Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.

Childhood trauma and cognitive functioning in mood disorders: A systematic review.

BACKGROUND: Cognitive impairment is a core feature of mood disorders and has been identified as an important treatment target. A better understanding of the factors contributing to cognitive impairment in mood disorders would be beneficial in developing interventions to address cognitive impairment. One key factor is childhood trauma. The aim of this review was to systematically synthesise and review research examining associations between reported childhood trauma and cognitive functioning in mood disorders. METHODS: Studies in adult samples examining the relationship between objective cognitive function and reported childhood trauma in major depressive disorder and/or bipolar disorder (in-episode or euthymia) were identified. Searches were conducted on PubMed, Embase and PsycINFO until January 2022. A narrative review technique was used due to the heterogeneity of group comparisons, cognitive tests and data analysis across studies. RESULTS: Seventeen studies met the criteria for inclusion (mood disorders N = 1723, healthy controls N = 797). Evidence for childhood trauma being related to poorer cognitive functioning was consistent across global cognitive functioning and executive function domains for euthymic patients and psychomotor speed for in-episode patients. There was mixed evidence for verbal learning and memory and executive function for in-episode patients. Identification of patterns within other domains was difficult due to limited number of studies. CONCLUSION: Findings from this review suggest childhood trauma is associated with poorer cognitive functioning in people with mood disorders. Targeted interventions to improve cognition may be warranted for this group.

Barriers to and facilitators of success for early and Mid-Career professionals focused on bipolar disorder: A global needs survey by the International Society for Bipolar Disorders.

INTRODUCTION: The International Society for Bipolar Disorders created the Early Mid-Career Committee (EMCC) to support career development of the next generation of researchers and clinicians specializing in bipolar disorder (BD). To develop new infrastructure and initiatives, the EMCC completed a Needs Survey of the current limitations and gaps that restrict recruitment and retention of researchers and clinicians focused on BD. METHODS: The EMCC Needs Survey was developed through an iterative process, relying on literature and content expertise of workgroup members. The survey included 8 domains: navigating transitional career stages, creating and fostering mentorship, research activities, raising academic profile, clinical-research balance, networking and collaboration, community engagement, work-life balance. The final survey was deployed from May to August 2022 and was available in English, Spanish, Portuguese, Italian, and Chinese. RESULTS: Three hundred participants across six continents completed the Needs Survey. Half of the participants self-identified as belonging to an underrepresented group in health-related sciences (i.e., from certain gender, racial, ethnic, cultural, or disadvantaged backgrounds including individuals with disabilities). Quantitative results and qualitative content analysis revealed key barriers to pursuing a research career focused on BD with unique challenges specific to scientific writing and grant funding. Participants highlighted mentorship as a key facilitator of success in research and clinical work. CONCLUSION: The results of the Needs Survey are a call to action to support early- and midcareer professionals pursuing a career in BD. Interventions required to address the identified barriers will take coordination, creativity, and resources to develop, implement, and encourage uptake but will have long-lasting benefits for research, clinical practice, and ultimately those affected by BD.

Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force.

BACKGROUND: Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations. METHODS: The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials. RESULTS: We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking. CONCLUSIONS: Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.

Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force.

BACKGROUND: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions. METHODS: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist. RESULTS: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred. CONCLUSIONS: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out-of-scanner tests.

A randomised controlled trial of psychotherapy and cognitive remediation to target cognition in mood disorders.

OBJECTIVE: To examine the impact of a treatment package combining Interpersonal and Social Rhythm Therapy (IPSRT) and cognitive remediation (CR), vs IPSRT alone, on cognition, functioning, and mood disturbance outcomes in mood disorders. METHODS: A pragmatic randomised controlled trial in adults with bipolar disorder (BD) or major depressive disorder (MDD), recently discharged from mental health services in Christchurch, New Zealand, with subjective cognitive difficulties. Individuals were randomised to a 12-month course of IPSRT with CR (IPSRT-CR), or without CR (IPSRT). In IPSRT-CR, CR was incorporated into therapy sessions from approximately session 5 and continued for 12 sessions. The primary outcome was change in Global Cognition (baseline to 12 months). RESULTS: Sixty-eight individuals (BD n = 26, MDD n = 42; full/partial remission n = 39) were randomised to receive IPSRT-CR or IPSRT (both n = 34). Across treatment arms, individuals received an average of 23 IPSRT sessions. Change in Global Cognition did not differ between arms from baseline to treatment-end (12 months). Psychosocial functioning and longitudinal depression symptoms improved significantly more in the IPSRT compared with IPSRT-CR arm over 12 months, and all measures of functioning and mood symptoms showed moderate effect size differences favouring IPSRT (0.41-0.60). At 18 months, small to moderate, non-significant benefits (0.26-0.47) of IPSRT vs IPSRT-CR were found on functioning and mood outcomes. CONCLUSIONS: Combining two psychological therapies to target symptomatic and cognitive/functional recovery may reduce the effect of IPSRT, which has implications for treatment planning in clinical practice and for CR trials in mood disorders.

Randomised controlled trial of Interpersonal and Social Rhythm Therapy and group-based Cognitive Remediation versus Interpersonal and Social Rhythm Therapy alone for mood disorders: study protocol.

BACKGROUND: Individuals with mood disorders frequently experience cognitive impairment, which impacts on the long-term trajectory of the disorders, including being associated with persisting difficulties in occupational and psychosocial functioning, residual mood symptoms, and relapse. Current first-line treatments for mood disorders do little to improve cognitive function. Targeting cognition in clinical research is thus considered a priority. This protocol outlines a prospectively-registered randomised controlled trial (RCT) which examines the impact of adding group-based Cognitive Remediation (CR) to Interpersonal and Social Rhythm Therapy (IPSRT-CR) for individuals with mood disorders. METHODS: This is a pragmatic, two-arm, single-blinded RCT comparing IPSRT-CR with IPSRT alone for adults (n = 100) with mood disorders (Major Depressive Disorder or Bipolar Disorder) with subjective cognitive difficulties, on discharge from Specialist Mental Health Services in Christchurch, New Zealand. Both treatment arms will receive a 12-month course of individual IPSRT (full dose = 24 sessions). At 6 months, randomisation to receive, or not, an 8-week group-based CR programme (Action-based Cognitive Remediation - New Zealand) will occur. The primary outcome will be change in Global Cognition between 6 and 12 months (treatment-end) in IPSRT-CR versus IPSRT alone. Secondary outcomes will be change in cognitive, functional, and mood outcomes at 6, 12, 18, and 24 months from baseline and exploratory outcomes include change in quality of life, medication adherence, rumination, and inflammatory markers between treatment arms. Outcome analyses will use an intention-to-treat approach. Sub-group analyses will assess the impact of baseline features on CR treatment response. Participants' experiences of their mood disorder, including treatment, will be examined using qualitative analysis. DISCUSSION: This will be the first RCT to combine group-based CR with an evidence-based psychotherapy for adults with mood disorders. The trial may provide valuable information regarding how we can help promote long-term recovery from mood disorders. Many issues have been considered in developing this protocol, including: recruitment of the spectrum of mood disorders, screening for cognitive impairment, dose and timing of the CR intervention, choice of comparator treatment, and choice of outcome measures. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12619001080112 . Registered on 6 August 2019.

Rate of polycystic ovary syndrome in mental health disorders: a systematic review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with increased risk of many mental health conditions, including mood and anxiety disorders. Whether PCOS is more common in mental health conditions than in the general population is less clear. A systematic review investigating this question may provide clarity regarding whether increased prevalence of PCOS is seen in particular mental health disorders, and thus, whether screening female mental health patients for PCOS is warranted. AIMS: To systematically synthesise and review research examining rates of PCOS in mental health disorders. METHODS: Peer-reviewed articles assessing the prevalence of PCOS within a sample of reproductive-aged females with a diagnosis of Axis I or II mental health disorder were included. Key studies were identified through a comprehensive search of PubMed and Web of Science. RESULTS: Eleven studies met inclusion criteria, assessing rate of diagnosed PCOS in samples with bipolar disorder (n = 7), autism spectrum disorders (ASD; n = 2), bulimia nervosa (n = 1), and post-traumatic stress disorder (PTSD; n = 1). Overall, there was limited evidence of elevated rates of PCOS in bipolar disorder, compared with population estimates or healthy control group rates. In ASD, bulimia nervosa, and PTSD samples, significantly increased rates of PCOS were reported compared with healthy control samples, although studies were relatively small. CONCLUSIONS: This review highlights complexities and methodological considerations in this area of research. There are a limited number of studies assessing PCOS in mental health samples, and thus, important areas of future research have been identified. TRIAL REGISTRATION: This systematic review was registered on PROSPERO (ID: CRD42020151420; https://www.crd.york.ac.uk/prospero/ ) on 28 April 2020.

Free testosterone is related to aspects of cognitive function in women with and without polycystic ovary syndrome.

Evidence suggests impairment in aspects of cognitive function in women with polycystic ovary syndrome (PCOS). Direct effects of raised testosterone levels associated with PCOS are a potential mechanism. We aimed to explore the relationship between testosterone levels and cognitive functioning in women. Women with a range of testosterone levels, including women with PCOS, were recruited. Depressive and anxiety symptoms were measured by self-report. Participants underwent a comprehensive battery of cognitive tests assessing psychomotor speed, visuospatial learning and memory, verbal learning and memory, and executive function. Free testosterone serum levels were assessed. All measures were completed at the same time point. Correlation analysis (Spearman's Rho) was used to explore associations between free testosterone and cognitive test variables. Eighty-one women were recruited, with 40 meeting diagnostic criteria for PCOS. Free testosterone was normally distributed, with significant overlap between women with PCOS and controls. Mean depressive and anxiety symptoms were in the mild range. Higher free testosterone levels were significantly correlated with poorer performance on measures assessing psychomotor speed and visuospatial learning. These significant correlations remained after adjusting for confounders (premorbid verbal IQ, depressive, and anxiety symptoms). Higher free testosterone levels in women were associated with poorer cognitive function, specifically psychomotor speed and visuospatial learning. Women with PCOS and raised free testosterone levels may experience impairment in these aspects of cognitive function which are not accounted for by mood or anxiety symptoms.

Effects of psychotherapy on comorbid bipolar disorder and substance use disorder: A systematic review.

OBJECTIVES: This review aim was to examine whether psychotherapy is more or less effective in patients with SUD, compared to those without; whether there is a differential effect of a particular psychotherapy in patients with SUD. METHODS: A quantitative systematic review following the Cochrane Handbook of Systematic Reviews was used. RESULTS: Five studies of psychotherapy for BD and two studies of an integrated psychotherapy for comorbid BD and SUD were included in the review. Five studies provided a sub-analysis of the effect of SUD on overall outcomes with only one finding an overall detrimental effect. The results indicated equal, if not better outcomes for individuals with comorbid BD and SUD. CONCLUSION: There was little evidence that interventions targeted at both BD and SUD may be more efficacious. Further research in to psychotherapeutic treatment for BD should include individuals with comorbid SUD, and analyse substance use as an outcome. Additionally, research into treatments specifically developed for these commonly comorbid disorders is indicated.

Systematic review of the effects of evidence-based psychotherapies on neurocognitive functioning in mood disorders.

OBJECTIVE: Neurocognitive impairment is considered a core feature of mood disorders. Research has shown that neurocognitive impairment often persists beyond mood symptom resolution and can have significant deleterious effects on interpersonal relationships, academic achievement, occupational functioning and independent living. As such, neurocognitive impairment has become an important target for intervention. In this systematic review, we aimed to examine the extant literature to ascertain whether current standard evidence-based psychotherapies can improve neurocognitive functioning in mood disorders. METHOD: Studies examining changes in neurocognitive functioning following evidence-based psychotherapy were identified using MEDLINE, PsycINFO and Web of Science databases. Given the heterogeneity of study procedures, treatment protocols and patient samples, a narrative rather than meta-analytic review technique was employed. RESULTS: Nineteen studies (21 articles) met inclusion criteria. There was preliminary evidence of improved executive functioning following evidence-based psychotherapy for Major Depressive Disorder and Bipolar Disorder. There was also some signal of reduced negative biases in emotional information processing following psychotherapy in depression. Due to methodological variability across studies however, it was difficult to draw clear conclusions. CONCLUSION: Findings from the current review suggest that evidence-based psychotherapies may influence some aspects of neurocognitive functioning in mood disorders. This continues to be an ongoing area of importance and warrants further research.

Patients' Perceptions of Functional Improvement in Psychotherapy for Mood Disorders.

OBJECTIVE: This study aimed to examine participants' experiences of interpersonal and social rhythm therapy, with or without cognitive remediation, and the impact of this intervention on their functioning. METHODS: This qualitative study drew data from follow-up interviews of 20 participants who completed the 12-month intervention as part of a randomized controlled trial. The qualitative data were collected through semistructured interviews and were analyzed with thematic analysis. RESULTS: The 20 participants (11 men, 9 women, ages 22-55, median age=32) reported that interpersonal and social rhythm therapy (content and process) as an adjunct to medication, alone or in combination with cognitive remediation, was effective in improving their functioning. They described these improvements as facilitated by a new sense of control and confidence, ability to focus, new communication and problem-solving skills, and better daily routines. CONCLUSIONS: Participants with recurrent mood disorders described improved functioning related to therapies that formulate their mood disorder in terms of a model, such as interpersonal and social rhythm therapy with or without cognitive remediation, that provides an understandable and evidence-based rationale, facilitates a sense of control and confidence by supporting the person in undertaking practical routines that can be integrated into daily life, focuses on communication and problem-solving skills, and engenders a sense of hope by working with the person to develop self-management strategies relevant to their specific symptom experiences and the life they choose to live.

Improvement in cognitive function in young people with bipolar disorder: Results from participants in an 18-month randomised controlled trial of adjunctive psychotherapy.

OBJECTIVE: To examine the effects of 18 months of intensive stabilisation with medication management and Interpersonal and Social Rhythm Therapy or Non-specific Supportive Clinical Management on cognitive function in young people with bipolar disorder. Determinants of change in cognitive function over the 18 months of the trial were also examined. METHOD: Patients aged 15-36 years with Bipolar I Disorder, Bipolar II Disorder and Bipolar Not Otherwise Specified were recruited. From a battery of cognitive tests, change scores for pre-defined domains of cognitive function were created based on performance at baseline and follow-up. Change was compared between the two therapy groups. Regression analysis was used to determine the impact of a range of clinical variables on change in cognitive performance between baseline and follow-up. RESULTS: One hundred participants were randomised to Interpersonal and Social Rhythm Therapy (n = 49) or Non-specific Supportive Clinical Management (n = 51). Seventy-eight patients underwent cognitive testing at baseline and 18 months. Across both groups, there were significant improvements in a Global Cognitive Composite score, Executive Function and Psychomotor Speed domains from baseline to 18 months. Lower scores at baseline on all domains were associated with greater improvement over 18 months. Overall, there was no difference between therapies in change in cognitive function, either in a global composite score or change in domains. CONCLUSION: While there was no difference between therapy groups, intensive stabilisation with psychological therapy was associated with improved cognitive function, particularly in those patients with poorer cognitive function at baseline. However, this was not compared with treatment as usual so cannot be attributed necessarily to the therapies.

Systematic Monitoring of Cognitive Function During Electroconvulsive Therapy: A Retrospective Analysis of Data From a Service Using a Short Cognitive Testing Battery.

OBJECTIVE: International guidelines suggest repeating cognitive testing at intervals throughout a course of electroconvulsive therapy (ECT) to monitor its effects on cognitive function. However, it is apparent that few services do this, and an optimal battery of testing has not yet been established. We aimed to evaluate the utility of such routine cognitive testing in a clinic where patients had been routinely tested at intervals throughout a course of ECT. METHODS: All patients referred for ECT at a public ECT clinic were offered routine cognitive testing to monitor cognitive function during their course of ECT. Testing was conducted at baseline and after 3, 6, and 9 treatments. Analyses examined whether change in individual measures predicted reduction in autobiographical memory at subsequent measures and whether the results that were given to clinicians informed treatment decisions. RESULTS: Changes in cognitive test results were not associated with clinician decisions to change treatment parameters. Only change in digit span forwards after 3 treatments was associated with later reduction in Colombia University Autobiographical Interview - Short Form (CUAMI-SF) of greater than 25%, with a larger improvement in digit span forwards being associated with greater chance of having a 25% reduction in CUAMI-SF. CONCLUSIONS: There was no evidence that the screening undertaken in this clinic had been helpful in determining treatment decisions or that changes in cognitive tests predicted in a reliable way who would later experience changes in autobiographical memory. However, follow-up testing was not completed reliably, and longer-term data regarding autobiographical memory were not collected.

Interpersonal and Social Rhythm Therapy for Patients With Major Depressive Disorder.

OBJECTIVE: This study aimed to conduct a safety analysis among patients with major depressive disorder receiving interpersonal and social rhythm therapy (IPSRT) with and without cognitive remediation. METHODS: This preliminary safety analysis of the outcomes of patients with major depressive disorder was part of a larger randomized controlled trial (RCT) in which patients with bipolar disorder and major depressive disorder received IPSRT; half were randomly assigned to receive additional cognitive remediation. The study focused on patients with major depressive disorder because IPSRT had not been trialed with this group; their outcomes were compared with those of patients with bipolar disorder. Data from the first 30 RCT participants were used to examine whether the intervention had adverse effects, whether mood symptoms and functioning improved over 12 months, and whether there was a signal of benefit. Mood symptoms were measured at baseline and 12 months with the Longitudinal Interval Follow-Up Evaluation and the Quick Inventory of Depressive Symptoms-Self-Reported; functioning was measured with the Social Adjustment Scale. RESULTS: A total of 63% (N=19) of participants were diagnosed with bipolar disorder and 27% (N=11) with major depressive disorder. No adverse effects were found for those with major depressive disorder, and improvements were seen in mean depressive and functioning scores at 12 months compared with baseline, with moderate to large effect sizes. CONCLUSIONS: IPSRT may be a clinically effective intervention for patients with major depressive disorder. Outcomes related to cognitive functioning and the effects of cognitive remediation will be reported at the end of the trial.

Activation therapy for the treatment of inpatients with depression - protocol for a randomised control trial compared to treatment as usual.

BACKGROUND: Inpatients with depression have a poor long term outcome with high rates of suicide, high levels of morbidity and frequent re-admission. Current treatment often relies on pharmacological intervention and focuses on observation to maintain safety. There is significant neurocognitive deficit which is linked to poor functional outcomes. As a consequence, there is a need for novel psychotherapeutic interventions that seek to address these concerns. METHODS: We combined cognitive activation and behavioural activation to create activation therapy (AT) for the treatment of inpatient depression and conducted a small open label study which demonstrated acceptability and feasibility. We propose a randomised controlled trial which will compare treatment as usual (TAU) with TAU plus activation therapy for adult inpatients with a major depressive episode. The behavioural activation component involves therapist guided re-engagement with previously or potentially rewarding activities. The cognitive activation aspect utilises computer based exercises which have been shown to improve cognitive function. DISCUSSION: The proposed randomised controlled trial will examine whether or not the addition of this therapy to TAU will result in a reduced re-hospitalisation rate at 12 weeks post discharge. Subjective change in activation and objectively measured change in activity levels will be rated, and the extent of change to neurocognition will be assessed. TRIAL REGISTRATION: Unique trial number: U1111-1190-9517. Australian New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12617000024347p .

Traumatic imagery following glucocorticoid administration in earthquake-related post-traumatic stress disorder: A preliminary functional magnetic resonance imaging study.

OBJECTIVE: Post-traumatic stress disorder involves excessive retrieval of traumatic memories. Glucocorticoids impair declarative memory retrieval. This preliminary study examined the effect of acute hydrocortisone administration on brain activation in individuals with earthquake-related post-traumatic stress disorder compared with earthquake-exposed healthy individuals, during retrieval of traumatic memories. METHOD: Participants exposed to earthquakes with (n = 11) and without post-traumatic stress disorder (n = 11) underwent two functional magnetic resonance imaging scans, 1-week apart, in a double-blind, placebo-controlled, counter-balanced design. On one occasion, they received oral hydrocortisone (20 mg), and on the other, placebo, 1 hour before scanning. Symptom provocation involved script-driven imagery (traumatic and neutral scripts) and measures of self-reported anxiety. RESULTS: Arterial spin labelling showed that both post-traumatic stress disorder and trauma-exposed controls had significantly reduced cerebral blood flow in response to retrieval of traumatic versus neutral memories in the right hippocampus, parahippocampal gyrus, calcarine sulcus, middle and superior temporal gyrus, posterior cingulate, Heschl's gyrus, inferior parietal lobule, angular gyrus, middle occipital gyrus, supramarginal gyrus, lingual gyrus and cuneus, and the left prefrontal cortex. Hydrocortisone resulted in non-significant trends of increasing subjective distress and reduced regional cerebral blood flow in the left inferior frontal gyrus, left anterior cingulate gyrus, middle temporal gyrus, cerebellum, postcentral gyrus and right frontal pole, during the trauma script. CONCLUSION: Findings do not fit with some aspects of the accepted neurocircuitry model of post-traumatic stress disorder, i.e., failure of the medial prefrontal cortex to quieten hyperresponsive amygdala activity, and the potential therapeutic benefits of hydrocortisone. They do, however, provide further evidence that exposure to earthquake trauma, regardless of whether post-traumatic stress disorder eventuates, impacts brain activity and highlights the importance of inclusion of trauma-exposed comparisons in studies of post-traumatic stress disorder.

Earthquake brain: Impairment of spatial memory following long-term earthquake-related stress.

OBJECTIVES: The primary aim of this study was to investigate neuropsychological function in patients with earthquake-related posttraumatic stress disorder, compared with earthquake-exposed but resilient controls. We hypothesised that individuals with posttraumatic stress disorder would have poorer neuropsychological performance on tests of verbal and visuospatial learning and memory compared with the earthquake-exposed control group. The availability of groups of healthy patients from previous studies who had been tested on similar neuropsychological tasks prior to the earthquakes allowed a further non-exposed comparison. METHOD: In all, 28 individuals with posttraumatic stress disorder and 89 earthquake-exposed controls completed tests of verbal and visuospatial learning and memory and psychomotor speed. Further comparisons were made with non-exposed controls who had been tested before the earthquakes. RESULTS: No significant difference in performance on tests of verbal or visuospatial memory was found between the earthquake-exposed groups (with and without posttraumatic stress disorder), but the posttraumatic stress disorder group was significantly slowed on tests of psychomotor speed. Supplementary comparison with historical, non-exposed control groups showed that both earthquake-exposed groups had poorer performance on a test of visuospatial learning. CONCLUSION: The key finding from this study is that there were no differences in verbal or visuospatial learning and memory in individuals with posttraumatic stress disorder compared with similarly earthquake-exposed controls. Compared with non-exposed controls, both earthquake-exposed groups had poorer performance on a test of visuospatial (but not verbal) learning and memory. This offers preliminary evidence suggesting that it is earthquake (trauma) exposure itself, rather than the presence of posttraumatic stress disorder that affects aspects of neuropsychological functioning. If replicated, this may have important implications for how information is communicated in a post-disaster context.