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.

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.

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.

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.

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.

Prevalence of cognitive impairment in major depression and bipolar disorder.

OBJECTIVES: The current study examines prevalence of cognitive impairment in four mood disorder samples, using four definitions of impairment. The impact of premorbid IQ on prevalence was examined, and the influence of treatment response. METHODS: Samples were: (i) 58 inpatients in a current severe depressive episode (unipolar or bipolar), (ii) 69 unmedicated outpatients in a mild to moderate depressive episode (unipolar or bipolar), (iii) 56 outpatients with bipolar disorder, in a depressive episode, and (iv) 63 outpatients with bipolar disorder, currently euthymic. Cognitive assessment was conducted after treatment in Studies 1 (6 weeks of antidepressant treatment commenced on admission) and 2 (16-week course of cognitive behaviour therapy or schema therapy), allowing the impact of treatment response to be assessed. All mood disorder samples were compared with healthy control groups. RESULTS: The prevalence of cognitive impairment was highest for the inpatient depression sample (Study 1), and lowest for the outpatient depression sample (Study 2). Substantial variability in rates was observed depending on the definition of impairment used. Correcting cognitive performance for premorbid IQ had a significant impact on the prevalence of cognitive impairment in the inpatient depression sample. There was minimal evidence that treatment response impacted on prevalence of cognitive impairment, except in the domain of psychomotor speed in inpatients. CONCLUSIONS: As interventions aiming to improve cognitive outcomes in mood disorders receive increasing research focus, the issue of setting a cut-off level of cognitive impairment for screening purposes becomes a priority. This analysis demonstrates important differences in samples likely to be recruited depending on the definition of cognitive impairment and begins to examine the importance of premorbid IQ in determining who is impaired.

Clinical response to treatment in inpatients with depression correlates with changes in activity levels and psychomotor speed.

BACKGROUND: Monitoring clinical response to treatment in depressed inpatients, particularly identifying early improvement, may be sub-optimal. This may impact adversely on patients through longer admissions and sub-optimal pharmacotherapy. Psychomotor speed is a prominent neuropsychological function which changes as recovery occurs. This study examines simple techniques used to quantify psychomotor change and their potential to contribute to monitoring recovery. METHODS: Activity levels were continuously monitored in patients diagnosed with a major depressive episode from four acute psychiatric wards using two actigraphs (commercial and scientific) for 3 weeks and linear regression used to calculate a gradient to express rate of change. Psychomotor speed was assessed using the simple Coin Rotation Task. Mood and functioning were rated using the Quick Inventory of Depressive Symptoms, Clinical Global Impression Scale and Functioning Assessment Short Test. The assessments were completed at baseline and follow-up (3 weeks), and correlations were calculated for all change measures. RESULTS: In all, 24 inpatients were recruited but not all completed baseline and follow-up measures. Change in activity count ( N = 16) and psychomotor speed ( N = 13) correlated significantly with improvement in clinical measures of depressive symptoms. Actigraphs were acceptable to hospital inpatients. LIMITATIONS: The limited size of this pilot study precludes the analysis of predictive power or the influence of other variables such as depression subtypes, age, gender or variations related to medications. CONCLUSION: Early change in simple activity and psychomotor speed warrant further investigation for utility in measuring treatment response in depressed inpatients.