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In this thoroughly revised and updated second edition, the emphasis remains on providing a practical and up-to-date guide for the practicing pathologist when evaluating peripheral blood, bone marrow and lymph node specimens from pediatric patients. Over 400 high quality colour figures aid accuratecountries, the use of molecular diagnostics, and the role of flow cytometry in diagnosis and post-therapy monitoring of hematologic malignancies. The importance of unique diagnostic features of benign and malignant hematologic disorders in children is retained, with chapters authored by experienced pediatric hematopathologists and clinical scientists drawn from major children's hospitals across the US, Europe and Africa. The print book comes with access to the text and expandable figures online at Cambridge Core, which can be accessed via the code printed on the inside of the cover.
Synthetic Aperture Radar Interferometry (InSAR) is an active remote sensing method that uses repeated radar scans of the Earth's solid surface to measure relative deformation at centimeter precision over a wide swath. It has revolutionized our understanding of the earthquake cycle, volcanic eruptions, landslides, glacier flow, ice grounding lines, ground fluid injection/withdrawal, underground nuclear tests, and other applications requiring high spatial resolution measurements of ground deformation. This book examines the theory behind and the applications of InSAR for measuring surface deformation. The most recent generation of InSAR satellites have transformed the method from investigating 10's to 100's of SAR images to processing 1000's and 10,000's of images using a wide range of computer facilities. This book is intended for students and researchers in the physical sciences, particularly for those working in geophysics, natural hazards, space geodesy, and remote sensing. This title is also available as Open Access on Cambridge Core.
Few studies have examined attention-deficit/hyperactivity disorder (ADHD) symptoms in middle- and older-aged adults. We aim to examine the phenotypic expression of ADHD symptoms in these age groups.
Methods
This study comprised a random sample (N = 1,562) from the US Health and Retirement Study 2016, a representative US sample aged 50 years and over. ADHD symptoms were assessed based on the Adult ADHD Self-Report Scale.
Results
In the primary analysis, 10 competing confirmatory factor analytic models of ADHD symptoms in middle- and older-aged adults were compared. The best-fitting model was hierarchical with a general ADHD factor at the apex and underneath symptom factors of inattention, hyperactivity, and impulsivity (ꭓ2 = 319.34, df = 91.71, P = 0.00, TLI = 0.98, CFI = 0.96, RMSEA = 0.04, 95% CI = 0.04–0.05). In complementary analyses, this model was a satisfactory fit to the data: (1) in individuals without a history of cognitive impairment or dementia, and when the general ADHD factor was specified to load on (2) cognitive function, (3) depressive symptoms (which showed adequate fit), and (4) ADHD polygenic scores, (5) in middle- and older-aged adults, and (6) when weighted to represent the US population.
Conclusions
These results imply a hierarchical representation of ADHD symptoms in middle- and older-aged adults consisting of a general factor at the apex with neurocognitive and genetic correlates and underneath symptom factors of inattention, hyperactivity, and impulsivity. Collectively, this model offers a novel framework to study the mechanisms of ADHD symptoms in middle- and older-aged adults and points to treatment targets.
Adverse childhood experiences (ACEs) are associated with physical and mental health difficulties in adulthood. This study examines the associations of ACEs with functional impairment and life stress among military personnel, a population disproportionately affected by ACEs. We also evaluate the extent to which the associations of ACEs with functional outcomes are mediated through internalizing and externalizing disorders.
Methods
The sample included 4,666 STARRS Longitudinal Study (STARRS-LS) participants who provided information about ACEs upon enlistment in the US Army (2011–2012). Mental disorders were assessed in wave 1 (LS1; 2016–2018), and functional impairment and life stress were evaluated in wave 2 (LS2; 2018–2019) of STARRS-LS. Mediation analyses estimated the indirect associations of ACEs with physical health-related impairment, emotional health-related impairment, financial stress, and overall life stress at LS2 through internalizing and externalizing disorders at LS1.
Results
ACEs had significant indirect effects via mental disorders on all functional impairment and life stress outcomes, with internalizing disorders displaying stronger mediating effects than externalizing disorders (explaining 31–92% vs 5–15% of the total effects of ACEs, respectively). Additionally, ACEs exhibited significant direct effects on emotional health-related impairment, financial stress, and overall life stress, implying ACEs are also associated with these longer-term outcomes via alternative pathways.
Conclusions
This study indicates ACEs are linked to functional impairment and life stress among military personnel in part because of associated risks of mental disorders, particularly internalizing disorders. Consideration of ACEs should be incorporated into interventions to promote psychosocial functioning and resilience among military personnel.
Targeting the glutamatergic system is posited as a potentially novel therapeutic strategy for psychotic disorders. While studies in subjects indicate that antipsychotic medication reduces brain glutamatergic measures, they were unable to disambiguate clinical changes from drug effects.
Aims
To address this, we investigated the effects of a dopamine D2 receptor partial agonist (aripiprazole) and a dopamine D2 receptor antagonist (amisulpride) on glutamatergic metabolites in the anterior cingulate cortex (ACC), striatum and thalamus in healthy controls.
Method
A double-blind, within-subject, cross-over, placebo-controlled study design with two arms (n = 25 per arm) was conducted. Healthy volunteers received either aripiprazole (up to 10 mg/day) for 7 days or amisulpride (up to 400 mg/day) and a corresponding period of placebo treatment in a pseudo-randomised order. Magnetic resonance spectroscopy (1H-MRS) was used to measure glutamatergic metabolite levels and was carried out at three different time points: baseline, after 1 week of drug and after 1 week of placebo. Values were analysed as a combined measure across the ACC, striatum and thalamus.
Results
Aripiprazole significantly increased glutamate + glutamine (Glx) levels compared with placebo (β = 0.55, 95% CI [0.15, 0.95], P = 0.007). At baseline, the mean Glx level was 8.14 institutional units (s.d. = 2.15); following aripiprazole treatment, the mean Glx level was 8.16 institutional units (s.d. = 2.40) compared with 7.61 institutional units (s.d. = 2.36) for placebo. This effect remained significant after adjusting for plasma parent and active metabolite drug levels. There was an observed increase with amisulpride that did not reach statistical significance.
Conclusions
One week of aripiprazole administration in healthy participants altered brain Glx levels as compared with placebo administration. These findings provide novel insights into the relationship between antipsychotic treatment and brain metabolites in a healthy participant cohort.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Values are closely linked to emotions and patients with BPD experience significant fluctuations in their emotions. Psycho-education about the hierarchy, proximity, and temporality of values offers an opportunity to reduce impulsivity and increase hope.
Most effective forms of therapy address personal agency. For this, the clinician needs to create a non-blaming, non-judgemental, and compassionate milieu which can enable the patient to take responsibility for their actions. Values-based interventions can improve agency, increase motivation, and help the patient find meaning, which is negatively associated with depression, suicidality, and self-harm. Early empirical evidence supports the usefulness of working with the patient’s values in therapy using acceptance and commitment therapy (ACT), a modality that focusses on acting in accordance with one’s stated values. Empirical evidence from longitudinal observation suggests that an increase in agency in the patient’s life narrative is part of the recovery process.
Patients with BPD follow a different path in terms of recovery. Patients often find the word ‘recovery’ problematic and many feel that ‘discovery’ describes their journey more accurately. A significant proportion of people with BPD feel that they are not ill in the same way as people with other major mental illnesses but that they need help and support.
The person’s values determine the meaning structure of the world they live in and drive their actions. The depressed patient’s values tend to change dramatically over the weeks and usually return to normal. At the height of their illness, patients can constantly feel that they are transgressing important personal and group values.
Examining the values at play is similar to creating a map with three dimensions: (1) the level of organization/proximity to primary stakeholders; (2) the hierarchy; and (3) the temporality of values. The patient’s values can be misaligned with those of others temporarily owing to the illness, and value-mapping can facilitate realignment. Changes in value hierarchy are often necessary for recovery. These changes can be dramatic and can happen at a faster pace whilst the person is becoming ill and during recovery.
The patient can be temporarily cut off from the values they would normally hold. Besides records of their former wishes and collateral information, sources of knowledge about value changes include peer support workers, first-hand narratives, philosophical and social scientific studies, media reports, and art portrayal of depression. Changes in one’s life narrative are also essential for recovery and resilience. The patient’s social environment, including the professionals, can facilitate (or hinder) this.
The different needs, concerns, and preferences of the professions constituting the multidisciplinary team (MDT), including medicine, psychology, nursing, and social work, reflect the hybrid nature of psychiatry and the knowledge and skills required for clinical practice.
Neuroscience has evolved at impressive speed over recent decades. Many of its findings have relevance to psychiatry but are rarely directly translatable into clinical practice. Improving understanding of the psychological dimension of mental illness has led to new treatments with similar efficacy to medications. Our current approach to treating mental illness has also benefited greatly from insights from sociology and anthropology. The value conflicts relating to liberty and personal autonomy versus the medical value of restoring health and societal values around managing risk have led to the development of legal frameworks to aid clinical decision-making. These are, however, far from perfect, and values-based practice (VBP) principles could meaningfully contribute to improving them.
Although traditionally medicine sat at the top of the hierarchy in the MDT, this hierarchy has become more horizontal in recent decades. Close working together with social care is key, but there are pros and cons for both integrated and separate services. Values-based practice can ease some of the tensions in MDT working.
Current and historical practice, personal life history, and culture have a significant impact on the values of practitioners in psychiatry. Most psychiatrists have a strong medical identity but recognize that to be a good clinician they need more than just their biomedical knowledge and skills.
The new UK training curricula reflect the changing value landscape, shifting away from the biological and the psychological and the increasing emphasis on safeguarding. Now explicitly included are VBP principles such as partnership; person-centred care; practice being based on both evidence and values; multidisciplinary working; a model drawing on the social sciences, neurosciences, and the humanities; and clinicians needing to understand the impact of culture, religion, and social systems. Co-production, the doctor–patient power imbalance, protected characteristics, the relevance of the history of psychiatry, and sustainability appear as new additions.
The media portrayal of psychiatry helps the public to understand mental illness and psychiatry, shapes public attitudes and stigma, influences treatment-seeking, scrutinizes how people with mental illness are treated by psychiatry and wider society, and has the potential to protect (but also to harm) people. Despite some improvements in recent decades, there are still examples of coverage maintaining negative stereotypes, and appropriate guidelines are needed.
Psychopathological phenomenology and existential psychotherapy may help us overcome the challenges of integrating the different dimensions of mental illness and developing new treatments. Better characterization of symptoms/syndromes can improve classification and causal modelling, whereas existential psychotherapy has added to our understanding of the influence of our position in the world and in history.
Motivational interviewing has many similarities to VBP. It can increase the person’s agency by drawing out personal meaning and the importance of change. A crucial insight from it is that saying out loud what our values are can greatly enhance our understanding of them. Treatment may mean reducing conflict between the person’s core values by helping the person recognize their environment’s affordances more efficiently or improve their sense-making and thereby alter their values.
Psychiatry has been pioneering in embracing alternative meanings of recovery. The most important consequence of this was that it enabled discussions about recovery as living well with mental ill-health. Co-production has helped to reframe and enhance the relationship between ‘doctor’ and ‘patient’, leading to better outcomes for all.
Recovery together with co-production will enable constructive partnerships between all those affected by mental ill-health to play their part in progressive psychiatry and more progressive communities.
Developing a satisfactory explanation of the pathomechanism of mental illness, developing biomarkers to aid diagnosis, developing an aetiological classification system, and developing effective treatments to achieve both symptom elimination and functional recovery has so far remained the holy grail of psychiatry for most conditions. To make progress, psychiatric research needs to integrate the biological, psychological, sociocultural, and existential dimensions of mental illness and incorporate and work with values more efficiently. This chapter offers a methodology for this through first describing value-mapping and then elucidating the potential contribution of qualitative and mixed-method studies, phenomenological, hermeneutic, and other idiographic approaches, interpretative phenomenological analysis, analytic induction, quasi-judicial approaches, and the history of psychiatry.
An essential prerequisite of any breakthrough here would be going back to the person level. Research centres would need to become truly multidisciplinary to bring together researchers with expertise in the relevant natural and social sciences and the medical humanities as well as experts by experience for effective co-production.
The history of psychology shows strong parallels with that of psychiatry. At its inception, psychology placed itself between the natural and the social sciences, which was reflected in its conceptual and methodological choices. Historically, no single school of thought within psychology managed to provide a full explanation of mental illness, but they all had the potential to advance our understanding and complemented each other. The usefulness of any psychological approach for psychiatry is determined to a large degree by how much it can incorporate person-centredness and agency into its theory and research. This is an area where psychology has benefited from more (rather than less) social science and humanities input during its history. This chapter contrasts four major schools of thought in psychology from this perspective: psychoanalysis and behaviourism as well as cognitive and humanistic psychology. Psychoanalysis focussed on the whole person and managed to incorporate values and ethics into its epistemology more than other approaches could; in addition to recognizing the role of psychological trauma and conflict and of meaning, this was one of its crucial contributions to psychiatry.
Even though values are crucial to our understanding of psychiatry, prevailing models of mental illness fail to properly integrate them. Neuroscience has produced a large amount of knowledge, but it needs to be augmented to fully integrate other relevant dimensions, such as the experiential, the social, and the existential. Engel’s biopsychosocial model, Leigh’s genetic-memetic model, the enactive model (e.g., in Haan), and the hybrid model by Berrios and Markova all foreshadow a new epistemology that, when worked out fully, will be able to achieve that and provide robust theoretical foundations for psychiatry.
A key problem in psychiatry is resolving disputes about mental capacity that often relate to the patient’s values being at odds with those of others. A new, VBP-informed stakeholders’ tribunal, including a philosopher, a VBP-trained clinician, and optional members with expertise relevant to the case, could provide a good process for working with these values.
Choosing our instrumental values appropriately at the person and societal levels is key to the prevention and treatment of mental illness. However, psychiatry needs to make it clear that it is only one of the players, and if these values are to be fully realized, public health, government, and the public need to work collaboratively.