Piloting the 'Youth Early-intervention Study' ('YES'): Preliminary functional outcomes of a randomized controlled trial targeting social participation and physical well-being in young people with emerging mental disorders.

INTRODUCTION: Young people with mental disorders present with diverse social, vocational, physical, and developmental needs. However, multifaceted interventions are rare. We examine the effectiveness of a clinical trial targeting social participation and physical well-being in young people accessing clinical services. METHODS: The 'Youth Early-intervention Study' ('YES') was an unblinded, two-phase, pilot randomized controlled trial offered as an adjunct to standard clinical care, consisting of group activities. Mixed effects models were used to examine functional outcomes over time measured by the 'Social and Occupational Functioning Assessment Scale', 'Functioning Assessment Short Test', and 'Brief Disability Questionnaire' (items 7 and 8). RESULTS: 133 participants aged 14-25 were recruited. 87 participants completed both arms and 83 participants completed a 12-month post-trial assessment. Functioning improved across all outcomes. While diagnoses differed in functioning at baseline (lower functioning in psychotic and bipolar disorders compared to depression), they did not differ in the rate of improvement across any measure. Randomization groups did not differ in baseline functioning or the rate of improvement, suggesting a non-specific impact of the intervention. Engagement with education increased from 11% at baseline to 51% at 12-months post-trial and full-time employment increased from 8% at baseline to 20% at 12-months post-trial. LIMITATIONS: Small sample, no control group, and unmeasured potential moderators (e.g. neurocognitive impairment). CONCLUSIONS: 'YES' was effective and preliminary positive outcomes were observed across all functional outcomes. Future studies should compare the 'YES' intervention to a treatment-as-usual control condition and conduct a multi-centre trial across early intervention service sites.

Piloting a parent and patient decision aid to support clinical trial decision making in childhood cancer.

OBJECTIVE: Families of a child with cancer can find the decision to enrol in a clinical trial challenging and often misunderstand key concepts that underpin trials. We pilot tested "Delta," an online and booklet decision aid for parents with a child with cancer, and adolescents with cancer, deciding whether or not to enrol in a clinical trial. METHODS: We developed Delta in accordance with the International Patient Decision Aid Standards. We conducted a pre-post pilot with parents with a child, and adolescents, who had enrolled in a paediatric phase III clinical trial for newly diagnosed acute lymphoblastic leukaemia. Parents (n = 37) and adolescents (n = 3) completed a questionnaire before and after using Delta (either the website or booklet, based on their preference). RESULTS: Twenty-three parents (62.2%) and three adolescents (100%) reviewed the Delta website. Parents rated Delta as highly acceptable in regard to being clearly presented, informative, easy to read, useful, visually appealing, and easy to use. All participants reported that they would recommend Delta to others and that it would have been useful when making their decision. Parents' subjective (Mdiff= 10.8, SDdiff  = 15.69, P < .001) and objective (OR = 2.25, 95% CI, 1.66-3.04; P < .001) clinical trial knowledge increased significantly after reviewing Delta. CONCLUSIONS: To our knowledge, Delta is the first reported decision aid, available online and as a booklet, for parents and adolescents deciding whether or not to enrol in a paediatric oncology clinical trial. Our study suggests that Delta is acceptable, feasible, and potentially useful.

Salivary cortisol reveals overt and hidden anxiety in survivors of childhood cancer attending clinic.

BACKGROUND: Symptoms of anxiety may arise from fear of cancer recurrence and memories of traumatic experiences during treatment. This study aimed to identify changes in mental health and cortisol, a biological marker of stress, associated with oncology surveillance clinic attendance. METHODS: Adolescent and young adult (AYA) survivors of childhood cancer (aged 12-30 years, N = 46) attending a survivorship clinic were recruited. The State-Trait Anxiety Inventory, an anxiety self-rating and open answer question, and salivary cortisol collections were completed two weeks before and one day before clinic, on clinic day and two weeks after. RESULTS: Trait anxiety scores were consistent with the normal population. State anxiety scores two weeks after clinic were significantly lower than baseline (p = 0.02). Cortisol diurnal slopes were flatter than baseline after clinic (p = 0.02). Evening cortisol levels were significantly higher than baseline two weeks post clinic (p = 0.02). LIMITATIONS: Combined results from biological and psychometric assessments can be difficult to interpret. Larger cohorts will further delineate cortisol pathway activity and distress in AYA cancer survivors. CONCLUSIONS: Psychometric evidence indicates that AYA survivors of childhood cancer perceive themselves to be less anxious after a survivorship clinic visit. Biological evidence, however, indicates a dysregulation of the hypothalamic-pituitary-adrenal axis which may be linked to clinic attendance. Weak correlations suggest that cortisol may not be a reliable indicator of self-perceived anxiety. This may be due to confounding lifestyle factors influencing the stress response or potential 'coping strategies' developed during past treatment experience which may, hypothetically, have masked self-perceived anxiety.

Two Sides of the Same Coin: Cannabis Dependence and Mental Health Problems in Help-Seeking Adolescent and Young Adult Outpatients.

The aim of the current study was to delineate the psychiatric profile of cannabis dependent young people (14-29 years old) with mental health problems (N = 36) seeking treatment via a research study. To do so, the Structured Clinical Interview for DSM-IV-TR Axis I Disorders and the Structured Clinical Interview for DSM-IV Childhood Diagnoses were used to obtain DSM-IV diagnoses, while a modified Timeline Followback interview and self-reports were used to measure cannabis use, cannabis-related problems, and impairment. Most individuals had at least two Axis I disorders in addition to cannabis dependence. Anxiety disorders were common, with posttraumatic stress disorder, social phobia, and generalised anxiety disorder accounting for the majority of these diagnoses. On average, young people reported a moderate degree of dependence and functional impairment, and a substantial number of cannabis-related problems. Although both males and females reported using similar quantities of cannabis per month, females reported using cannabis more frequently than males. The current data suggest that young people who present for cannabis use treatment in the context of a mental health issue may have a variety of psychiatric problems that need addressed and that males and females may have slightly different profiles. If cannabis use treatments are to advance for this population, more attention needs to be paid to the complex issues that young people present to treatment with.

Neurophysiological biomarkers support bipolar-spectrum disorders within psychosis cluster.

BACKGROUND: Mismatch negativity (MMN) and P3a are event-related potentials that index deviance detection and the orienting response, respectively. We have previously shown that the MMN/P3a complex is impaired in patients with schizophrenia and affective spectrum psychoses, which suggests that it may index a common pathophysiology and argues against the purported specificity in schizophrenia. Further research is warranted to determine whether patients with bipolar-spectrum disorders show similar impairments in these biomarkers. METHODS: We assessed patients aged 15-30 years with early schizophrenia-spectrum disorders (schizophrenia, schizoaffective disorder, schizophreniform disorder), early bipolar-spectrum disorders (bipolar I or II, with and without psychotic features) and healthy, matched controls. We acquired MMN/P3a amplitudes during a 2-tone, auditory paradigm with 8% duration deviants. Clinical, psychosocial and neuro psychological assessments were also undertaken. RESULTS: We included 20 patients with schizophrenia-spectrum disorders, 20 with bipolar-spectrum disorders and 20 controls in our study. Both patient groups showed significantly reduced frontocentral MMN and central P3a amplitudes. The schizophrenia-spectrum group had additional impairments in left temporal MMN and frontal P3a. Both patient groups performed worse than controls across psychosocial and clinical measures; however, only the schizophrenia-spectrum group performed significantly worse than controls for cognitive measures. Correlational analyses between patient groups revealed associations between frontocentral or left temporal MMN and psychiatric symptomatology or quality of life measures. LIMITATIONS: Limitations to our study include the modest sample size and the lack of control with regards to the effects of other (i.e., nonantipsychotic) psychotropic medications. CONCLUSION: Compared with patients in early stages of schizophrenia-spectrum disorders, those in the early stages of bipolar-spectrum disorders are similarly impaired in established biomarkers for schizophrenia. These findings support a shared diathesis model for psychotic and bipolar disorders. Furthermore, MMN/P3a may be a biomarker for a broader pathophysiology that overlaps traditional diagnostic clusters.

Delayed preattentional functioning in early psychosis patients with cannabis use.

RATIONALE: Cannabis use is prevalent among the early psychosis (EP) population. The event-related potentials, mismatch negativity (MMN) and P3a are reduced in EP. Cannabinoids have been shown to modulate N-methyl-D-aspartate receptors which are involved in MMN generation. OBJECTIVES: This study is the first to investigate the effects of cannabis use on MMN/P3a in EP. METHODS: EP was defined as a history of psychosis or psychotic symptoms with no progression to date to chronic schizophrenia. Twenty-two EP patients with cannabis use (EP + CANN), 22 non-cannabis-using EP patients (EP-CANN) and 21 healthy controls participated in this study. MMN/P3a was elicited using a two-tone, auditory paradigm with 8% duration deviants. RESULTS: As expected, EP-CANN showed marked reductions in MMN/P3a amplitudes compared to controls. However, EP + CANN showed evidence of a different pattern of neurophysiological expression of MMN/P3a compared to non-using patients, most notably in terms of delayed frontal MMN/P3a latencies. CONCLUSIONS: This study provides further evidence that MMN/P3a deficits are present during early psychosis and suggests that this biomarker may have utility in differentiating substance- from non-substance-related psychoses.

MMN/P3a deficits in first episode psychosis: comparing schizophrenia-spectrum and affective-spectrum subgroups.

BACKGROUND: Reduced mismatch negativity (MMN) and P3a amplitudes are neurophysiological biomarkers for schizophrenia that index deviance detection and the orienting response, respectively. First-episode psychosis (FEP) patients show reduced amplitudes of the 'MMN/P3a complex', but it is unclear whether this occurs across the FEP spectrum. METHODS: Fifty-three young people (17-36 years) were assessed: 17 FEP affective-spectrum (bipolar disorder with psychotic features and major depressive disorder with psychotic features), 18 FEP schizophrenia-spectrum (schizophrenia, schizoaffective disorder, and schizophreniform disorder), and 18 healthy controls. MMN/P3a was acquired during a two-tone, auditory paradigm with 8% duration deviants. Clinical, psychosocial and neuropsychological assessments were also undertaken. RESULTS: FEP schizophrenia- and FEP affective-spectrum showed significantly reduced fronto-central MMN and central P3a amplitudes compared to controls. FEP subgroups also showed significantly poorer cognitive and psychosocial functioning. The combined FEP sample showed significant correlations between fronto-central MMN amplitudes and cognitive measures. DISCUSSION: FEP schizophrenia-spectrum and FEP affective-spectrum were similarly impaired in two biomarkers for schizophrenia. FEP subgroups showed impairments in fronto-central MMN consistent with chronic patients. Similarly, both subgroups showed reductions in P3a; although the affective subgroup showed an 'intermediate' frontal response. These findings suggest that FEP patients with both affective and schizophrenia spectrum diagnoses share common neurobiological disturbances in deviance detection/orienting processes in the early phase of illness.

Chronic cannabis users show altered neurophysiological functioning on Stroop task conflict resolution.

RATIONALE: Chronic cannabis use has been related to deficits in cognition (particularly memory) and the normal functioning of brain structures sensitive to cannabinoids. There is increasing evidence that conflict monitoring and resolution processes (i.e. the ability to detect and respond to change) may be affected. OBJECTIVES: This study examined the ability to inhibit an automatic reading response in order to activate a more difficult naming response (i.e. conflict resolution) in a variant of the discrete trial Stroop colour-naming task. METHODS: Event-related brain potentials to neutral, congruent and incongruent trials were compared between 21 cannabis users (mean 16.4 years of near daily use) in the unintoxicated state and 19 non-using controls. RESULTS: Cannabis users showed increased errors on colour-incongruent trials (e.g. "RED" printed in blue ink) but no performance differences from controls on colour congruent (e.g. "RED" printed in red ink) or neutral trials (e.g. "*****" printed in green ink). Poorer incongruent trial performance was predicted by an earlier age of onset of regular cannabis use. Users showed altered expression of a late sustained potential related to conflict resolution, evident by opposite patterns of activity between trial types at midline and central sites, and altered relationships between neurophysiological and behavioural outcome measures not evident in the control group. CONCLUSIONS: These findings indicate that chronic use of cannabis may impair the brain's ability to respond optimally in the presence of events that require conflict resolution and hold implications for the ability to refrain from substance misuse and/or maintain substance abstention behaviours.

Chronic use of cannabis and poor neural efficiency in verbal memory ability.

INTRODUCTION: The endogenous cannabinoid system is sensitive to the introduction of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, which are known to impact upon memory functioning. We sought to examine the impact of chronic cannabis use upon memory-related brain function via examination of the subsequent memory effect (SME) of the event-related potential (ERP). METHODS: The SME is predictive of recall outcome and originates in structures that are dense with cannabinoid receptors (hippocampus and parahippocampus). The SME and performance on a verbal memory task were compared between 24 cannabis users (mean 17 years of near daily use) in the unintoxicated state and 24 non-using controls. The task involved the presentation of word lists, each with a short delay before recall. ERPs were recorded during encoding and later averaged by outcome (correctly recalled/not recalled). RESULTS: Cannabis users showed poorer recall and altered patterns of SME activation: specifically, attenuation of the negative N4 and an increase in the late positive component. Duration of cannabis use and age of initial use correlated significantly with SME amplitudes. A longer history of use also correlated with greater recall that was related to N4 expression. DISCUSSION: The results indicate that relative to non-using controls, chronic users of cannabis have altered memory-related brain activation in the form of dysfunctional SME production and/or poorer neural efficiency, which is associated with deficits in memory recall. Greater alteration was associated with a longer history of cannabis use and an earlier onset of use. Neuroadaptation to the effects of chronic exposure may additionally play a role.