Andrew Frankland

Reduced Inferior Frontal Gyrus Activation During Response Inhibition to Emotional Stimuli in Youth at High Risk of Bipolar Disorder

BACKGROUND Functional brain imaging of young people at increased genetic risk for bipolar disorder provides a means of identifying potential endophenotypes for this condition. Dysfunctional neural mechanisms for the cognitive control of emotion are implicated in the genetic predisposition to bipolar disorder, with aberrant activity in frontocortical, striatal, and limbic brain regions previously reported in subjects with established bipolar disorder during inhibitory and emotion processing tasks. METHODS Functional brain activity during inhibition of emotional material in young people at increased genetic risk for bipolar disorder was investigated using a facial-emotion go/no-go task during functional magnetic resonance imaging. Data from 47 genetically high-risk individuals aged 18 to 30 years with at least one first-degree relative with bipolar disorder were compared with 49 control subjects (within the same age range but without a family history of bipolar disorder or other severe mental illness). RESULTS Whole-brain corrected analyses revealed a highly specific and significant lack of recruitment of the inferior frontal gyrus when inhibiting responses to fearful faces in the high-risk participants compared with control subjects (p = .011, family-wise error, peak voxel). CONCLUSIONS Impaired inhibitory function of the inferior frontal cortex may represent a trait marker of vulnerability to bipolar disorder. That this finding was revealed during inhibition of emotional material further implicates dysregulated frontolimbic brain networks as a potential neurocognitive endophenotype for bipolar disorder and provides evidence for pre-existing functional disturbances in those at high genetic risk for bipolar disorder.

Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms

Mitchell PB, Johnston AK, Frankland A, Slade T, Green MJ, Roberts G, Wright A, Corry J, Hadzi‐Pavlovic D. Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms.

Does age affect sexual behaviour among gay men in Sydney, Melbourne and Brisbane, Australia?

Abstract Concern internationally that young gay men are at increased risk of HIV infection has not been reflected in earlier findings in Australia where younger men have not been found to be at increased likelihood to engage in unprotected anal intercourse with casual partners (UAIC). There has, however, been little attention paid to the issue of age in relation to HIV risk behaviour in Australia in recent years. In 2007, among men who completed Gay Community Periodic Survey questionnaires in Sydney, Melbourne and Brisbane, Australia, younger men were more likely to report being in relatively short-term monogamous relationships than were their older counterparts. They were also less likely to know their own or their partners’ HIV serostatus. Men aged less than 25 years reported fewer recent partners and were less likely to report sex with casual male partners in the previous six months (p<0.001). Younger men were also less likely to engage in group sex. Approximately, one-quarter of the sample reported engaging in any UAIC in the previous six months during each year of the survey. Younger men were no less likely to report UAIC overall, but they were somewhat more likely to report taking the receptive position during UAIC. While age is a consideration in the assessment of risk of HIV transmission among gay men, this risk is dependent upon the context in which it occurs: Age mixing may be an important consideration in understanding HIV risk among young gay men.

Network dysfunction of emotional and cognitive processes in those at genetic risk of bipolar disorder

The emotional and cognitive vulnerabilities that precede the development of bipolar disorder are poorly understood. The inferior frontal gyrus-a key cortical hub for the integration of cognitive and emotional processes-exhibits both structural and functional changes in bipolar disorder, and is also functionally impaired in unaffected first-degree relatives, showing diminished engagement during inhibition of threat-related emotional stimuli. We hypothesized that this functional impairment of the inferior frontal gyrus in those at genetic risk of bipolar disorder reflects the dysfunction of broader network dynamics underlying the coordination of emotion perception and cognitive control. To test this, we studied effective connectivity in functional magnetic resonance imaging data acquired from 41 first-degree relatives of patients with bipolar disorder, 45 matched healthy controls and 55 participants with established bipolar disorder. Dynamic causal modelling was used to model the neuronal interaction between key regions associated with fear perception (the anterior cingulate), inhibition (the left dorsolateral prefrontal cortex) and the region upon which these influences converge, namely the inferior frontal gyrus. Network models that embodied non-linear, hierarchical relationships were the most strongly supported by data from our healthy control and bipolar participants. We observed a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral prefrontal cortex to the inferior frontal gyrus that is unique to the at-risk cohort. Non-specific, non-hierarchical mechanisms appear to compensate for this network disturbance. We thus establish a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control in those at high genetic risk for bipolar disorder.

Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder

BACKGROUND Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives. METHOD Neurocognitive and social cognitive ability was examined in 99 young people (age range 16-30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD. RESULTS Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs. CONCLUSIONS Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.

Functional Dysconnection of the Inferior Frontal Gyrus in Young People With Bipolar Disorder or at Genetic High Risk

BACKGROUND Bipolar disorder (BD) is characterized by a dysregulation of affect and impaired integration of emotion with cognition. These traits are also expressed in probands at high genetic risk of BD. The inferior frontal gyrus (IFG) is a key cortical hub in the circuits of emotion and cognitive control, and it has been frequently associated with BD. Here, we studied resting-state functional connectivity of the left IFG in participants with BD and in those at increased genetic risk. METHODS Using resting-state functional magnetic resonance imaging we compared 49 young BD participants, 71 individuals with at least one first-degree relative with BD (at-risk), and 80 control subjects. We performed between-group analyses of the functional connectivity of the left IFG and used graph theory to study its local functional network topology. We also used machine learning to study classification based solely on the functional connectivity of the IFG. RESULTS In BD, the left IFG was functionally dysconnected from a network of regions, including bilateral insulae, ventrolateral prefrontal gyri, superior temporal gyri, and the putamen (p < .001). A small network incorporating neighboring insular regions and the anterior cingulate cortex showed weaker functional connectivity in at-risk than control participants (p < .006). These constellations of regions overlapped with frontolimbic regions that a machine learning classifier selected as predicting group membership with an accuracy significantly greater than chance. CONCLUSIONS Functional dysconnectivity of the IFG from regions involved in emotional regulation may represent a trait abnormality for BD and could potentially aid clinical diagnosis.

Anxiety, stress and perfectionism in bipolar disorder

BACKGROUND Previous reports have highlighted perfectionism and related cognitive styles as a psychological risk factor for stress and anxiety symptoms as well as for the development of bipolar disorder symptoms. The anxiety disorders are highly comorbid with bipolar disorder but the mechanisms that underpin this comorbidity are yet to be determined. METHOD Measures of depressive, (hypo)manic, anxiety and stress symptoms and perfectionistic cognitive style were completed by a sample of 142 patients with bipolar disorder. Mediation models were used to explore the hypotheses that anxiety and stress symptoms would mediate relationships between perfectionistic cognitive styles, and bipolar disorder symptoms. RESULTS Stress and anxiety both significantly mediated the relationship between both self-critical perfectionism and goal attainment values and bipolar depressive symptoms. Goal attainment values were not significantly related to hypomanic symptoms. Stress and anxiety symptoms did not significantly mediate the relationship between self-critical perfectionism and (hypo)manic symptoms. LIMITATIONS 1. These data are cross-sectional; hence the causality implied in the mediation models can only be inferred. 2. The clinic patients were less likely to present with (hypo)manic symptoms and therefore the reduced variability in the data may have contributed to the null findings for the mediation models with (hypo) manic symptoms. 3. Those patients who were experiencing current (hypo)manic symptoms may have answered the cognitive styles questionnaires differently than when euthymic. CONCLUSION These findings highlight a plausible mechanism to understand the relationship between bipolar disorder and the anxiety disorders. Targeting self-critical perfectionism in the psychological treatment of bipolar disorder when there is anxiety comorbidity may result in more parsimonious treatments.

Living serodiscordantly in Papua New Guinea: sexual practices of HIV-positive people on ART by serostatus of regular heterosexual partner

Abstract This paper examines condom use in intimate relationships amongst Papua New Guineans on antiretroviral therapy (ART). These findings are from a mixed-method study in six provinces throughout Papua New Guinea (PNG). A total of 374 HIV-positive adult Papua New Guineans, over the age of 16 and on ART for more than two weeks were recruited using a non-probability, convenience sampling methodology. Participants were recruited through ART prescribing sites, People Living with HIV/AIDS (PLWHA) drop-in clinics and support groups. A small number (36) also participated in in-depth interviews. Of the sample 226 (60.4%) were women and 148 (39.6%) were men. The majority of the sample was aged below 40 years, with a median age of 30 years. Of the sample who were in a regular relationship 64.7% identified themselves as being in a relationship where both they and their partner were HIV-positive (seroconcordant). Smaller proportions (21.0%) reported being in a relationship with a HIV-negative partner (serodiscordant), or in a relationship where they were not aware of their partners HIV status (14.3%). The majority of participants who reported having a regular partner also reported having disclosed their HIV serostatus to their partner (91.8%). A significantly greater proportion of participants who reported being in relationships where they did not know the status of their partner, also reported living in the Southern Region of PNG (52.9%), while the majority of those in seroconcordant relationships lived in the Highlands Region (71.2%). There did not appear to be any differences in sexual practice of using condoms between the three groups. Knowledge of serostatus is important for “positive prevention”.

Barriers and Facilitators for Adherence to Antiretroviral Therapy in Papua New Guinea

Papua New Guinea (PNG) is in a phase of scaling up access to antiretroviral therapy (ART), and adherence to the newly available drug therapy is becoming an important issue. This paper examines adherence to ART in a sample of 374 HIV-positive people in six provinces in PNG. Participants were recruited to the study using non-probability sampling. Sixty-two % of participants reported complete adherence (no missed or late doses in the past week) and 79% reported not missing any doses in the last week. Revival church members were significantly more likely to report having missing a treatment dose(s) (66%). Those living in the Highlands and those attending Catholic health clinics were significantly more likely to be adherent to their treatment. Age, gender, marital status, education level and employment type did not show significant association with treatment adherence. Adherence rates in PNG are not alarming, indicating that people with HIV can adhere to treatment despite the challenges of living in PNG.

Current issues in care and support for HIV-positive gay men in Sydney.

We explored current access to care among HIV-positive people in Australia. In 2006, 270 HIV-positive gay men from a community-based Positive Health cohort in Sydney were asked about their health (including medical and social) service needs and, subsequently, about difficulty in accessing services. We report the prevalence of specific needs, barriers and associated factors. Participants most commonly used general practitioners (64%) for HIV management and needed at least one HIV-related medical service (usually several: doctors experienced in HIV management, dentists and hospital pharmacies). Most participants were able to access them. Barriers in accessing services were related to their convenience rather than lack or quality. Cost emerged as a substantial barrier to dental care and psychological counselling (91% and 48% respectively of those in need). Need for an HIV-related social service was reported by 46% of respondents. Difficulties in accessing these related to poor services and staff attitudes. Income was associated with limited access to multiple services. In Australia, HIV-related medical service needs outweigh those for social services. Complex health services remain essential to HIV-positive people, but some services are currently not meeting their needs. To remain adequate, services need to understand and constantly adapt to the changing needs of HIV-positive people.