Original Articles
Frequency and temporal sequence of clinical features in adults with anti-NMDA receptor encephalitis presenting with psychiatric symptoms
- Ronald J. Gurrera
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- Published online by Cambridge University Press:
- 18 December 2018, pp. 2709-2716
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Background
Anti-NMDA receptor (NMDAr) encephalitis is the most common autoimmune encephalitis in adults. It mimics psychiatric disorders so often that most patients are initially referred to a psychiatrist, and many are misdiagnosed. Without prompt and effective treatment, patients are likely to suffer a protracted course with significant residual disability, or death. This study focuses on the frequency and chronology of salient clinical features in adults with anti-NMDAr encephalitis who are likely to be first evaluated by a psychiatrist because their presentation suggests a primary psychiatric disorder.
MethodsA systematic search of PubMed and EMBASE databases identified published reports of anti-NMDAr encephalitis associated with prominent behavioral or psychiatric symptoms. After eliminating redundancies, the frequencies and relative timing of clinical features were tabulated. Signs and symptoms were assigned temporal ranks based on the timing of their first appearance relative to the first appearance of other signs and symptoms in each patient; median ranks were used to compare temporal sequencing of both individual features and major symptom domains.
ResultsTwo hundred thirty unique cases (185 female) met study inclusion criteria. The most common features were seizures (60.4%), disorientation/confusion (42.6%), orofacial dyskinesias (39.1%), and mutism/staring (37.4%). Seizures, fever, and cognitive dysfunction were often the earliest features to emerge, but psychiatric features predominated and sequencing varied greatly between individuals.
ConclusionsClinicians should consider anti-NMDAr encephalitis when new psychiatric symptoms are accompanied by a recent viral prodrome, seizures or unexplained fever, or when the quality of the psychiatric symptoms is unusual (e.g. non-verbal auditory hallucinations).
HOMA-IR increase after antidepressant treatment in depressed patients with the Met allele of the Val66Met BDNF genetic polymorphism
- Séverine Martin, Romain Colle, Khalil El Asmar, Adrien Rigal, Albane Vievard, Bruno Feve, Laurent Becquemont, Céline Verstuyft, Emmanuelle Corruble
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- Published online by Cambridge University Press:
- 11 December 2018, pp. 2364-2369
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Background
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with response to antidepressant drugs in depressed patients and with metabolic side effects after antipsychotic treatment. This study aims to assess the association between this polymorphism and insulin resistance after antidepressant treatment in depressed patients.
MethodsOne hundred forty-eight Caucasian patients with a current unipolar major depressive episode (DSM IV-TR) were genotyped for the BDNF Val66Met polymorphism and assessed at baseline and after 3 and 6 months of antidepressant treatment for the ‘Homoeostasis model assessment of insulin resistance’ (HOMA-IR) index, a valid measure of insulin resistance based on fasting plasma insulinaemia and glycaemia. Because validity assumptions were fulfilled, data were analysed using analysis of variance for repeated measures.
ResultsThe 52 (35%) Met carriers and 96 (65%) Val/Val patients were not different at baseline for clinical characteristics and HOMA-IR. A significant Val66Met × time interaction (p = 0.02), a significant time effect (p = 0.03) and a significant Val66Met effect (p = 0.0497) were shown for HOMA-IR. A significant Val66Met × time interaction (p = 0.01) and a significant time effect (p = 0.003) were shown for fasting glycaemia. HOMA-IR and fasting glycaemia changes after antidepressant treatment were significantly higher in Met carrier than in Val/Val patients (HOMA-IR changes: Met: 0.71 ± 3.29 v. Val/Val: −0.16 ± 1.34, t = 2.3, df = 146, p = 0.02, glycaemia changes: Met: 0.09 ± 0.30 v. Val/Val: 0.02 ± 0.16, t = −2.0, df = 146, p = 0.045).
ConclusionsThe Met allele of the Val66Met BDNF polymorphism confers to depressed patients a higher risk of insulin-resistance after antidepressant treatment. These patients could benefit from specific monitoring of metabolism and preventive measures.
A predictive model for conversion to psychosis in clinical high-risk patients
- Adam J. Ciarleglio, Gary Brucato, Michael D. Masucci, Rebecca Altschuler, Tiziano Colibazzi, Cheryl M. Corcoran, Francesca M. Crump, Guillermo Horga, Eugénie Lehembre-Shiah, Wei Leong, Scott A. Schobel, Melanie M. Wall, Lawrence H. Yang, Jeffrey A. Lieberman, Ragy R. Girgis
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- Published online by Cambridge University Press:
- 28 June 2018, pp. 1128-1137
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Background
The authors developed a practical and clinically useful model to predict the risk of psychosis that utilizes clinical characteristics empirically demonstrated to be strong predictors of conversion to psychosis in clinical high-risk (CHR) individuals. The model is based upon the Structured Interview for Psychosis Risk Syndromes (SIPS) and accompanying clinical interview, and yields scores indicating one's risk of conversion.
MethodsBaseline data, including demographic and clinical characteristics measured by the SIPS, were obtained on 199 CHR individuals seeking evaluation in the early detection and intervention for mental disorders program at the New York State Psychiatric Institute at Columbia University Medical Center. Each patient was followed for up to 2 years or until they developed a syndromal DSM-4 disorder. A LASSO logistic fitting procedure was used to construct a model for conversion specifically to a psychotic disorder.
ResultsAt 2 years, 64 patients (32.2%) converted to a psychotic disorder. The top five variables with relatively large standardized effect sizes included SIPS subscales of visual perceptual abnormalities, dysphoric mood, unusual thought content, disorganized communication, and violent ideation. The concordance index (c-index) was 0.73, indicating a moderately strong ability to discriminate between converters and non-converters.
ConclusionsThe prediction model performed well in classifying converters and non-converters and revealed SIPS measures that are relatively strong predictors of conversion, comparable with the risk calculator published by NAPLS (c-index = 0.71), but requiring only a structured clinical interview. Future work will seek to externally validate the model and enhance its performance with the incorporation of relevant biomarkers.
Risk of dementia associated with psychotic disorders in later life: the health in men study (HIMS)
- Osvaldo P. Almeida, Andrew H. Ford, Graeme J. Hankey, Bu B. Yeap, Jonathan Golledge, Leon Flicker
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- 22 March 2018, pp. 232-242
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Background
Recent research has identified several potentially modifiable risk factors for dementia, including mental disorders. Psychotic disorders, such as schizophrenia and delusional disorder, have also been associated with increased risk of cognitive impairment and dementia, but currently available data difficult to generalise because of bias and confounding. We designed the present study to investigate if the presence of a psychotic disorder increased the risk of incident dementia in later life.
MethodsProspective cohort study of a community-representative sample of 37 770 men aged 65–85 years who were free of dementia at study entry. They were followed for up to 17.7 years using electronic health records. Clinical diagnoses followed the International Classification of Diseases guidelines. As psychotic disorders increase mortality, we considered death a competing risk.
ResultsA total of 8068 (21.4%) men developed dementia and 23 999 (63.5%) died during follow up. The sub-hazard ratio of dementia associated with a psychotic disorder was 2.67 (95% CI 2.30–3.09), after statistical adjustments for age and prevalent cardiovascular, respiratory, gastrointestinal and renal diseases, cancer, as well as hearing loss, depressive and bipolar disorders, and alcohol use disorder. The association between psychotic disorder and dementia risk varied slightly according to the duration of the psychotic disorder (highest for those with the shortest illness duration), but not the age of onset. No information about the use of antipsychotics was available.
ConclusionOlder men with a psychotic disorder have nearly three times greater risk of developing dementia than those without psychosis. The pathways linking psychotic disorders to dementia remain unclear but may involve mechanisms other than those associated with Alzheimer's disease and other common dementia syndromes.
Mediators of increased self-harm and suicidal ideation in sexual minority youth: a longitudinal study
- O. A. Oginni, E. J. Robinson, A. Jones, Q. Rahman, K. A. Rimes
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- Published online by Cambridge University Press:
- 23 November 2018, pp. 2524-2532
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Background
Sexual minority youth have elevated suicidal ideation and self-harm compared with heterosexual young people; however, evidence for mediating mechanisms is predominantly cross-sectional. Using a longitudinal design, we investigated self-esteem and depressive symptoms as mediators of increased rates of suicidal ideation or self-harm (SISH) among sexual minority youth, and the roles of childhood gender nonconformity (CGN) and sex as moderators of these relationships.
MethodIn total, 4274 youth from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort reported sexual orientation at age 15 years, and past-year SISH at age 20 years. Self-esteem and depressive symptoms were assessed at ages 17 and 18 years, respectively. CGN was measured at 30–57 months. Covariates included sociodemographic variables and earlier measures of mediator and outcome variables. Mediation pathways were assessed using structural equation modelling.
ResultsSexual minority youth (almost 12% of the sample) were three times more likely than heterosexual youth to report past-year SISH (95% confidence interval 2.43–3.64) at 20 years. Two mediation pathways were identified: a single mediator pathway involving self-esteem and a multiple-mediated pathway involving self-esteem and depressive symptoms. Although CGN was associated with past-year SISH, it did not moderate any mediation pathways and there was no evidence for moderation by sex.
ConclusionsLower self-esteem and increased depressive symptoms partly explain the increased risk for later suicidal ideation and self-harm in sexual minority youth. Preventive strategies could include self-esteem-enhancing or protecting interventions, especially in female sexual minority youth, and treatment of depression.
Individualized prediction of dispositional worry using white matter connectivity
- Chunliang Feng, Zaixu Cui, Dazhi Cheng, Rui Xu, Ruolei Gu
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- Published online by Cambridge University Press:
- 25 October 2018, pp. 1999-2008
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Background
Excessive worry is a defining feature of generalized anxiety disorder and is present in a wide range of other psychiatric conditions. Therefore, individualized predictions of worry propensity could be highly relevant in clinical practice, with respect to the assessment of worry symptom severity at the individual level.
MethodsWe applied a multivariate machine learning approach to predict dispositional worry based on microstructural integrity of white matter (WM) tracts.
ResultsWe demonstrated that the machine learning model was able to decode individual dispositional worry scores from microstructural properties in widely distributed WM tracts (mean absolute error = 10.46, p < 0.001; root mean squared error = 12.82, p < 0.001; prediction R2 = 0.17, p < 0.001). WM tracts that contributed to worry prediction included the posterior limb of internal capsule, anterior corona radiate, and cerebral peduncle, as well as the corticolimbic pathways (e.g. uncinate fasciculus, cingulum, and fornix) already known to be critical for emotion processing and regulation.
ConclusionsThe current work thus elucidates potential neuromarkers for clinical assessment of worry symptoms across a wide range of psychiatric disorders. In addition, the identification of widely distributed pathways underlying worry propensity serves to better improve the understanding of the neurobiological mechanisms associated with worry.
Trauma-associated anterior cingulate connectivity during reward learning predicts affective and anxiety states in young adults
- Kristen L. Eckstrand, Lindsay C. Hanford, Michele A. Bertocci, Henry W. Chase, Tsafrir Greenberg, Jeanette Lockovich, Ricki Stiffler, Haris A. Aslam, Simona Graur, Genna Bebko, Erika E. Forbes, Mary L. Phillips
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- Published online by Cambridge University Press:
- 19 September 2018, pp. 1831-1840
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Background
Trauma exposure is associated with development of depression and anxiety; yet, some individuals are resilient to these trauma-associated effects. Differentiating mechanisms underlying development of negative affect and resilience following trauma is critical for developing effective interventions. One pathway through which trauma could exert its effects on negative affect is reward-learning networks. In this study, we examined relationships among lifetime trauma, reward-learning network function, and emotional states in young adults.
MethodsOne hundred eleven young adults self-reported trauma and emotional states and underwent functional magnetic resonance imaging during a monetary reward task. Trauma-associated neural activation and functional connectivity were analyzed during reward prediction error (RPE). Relationships between trauma-associated neural functioning and affective and anxiety symptoms were examined.
ResultsNumber of traumatic events was associated with greater ventral anterior cingulate cortex (vACC) activation, and lower vACC connectivity with the right insula, frontopolar, inferior parietal, and temporoparietal regions, during RPE. Lower trauma-associated vACC connectivity with frontoparietal regions implicated in regulatory and decision-making processes was associated with heightened affective and anxiety symptoms; lower vACC connectivity with insular regions implicated in interoception was associated with lower affective and anxiety symptoms.
ConclusionsIn a young adult sample, two pathways linked the impact of trauma on reward-learning networks with higher v. lower negative affective and anxiety symptoms. The disconnection between vACC and regions implicated in decision-making and self-referential processes may reflect aberrant regulatory but appropriate self-focused mechanisms, respectively, conferring risk for v. resilience against negative affective and anxiety symptoms.
Depression and cause-specific mortality in an ethnically diverse cohort from the UK: 8-year prospective study
- Jayati Das-Munshi, Chin-Kuo Chang, Peter Schofield, Robert Stewart, Martin J. Prince
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- Published online by Cambridge University Press:
- 05 September 2018, pp. 1639-1651
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Background
Depression is associated with increased mortality, however, little is known about its variation by ethnicity.
MethodsWe conducted a cohort study of individuals with ICD-10 unipolar depression from secondary mental healthcare, from an ethnically diverse location in southeast London, followed for 8 years (2007–2014) linked to death certificates. Age- and sex- standardised mortality ratios (SMRs), with the population of England and Wales as a standard population were derived. Hazard ratios (HRs) for mortality were derived through multivariable regression procedures.
ResultsData from 20 320 individuals contributing 91 635 person-years at risk with 2366 deaths were used for analyses. SMR for all-cause mortality in depression was 2.55(95% CI 2.45–2.65), with similar trends by ethnicity. Within the cohort with unipolar depression, adjusted HR (aHRs) for all-cause mortality in ethnic minority groups relative to the White British group were 0.62(95% CI 0.53–0.74) (Black Caribbean), 0.53(95% CI 0.39–0.72) (Black African) and 0.69(95% CI 0.52–0.90) (South Asian). Male sex and alcohol/substance misuse were associated with an increased all-cause mortality risk [aHR:1.94 (95% CI 1.68–2.24) and aHR:1.18 (95% CI 1.01–1.37) respectively], whereas comorbid anxiety was associated with a decreased risk [aHR: 0.72(95% CI 0.58–0.89)]. Similar associations were noted for natural-cause mortality. Alcohol/substance misuse and male sex were associated with a near-doubling in unnatural-cause mortality risk, whereas Black Caribbean individuals with depression had a reduced unnatural-cause mortality risk, relative to White British people with depression.
ConclusionsAlthough individuals with depression experience an increased mortality risk, marked heterogeneity exists by ethnicity. Research and practice should focus on addressing tractable causes underlying increased mortality in depression.
Impact of number of episodes on neurocognitive trajectory in bipolar disorder patients: a 5-year follow-up study
- Eva María Sánchez-Morla, Ana López-Villarreal, Estela Jiménez-López, Ana Isabel Aparicio, Vicente Martínez-Vizcaíno, Rodriguez-Jimenez Roberto, Eduard Vieta, José-Luis Santos
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- Published online by Cambridge University Press:
- 25 July 2018, pp. 1299-1307
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Background
The neurocognitive trajectory in bipolar disorder (BD) is variable, with controversial findings, and most evidence come from cross-sectional studies. We aimed to examine the course of neurocognitive functioning in a sample of euthymic BD patients in comparison with a control group during a 5-year follow-up.
MethodsNinety-nine euthymic bipolar patients and 40 healthy controls were assessed using a comprehensive neurocognitive battery (six neurocognitive domains) at baseline (T1) and then at 5-year follow-up (T2) in a longitudinal study.
ResultsNo evidence of a progression in neurocognitive dysfunction was found either in cognitive composite index or in any of the neurocognitive domains for the whole cohort. However, there was a negative correlation between number of manic episodes and hospitalisations due to manic episodes and change in neurocognitive composite index (NCI) during the follow-up. Moreover, patients with higher number of manic and hypomanic episodes have a greater decrease in NCI, working memory and visual memory. History of psychotic symptoms was not related to the trajectory of neurocognitive impairment.
ConclusionsOur results suggest that, although the progression of cognitive decline is not a general rule in BD, BD patients who have a greater number of manic or hypomanic episodes may constitute a subgroup characterised by the progression of neurocognitive impairment. Prevention of manic and hypomanic episodes could have a positive impact on the trajectory of cognitive function.
Mapping the neuroanatomic substrates of cognition in familial attention deficit hyperactivity disorder
- Rachel Muster, Saadia Choudhury, Wendy Sharp, Steven Kasparek, Gustavo Sudre, Philip Shaw
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- 24 May 2018, pp. 590-597
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Background
While the neuroanatomic substrates of symptoms of attention deficit hyperactivity disorder (ADHD) have been investigated, less is known about the neuroanatomic correlates of cognitive abilities pertinent to the disorder, particularly in adults. Here we define the neuroanatomic correlates of key cognitive abilities and determine if there are associations with histories of psychostimulant medication.
MethodsWe acquired neuroanatomic magnetic resonance imaging data from 264 members of 60 families (mean age 29.5; s.d. 18.4, 116 with ADHD). Using linear mixed model regression, we tested for associations between cognitive abilities (working memory, information processing, intelligence, and attention), symptoms and both cortical and subcortical volumes.
ResultsSymptom severity was associated with spatial working memory (t = −3.77, p = 0.0002), processing speed (t = −2.95, p = 0.004) and a measure of impulsive responding (t = 2.19, p = 0.03); these associations did not vary with age (all p > 0.1). Neuroanatomic associations of cognition varied by task but centered on prefrontal, lateral parietal and temporal cortical regions, the thalamus and putamen. The neuroanatomic correlates of ADHD symptoms overlapped significantly with those of working memory (Dice's overlap coefficient: spatial, p = 0.003; verbal, p = 0.001) and information processing (p = 0.02). Psychostimulant medication history was associated with neither cognitive skills nor with a brain–cognition relationships.
ConclusionsDiagnostic differences in the cognitive profile of ADHD does not vary significantly with age; nor were cognitive differences associated with psychostimulant medication history. The neuroanatomic substrates of working memory and information overlapped with those for symptoms within these extended families, consistent with a pathophysiological role for these cognitive skills in familial ADHD.
Cross-sectional and prospective inter-relationships between depressive symptoms, vascular disease and cognition in older adults
- Louise Mewton, Simone Reppermund, John Crawford, David Bunce, Wei Wen, Perminder Sachdev
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- 29 October 2018, pp. 2168-2176
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Background
It has been proposed that vascular disease is the mechanism linking depression and cognition, but prospective studies have not supported this hypothesis. This study aims to investigate the inter-relationships between depressive symptoms, cognition and cerebrovascular disease using a well-characterised prospective cohort.
MethodData came from waves 1 (2005–2007) and 2 (2007–2009) of the Sydney Memory and Ageing Study (n = 462; mean age = 78.3 years).
ResultsAt wave 1, there was an association between depressive symptoms and white matter hyperintensity (WMH) volume [b = 0.016, t(414) = 2.34, p = 0.020]. Both depressive symptoms [b = −0.058, t(413) = −2.64, p = 0.009] and WMH volume [b = −0.011, t(413) = −3.77, p < 0.001], but not stroke/transient ischaemic attack (TIA) [b = −0.328, t(413) = −1.90, p = 0.058], were independently associated with lower cognition. Prospectively, cerebrovascular disease was not found to predict increasing depressive symptoms [stroke/TIA: b = −0.349, t(374.7) = −0.76, p = 0.448; WMH volume: b = 0.007, t(376.3) = 0.875, p = 0.382]. Depressive symptoms predicted increasing WMH severity [b = 0.012, t(265.9) = −3.291, p = 0.001], but not incident stroke/TIA (odds ratio = 0.995; CI 0.949–1.043; p = 0.820). When examined in separate models, depressive symptoms [b = −0.027, t(373.5) = −2.16, p = 0.032] and a history of stroke/TIA [b = −0.460, t(361.2) = −4.45, p < 0.001], but not WMH volume [b = 0.001, t(362.3) = −0.520, p = 0.603], predicted declines in cognition. When investigated in a combined model, a history of stroke/TIA remained a predictor of cognitive decline [b = −0.443, t(360.6) = −4.28, p < 0.001], whilst depressive symptoms did not [b = −0.012, t(359.7) = −0.96, p = 0.336].
ConclusionsThis study is contrasted with previous prospective studies which indicate that depressive symptoms predict cognitive decline independently of vascular disease. Future research should focus on further exploring the vascular mechanisms underpinning the relationship between depressive symptoms and cognition.
Defining a combined constellation of complicated bereavement and PTSD and the psychosocial correlates associated with the pattern amongst refugees from West Papua
- Alvin Kuowei Tay, Susan Rees, Natalino Tam, Moses Kareth, Derrick Silove
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- Published online by Cambridge University Press:
- 28 August 2018, pp. 1481-1489
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Background
Refugees are at risk of experiencing a combined constellation of complicated bereavement and posttraumatic stress disorder (PTSD) symptoms following exposure to complex traumas associated with personal threat and loss. Features of identity confusion are central to both complicated bereavement and PTSD and these characteristics may be particularly prominent amongst refugees from traditional cultures displaced from their homelands, families, and kinship groups. We investigate whether a combined pattern of complicated bereavement and PTSD can be identified amongst West Papuan refugees participating in an epidemiological survey (n = 486, response rate: 85.8%) in a remote town in Papua New Guinea.
MethodsLatent class analysis was applied to derive subpopulations of refugees based on symptoms of complicated bereavement and PTSD. Associations were examined between classes and traumatic loss events, post-migration living difficulties (PMLDs), and psychosocial support systems.
ResultsThe four classes identified comprised a complicated bereavement class (11%), a combined posttraumatic bereavement class (10%), a PTSD class (11%), and a low symptom class (67%). Symptoms of identity confusion were prominent in the posttraumatic bereavement class. Compared with the low symptom class, the combined posttraumatic bereavement class reported greater exposure to traumatic loss events (OR 2.43, 95% CI 1.11–5.34), PMLDs (OR 2.24, 95% CI 1.01–4.6), disruptions to interpersonal bonds and networks (OR 3.3, 95% CI 1.47–7.38), and erosion of roles and identities (OR 2.18, 95% CI 1.11–4.27).
ConclusionsRefugees appear to manifest a combined pattern of complicated bereavement and PTSD symptoms in which identity confusion is a prominent feature. This response appears to reflect the combined impact of high levels of exposure to traumatic losses, PMLDs, and disruption of relevant psychosocial systems.
Frontostriatal functional connectivity and striatal dopamine synthesis capacity in schizophrenia in terms of antipsychotic responsiveness: an [18F]DOPA PET and fMRI study
- Seoyoung Kim, Wi Hoon Jung, Oliver D. Howes, Mattia Veronese, Federico E. Turkheimer, Yun-Sang Lee, Jae Sung Lee, Euitae Kim, Jun Soo Kwon
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- Published online by Cambridge University Press:
- 21 November 2018, pp. 2533-2542
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Background
Given that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine.
MethodsTwenty-four symptomatically stable patients with schizophrenia were recruited from Seoul National University Hospital, 12 of which responded to first-line antipsychotic drugs (first-line AP group) and 12 under clozapine (clozapine group), along with 12 matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging and [18F]DOPA PET scans.
ResultsNo significant difference was found in the total PANSS score between the patient groups. Voxel-based analysis showed a significant correlation between frontal FC to the associative striatum and the influx rate constant of [18F]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R2 = 0.019, p = 0.665; first-line AP group: R2 = 0.675, p < 0.001; clozapine group: R2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups.
ConclusionsThe relationship between striatal dopamine synthesis capacity and frontostriatal FC is different between responders to first-line treatment and clozapine treatment in schizophrenia, indicating that a different pathophysiology could underlie schizophrenia in patients who respond to first-line treatments relative to those who do not.
Cognitive functioning following discontinuation of antipsychotic medication. A naturalistic sub-group analysis from the OPUS II trial
- Nikolai Albert, Lasse Randers, Kelly Allott, Heidi Dorthe Jensen, Marianne Melau, Carsten Hjorthøj, Merete Nordentoft
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- 30 July 2018, pp. 1138-1147
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Background
The effect of antipsychotics medication on cognitive functioning in patients diagnosed with schizophrenia is poorly understood. Some studies of second generation antipsychotics indicated that they improved cognitive functioning while other studies have found that they decrease the level of cognitive functioning.
MethodWe included patients with schizophrenia who were in treatment with antipsychotics 1.5 years (baseline) after initiation of treatment and followed them up 3.5 years later (n = 189). At follow-up 60 (32%) had discontinued their antipsychotic treatment and 129 (68%) were still taking antipsychotics. Using the Brief Assessment of Cognition in Schizophrenia (BACS) we assessed cognition at baseline and follow-up.
ResultsThe patients who discontinued their medication had a higher level of cognitive functioning in all domains at baseline, as well as Global cognitive function [mean z-score −1.50 (s.d. 1.24) v. −2.27 (s.d. 1.30), p = 0.00015]. After controlling for relevant confounders those who discontinued antipsychotic medication improved significantly more than those who remained on antipsychotic medication during the course of the follow-up on the Token Motor task [estimated mean change difference −0.46 (95% CI −0.89 to −0.04)], the Speed of Processing Domain [estimated mean change difference −0.38 (95% CI −0.68 to −0.08)] and global cognition [estimated mean change difference −0.36 (95% CI −0.66 to −0.07)].
ConclusionDue to the naturalistic design, we cannot conclude on the direction of the relationship between antipsychotics and cognition. There is no evidence that discontinuation of medication had a negative effect on cognitive functioning. Rather, we found that that discontinuation of medication was associated with better cognitive functioning.
Common genetic contributions to high-risk trauma exposure and self-injurious thoughts and behaviors
- Leah S. Richmond-Rakerd, Timothy J. Trull, Ian R. Gizer, Kristin McLaughlin, Emily M. Scheiderer, Elliot C. Nelson, Arpana Agrawal, Michael T. Lynskey, Pamela A.F. Madden, Andrew C. Heath, Dixie J. Statham, Nicholas G. Martin
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- Published online by Cambridge University Press:
- 06 May 2018, pp. 421-430
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Background
Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences.
MethodsMultivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24–42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project.
ResultsThe prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [rG = 0.59, 95% confidence interval (CI) (0.37–0.81)] and women [rG = 0.56 (0.49–0.63)]. Unique environmental influences were modestly correlated in women [rE = 0.23 (0.01–0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females.
ConclusionsIndividuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma.
Attention-deficit/hyperactivity disorder and clinically diagnosed obesity in adolescence and young adulthood: a register-based study in Sweden
- Qi Chen, Catharina A. Hartman, Ralf Kuja-Halkola, Stephen V. Faraone, Catarina Almqvist, Henrik Larsson
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- Published online by Cambridge University Press:
- 17 September 2018, pp. 1841-1849
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Background
A recent family study of young adult males suggests a shared familial liability between attention-deficit/hyperactivity disorder (ADHD) and high body mass index (BMI), and a genome-wide meta-analysis reported a genetic correlation of 0.26 between ADHD and BMI. To date, it is unclear whether these findings generalize to the relationship between ADHD and clinically diagnosed obesity.
MethodBy linking the Swedish national registers, we identified 25 38 127 individuals born between 1973 and 2000, together with their siblings and cousins. The risk of clinical obesity in individuals with ADHD was compared with the risk in those without ADHD. The relative contributions of genetic and environmental factors to the association between ADHD and clinical obesity were examined via assessment of the familial co-aggregation of the two conditions and quantitative genetic analysis.
ResultsIndividuals with ADHD were at an increased risk of clinical obesity compared with those without (risk difference 3.73%, 95% confidence interval (CI) 3.55–3.90%; risk ratio 3.05, 95% CI 2.95–3.15). Familial co-aggregation of ADHD and clinical obesity was detected and the strength of the co-aggregation decreased by decreasing genetic relatedness. The correlation between the liabilities to ADHD and clinical obesity can be entirely attributed to their genetic correlation (rg 0.30, 95% CI 0.17–0.44).
ConclusionThe association between ADHD and clinical obesity in adolescence and young adulthood can be entirely attributed to genetic underpinnings shared by the two conditions. Children with ADHD should be monitored for weight gain so that preventive measures can be taken for those on a suboptimal trajectory.
Psychopathologic structure of bipolar disorders: exploring dimensional phenotypes, their relationships, and their associations with bipolar I and II disorders
- Ji Hyun Baek, Kyooseob Ha, Yongkang Kim, Young-ah Cho, So Yung Yang, Yujin Choi, Sung-Lee Jang, Taesung Park, Tae Hyon Ha, Kyung Sue Hong
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- Published online by Cambridge University Press:
- 17 October 2018, pp. 2177-2185
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Background
Given its diverse disease courses and symptom presentations, multiple phenotype dimensions with different biological underpinnings are expected with bipolar disorders (BPs). In this study, we aimed to identify lifetime BP psychopathology dimensions. We also explored the differing associations with bipolar I (BP-I) and bipolar II (BP-II) disorders.
MethodsWe included a total of 307 subjects with BPs in the analysis. For the factor analysis, we chose six variables related to clinical courses, 29 indicators covering lifetime symptoms of mood episodes, and 6 specific comorbid conditions. To determine the relationships among the identified phenotypic dimensions and their effects on differentiating BP subtypes, we applied structural equation modeling.
ResultsWe selected a six-factor solution through scree plot, Velicer's minimum average partial test, and face validity evaluations; the six factors were cyclicity, depression, atypical vegetative symptoms, elation, psychotic/irritable mania, and comorbidity. In the path analysis, five factors excluding atypical vegetative symptoms were associated with one another. Cyclicity, depression, and comorbidity had positive associations, and they correlated negatively with psychotic/irritable mania; elation showed positive correlations with cyclicity and psychotic/irritable mania. Depression, cyclicity, and comorbidity were stronger in BP-II than in BP-I, and they contributed significantly to the distinction between the two disorders.
ConclusionsWe identified six phenotype dimensions; in addition to symptom features of manic and depressive episodes, various comorbidities and high cyclicity constructed separate dimensions. Except for atypical vegetative symptoms, all factors showed a complex interdependency and played roles in discriminating BP-II from BP-I.
Public knowledge, attitudes, social distance and reporting contact with people with mental illness 2009–2017
- Emily J. Robinson, Claire Henderson
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- Published online by Cambridge University Press:
- 20 December 2018, pp. 2717-2726
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Background
Our aim was to investigate patterns of change in public knowledge, attitudes, desire for social distance and reporting having contact with people with mental health problems in England during the Time to Change (TTC) programme to reduce stigma and discrimination 2009–2017.
MethodsUsing data from an annual face-to-face survey of a nationally representative quota sample of adults, we evaluated longitudinal trends of the outcome measures with regression analyses and made assumptions on the basis of a simple random sample. We tested interactions between year and demographic subgroups.
ResultsThere were improvements in all outcomes in 2017 compared with baseline measures (2008 or 2009). Reported in s.d. units [95% confidence interval (CI)], the improvement for knowledge was 0.17 (0.10–0.23); for attitudes 0.25 (0.18–0.31); and for social distance 0.29 (0.23–0.35). A higher likelihood of reporting contact was also associated with most recent survey year (odds ratio 1.47, 95% CI 1.27–1.71). Statistically significant interactions between year and region of England suggest greatest improvements in attitudes and intended behaviour in London, where both outcomes were significantly worse in the early years of the survey. However, for attitudes, this interaction was only significant among women. Other significant interactions suggest that attitudes improved most in the target age group (25–44).
ConclusionsThe results provide support for the effectiveness of TTC across demographic groups. However, other societal changes may influence the results, such as the increasing prevalence of common mental disorder in young women.
Reduced immunity to measles in adults with major depressive disorder
- Bart N. Ford, Robert H. Yolken, Faith B. Dickerson, T. Kent Teague, Michael R. Irwin, Martin P. Paulus, Jonathan Savitz
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- Published online by Cambridge University Press:
- 19 March 2018, pp. 243-249
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Background
Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination.
MethodsIgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963.
ResultsRelative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24–0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26–0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles.
ConclusionsIndividuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.
A randomized controlled trial of working memory and processing speed training in schizophrenia
- B.D. Cassetta, L.M. Tomfohr-Madsen, V.M. Goghari
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- Published online by Cambridge University Press:
- 03 October 2018, pp. 2009-2019
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Background
Although prior research has shown that cognitive training may improve cognition for schizophrenia patients, it is currently unclear which domains of cognition should be targeted in training. One suggestion is to target low- or mid-level cognitive processes. In particular, working memory (WM) and processing speed (PS) have been named as two key areas of impairment in schizophrenia, and two domains of cognition that are linked to higher-order cognition and daily functioning. This study aimed to investigate the near-transfer (transfer of gains to related contexts), far-transfer (transfer of gains to unrelated contexts), and real-world gains associated with WM and PS training in schizophrenia.
MethodsEighty-three participants with schizophrenia were recruited and randomly assigned to computerized WM training, PS training, or a no-training control group. Outcome measures included WM, PS, fluid intelligence, executive functioning, social cognition, and daily functioning and symptoms.
ResultsPS training led to significant gains in untrained PS tasks, as well as gains in far-transfer tasks that required speed of processing. WM training did not lead to gains in untrained WM tasks and showed inconsistent effects on some far-transfer tasks.
ConclusionsThese results suggest some benefit of domain-specific cognitive training, specifically PS training, in schizophrenia. Far-transfer of gains to other cognitive domains and to real-world functioning may not occur after targeted WM or PS training, though non-specific effects (e.g. through behavioral activation, increased motivation) may lead to improvements in some tasks. Future studies should continue to investigate the mechanisms by which cognitive training may enhance cognition and functioning in schizophrenia.