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To derive scores for mental disorganization and impoverishment from commonly used rating scales, and test the hypothesis that disorganization and impoverishment, along with impaired cognition and role-function reflect a latent variable that is a plausible candidate for the putative core deficit.
For more than 100 years, disorganization and impoverishment of mental activity have been recognised as fundamental symptoms of schizophrenia. These symptoms may reflect a core brain process underlying persisting disability. Delusions and hallucinations have been regarded as accessory features. The psychopathological processes predisposing to persisting disability in schizophrenia are poorly understood. The delineation of a core deficit underlying persisting disability would be potentially of great value in predicting outcome and developing improved treatment.
Patients aged 18–55 years were included if: they satisfied DSM IV criteria for schizophrenia or schizoaffective disorder. Healthy controls were recruited by public advertisement and selected to match the patient group in age and sex. Study sample included 39 participants with schizophrenia, 1 with schizoaffective disorder and 44 matched healthy controls. We derived disorganization and impoverishment scores from three symptom scales: PANSS, SSPI and CASH. We computed composite scores for disorganization and for impoverishment and employed Confirmatory Factor Analysis to test the hypothesis that a single factor accounts for the relationships between disorganization, impoverishment, cognitive impairment and impaired role function. We assessed the relationship between this latent “core deficit” and diminished Post Movement Beta Rebound (PMBR), an electrophysiological measure from Magnetoencephalography (MEG), associated with persisting brain disorders.
Fit indices for the single factor model from CFA indicated a good fit: χ2(2) = 1.817, p = .403; RMSEA <.001 GFI = .979. PMBR was significantly reduced in the schizophrenia group compared to healthy controls, t (68) = 3.55, p < .001. Within the patient group, PMBR was significantly and negatively correlated with the CFA factor scores representing the Core Deficit score, r=−.543, p < .01, indicating that high core deficit scores were associated with reduced PMBR. PMBR was significantly correlated with the composite Disorganization score, r=−.521, p < .001.
Our findings demonstrate that the shared variance between impoverishment (psychomotor poverty); disorganization; cognitive impairment; and impaired role function can be accounted for by a latent variable that can reasonably be described as the core deficit of classical schizophrenia. The demonstration that the severity of the putative core deficit is correlated with the reduction in PMBR provides evidence that the core deficit is associated with an identifiable abnormality of brain dysfunction.
Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.
Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.
Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.
Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.
Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation.
This retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith–Hamilton Pleasure Scale (SHAPS).
Following four infusions, both cohorts reported a significant reduction in QIDS-SR16 Total Score (F (4, 648) = 73.4, P < .001), SI (F (4, 642) = 28.6, P < .001), GAD-7 (F (2, 265) = 53.8, P < .001), and SHAPS (F (2, 302) = 45.9, P < .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16 Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction.
IV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.
In southern Australia, annual sowthistle and prickly lettuce have become more prevalent following the adoption of reduced tillage cropping systems. They are especially problematic in lentil and other pulse crops, which are weakly competitive and have few herbicide options available for POST control of broadleaf weeds. This study aimed to evaluate the influence of management in a previous cereal crop on weed densities in a subsequent crop. At two field sites, crop seeding density and POST herbicide treatments (a conventional choice that included metsulfuron-methyl and MCPA; and a proactive choice that included bromoxynil, picolinafen, and MCPA) were applied to a wheat crop, and weed density was assessed at the beginning of the following season to measure for a legacy effect of the treatments. Study site populations were also screened for herbicide resistance and were found to have high (≥90% survival) ALS inhibitor resistance. Crop competition treatments had no effect on weed populations, and effects of herbicide treatment were significant at only one of the sites. At this site, both herbicide treatments had lower weed densities than the nontreated in the first year, but the legacy effect was only significant for annual sowthistle density in the proactive treatment. At both sites, even where weeds were extremely sparse or completely controlled following herbicide treatment in the first year, moderate densities were observed the following year, indicating that colonization from the seedbank or adjacent areas could be contributing to weed numbers. Weed density assessments and accurate knowledge of the herbicide resistance status of target weeds should guide herbicide selection to maximize control.
Higher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD).
Adults (N = 230) with TRD received four infusions of IV ketamine at a community-based clinic. Changes in symptoms of depression (ie, Quick Inventory for Depressive Symptomatology-Self-Report 16; QIDS-SR16), suicidal ideation (SI; ie, QIDS-SR16 SI item), anxiety (ie, Generalized Anxiety Disorder-7 Scale), anhedonic severity (ie, Snaith–Hamilton Pleasure Scale), and functioning (ie, Sheehan Disability Scale) following infusions were evaluated. Participants were stratified by BMI as normal (18.0-24.9 kg/m2; n = 72), overweight (25-29.9 kg/m2; n = 76), obese I (30-34.9 kg/m2; n = 47), or obese II (≥35.0 kg/m2; n = 35).
Similar antidepressant effects with repeat-dose ketamine were reported between BMI groups (P = .261). In addition, categorical partial response (P = .149), response (P = .526), and remission (P = .232) rates were similar between the four BMI groups.
The findings are limited by the observational, open-label design of this retrospective analysis. Pretreatment BMI did not predict response to IV ketamine, which was effective regardless of BMI.
In the Introduction to his Treatise of Human Nature, David Hume credits “my Lord Shaftesbury” as one of the “philosophers in England, who have begun to put the science of man on a new footing.” I describe aspects of Shaftesbury’s philosophy that justify the credit Hume gives him. I focus on Shaftesbury’s refutation of psychological egoism, his examination of partiality, and his views on how to promote impartial virtue. I also discuss Shaftesbury’s political commitments, and raise questions about recent interpretations that have taken his Characteristicks to be a polemic, partisan text.
Recent literature suggests that over 70% of cases of antibody-mediated encephalitis present to psychiatry services with features of psychosis predominantly.
To investigate the seroprevalence of N-Methyl-D-Aspartate receptor antibodies (NMDAr-Ab) in patients with first episode psychosis (FEP)
Following ethical approval, all cases meeting entry criteria were invited to participate. Participants were interviewed with SCID to obtain a DSM diagnosis. NMDAr-Ab were identified in serum by cell based assay using co-transfected Human Embryonic Kidney (HEK)cells. Positive cases were reviewed by clinical neurology. Decision to treat with immunotherapy was made on a case by case basis.
85/115 (72%) of patients with FEP entered the study. 49 (58%) participants were male, mean age (SD) 37 (15.7) years. 42 (52%) were outpatients at the time of assessment. Four cases (5%) were serum NMDAr-Ab positive. 3 of these cases were male, age 48 (16.3) years. All four were admitted as inpatients with normal brain MRI imaging. One case (female, 55) was confirmed as NMDAr-Ab encephalitis based on case presentation, EEG demonstrating bilateral cerebral dysfunction and NMDAr-Ab in CSF. Immunotherapy treatment lead to clinical improvement. In remaining cases, EEG was normal and CSF negative. All 3 of these cases showed clinical improvement following psychiatric treatment as usual.
Our findings support the current estimates as to NMDAr-Ab prevalence in FEP. Increased awareness has lead to rapid treatment of florid cases of NMDAr-Ab encephalitis in our service. Additional seropositive cases are being followed with neuro-cognitive testing for any evidence of decline.
Trichotillomania has been found to be associated with mood disorders, particularly bipolar disorder. Trichotillomania has shared similarities with bipolar disorder by virtue of phenomenology, co-morbidity, and psychopharmacologic observations. In the past, trichotillomania with comorbid bipolar disorder was treated with lithium and sodium valproate. There has been little, if any, literature on using asenapine to augment treatment in patients with trichotillomania with comorbid bipolar disorder. A patient presented with hair-pulling episodes for a year, resulting in bald scalp patches. She had no mood symptoms prior to this. She developed low mood, anhedonia, poor sleep and poor appetite subsequently as she could not stop pulling her hair. She was started on escitalopram 10 mg daily for he depressive symptoms. Three years later, she developed hypomanic symptoms such as irritability and spending sprees. Her hair pulling behaviour worsened at this time. At this point, a diagnosis of bipolar disorder type 2 was considered and she was started on lithium 300 mg daily. Her escitalopram was discontinued. As her mood was still labile 10 months later, asenapine was added to augment lithium in the treatment of the bipolar disorder. With asenapine, her hair pulling frequency started to decrease rapidly. Asenapine was increased to 10 mg daily and her hair pulling ceased. Her mood also stabilized and she no longer had erratic periods of mood lability. In conclusion, asenapine augmentation of lithium has potential to be used in patients who have trichotillomania with comorbid bipolar disorder due to its unique receptor profile.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Waardenburg syndrome (WS) is a rare genetic disorder characterised by varying degrees of sensorineural deafness, dystopia canthorum, musculokeletal defects, pigmentation anomalies such as bright blue iris, greying hair and in some cases intestinal pathology.
A 21-year-old Chinese gentleman, diagnosed with WS type 1 (Figs. 1 and 2) at the age of two, presented at the emergency unit with manic symptoms for the past one month such as irritability, grandiosity, flight of ideas and reduced need for sleep. With regards to social integration, he had features suggestive of autism spectrum disorder (ASD). He often played by himself and was fixated on particular toys. He was eventually admitted to the psychiatric ward for acute management of mania. He was stabilised on olanzapine 10 mg BD and sodium valproate 600 mg BD. His sodium valproate was cross-titrated with lithium in the ward and his manic features gradually subsided. He was discharged well after 2 weeks of admission with lithium 300 mg BD and olanzapine 10 mg BD. WS type 1 has been localised to the locus 2q35 and researchers have identified that a tetranucleotide repeat marker on 2q35 is strongly associated with recurrent mood symptoms.
In conclusion, it is important to note that individuals with WS may be at higher risk to develop ASD and mood disorders.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Diet modifies the risk of colorectal cancer (CRC), and inconclusive evidence suggests that yogurt may protect against CRC. We analysed the data collected from two separate colonoscopy-based case–control studies. The Tennessee Colorectal Polyp Study (TCPS) and Johns Hopkins Biofilm Study included 5446 and 1061 participants, respectively, diagnosed with hyperplastic polyp (HP), sessile serrated polyp, adenomatous polyp (AP) or without any polyps. Multinomial logistic regression models were used to derive OR and 95 % CI to evaluate comparisons between cases and polyp-free controls and case–case comparisons between different polyp types. We evaluated the association between frequency of yogurt intake and probiotic use with the diagnosis of colorectal polyps. In the TCPS, daily yogurt intake v. no/rare intake was associated with decreased odds of HP (OR 0·54; 95 % CI 0·31, 0·95) and weekly yogurt intake was associated with decreased odds of AP among women (OR 0·73; 95 % CI 0·55, 0·98). In the Biofilm Study, both weekly yogurt intake and probiotic use were associated with a non-significant reduction in odds of overall AP (OR 0·75; 95 % CI 0·54, 1·04) and (OR 0·72; 95 % CI 0·49, 1·06) in comparison with no use, respectively. In summary, yogurt intake may be associated with decreased odds of HP and AP and probiotic use may be associated with decreased odds of AP. Further prospective studies are needed to verify these associations.
Shiga toxin-producing Escherichia coli (STEC) infections are a significant public health issue, with foodborne transmission causing >1 million illnesses worldwide each year. We conducted a systematic review and meta-analysis (PROSPERO registry # CRD42017074239), to determine the relative association of different food types with sporadic illnesses caused by STEC. Searches were conducted from 01 August to 30 September 2017, using bibliographic and grey literature databases, websites and expert consultation. We identified 22 case-control studies of sporadic STEC infection in humans, from 10 countries within four World Health Organization subregions, from 1985 to 2012. We extracted data from 21 studies, for 237 individual measures in 11 food categories and across three status types (raw or undercooked, not raw and unknown). Beef was the most significant food item associated with STEC illness in the Americas and Europe, but in the Western Pacific region, chicken was most significant. These findings were not significantly moderated by the raw or cooked status of the food item, nor the publication year of the study. Data from the African, South-East Asian and Eastern Mediterranean subregions were lacking and it is unclear whether our results are relevant to these regions.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
Fetal growth restriction (FGR) and preterm birth are frequent co-morbidities, both are independent risks for brain injury. However, few studies have examined the mechanisms by which preterm FGR increases the risk of adverse neurological outcomes. We aimed to determine the effects of prematurity and mechanical ventilation (VENT) on the brain of FGR and appropriately grown (AG, control) lambs. We hypothesized that FGR preterm lambs are more vulnerable to ventilation-induced acute brain injury. FGR was surgically induced in fetal sheep (0.7 gestation) by ligation of a single umbilical artery. After 4 weeks, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Brains and cerebrospinal fluid (CSF) were collected for analysis of molecular and structural indices of early brain injury. FGRVENT lambs had increased oxidative cell damage and brain injury marker S100B levels compared with all other groups. Mechanical ventilation increased inflammatory marker IL-8 within the brain of FGRVENT and AGVENT lambs. Abnormalities in the neurovascular unit and increased blood–brain barrier permeability were observed in FGRVENT lambs, as well as an altered density of vascular tight junctions markers. FGR and AG preterm lambs have different responses to acute injurious mechanical ventilation, changes which appear to have been developmentally programmed in utero.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.