Alexis E Cullen

Karolinska Institutet (KI) · Department of Clinical Neuroscience

Background The components of care delivered by Early Intervention in Psychosis (EIP) services vary, but the impact on patient experience is unknown. Objective To investigate associations between components of care provided by EIP services in England and patient-reported outcomes. Methods 2374 patients from EIP services in England were surveyed du...

Background: Despite accumulating evidence of an association between stressful life events and psychosis relapse, the extent to which this is a causal relationship remains unclear. We aimed to examine the association between exposure to, and number of, stressful life events after initial psychosis onset and psychosis relapse. Methods: In this 2-y...

Unlabelled: Postpartum psychosis is defined as a psychotic episode occurring within 4 to 6 weeks of childbirth. While there is robust evidence that adverse life events are associated with the onset and relapse of psychosis outside the postpartum period, the extent to which these contribute to postpartum psychosis is less clear. This systematic rev...

Background: Previous studies suggest that migrants tend to utilise antipsychotics less often than their native-born peers. However, studies examining antipsychotic use among refugees with psychosis are lacking. Aims: To compare the prevalence of antipsychotic drug use during the first 5 years of illness among refugees and Swedish-born individual...

Psychosocial stress is a well-established risk factor for psychosis, yet the neurobiological mechanisms underlying this relationship have yet to be fully elucidated. Much of the research in this field has investigated hypothalamic-pituitary-adrenal (HPA) axis function and immuno-inflammatory processes among individuals with established psychotic di...

Background: Psychological and pharmacological therapies are the recommended first-line treatments for common mental disorders (CMDs) but may not be universally accessible or utilised. Aims: To determine the extent to which primary care patients with CMDs receive treatment and the impact of sociodemographic, work-related and clinical factors on t...

Background International migration has increased during the past years and little is known about the mortality of young adult immigrants and refugees that came to Sweden as children. This study aimed to investigate 1) the risk of all-cause and cause-specific mortality in young accompanied and unaccompanied refugees and non-refugee immigrants compar...

Background: Changes in Swedish national insurance policies over time and/or migration-related health inequalities may influence the risk for labour market marginalization (LMM) in refugees as compared to the Swedish-born host population. This study aimed to investigate potential period effects in the association between refugee status and the risk...

Objectives: The aims were to investigate the associations between specific mental and somatic disorders and subsequent all-cause and cause-specific mortality (suicide, external and other causes) in young refugees and non-refugee migrants compared with Swedish-born individuals of similar age. Methods: In this register-based prospective cohort stu...

Poor verbal learning and memory function is well-documented among individuals with schizophrenia and those at clinical high-risk for psychosis. This study aimed to identify these impairments among children aged 9–12 years with different schizophrenia risk profiles (family history or antecedents of schizophrenia, each of higher[H] or lower[L] risk l...

Background In youth at clinical high-risk for psychosis, cortisol elevations predict transition to psychosis, but it is unclear whether cortisol alterations are evident at an earlier clinical stage. We investigated whether cortisol levels and stressors in childhood were associated with later attenuated psychotic (AP) symptoms. Methods A sample of...

IntroductionNeuronal antibodies can cause encephalopathy syndromes often presenting with subacute cognitive impairment, sometimes resembling neurodegenerative dementias.Methods We searched Medline and Embase for studies reporting associations between neuronal surface antibodies in all-cause dementia versus controls. Random-effects meta-analysis was...

Background In youth at clinical high-risk for psychosis, elevated cortisol levels predict subsequent onset of psychotic disorder. However, it is unclear whether cortisol alterations are evident at an earlier clinical stage and promote progression of psychosis expression. The present study aimed to address this issue by investigating whether cortiso...

Background : The objective of this study was to investigate whether persistence of antidepressant use differs between refugee youth and Swedish-born youth after a diagnosis of a common mental disorder (CMD), and if clinical and sociodemographic factors are associated with antidepressant discontinuation. Methods : Youth aged 16-25 years, with an in...

Background: Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation. Methods: Patients with treatment-resistant schizophrenia commenced on cloz...

Background Fibromyalgia is a chronic condition characterised by widespread musculoskeletal pain. Although accumulating evidence suggests that exposure to stressful events increases the risk for this complex disorder, this is the first meta-analysis to compare the impact of a full range of lifetime stressors (e.g. physical trauma through to emotiona...

Background Antibodies targeting the N-methyl-D-aspartate receptor (NMDAR) have been detected in patients with psychosis. However, studies measuring the IgG subclass in serum have provided variable estimates of prevalence, and it is unclear whether these antibodies are more common in patients than controls. Because these inconsistencies could be due...

Obsessive–compulsive disorder (OCD) and autism spectrum disorders (ASD) commonly co-occur and are considered challenging to manage when they co-occur in youth. However, clinical characteristics and prognosis of this group remain poorly understood. This study examined the prevalence, clinical correlates and outcomes of paediatric OCD co-occurring wi...

Relapse rates among individuals with psychotic disorders are high. In addition to the financial burden placed on clinical services, relapse is associated with worse long-term prognosis and poorer quality of life. Robust evidence indicates that stressful life events commonly precede the onset of the first psychotic episode; however, the extent to wh...

Aim Low self‐esteem (LSE) has been reported among individuals with psychosis and is hypothesized to act as a risk and maintenance factor for the disorder. However, the extent to which LSE also characterizes individuals deemed at ultra‐high risk (UHR) for psychosis (who present features consistent with the prodromal phase of illness), has yet to be...

Background Cognitive impairments in childhood are associated with increased risk of schizophrenia in later life, but the extent to which poor academic achievement is associated with the disorder is unclear. Methods Major databases were searched for articles published in English up to 31 December 2019. We conducted random-effects meta-analyses to:...

Letter to the editor

Background Individuals with established psychosis and those at high-risk for the disorder have been found to show abnormalities within the hypothalamic-pituitary-adrenal (HPA) axis, including elevations in basal and diurnal cortisol, but a blunted cortisol awakening response. However, the extent to which these features are associated with psychosoc...

Aims Around 15% of patients at clinical high risk for psychosis (CHR‐P) experience symptomatic remission and functional recovery at follow‐up, yet the definition of a good outcome (GO) in this population requires further development. Outcomes are typically designed and rated by clinicians rather than patients, to measure adverse as opposed to GOs....

Objectives Limited evidence is available regarding the effect of community treatment orders (CTOs) on mortality and readmission to psychiatric hospital. We compared clinical outcomes between patients placed on CTOs to a control group of patients discharged to voluntary community mental healthcare. Design and setting An observational study using de...

Whilst elevations in basal cortisol levels have been reported among individuals at-risk for psychosis, the extent to which this represents hyperresponsivity of the hypothalamic-pituitary-adrenal (HPA) axis to psychosocial stressors encountered in the natural environment is currently unclear. We aimed to examine stressor-cortisol concordance among y...

Psychotic disorders can be exacerbated by the hormonal changes associated with childbirth, but the extent to which exacerbations occur with the menstrual cycle is unclear. We addressed this issue by conducting a systematic review. Embase, Medline, and PsychINFO databases were searched for studies that measured exacerbations of psychotic disorders i...

Objectives The pathoetiology of Schizophrenia remains elusive, however, a growing body of literature suggests immune dysfunction may contribute. Clozapine, an atypical antipsychotic, has superior efficacy in treatment-resistant Schizophrenia compared to other antipsychotics – however underlying mechanisms remain unknown. Clozapine has recognised im...

Background: Pituitary volume (PV) abnormalities, representing one of several markers of hypothalamic-pituitary-adrenal (HPA) axis dysregulation, have been observed in psychosis, with variable patterns across illness stages. Typically, enlargements characterise first-episode patients, with reductions observed in those with chronic illness relative...

Background: A relationship between non-neurological autoimmune (NNAI) disorders and psychosis has been widely reported but not yet subjected to meta-analysis. We conducted the first meta-analysis examining the association between NNAI disorders and psychosis and investigated the effect of 1) temporality (as determined by study design), 2) psychiat...

Background The extent to which poor academic achievement is associated with later schizophrenia is unclear. The aim of the present study was to update our prior meta-analyses which examined academic achievement in youth aged 16 years or younger who later developed schizophrenia or schizophrenia spectrum disorders (SSD) and those who did not (Dickso...

Background Individuals with established psychosis are characterised by a distinct pattern of hypothalamic-pituitary-adrenal (HPA) axis dysfunctions which include both elevated daytime cortisol levels and a blunted cortisol awakening response (CAR). Whilst these patterns of dysfunction have also been observed among those at elevated risk for the dis...

Background Accumulated evidence from non-human animal studies suggests that the prominent deficits in memory and executive function that characterise individuals with psychosis may, at least in part, be due to the effects of stress on the brain regions that support these functions. However, studies of patients with established psychosis have yielde...

Background Among adults with schizophrenia, evidence suggests that premorbid deficits in different cognitive domains follow distinct developmental courses during childhood and adolescence. The aim of this study was to delineate trajectories of adolescent cognitive functions prospectively among different groups of youth at‐risk for schizophrenia, re...

Background: The recall of conditionally discharged forensic patients in England is a formal order from the Ministry of Justice under the Mental Health Act (1983) which has the power to revoke conditional release and direct readmission to hospital. Recall has significant implications for the individual and for hospital services, but despite this, l...

Objective Organic psychosis (OP) is where psychosis is due to an identified medical illness and have been considered separately from nonorganic psychotic (NP) disorders. Despite being a clinically important topic with different treatment options and healthcare pathways very little is known about OP in terms of prevalence, the relative frequency of...

Elevated C-reactive protein (CRP), a non-specific biomarker of systemic bodily inflammation, has been associated with more pronounced cognitive impairments in adults with psychiatric disorders, particularly in the domains of memory and executive function. Whether this association is present in early life (i.e., the time at which the cognitive impai...

Background Seclusion (the isolation of a patient in a locked room) and transfer to a psychiatric intensive care unit (PICU; a specialised higher-security ward with higher staffing levels) are two common methods for the management of disturbed patient behaviour within acute psychiatric hospitals. Some hospitals do not have seclusion rooms or easy a...

Background: Epidemiological studies conducted over the past 50 years have observed an increased prevalence of psychosis among individuals with nonneurological autoimmune disorders relative to the general population, with the notable exception of rheumatoid arthritis. Whether this association reflects shared risk factors (e.g., infections or genetic...

Background: Psychotic disorders due to an identified medical illness are classified using the term “organic,” and have been considered separately from “nonorganic” psychotic disorders. Despite having different treatment options and health-care pathways, and with growing criticism of the organic/nonorganic dichotomy in psychotic disorders, very litt...

Background Previous studies have investigated factors associated with outcome at Mental Health Review Tribunals (MHRTs) in forensic psychiatric patients; however, dynamic variables such as treatment compliance and substance misuse have scarcely been examined, particularly in UK samples. We aimed to determine whether dynamic factors related to behav...

Over the past decade, our understanding of the role of stress in serious mental illness has become more sophisticated. In this paper, we revisit the neural diathesis-stress model of schizophrenia that was initially proposed in 1997 and updated in 2008. In light of cumulative research findings, we must now encompass evidence on the premorbid periods...

Aims Within acute psychiatric inpatient services, patients exhibiting severely disturbed behaviour can be transferred to a psychiatric intensive care unit (PICU) and/or secluded in order to manage the risks posed to the patient and others. However, whether specific patient groups are more likely to be subjected to these coercive measures is unclear...

Aims: To compare across different service configurations the acceptability of containment methods to acute ward staff and the speed of initiation of manual restraint. Background: One of the primary remits of acute inpatient psychiatric care is the reduction of risks. Where risks are higher than normal, patients can be transferred to a psychiatri...

Background: The hypothalamic-pituitary-adrenal (HPA) axis disturbances observed in psychosis might feasibly contribute to some of the structural brain abnormalities associated with the disorder (i.e., via the potentially toxic effects of elevated glucocorticoid levels on the brain). However, the association between brain structure and cortisol has...

Background Studies indicate that risk of mortality is higher for patients admitted to acute hospitals at the weekend. However, less is known about clinical outcomes among patients admitted to psychiatric hospitals. Aims To investigate whether weekend admission to a psychiatric hospital is associated with worse clinical outcomes. Method Data were ob...

Purpose: The London Child Health and Development Study (CHADS) is a prospective, longitudinal investigation of children, sampled from the general community aged 9-11 years and assessed biennially, who present premorbid risk markers for schizophrenia. The study aims to characterise developmental trajectories of psychological, cognitive, and biologi...

Background Previous studies indicate that risk of mortality is higher for patients admitted to acute hospitals at the weekend. Thus, there is a drive to move towards provision of a 7 day health-care service in the UK. However, less is known about variations in clinical outcomes among patients admitted to psychiatric hospitals. We sought to investig...

Background Rates of reoffending and recall are high among released male prisoners with personality disorder. There is a need for innovative intervention to reduce offending and increase staff confidence in working with such men. Aim The aim of this study was to evaluate the effectiveness of a novel intervention consisting of training and consultat...

In 2010, following a series of high-profile absconding incidents, electronic monitoring (EM) using Global Positioning System technology for patients on leave was trialled as part of a comprehensive protocol for risk management and recovery. We conducted a preliminary evaluation of effect on leave and leave violation. The total number of leave episo...

Background: Incidents of absconsion in forensic psychiatric units can have potentially serious consequences, yet surprisingly little is known about the characteristics of patients who abscond from these settings. The few previous studies conducted to date have employed retrospective designs, and no attempt has been made to develop an empirically-d...

Pituitary volume enlargements have been observed among individuals with first-episode psychosis. These abnormalities are suggestive of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, which may contribute to the development of psychosis. However, the extent to which these abnormalities characterize individuals at elevated risk for schizophr...

Although screening has become an established procedure in prison health care, some difficulties persist. In attempts to improve this, many local adaptations have been introduced, but few have been evaluated. We introduced an adaptation – mental health expertise (a Community Psychiatric Nurse, CPN) – into the reception area of a busy remand prison,...

Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onse...

Notwithstanding the logistical and ethical issues that make this sensitive research difficult to accomplish, we agree that prospective investigations of children followed from early childhood offer the best prospect for identifying mechanisms underpinning the relationship between childhood adversity and later outcomes such as mental health, social...

Psychological stress is implicated in the development of schizophrenia, but little is known about experiences of stress among children at elevated risk for the disorder. To examine stressor exposure and reactivity in children with different vulnerability profiles for schizophrenia: (a) children presenting multiple antecedents of schizophrenia (ASz...

This was a presentation of my undergraduate dissertation thesis, which investigated the association between C-reactive protein (CRP; a bio-marker of systemic bodily inflammation) and cognitive function in a community sample of children. The relationship was investigated using a novel form of CRP measurement; salivary CRP analysis. Results partially...

Distributed abnormalities of gray matter (GM) and white matter (WM) volume characterize individuals experiencing their first episode of schizophrenia. Regions of abnormality are present already, albeit less extensively, during the prodromal phase of illness. This study aimed to determine whether putatively at-risk children, aged 9-12 years, who pre...

Objective: Despite a large evidence base indicating that cognitive skills programs can reduce reoffending in individuals without mental illness, there have been no randomized controlled trials (RCTs) to determine their effectiveness in mentally disordered offenders (MDOs). In the first RCT of a cognitive skills program for MDOs, we aimed to invest...