The relation of basic self-disturbance to self-harm, eating disorder symptomatology and other clinical features: Exploration in an early psychosis sample.

BACKGROUND AND AIMS: The notion of basic self-disturbance has been proposed as a core feature of schizophrenia-spectrum disorders and as an indicator of future transition to psychosis in high-risk populations. However, the relation of this notion to many clinical characteristics has not been explored. The aim of this study was: (a) to investigate the distribution of self-disturbance and other symptoms dimensions in ultra-high risk (UHR), first-episode psychosis (FEP) and healthy control groups; and (b) to explore the association of self-disturbance with a history of self-harm, suicidal attempt, eating disorder symptomatology, school bullying victimization and sexual or physical abuse. METHODS: Patients with UHR status (n = 38) or FEP (n = 26) and healthy controls (n = 33) were assessed with the Examination of Anomalous Self-Experience (EASE) and the Comprehensive Assessment of at Risk Mental States (CAARMS). The clinical-historical variables were assessed through medical records. RESULTS: The FEP group scored significantly higher on the EASE than the UHR group, which scored significantly higher than the healthy control group, which had a very low score. Multivariate logistic regression analyses revealed that higher EASE score was significantly associated with a history of self-harm, disordered eating and bullying victimization (but not with suicide attempts or sexual/physical abuse) after controlling for positive, negative and depressive symptoms. CONCLUSION: These novel findings suggest that self-disturbance may be related to a history of school bullying victimization, self-harm and eating disorder symptomatology in patients with or at-risk of psychosis. If further confirmed, these findings are potentially relevant to clinical risk assessment and therapy.

Broad clinical high-risk mental state (CHARMS): Methodology of a cohort study validating criteria for pluripotent risk.

AIM: The development of the ultra-high risk (UHR) criteria for psychosis created a new paradigm for the prevention research in psychiatry. Since (1) prevention research faces the challenge of achieving adequate statistical power when focusing on single low-incidence syndromes and (2) early clinical phenotypes are overlapping and non-specific, this study broadens the UHR state beyond psychosis as an outcome. The CHARMS (clinical high at-risk mental state) study aims to prospectively validate a set of trans-diagnostic criteria to identify help-seeking young people at risk of developing a range of serious mental illnesses. METHODS: This paper describes the methodology of the CHARMS study, which involves applying the CHARMS criteria to a cohort of help-seeking young people aged 12 to 25 attending youth mental health services in Melbourne. New referrals meeting the CHARMS criteria are allocated to the CHARMS+ group; referrals not meeting CHARMS threshold are allocated to CHARMS- group (control group); referrals meeting criteria for a full-threshold disorder are excluded. Transition status and clinical and functional outcomes are re-assessed at 6 and 12 months. CONCLUSIONS: This study will be the first to introduce and validate clinical criteria to identify a broader at-risk patient population, which may facilitate young people's access to clinical services and early treatment by reducing the reliance on "caseness" defined according to current diagnostic categories being required for service entry. These criteria may introduce a new, trans-diagnostic approach for understanding risk factors and pathogenic mechanisms that drive the onset of severe mental illness and the next generation of preventive intervention trials.

Opening the Black Box of Cognitive-Behavioural Case Management in Clients with Ultra-High Risk for Psychosis.

BACKGROUND: Cognitive-behavioural therapy (CBT) is the first-choice treatment in clients with ultra-high risk (UHR) for psychosis. However, CBT is an umbrella term for a plethora of different strategies, and little is known about the association between the intensity and content of CBT and the severity of symptomatic outcome. METHODS: A sample of 268 UHR participants received 6 months of CBT with case management (CBCM) in the context of the multi-centre NEURAPRO trial with monthly assessments of attenuated psychotic symptoms (APS). Using multilevel regressions and controlling for the initial severity of APS, the associations between (1) number of CBCM sessions received and severity of APS and (2) specific CBCM components and severity of APS were investigated. RESULTS: In month 1, a higher number of sessions and more assessment of symptoms predicted an increase in APS, while in month 3, a higher number of sessions and more monitoring predicted a decrease in the level of APS. More therapeutic focus on APS predicted an overall increase in APS. CONCLUSIONS: Our findings indicate that the association between intensity/content of CBCM and severity of APS in a sample of UHR participants depends on the length of time in treatment. CBCM may positively impact the severity of APS later in the course of treatment. Therefore, it would seem important to keep UHR young people engaged in treatment beyond this initial period. Regarding the specific content of CBCM, a therapeutic focus on APS may not necessarily be beneficial in reducing the severity of APS, a possibility in need of further investigation.

Executive control network connectivity strength protects against relapse to cocaine use.

Cocaine addiction is characterized by notoriously high relapse rates following treatment. Recent efforts to address poor treatment outcomes have turned to potential neural markers of relapse risk. Accordingly, the present study examined resting state functional connectivity (rsFC) within and between three large-scale cortical networks: the default mode network (DMN), salience network (SN) and executive control network (ECN). All three have been implicated in relapse-related phenomena including craving, withdrawal and executive control deficits. Forty-five cocaine-dependent individuals and 22 healthy controls completed 6-min resting fMRI scans, The Wisconsin Card Sorting Task, Continuous Performance Test and Cocaine Craving Questionnaire. Cocaine-dependent individuals completed all measures in the final week of a residential treatment episode. Ten control and 9 abstinent cocaine-dependent individuals returned for 3-6 month follow-up scan visits. A group-level independent component analysis was employed to generate ECN, DMN and SN components. For individuals abstinent up to day 30 post-treatment (n = 21), we found enhanced pre-discharge rsFC between the left ECN and both the right ECN and SN as well as between the right ECN and left ECN. Left ECN rsFC effects remained elevated 3-6 months later among abstinent cocaine-dependent individuals. Relapse was related to fewer years of education and more years smoking but no other demographic, clinical, treatment and neurocognitive characteristics. Findings suggest that interhemispheric ECN and ECN-SN connectivity strength may protect against relapse to cocaine use following treatment. These patterns of enhanced interhemispheric network connectivity may reflect a greater capacity to engage executive control processes when faced with opportunities to use cocaine post-treatment.

Basal Hippocampal Activity and Its Functional Connectivity Predicts Cocaine Relapse.

BACKGROUND: Cocaine-induced neuroplastic changes may result in a heightened propensity for relapse. Using regional cerebral blood flow (rCBF) as a marker of basal neuronal activity, this study assessed alterations in rCBF and related resting state functional connectivity (rsFC) to prospectively predict relapse in patients following treatment for cocaine use disorder (CUD). METHODS: Pseudocontinuous arterial spin labeling functional magnetic resonance imaging and resting blood oxygen level-dependent functional magnetic resonance imaging data were acquired in the same scan session in abstinent participants with CUD before residential treatment discharge and in 20 healthy matched control subjects. Substance use was assessed twice weekly following discharge. Relapsed participants were defined as those who used stimulants within 30 days following treatment discharge (n = 22); early remission participants (n = 18) did not. RESULTS: Voxel-wise, whole-brain analysis revealed enhanced rCBF only in the left posterior hippocampus (pHp) in the relapsed group compared with the early remission and control groups. Using this pHp as a seed, increased rsFC strength with the posterior cingulate cortex (PCC)/precuneus was seen in the relapsed versus early remission subgroups. Together, both increased pHp rCBF and strengthened pHp-PCC rsFC predicted relapse with 75% accuracy at 30, 60, and 90 days following treatment. CONCLUSIONS: In CUD participants at risk of early relapse, increased pHp basal activity and pHp-PCC circuit strength may reflect the propensity for heightened reactivity to cocaine cues and persistent cocaine-related ruminations. Mechanisms to mute hyperactivated brain regions and delink dysregulated neural circuits may prove useful to prevent relapse in patients with CUD.

Cortico-amygdala coupling as a marker of early relapse risk in cocaine-addicted individuals.

Addiction to cocaine is a chronic condition characterized by high rates of early relapse. This study builds on efforts to identify neural markers of relapse risk by studying resting-state functional connectivity (rsFC) in neural circuits arising from the amygdala, a brain region implicated in relapse-related processes including craving and reactivity to stress following acute and protracted withdrawal from cocaine. Whole-brain resting-state functional magnetic resonance imaging connectivity (6 min) was assessed in 45 cocaine-addicted individuals and 22 healthy controls. Cocaine-addicted individuals completed scans in the final week of a residential treatment episode. To approximate preclinical models of relapse-related circuitry, separate seeds were derived for the left and right basolateral (BLA) and corticomedial (CMA) amygdala. Participants also completed the Iowa Gambling Task, Wisconsin Card Sorting Test, Cocaine Craving Questionnaire, Obsessive-Compulsive Cocaine Use Scale and Personality Inventory. Relapse within the first 30 days post-treatment (n = 24) was associated with reduced rsFC between the left CMA and ventromedial prefrontal cortex/rostral anterior cingulate cortex (vmPFC/rACC) relative to cocaine-addicted individuals who remained abstinent (non-relapse, n = 21). Non-relapse participants evidenced reduced rsFC between the bilateral BLA and visual processing regions (lingual gyrus/cuneus) compared to controls and relapsed participants. Early relapse was associated with fewer years of education but unrelated to trait reactivity to stress, neurocognitive and clinical characteristics or cocaine use history. Findings suggest that rsFC within neural circuits implicated in preclinical models of relapse may provide a promising marker of relapse risk in cocaine-addicted individuals. Future efforts to replicate the current findings and alter connectivity within these circuits may yield novel interventions and improve treatment outcomes.

Striatal-insula circuits in cocaine addiction: implications for impulsivity and relapse risk.

BACKGROUND: Dysregulated striatal functioning coupled with executive control deficits arising from abnormal frontal cortical function are considered key mechanisms in the development and maintenance of cocaine addiction. The same features are thought to underlie high trait impulsivity observed in cocaine-addicted populations. OBJECTIVES: Employing resting state functional connectivity, the current study sought to identify cortico-striatal circuit alterations in cocaine addiction and examine the degree to which circuit connectivity contributes to relapse risk and impulsivity among cocaine-addicted individuals. METHODS: Whole-brain resting-state functional magnetic resonance imaging connectivity was assessed in 45 cocaine-addicted individuals relative to 22 healthy controls using seed volumes in the left and right caudate, putamen and nucleus accumbens. Cocaine-addicted individuals completed scans in the final week of a 2-4 weeks residential treatment episode. Relapse by day 30 post-discharge served to separate cocaine-addicted individuals into relapse and non-relapse groups. All participants completed the Barratt Impulsivity Scale (BIS-11a). RESULTS: Cocaine-addicted individuals exhibited reduced positive connectivity between the bilateral putamen and posterior insula and right postcentral gyrus. Group differences were primarily driven by reduced connectivity in relapse individuals relative to controls. No relapse versus non-relapse differences emerged. Impulsivity (BIS-11a) was higher in cocaine-addicted participants, an effect that was partially mediated by reduced putamen-posterior insula connectivity in this group. CONCLUSION: Cocaine addiction, relapse risk and impulsivity were associated with reduced connectivity in putamen-posterior insula/postcentral gyrus circuits implicated in temporal discounting and habitual responding. Findings provide new insight into the neurobiological mechanisms underlying impulsivity and relapse in cocaine addiction.

Resting state functional connectivity in addiction: Lessons learned and a road ahead.

Despite intensive scientific investigation and public health imperatives, drug addiction treatment outcomes have not significantly improved in more than 50 years. Non-invasive brain imaging has, over the past several decades, contributed important new insights into the neuroplastic adaptations that result from chronic drug intake, but additional experimental approaches and neurobiological hypotheses are needed to better capture the totality of the motivational, affective, cognitive, genetic and pharmacological complexities of the disease. Recent advances in assessing network dynamics through resting-state functional connectivity (rsFC) may allow for such systems-level assessments. In this review, we first summarize the nascent addiction-related rsFC literature and suggest that in using this tool, circuit connectivity may inform specific neurobiological substrates underlying psychological dysfunctions associated with reward, affective and cognitive processing often observed in drug addicts. Using nicotine addiction as an exemplar, we subsequently provide a heuristic framework to guide future research by linking recent findings from intrinsic network connectivity studies with those interrogating nicotine's neuropharmacological actions. Emerging evidence supports a critical role for the insula in nicotine addiction. Likewise, the anterior insula, potentially together with the anterior cingulate cortex, appears to pivotally influence the dynamics between large-scale brain networks subserving internal (default-mode network) and external (executive control network) information processing. We suggest that a better understanding of how the insula modulates the interaction between these networks is critical for elucidating both the cognitive impairments often associated with withdrawal and the performance-enhancing effects of nicotine administration. Such an understanding may be usefully applied in the design and development of novel smoking cessation treatments.

The effect of stimulus modality and task difficulty on attentional modulation of blink startle.

The effects of the sensory modality of the lead stimulus and of task difficulty on attentional modulation of the electrical and acoustic blink reflex were examined. Participants performed a discrimination and counting task with either two acoustic, two visual, or two tactile lead stimuli. In Experiment 1, facilitation of the electrically elicited blink was greater during task-relevant than during task-irrelevant lead stimuli. Increasing task difficulty enhanced magnitude facilitation for acoustic lead stimuli. In Experiment 2, acoustic blink facilitation was greater during task-relevant lead stimuli, but was unaffected by task difficulty. Experiment 3 showed that a further increase in task difficulty did not affect acoustic blink facilitation during visual lead stimuli. The observation that blink reflexes are facilitated by attention in the present task domain is consistent across a range of stimulus modality and task difficulty conditions.

Attentional blink modulation during sustained and after discrete lead stimuli presented in three sensory modalities.

Previous studies found larger attentional modulation of acoustic blinks during task-relevant than during task-irrelevant acoustic or visual, but not tactile, lead stimuli. Moreover, blink modulation was larger overall during acoustic lead stimuli. The present experiment investigated whether these results reflect modality specificity of attentional blink modulation or effects of continuous stimulation. Participants performed a discrimination and counting task with acoustic, visual, or tactile lead stimuli. Stimuli were presented sustained or consisted of two short discrete stimuli. The sustained condition replicated previous results. In the discrete condition, blinks were larger during task-relevant than during task-irrelevant stimuli in all groups regardless of lead stimulus modality. Thus, previous results that seemed consistent with modality-specific accounts of attentional blink modulation reflect effects of continuous stimulus input.

Lead stimulus modality change and the attentional modulation of the acoustic and electrical blink reflex.

Two experiments investigated the effects of the sensory modality of the lead and of the blink-eliciting stimulus during lead stimulus modality change on blink modulation at lead intervals of 2500 and 3500 ms. Participants were presented with acoustic, visual, or tactile change stimuli after habituation training with lead stimuli from the same or a different sensory modality. In Experiment 1, latency and magnitude of the acoustic blink were facilitated during a change to acoustic or visual lead stimuli, but not during a change to tactile lead stimuli. After habituation to acoustic lead stimuli, blink magnitude was smaller during tactile change stimuli than during habituation stimuli. The latter finding was replicated in Experiment 2 in which blink was elicited by electrical stimulation of the trigeminal nerve. The consistency of the findings across different combinations of lead stimulus and blink-eliciting stimulus modalities does not support a modality-specific account of attentional blink modulation. Rather, blink modulation during generalized orienting reflects modality non-specific processes, although modulation may not always be found during tactile lead stimuli.