Cross-pollination in seed-blended refuge and selection for Vip3A resistance in a lepidopteran pest as detected by genomic monitoring.

The evolution of pest resistance to management tools reduces productivity and results in economic losses in agricultural systems. To slow its emergence and spread, monitoring and prevention practices are implemented in resistance management programs. Recent work suggests that genomic approaches can identify signs of emerging resistance to aid in resistance management. Here, we empirically examined the sensitivity of genomic monitoring for resistance management in transgenic Bt crops, a globally important agricultural innovation. Whole genome resequencing of wild North American Helicoverpa zea collected from non-expressing refuge and plants expressing Cry1Ab confirmed that resistance-associated signatures of selection were detectable after a single generation of exposure. Upon demonstrating its sensitivity, we applied genomic monitoring to wild H. zea that survived Vip3A exposure resulting from cross-pollination of refuge plants in seed-blended plots. Refuge seed interplanted with transgenic seed exposed H. zea to sublethal doses of Vip3A protein in corn ears and was associated with allele frequency divergence across the genome. Some of the greatest allele frequency divergence occurred in genomic regions adjacent to a previously described candidate gene for Vip3A resistance. Our work highlights the power of genomic monitoring to sensitively detect heritable changes associated with field exposure to Bt toxins and suggests that seed-blended refuge will likely hasten the evolution of resistance to Vip3A in lepidopteran pests.

Long-term health-related quality of life in head and neck cancer survivors: A large multinational study.

Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.

DNA Logic Gates Integrated on DNA Substrates in Molecular Computing.

Due to nucleic acid's programmability, it is possible to realize DNA structures with computing functions, and thus a new generation of molecular computers is evolving to solve biological and medical problems. Pioneered by Milan Stojanovic, Boolean DNA logic gates created the foundation for the development of DNA computers. Similar to electronic computers, the field is evolving towards integrating DNA logic gates and circuits by positioning them on substrates to increase circuit density and minimize gate distance and undesired crosstalk. In this minireview, we summarize recent developments in the integration of DNA logic gates into circuits localized on DNA substrates. This approach of all-DNA integrated circuits (DNA ICs) offers the advantages of biocompatibility, increased circuit response, increased circuit density, reduced unit concentration, facilitated circuit isolation, and facilitated cell uptake. DNA ICs can face similar challenges as their equivalent circuits operating in bulk solution (bulk circuits), and new physical challenges inherent in spatial localization. We discuss possible avenues to overcome these obstacles.

Sensitivity to psychosocial influences at age 3 predicts mental health in middle childhood.

Children vary in how sensitive they are to experiences, with consequences for their developmental outcomes. In the current study, we investigated how behavioral sensitivity at age 3 years predicts mental health in middle childhood. Using a novel repeated measures design, we calculated child sensitivity to multiple psychological and social influences: parent praise, parent stress, child mood, and child sleep. We conceptualized sensitivity as the strength and direction of the relationship between psychosocial influences and child behavior, operationalized as toothbrushing time, at age 3 years. When children were 5-7 years old (n = 60), parents reported on children's internalizing and externalizing problems. Children who were more sensitive to their parents' praise at age 3 had fewer internalizing (r = -0.37, p = 0.016, pFDR = 0.042) and externalizing (r = -0.35, p = 0.021, pFDR = 0.042) problems in middle childhood. Higher average parent praise also marginally predicted fewer externalizing problems (r = -0.33, p = 0.006, pFDR = 0.057). Child sensitivity to mood predicted fewer internalizing (r = -0.32, p = 0.013, pFDR = 0.042) and externalizing (r = -0.38, p = 0.003, pFDR = 0.026) problems. By capturing variability in how children respond to daily fluctuations in their environment, we can contribute to the early prediction of mental health problems and improve access to early intervention services for children and families who need them most. RESEARCH HIGHLIGHTS: Children differ in how strongly their behavior depends on psychosocial factors including parent praise, child mood, child sleep, and parent stress. Children who are more sensitive to their parents' praise at age 3 have fewer internalizing and externalizing problems at age 5-7 years. Child sensitivity to mood also predicts fewer internalizing and externalizing problems.

Nurturing innovation, catalyzing change: Honoring the legacy of Dr. C. Barr Taylor in the eating disorders field.

This Virtual Issue of the International Journal of Eating Disorders honors the legacy of the late Dr. C. Barr Taylor in the eating disorders (EDs) field. For decades, Dr. Taylor led the way in not only conducting the research needed to achieve the ultimate goal of making affordable, accessible, and evidence-based care for EDs available to all, but also nurturing the next generation of scientific leaders and innovators. Articles included in this Virtual Issue are a selection of Dr. Taylor's published works in the Journal in the past decade, spanning original research, ideas worth researching, commentaries, and a systematic review. We hope this Virtual Issue will inspire the next generation of research in EDs, and equally, if not more importantly, the next generation of young investigators in the field. We urge the field to continue and build upon Dr. Taylor's vision-to increase access to targeted prevention and intervention for EDs in innovative and forward-thinking ways-while embracing his unique and powerful mentorship style to lift up early career investigators and create a community of leaders to address and solve our field's biggest challenges.

Screening for psychosis risk in primary mental health care services - Implementation, prevalence and recovery trajectories.

OBJECTIVES: Early interventions improve outcomes for people at high risk of psychosis and are likely to be cost saving. This group tends to seek help for emotional problems - depression and anxiety - via primary care services, where early detection methods are poor. We sought to determine prevalence rates of high risk for psychosis in UK primary care mental health services and clinical outcomes following routinely delivered psychological therapies. METHODS: We used a brief screen designed for settings with low base rates and significant time constraints to determine prevalence of high risk for psychosis in UK 'Talking Therapies' services. We examined socio-demographic characteristics, presenting problems and recovery trajectories for this group, compared with people not at risk of psychosis. RESULTS: A 2-item screen selected for specificity yielded a prevalence rate of 3% in primary care mental health services. People at elevated risk of psychosis were younger and more likely to report at least one long-term physical condition. This group presented with higher levels of depression, anxiety and trauma symptoms at assessment and were less likely to have recovered at the end of treatment, compared to people not at risk. CONCLUSIONS: Very brief screening tools can be implemented in busy health care settings. The 3% of referrals to UK primary care psychological therapies services at elevated risk of psychosis typically present with more severe symptoms and greater levels of comorbidity and may require augmented interventions to recover fully.

Genome evolution in an agricultural pest following adoption of transgenic crops.

Replacing synthetic insecticides with transgenic crops for pest management has been economically and environmentally beneficial, but these benefits erode as pests evolve resistance. It has been proposed that novel genomic approaches could track molecular signals of emerging resistance to aid in resistance management. To test this, we quantified patterns of genomic change in Helicoverpa zea, a major lepidopteran pest and target of transgenic Bacillus thuringiensis (Bt) crops, between 2002 and 2017 as both Bt crop adoption and resistance increased in North America. Genomic scans of wild H. zea were paired with quantitative trait locus (QTL) analyses and showed the genomic architecture of field-evolved Cry1Ab resistance was polygenic, likely arising from standing genetic variation. Resistance to pyramided Cry1A.105 and Cry2Ab2 toxins was controlled by fewer loci. Of the 11 previously described Bt resistance genes, 9 showed no significant change over time or major effects on resistance. We were unable to rule out a contribution of aminopeptidases (apns), as a cluster of apn genes were found within a Cry-associated QTL. Molecular signals of emerging Bt resistance were detectable as early as 2012 in our samples, and we discuss the potential and pitfalls of whole-genome analysis for resistance monitoring based on our findings. This first study of Bt resistance evolution using whole-genome analysis of field-collected specimens demonstrates the need for a more holistic approach to examining rapid adaptation to novel selection pressures in agricultural ecosystems.

Assessing Squarates as Amine-Reactive Probes.

Probes that covalently label protein targets facilitate the identification of ligand-binding sites. Lysine residues are prevalent in the proteome, making them attractive substrates for covalent probes. However, identifying electrophiles that undergo amine-specific, regioselective reactions with binding site lysine residues is challenging. Squarates can engage in two sequential conjugate addition-elimination reactions with amines. Nitrogen donation reduces the second reaction rate, making the mono squaramide a mild electrophile. We postulated that this mild electrophilicity would demand a longer residence time near the amine, affording higher selectivity for binding site lysines. Therefore, we compared the kinetics of squarate and monosquaramide amine substitution to alternative amine bioconjugation handles. The data revealed that N-hydroxy succinimidyl esters react 4 orders of magnitude faster, consistent with their labeling promiscuity. Squarate reactivity can be tuned by a substitution pattern. Electron-withdrawing groups on the vinylogous ester or amide increase reaction rates. Dithionosquarates react more rapidly than squarates, while vinylogous thioester analogs, dithiosquarates, react more slowly. We assessed squarate selectively using the UDP-sugar processing enzyme GlfT2 from Mycobacterium tuberculosis, which possesses 21 surface-exposed lysines. The reaction predominately modified one lysine proximal to a binding site to afford covalent inhibition. These findings demonstrate the selectivity of squaric esters and squaramides, which is a critical feature for affinity-based chemoproteomic probes.

Genomic regions underlying the species-specific mating songs of green lacewings.

Rapid species radiations provide insight into the process of speciation and diversification. The radiation of Chrysoperla carnea-group lacewings seems to be driven, at least in part, by their species-specific pre-mating vibrational duets. We associated genetic markers from across the genome with courtship song period in the offspring of a laboratory cross between Chrysoperla plorabunda and Chrysoperla adamsi, two species primarily differentiated by their mating songs. Two genomic regions were strongly associated with the song period phenotype. Large regions of chromosomes one and two were associated with song phenotype, as fewer recombination events occurred on these chromosomes relative to the other autosomes. Candidate genes were identified by functional annotation of proteins from the C. carnea reference genome. The majority of genes that are associated with vibrational courtship signals in other insects were found within QTL for lacewing song phenotype. Together these findings suggest that decreased recombination may be acting to keep together loci important to reproductive isolation between these species. Using wild-caught individuals from both species, we identified signals of genomic divergence across the genome. We identified several candidate genes both in song-associated regions and near divergence outliers including nonA, fruitless, paralytic, period, and doublesex. Together these findings bring us one step closer to identifying the genomic basis of a mating song trait critical to the maintenance of species boundaries in green lacewings.

Out-of-pocket expenses associated with pediatric heart transplantation.

INTRODUCTION: Heart transplantation in children is associated with high resource utilization. However, the financial burden on families and the association with patient and demographic factors remains unclear. This study aims to examine out-of-pocket expenses associated with pediatric heart transplantation. METHODS: An anonymous REDCap survey was distributed to caregivers of children who have undergone heart transplantation using social media, national organizations, and during clinic encounters from May through August 2022. RESULTS: There were a total of 146 respondents. The median monthly out-of-pocket expense was $250 (IQR $75-$500) and 20 respondents (13.7%) reported monthly expenses of >$1000. Families with commercial insurance reported significantly higher out-of-pocket expenses compared to those with government-sponsored insurance (median $350 vs. $100, p < .001). Families with government-sponsored insurance were most happy with their insurance coverage, followed by commercial insurance and then coverage through the Affordable Care Act (p < .001 for all pairwise comparisons). There was no statistically significant difference in overall transplant-related out-of-pocket expenses based on total household income (p = .222). Monthly out-of-pocket expense was not associated with the number of medications, type of immunosuppressants, or post-transplant complications including rejection, PTLD, or CAV (p = NS for all). Cardiac catheterizations and unplanned admissions were reported as the events that incurred the highest out-of-pocket expense. CONCLUSION: Families of children who have undergone heart transplantation can incur significant out-of-pocket expenses and strategies to mitigate this financial burden should be investigated.

Self-compassion as a mediator of the relationship between childhood sexual abuse and psychotic symptoms in clinical and non-clinical groups.

BACKGROUND: Previous research has shown a link between childhood sexual abuse (CSA) and more severe symptoms of psychosis. There is also evidence that self-compassion is a key mechanism linking adverse childhood experiences and mental health problems such as post-traumatic stress disorder and depression, but no research has examined these links in psychosis. METHODS: We analysed existing cross-sectional data, including 55 individuals with psychosis and 166 individuals from the general population. Participants completed standardized measures of CSA, self-compassion, paranoia, positive psychotic symptoms and distress linked to psychosis. RESULTS: The clinical group had higher scores on CSA and all psychosis measures, but we found no differences in self-compassion between the groups. Higher levels of CSA correlated with lower self-compassion and higher paranoia and positive symptoms in both groups. CSA also correlated with distress linked to psychosis in the non-clinical group. Lower self-compassion mediated the association between higher levels of CSA and more severe paranoia in both groups. In the non-clinical group, lower self-compassion also mediated the association between greater CSA and more positive psychotic symptoms and more severe distress. CONCLUSIONS: This is the first study to show that self-compassion mediates the link between CSA and both paranoia and psychotic symptoms in adulthood. Self-compassion may therefore be an important transdiagnostic candidate target in therapy to mitigate the impact of early adversity on paranoia in both clinical and non-clinical groups. Limitations include the small clinical sample and inclusion of a cannabis-using non-clinical sample, though recent cannabis use did not impact self-compassion levels.

Reintervention Before Bidirectional Cavopulmonary Shunt and Intermediate Outcomes in Children with Single Ventricle Who Underwent Main Pulmonary Artery Banding.

Unplanned reinterventions following pulmonary artery banding (PAB) in single ventricle patients are common before stage 2 palliation (S2P) but associated risk factors are unknown. We hypothesized that reintervention is more common when PAB is placed at younger age and with a looser band, reflected by lower PAB pressure gradient. Retrospective single center study of single ventricle patients undergoing PAB between Jan 2000 and Dec 2020. The association with reintervention and successful S2P was modeled using exploratory cause-specific hazard regression. A multivariable model was developed adjusting for clinical and statistically relevant predictors. The cumulative proportion of patients undergoing reintervention were summarized using a competing risk model. 77 patients underwent PAB at median (IQR) 47 (24-66) days and 3.73 (3.2-4.5) kg. Within18 months of PAB, 60 (78%) reached S2P, 9 (12%) died, 1 (1%) transplanted and 7 (9%) were alive without S2P. Within 18 months of PAB 10 (13%) patients underwent reintervention related to pulmonary blood flow modification: PAB adjustment (n = 6) and conversion to Damus-Kaye-Stansel/Blalock-Taussig-Thomas shunt (n = 4). 6/10 (60%) reached S2P following reintervention. A trend toward higher intervention in patients with a genetic syndrome (p-0.06) and weight < 3 kg (p-0.057) at time of PAB was noted. Only genetic syndrome was a risk factor associated with poor outcome (p-0.025). PAB has a reasonable outcome in SV patients with unobstructed systemic and pulmonary blood flow, but with a high reintervention rate. Only a quarter of patients with genetic syndromes reach S2P and further study is required to explore the benefits from an alternative palliative strategy.

Social Media as a Source of Medical Information for Parents of Premature Infants: A Content Analysis of Prematurity-Related Facebook Groups.

OBJECTIVE: Parents are increasingly turning to social media for medical recommendations. Our objective was to systematically examine posts on Facebook for parents of infants hospitalized in the neonatal intensive care unit (NICU) to analyze how advice on medical topics was requested and given, and whether this advice was potentially medically inappropriate. STUDY DESIGN: One hundred Facebook groups were screened for study eligibility. In each group, up to 400 posts on medical topics were evaluated. The first 10 comments of each post were classified based on content and presence of medical advice. Appropriateness of advice was evaluated by a neonatologist. RESULTS: Of 28 groups meeting study criteria, 10 permitted access for data collection. We identified 729 posts requesting medical advice of which 29% referenced the NICU period. Posts on diagnosis and development (30 and 32% of posts, respectively) were the most common topics, and most likely to receive advice (78 and 76% of posts on these topics, respectively). We identified 238 comments containing potentially inappropriate medical advice and 30 comments recommending going against medical advice. CONCLUSION: Parents are utilizing Facebook as a source of support and medical information. Parents are most likely to give development-related advice from their own parenting experiences. The high percentage of posts requesting advice about diagnosis and development in the post-NICU stage suggests parents seek increased anticipatory guidance. KEY POINTS: · Parents of premature infants use Facebook to obtain medical advice.. · Advice was at times potentially medically inappropriate.. · Much advice focused on the post-NICU period..

Why fake death? Environmental and genetic control of tonic immobility in larval lacewings (Neuroptera: Chrysopidae).

Tonic immobility is a passive antipredator strategy employed late in the predation sequence that may decrease individual mortality in prey animals. Here, we investigate how energetic state and genetic predisposition influence antipredator decision-making in green lacewing larvae, Chrysoperla plorabunda (Fitch), using simulated predatory encounters. We demonstrate that tonic immobility is a plastic response influenced by energetic resource limitation. Larvae exposed to 1 or 2 days of food deprivation initiate tonic immobility more often and with less physical provocation than individuals fed ad libitum. Recently molted individuals exposed to food deprivation, the individuals most energetically challenged, engage in tonic immobility at a higher rate than any other group. We also find that variation in antipredator strategy between individuals is partly the result of within-population genetic variation. We estimate the propensity to enter tonic immobility to have a broad-sense heritability of 0.502. Taken together our results suggest that larval lacewings under energetic stress are more likely to engage in tonic immobility. Yet, energetic state does not explain all within-population variation, as individuals can have a genetic predisposition for tonic immobility.

Suicidal ideation and attempts in adults seeking outpatient psychodynamic psychotherapy.

Suicide is an important cause of death in patients with mental health disorders, but little is known about the occurrence of suicidal ideation and attempts in outpatient psychotherapy patients. The aim of this study was to identify the proportion of patients with and correlates of suicidal ideation and attempts in community-based psychotherapy practices. Using 983 applications for reimbursement of psychotherapy from individual patients, reports about suicidal thoughts and suicide attempts were extracted along with demographic, biographic and clinical data. Multivariate logistic regression analysis was used to identify correlates of suicidal ideation and attempts by calculating odds ratios (ORs). Among the patients, 19% presented with suicidal thoughts (11% currently and 8% in the past) and 6% with suicide attempts. Important correlates of suicidal thoughts were male gender (OR 1.7), lower education (OR 1.8), early retirement (OR 2.9), death of a parent when younger than 5 years old (OR 3.3), violence experienced from various people (OR 2.1), self-harm behaviour (OR 7.9) and alcohol misuse (OR 1.7). Suicide attempts were associated with male gender (OR 5.6), lower education (OR 4.2), violence experienced from partner (OR 2.5) or from various people (OR 9.5) and self-harm behaviour (OR 15.0). These results show that the proportion of suicidal patients seeking outpatient psychotherapy is high. It should therefore be a central topic in clinical training. Biographic data such as the loss of a parent at an early age or experiencing violence are associated with who is at increased risk and should be explored in detail.

Emotional and non-emotional mental imagery and auditory verbal hallucinations (hearing voices): A systematic review of imagery assessment tools.

It is unknown to what extent mental imagery and auditory verbal hallucinations (AVHs) are related. Trials evaluating this issue used both emotional and non-emotional mental imagery tools, thereby complicating outcomes comparisons. Therefore, the present study aimed to systematically review the literature on mental imagery in individuals with AVHs to (1) inventory imagery assessment tools used in this population, (2) to collect information on the relation between emotional and non-emotional mental imagery in all sensory domains and AVHs and (3) to integrate the outcomes of this systematic review in a model of different mental imagery domains and related assessment tools. We conducted a systematic literature search in the PubMed Database. After full-text screening, 17 papers were included. Findings showed that a variety of assessment methods have been used to assess various aspects of mental imagery in people with AVHs, suggesting that there is a lack of agreed theoretical conceptualization of mental imagery and AVHs. In addition, the studies confirmed as was expected that non-emotional mental imagery seemed unrelated to AVHs whereas emotional mental imagery was related to AVHs. Lastly, we proposed a model of mental imagery domains and corresponding assessment methods distinguishing between emotional and non-emotional mental imagery.

"That was a tip from my physician"-Gender-specific pathways of patients and relatives to outpatient psychosocial cancer counselling centres-A qualitative study.

OBJECTIVE: This study aims to identify pathways patients and their relatives take to outpatient psychosocial cancer counselling centres. We had a special interest in how access for men can be eased. METHODS: Cancer patients and relatives were purposively sampled in two regions in Germany. Participants were either outpatient cancer counselling centres (OCCCs) users or non-users and participated in qualitative face-to-face interviews. We used different guidelines for users and non-users. The interviews were analysed using content analysis. RESULTS: One hundred and three people participated in the study. Important pathways to outpatient psychosocial cancer counselling centres for both men and women were: information about the service and its content, easy access (obtaining appointments quickly and without bureaucracy, close to home), and recommendations from another person, in particular from their treating physician. Pathways especially important for men are positive and repeated recommendations from their treating physician and other people they trust, organisation by others on the men's behalf, the Internet, the possibility to talk to a male counsellor, making it a routine in the hospital to refer distressed patients to the counselling services, and the emphasis on information sharing. Women reported more often than men that they discovered and accessed OCCCs via information material. CONCLUSIONS: Men in particular need recommendations from others, especially from their treating physician, in order to make use of psychosocial cancer counselling. In addition, stressing the provision of information instead of exploring and expressing emotions can ease access for men to cancer counselling.

Methodological approach for determining the Minimal Important Difference and Minimal Important Change scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module (EORTC QLQ-HN43) exemplified by the Swallowing scale.

PURPOSE: The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43. METHODS: In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods. RESULTS: From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14. CONCLUSIONS: For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.

How does insecure attachment lead to paranoia? A systematic critical review of cognitive, affective, and behavioural mechanisms.

BACKGROUND: The relationship between attachment and paranoia is now well established. There is good theoretical reason and evidence to indicate that attachment style affects cognitive, affective, and behavioural processes which, in turn, contribute to the maintenance of paranoia, but this research has not been integrated. We critically and systematically review research that examines relevant cognitive, affective, and behavioural processes, which may explain how attachment insecurity leads to paranoia and constitute key targets in psychotherapeutic interventions for people with psychosis. METHOD: We conducted three systematic searches across six databases (PsycINFO, CINAHL, Medline, Web of Science, Embase, and Google Scholar), from inception to September 2021, to investigate key cognitive, affective, and behavioural processes in the attachment-paranoia association. RESULTS: We identified a total of 1930 papers and critically reviewed 16. The literature suggests that negative self- and other-beliefs, inability to defuse from unhelpful cognitions, and use of maladaptive emotion regulation strategies mediate the association between attachment insecurity and paranoia in people with psychosis/psychotic experience. Attachment-secure people with psychosis are more likely to seek help and engage with services than attachment-insecure people. CONCLUSIONS: Attachment styles impact help-seeking behaviours in people with psychosis and are likely to influence paranoia via self- and other-beliefs, cognition fusion, and emotion regulation - these candidate mechanisms may be targeted in psychological therapy to improve clinical outcomes for people with psychosis, characterized by paranoia. PRACTITIONER POINTS: Insecure attachment is likely to lead to paranoia via negative beliefs about self and others, cognitive fusion, and use of maladaptive emotion regulation strategies. These mechanisms can be targeted in psychotherapeutic interventions for psychosis, such as cognitive behaviour therapy, to improve clinical and recovery outcomes. People with psychosis who are attachment-secure are more likely to seek help and engage with services than those who are attachment-insecure (particularly avoidant). Attachment style can be assessed to predict service engagement and help-seeking behaviours in people with psychosis. Attachment styles are important predictors of key cognitive, affective, and behavioural processes in people with psychosis. These processes can be assessed and incorporated into individualised formulations, and then targeted in therapy to effect psychotherapeutic change.