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Diagnosis in psychiatry faces familiar challenges. Validity and utility remain elusive, and confusion regarding the fluid and arbitrary border between mental health and illness is increasing. The mainstream strategy has been conservative and iterative, retaining current nosology until something better emerges. However, this has led to stagnation. New conceptual frameworks are urgently required to catalyze a genuine paradigm shift.
Methods
We outline candidate strategies that could pave the way for such a paradigm shift. These include the Research Domain Criteria (RDoC), the Hierarchical Taxonomy of Psychopathology (HiTOP), and Clinical Staging, which all promote a blend of dimensional and categorical approaches.
Results
These alternative still heuristic transdiagnostic models provide varying levels of clinical and research utility. RDoC was intended to provide a framework to reorient research beyond the constraints of DSM. HiTOP began as a nosology derived from statistical methods and is now pursuing clinical utility. Clinical Staging aims to both expand the scope and refine the utility of diagnosis by the inclusion of the dimension of timing. None is yet fit for purpose. Yet they are relatively complementary, and it may be possible for them to operate as an ecosystem. Time will tell whether they have the capacity singly or jointly to deliver a paradigm shift.
Conclusions
Several heuristic models have been developed that separately or synergistically build infrastructure to enable new transdiagnostic research to define the structure, development, and mechanisms of mental disorders, to guide treatment and better meet the needs of patients, policymakers, and society.
Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders.
Methods
The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration.
Results
Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006).
Conclusions
Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis.
A clinical concept that has been taken up with some enthusiasm in mental health services for young people experiencing major mental disorders is that of clinical staging, with the emphasis on identifying and intervening in youth with various ‘at-risk’, ‘sub-threshold’ or ‘attenuated’ syndromes, before the onset of first major episodes (Shah et al 2020). While these concepts were initially developed within the rather focused context of major psychotic disorders, they are now being deployed much more widely and applied to young people presenting with a variety of mental disorders (Hickie et al 2019; Shah 2019).
The needs of young people attending mental healthcare can be complex and often span multiple domains (e.g., social, emotional and physical health factors). These factors often complicate treatment approaches and contribute to poorer outcomes in youth mental health. We aimed to identify how these factors interact over time by modelling the temporal dependencies between these transdiagnostic social, emotional and physical health factors among young people presenting for youth mental healthcare.
Methods
Dynamic Bayesian networks were used to examine the relationship between mental health factors across multiple domains (social and occupational function, self-harm and suicidality, alcohol and substance use, physical health and psychiatric syndromes) in a longitudinal cohort of 2663 young people accessing youth mental health services. Two networks were developed: (1) ‘initial network’, that shows the conditional dependencies between factors at first presentation, and a (2) ‘transition network’, how factors are dependent longitudinally.
Results
The ‘initial network’ identified that childhood disorders tend to precede adolescent depression which itself was associated with three distinct pathways or illness trajectories; (1) anxiety disorder; (2) bipolar disorder, manic-like experiences, circadian disturbances and psychosis-like experiences; (3) self-harm and suicidality to alcohol and substance use or functioning. The ‘transition network’ identified that over time social and occupational function had the largest effect on self-harm and suicidality, with direct effects on ideation (relative risk [RR], 1.79; CI, 1.59–1.99) and self-harm (RR, 1.32; CI, 1.22–1.41), and an indirect effect on attempts (RR, 2.10; CI, 1.69–2.50). Suicide ideation had a direct effect on future suicide attempts (RR, 4.37; CI, 3.28–5.43) and self-harm (RR, 2.78; CI, 2.55–3.01). Alcohol and substance use, physical health and psychiatric syndromes (e.g., depression and anxiety, at-risk mental states) were independent domains whereby all direct effects remained within each domain over time.
Conclusions
This study identified probable temporal dependencies between domains, which has causal interpretations, and therefore can provide insight into their differential role over the course of illness. This work identified social, emotional and physical health factors that may be important early intervention and prevention targets. Improving social and occupational function may be a critical target due to its impacts longitudinally on self-harm and suicidality. The conditional independence of alcohol and substance use supports the need for specific interventions to target these comorbidities.
The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, and has been independently studied in clinical high-risk (CHR) and first-episode psychosis (FEP) populations. Notable in this literature, however, is that there are few studies directly comparing markers of stress response across progressive stages of illness. Here we examined the psychobiological response to the Trier Social Stress Test in 28 CHR (mean age 19.1) and 61 FEP (age 23.0) patients, in order to understand the stage(s) or trajectories in which differences in subjective stress or physiological response occur. The overall clinical sample had greater perceived stress and blunted cortisol (FEP + CHR, n = 89, age 21.7) compared with healthy controls (n = 45, age 22.9). Additional analyses demonstrated elevated heart rate and systolic blood pressure in FEP compared with CHR, but there were no further differences in physiological parameters (cortisol, heart rate, or blood pressure) between stage- or trajectory-based groups. Together, this suggests that individual stress response markers may differentially emerge at particular stages en route to psychosis – and demonstrates how stage-based analyses can shed light on the emergence and evolution of neurobiological changes in mental illness.
Rapid progression from the first identifiable symptom to the onset of first-episode psychosis (FEP) allows less time for early intervention. The aim of this study was to examine the association between the first identifiable symptom and the subsequent speed of illness progression.
Methods
Data were available for 390 patients attending a catchment-based early intervention service for FEP. Exposure to non-psychotic and subthreshold psychotic symptoms was retrospectively recorded using semi-structured interviews. Outcomes following the onset of the first identifiable symptom were (1) time to onset of FEP and (2) symptom incidence rate (i.e. number of symptoms emerging per person-year until FEP onset). These outcomes were respectively analyzed with Cox proportional hazards and negative binomial regressions.
Results
After Bonferroni correction, having a subthreshold psychotic (v. non-psychotic) symptom as the first symptom was not associated with time to FEP onset [hazard ratio (HR) = 1.39; 95% CI 0.94–2.04] but was associated with higher symptom incidence [incidence rate ratio (IRR) = 1.92; 95% CI 1.10–3.48]. A first symptom of suspiciousness was associated with shorter time to FEP onset (HR = 2.37; 95% CI 1.38–4.08) and higher symptom incidence rate (IRR = 3.20; 95% CI 1.55–7.28) compared to other first symptoms. In contrast, a first symptom of self-harm was associated with lower symptom incidence rate (IRR = 0.06; 95% CI 0.01–0.73) compared to other first symptoms. Several associations between symptoms and illness progression were moderated by the age at symptom onset.
Conclusions
Appreciating the content and timing of early symptoms can identify windows and treatment targets for early interventions in psychosis.
To assess the outcome of severe wasting in infants below 6 months of age.
Design:
A prospective observational study conducted between January 2017 and October 2018.
Setting:
A medical college-affiliated hospital in Eastern Delhi, catering mainly to the urban poor population.
Participants:
All children with severe wasting (weight-for-length Z-score (WLZ) < −3 sd) between 1 and 6 months of age, requiring hospitalisation.
Results:
Out of fifty children enrolled, during hospitalisation, forty-two (84 %) recovered (WLZ > −3 sd) and discharged; the median (interquartile range (IQR)) duration of stay was 9·5 (6·5, 13·0) d. After 100 d of enrolment, sustained cure (WLZ > −2 SD) could be achieved in only fifteen (30 %) infants, while another fourteen (28 %) recovered from severe wasting, but remained in moderately wasted state (WLZ between −2 and −3 sd). Overall, there were three (6 %) deaths (all during first week of hospitalisation); three (6 %) relapses and fifteen (30 %) defaulters (5, 5, 2, 1 and 2 defaulted during hospitalisation at day 15, day 60, day 75 and day 90, respectively).
Conclusions:
The overall recovery rate from severe wasting in infants below 6 months of age was below the acceptable levels. In order to achieve better long-term outcome, community linkage services after discharge from hospital are required for supervised feeding, close monitoring and supportive care.
Three broad social factors – childhood adversity, immigration, and urban living – are robustly associated with an increased risk of schizophrenia. To date, however, there is no consensus on what it is about these phenomena that raises the risk of psychotic illness. In 2005, J. P. Selten and E. Cantor-Graae proposed a “social defeat” hypothesis according to which the social determinants of schizophrenia are best characterized as experiences of social subordination. In recent years, the social-defeat hypothesis has been broadened to include experiences of social exclusion. In this chapter, we review the different versions of the social defeat hypothesis and argue that it fails to account for the urban effect. We further argue for the potential utility of paying greater attention to social science when theorizing about the social determinants of schizophrenia.
During a psychotic episode, patients frequently suffer from severe maladaptive beliefs known as delusions. Despite the abundant literature investigating the simple presence or absence of these beliefs, there exists little detailed knowledge regarding their actual content and severity at the onset of illness.
Aims
This study reports on delusions during the initiation of indicated treatment for first-episode psychosis (FEP).
Method
Data were systematically collected from a sample of 636 patients entering a catchment-based early intervention service for FEP. The average severity and frequency of each delusional theme at baseline was reported with the Scale for the Assessment of Positive Symptoms. Delusional severity (globally and per theme) was examined across a number of sociodemographic and clinical variables.
Results
Delusions were present in the vast majority of individuals experiencing onset of FEP (94%), with persecutory (77.7%) being the most common theme. Persecutory delusions remained consistent in severity across diagnoses, but were more severe with older age at onset of FEP. No meaningful differences in delusional severity were observed across gender, affective versus non-affective psychosis, or presence/absence of substance use disorder. Globally, delusion severity was associated with anxiety, but not depression. Delusions commonly referred to as passivity experiences were related to hallucinatory experiences.
Conclusions
This community sample offers a rare clinical lens into the severity and content of delusions in FEP. Although delusional severity was consistent across certain sociodemographic and clinical variables, this was not always the case. Future research should now consider the course of delusion themes over time.
We construct, for any set of primes $S$, a triangulated category (in fact a stable $\infty$-category) whose Grothendieck group is $S^{-1}\mathbf{Z}$. More generally, for any exact $\infty$-category $E$, we construct an exact $\infty$-category $S^{-1}E$ of equivariant sheaves on the Cantor space with respect to an action of a dense subgroup of the circle. We show that this $\infty$-category is precisely the result of categorifying division by the primes in $S$. In particular, $K_{n}(S^{-1}E)\cong S^{-1}K_{n}(E)$.
In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate.
Methods
In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers.
Results
Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring.
Conclusions
ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.
This paper discusses the concept and parameter design of a robust stair-climbing compliant modular robot, capable of tackling stairs with overhangs. Geometry modifications of the periphery of the wheels of our robot helped in tackling overhangs. Along with establishing a concept design, the robust design parameters are set to minimize performance variations. The Grey-based Taguchi method is applied to provide an optimal setting for the design parameters of the robot. The robot prototype is shown to have successfully scaled stairs of varying dimensions, with overhang, thus corroborating the analysis performed.
In this paper, we review the history of the concept of neuroplasticity as it relates to the understanding of neuropsychiatric disorders, using schizophrenia as a case in point. We briefly review the myriad meanings of the term neuroplasticity, and its neuroscientific basis. We then review the evidence for aberrant neuroplasticity and metaplasticity associated with schizophrenia as well as the risk for developing this illness, and discuss the implications of such understanding for prevention and therapeutic interventions. We argue that the failure and/or altered timing of plasticity of critical brain circuits might underlie cognitive and deficit symptoms, and may also lead to aberrant plastic reorganization in other circuits, leading to affective dysregulation and eventually psychosis. This “dysplastic” model of schizophrenia can suggest testable etiology and treatment-relevant questions for the future.
Recently, there has been increasing focus on prevention of mental illness,
early intervention and the promotion of mental health. The social
determinants of health and public health approaches are considered key.
Early intervention has focused on psychotic disorders but prevention has
not. This may in part reflect the fact that public health planners do not
have a clear model for how social determinants influence the risk of
developing a psychotic illness. Drawing on biological, genetic and
epidemiologic evidence regarding the relationship between social risk
factors and psychosis, this paper outlines a conceptual framework for
understanding how individual and ecological factors contribute and interact
to modulate the risk of developing psychotic illness. The framework asserts
that there are four dimensions: individual factors; ecological factors; the
interaction between individual and ecological factors; and time. It may help
those considering interventions to understand the multilevel and
multifactorial effects of social factors on the aetiology of psychotic
illness, to develop targeted strategies for the prevention of psychotic
illness and serve as a template for the assessment of initiatives.
One of the major challenges affecting the performance of Npn AlGaN/GaN heterojunction bipolar transistors (HBTs) is the high base access resistance, which is comprised of the base contact resistance and the base bulk resistance. A novel concept is proposed to reduce the base access resistance in Npn AlGaN/GaN HBTs by employing polarization-enhanced contacts and selective epitaxial growth of the base and emitter. In addition, this technique reduces the exposed base surface area, which results in a lower surface recombination current. Such a structure would enable better performance of AlGaN/GaN HBTs in terms of higher current gain and a lower offset voltage. Theoretical calculations on polarization-enhanced contacts predict p-type specific contact resistance lower than 10-5 Ωcm2. Experimental results using transmission line measurement (TLM) technique yield specific contact resistances of 5.6×10-4 Ωcm2 for polarization-enhanced p-type contacts and 7.8×10-2 Ωcm2 for conventional p-type contacts.
Diode ideality factors of 2.0–8.0 have been reported in GaN-based p-n junctions. These values are much higher than the expected values of 1.0–2.0 as per the Sah-Noyce-Shockley theory. We propose a fundamentally new model for the high ideality factors obtained in GaN-based diodes. This model is based on the effect of moderately doped unipolar heterojunctions as well as metal–semiconductor junctions in series with the p-n junction. A relation for the effective ideality factor of a system of junctions is developed. A detailed experimental study is performed on diodes fabricated from two different structures, a bulk GaN p-n junction structure and a p-n junction structure incorporating a p-type AlGaN/GaN superlattice. Bulk GaN p-n junction diode displays an ideality factor of 6.9, whereas the one with the superlattice structure displays an ideality factor of 4.0. In addition, device simulation results further strengthen the model by showing that moderately doped unipolar heterojunctions are rectifying and increase the effective ideality factor of a p-n junction structure.
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