torture exposure completed a clinical interview and functional magnetic resonance imaging scan where they viewed fear, happy and neutral faces. Between-group activations and neural coupling were examined as moderated by posttraumatic stress disorder symptom severity and cumulative trauma load. RESULTS: Posttraumatic stress disorder symptom severity and trauma load significantly moderated group differences in brain activation and connectivity patterns. Torture survivors deactivated the ventral striatum during happy processing compared to non-torture survivor controls as a function of increased posttraumatic stress disorder symptom severity - particularly avoidance symptoms. The ventral striatum was more strongly coupled with the inferior frontal gyrus in torture survivors. Torture survivors also showed left hippocampal deactivation to both fear and happy faces, moderated by trauma load, compared to controls. Stronger coupling between the hippocampus and frontal, temporoparietal and subcortical regions during fear processing was observed, with pathways being predicted by avoidance and hyperarousal symptoms. CONCLUSION: Torture exposure was associated with distinct brain activity and connectivity patterns during threat and reward processing, dependent on trauma exposure and posttraumatic stress disorder symptom severity. Torture appears to affect emotional brain functioning, and findings have the potential to guide more targeted interventions for torture survivors.

Lithium therapy and its interactions.

Lithium is one of the most effective mood stabilisers for people with a mood disorder. However, many of these patients are also taking other medicines that could potentially interact with lithium To minimise the risk of relapse, it is usually necessary to maintain the lithium serum concentration between 0.6 mmol/L and 0.8 mmol/L Lithium clearance is easily influenced by drugs that alter renal function such as ACE inhibitors, angiotensin receptor antagonists, diuretics, and non-steroidal anti-inflammatory drugs It is therefore prudent for prescribers to monitor and adjust the lithium dose to avoid adverse effects or loss of efficacy

Cognitive side-effects of electroconvulsive therapy: what are they, how to monitor them and what to tell patients.

BACKGROUND: Electroconvulsive therapy (ECT) is recommended in treatment guidelines as an efficacious therapy for treatment-resistant depression. However, it has been associated with loss of autobiographical memory and short-term reduction in new learning. AIMS: To provide clinically useful guidelines to aid clinicians in informing patients regarding the cognitive side-effects of ECT and in monitoring these during a course of ECT, using complex data. METHOD: A Committee of clinical and academic experts from Australia and New Zealand met to the discuss the key issues pertaining to ECT and cognitive side-effects. Evidence regarding cognitive side-effects was reviewed, as was the limited evidence regarding how to monitor them. Both issues were supplemented by the clinical experience of the authors. RESULTS: Meta-analyses suggest that new learning is impaired immediately following ECT but that group mean scores return at least to baseline by 14 days after ECT. Other cognitive functions are generally unaffected. However, the finding of a mean score that is not reduced from baseline cannot be taken to indicate that impairment, particularly of new learning, cannot occur in individuals, particularly those who are at greater risk. Therefore, monitoring is still important. Evidence suggests that ECT does cause deficits in autobiographical memory. The evidence for schedules of testing to monitor cognitive side-effects is currently limited. We therefore make practical recommendations based on clinical experience. CONCLUSIONS: Despite modern ECT techniques, cognitive side-effects remain an important issue, although their nature and degree remains to be clarified fully. In these circumstances it is useful for clinicians to have guidance regarding what to tell patients and how to monitor these side-effects clinically.

Role of self-focussed reappraisal of negative emotion in emergence of emotional symptoms in adolescent girls.

BACKGROUND: Adolescent subthreshold emotional symptoms arise from impaired self-referential information-processing and approach-avoidance behaviour network integration, which compromises goal evaluation and pursuit strategies. AIMS: We investigated whether impairment of negative emotion (goal) reappraisal strategies (self-focussing and self-distancing) generates emotional symptoms (emotional disorders precursors). METHOD: Using functional magnetic resonance imaging and a triple-network model (default mode, executive control and salience), functional connectivity differences within and between networks, and their modulation by task and relationships with emotional symptoms were determined in healthy adolescent girls (N = 202) grouped by presence or absence of emotional symptoms. RESULTS: The groups differed in spectral power distribution and in dorsal default mode network and right executive control network modulation when self-focussing and self-distancing, respectively. Girls without emotional symptoms had greater spectral power and less network modulation. Greater spectral power was associated with reduced emotional symptoms and less dorsal default mode network modulation when self-focussing. CONCLUSIONS: The early phases of anxiety and depressive disorders in adolescence are marked by emotional symptoms that usually emerge in the context of negative life events. To contend with the negative effect of such events, a typical reappraisal strategy is to distance oneself and switch the focus of one's thinking. This brain-imaging study in adolescent girls prone to the development of emotional disorders has found functional changes in key neural networks that are involved in reappraisal and shown that this process is impaired. This is important because it provides an early indication of these common disorders and a potential target for psychological interventions.

Interactions of OXTR rs53576 and emotional trauma on hippocampal volumes and perceived social support in adolescent girls.

Oxytocin (OXT) is a neuropeptide involved in social behaviour and is sensitive to environmental influences to alter individual vulnerability or resilience to stress resulting in both negative and positive outcomes. The effects of the OXT receptor (OXTR) single nucleotide polymorphism (SNP) rs53576 on hippocampal and amygdala structure and functions in adults are differentially associated with susceptibility to adversity and social behaviours, but this evidence is lacking in healthy adolescents. Adolescence is a developmental period characterised by neurobiological and psychosocial changes resulting in higher susceptibility to mood disorders, particularly among girls. As the brain is highly plastic at this stage, to understand psychosocial and emotional development, clarity of the interactions between rs53576 and adversity on hippocampal and amygdala volumes and social behaviours is needed. In this study, we investigated the interactions between rs53576 and emotional trauma (ET) exposure on hippocampal and amygdala volumes of adolescent girls, and associations with parenting style, perceived social support and bullying behaviour. Based on an unbiased and corrected analytical approach, we found smaller left hippocampal volumes in higher (hET) compared to minimally (mET) exposed AA homozygotes, but no differences in G allele carriers nor in the amygdala. Within the mET AA group, larger volumes were associated with peer perceived social support, but in their hET counterparts, smaller volumes were associated with familial perceived social support. This evidence supports an important role for the hippocampus in social behaviours but extends current knowledge to suggest that hippocampal social behavioural features are contextually dependent on rs53576.

Default mode dysfunction underpins suicidal activity in mood disorders.

BACKGROUND: Suicide is a serious and not uncommon consequence of mood disorders that occurs primarily when individuals are depressed. Understanding the neurobiology of suicidal activity (thoughts or behaviors) is likely to facilitate prevention. METHOD: Seventy-nine adult depressed mood disorder patients (MDP), of which 25 had attempted suicide at least once, and 66 healthy controls (HC) participated in this study. Resting-state functional MRI was used to identify neural activity differences between suicide attempters (SA) and non-attempters (NA). Specifically, differences were examined in functional connectivity both within and between four large cognitive networks [Executive Control (ECN), Default Mode (DMN), Salience (SN), and Basal Ganglia (BGN)] and their respective associations with suicidal activity. RESULTS: Compared to HCs, patients had greater posterior DMN activity, but less activity in the BGN, and less low-frequency spectral power in the dorso-medial DMN. Furthermore, increased posterior DMN activity in SA was associated with recent suicidal activity, whereas NA had reduced BGN activity and less dorso-medial DMN spectral power, the latter being associated with lifelong suicidal thinking. SA also had greater activity in midline circuitry compared to both HC and NA, and the pattern of BGN and DMN co-activity differed between SA and NA. CONCLUSIONS: DMN engagement raises the possibility that suicidal activity in mood disorder patients may be a consequence of impaired self-referential thought processing. Furthermore, differential BGN and DMN co-activation according to suicide attempt status suggests that attempting suicide perhaps alters cognitive flexibility. These insights are potentially useful for understanding the neural basis of suicide activity.

Switching antidepressants in the treatment of major depression: When, how and what to switch to?

BACKGROUND: Switching antidepressant medications is recommended when an initial antidepressant is not effective, when it is unable to be tolerated or when there are significant drug interactions. The aim of this paper is to review the evidence regarding when to switch antidepressants and the optimal approach to switching. METHODS: Clinical and academic experts in mood disorders from Australia and New Zealand (Treatment Algorithm Group, TAG) met to discuss the key considerations regarding switching antidepressants in the treatment of depression and formulate recommendations about switching strategies. RESULTS: While switching is recommended, there is limited data to guide on how best to approach switching antidepressants (e.g. whether to switch within class or out of class), and how to define the best time to consider switching. Broadly, switching within class after non-response is recommended for mild-moderate depression and out-of-class for patients with a more severe depression or melancholia. LIMITATIONS: There is a limited evidence-base to draw on to make definitive recommendations on switching approaches. CONCLUSIONS: Switching antidepressants is an appropriate strategy to use if there is a minimal response to an initial antidepressant. Further research is required to determine the optimal switching approach.