Feed intake in housed dairy cows: validation of a three-dimensional camera-based feed intake measurement system.

Measuring feed intake accurately is crucial to determine feed efficiency and for genetic selection. A system using three-dimensional (3D) cameras and deep learning algorithms can measure the volume of feed intake in dairy cows, but for now, the system has not been validated for feed intake expressed as weight of feed. The aim of this study was to validate the weight of feed intake predicted from the 3D cameras with the actual measured weight. It was hypothesised that diet-specific coefficients are necessary for predicting changes in weight, that the relationship between weight and volume is curvilinear throughout the day, and that manually pushing the feed affects this relationship. Twenty-four lactating Danish Holstein cows were used in a cross-over design with four dietary treatments, 2 × 2 factorial arranged with either grass-clover silage or maize silage as silage factor, and barley or dried beet pulp as concentrate factor. Cows were adapted to the diets for 11 d, and for 3 d to tie-stall housing before camera measurements. Six cameras were used for recording, each mounted over an individual feeding platform equipped with a weight scale. When building the predictive models, four cameras were used for training, and the remaining two for testing the prediction of the models. The most accurate predictions were found for the average feed intake over a period when using the starting density of the feed pile, which resulted in the lowest errors, 6% when expressed as RMSE and 5% expressed as mean absolute error. A model including curvilinear effects of feed volume and the impact of manual feed pushing was used on a dataset including daily time points. When cross-validating, the inclusion of a curvilinear effect and a feed push effect did not improve the accuracy of the model for neither the feed pile nor the feed removed by the cow between consecutive time points. In conclusion, measuring daily feed intake from this 3D camera system in the present experimental setup could be accomplished with an acceptable error (below 8%), but the system should be improved for individual meal intake measurements if these measures were to be implemented.

Clinical condition of cull sows before and after transport to slaughter - Effects of journey duration and a stationary period.

This factorial study was part of a project examining potential welfare challenges for cull sows in the pre-slaughter logistic chain, and examined effects of journey duration and presence of a longer pre-planned stop half-way during journeys on their post-transport clinical condition. The sows were transported 4, 6 or 8 h under conditions modelling typical Danish practice. In addition, across 49 journeys, effects of temperature inside the vehicle and time spent waiting before unloading at the slaughterhouse were examined. The results confirmed the findings of our earlier observational study, showing that the clinical conditions of cull sows deteriorated during transport, but also that none of the 578 sows arrived at the slaughterhouse in a condition that would have rendered them unfit for transport. A complex picture was found in relation to the clinical variables affected by journey duration, involvement of a longer pre-planned stop, and/or time spent waiting before unloading. This suggests that several factors contribute to the deterioration of the clinical condition of sows, but not consistently or as unequivocal causal factors, at least within the studied journey durations. Based on the deterioration in their clinical condition, especially for variables associated with heat stress and aggression, and knowing that the amount of time the sows are exposed to hazards such as aggressive pen mates, high temperatures and/or moving vehicles is dependent on the journey duration, keeping journeys as short as possible will most likely be advantageous. Future studies should also focus on how to optimise the social and microclimatic environment.

Postweaning growth and feeding behaviour in pigs: effect of heavier hybrid and weaning intact litters in farrowing pens for loose-housed sows.

Abrupt weaning of four-week-old pigs is associated with multiple stressors. Housing pigs in intact litters is a way to reduce the stress associated with moving and mixing of unfamiliar pigs. Furthermore, higher weaning weight may improve pigs' robustness against postweaning stressors. In the present study, it was investigated whether: (1) A heavier pig hybrid, and (2) weaning intact litters in the farrowing pen for loose-housed sows could increase postweaning feeding behaviour and growth. Two sow hybrids (DanBred LY (DB) and Topigs Norsvin TN70 (TN)) and two weaning strategies (the litter stayed intact in the farrowing pen after removing the sow (STAY), or two litters were moved and mixed in conventional weaner pens (MOVE)) were compared in a 2 × 2 factorial design. In total, 57 litters from four batches were included in the study. The TN hybrid sows gave birth to heavier piglets but smaller litter sizes and had more functional teats than DB sows. At weaning, TN pigs were heavier than DB. The number of feed trough (FT) visits on the day before weaning was low in both hybrids. On the day after weaning, the number of FT visits was higher in MOVE compared to STAY, and in TN-STAY compared to DB-STAY. The average daily gain the first two days postweaning was negative in both hybrids and weaning strategies but more pronounced in DB than TN, and STAY tended to lose more weight than MOVE. Over the entire 28-day postweaning period, there was an interaction between hybrid and weaning strategy in that TN-STAY (392 g/d) had higher growth than both TN-MOVE (251 g/d) and DB-MOVE (283 g/d), whereas growth of DB-STAY (316 g/d) was intermediate. In addition, higher weaning weight was associated with a lower number of FT visits and greater weight loss the first two days postweaning but higher growth over the 28-day postweaning period. The results show that abrupt weaning at four weeks of age causes weight loss the first days postweaning despite being housedas intact litters, most likely due to low feed consumption. However, the combination of a heavier pig hybrid and housing intact litters in the farrowing pen postweaning resulted in a higher growth performance over the 28-day postweaning period. In conclusion, pigs that are heavier at weaning reach better growth performance in the longer term, despite having the largest acute postweaning growth depression and fewest FT visits on the day before and after weaning.

Effects of changes in diet energy density and milking frequency and a single injection of cabergoline at dry-off on feeding behavior and rumination time in dairy cows.

Dry-off is a typical management practice, but research on the effects of dry-off on feeding behavior in high-yielding cows is limited. The present study investigated the effects of 2 diet energy densities: lactation diet (normal energy density, NORM) versus a lactation diet diluted with 30% straw (reduced energy density, REDU), both offered ad libitum, and 2 daily milking frequencies (2× vs. 1×) during the 7 d before dry-off day (d 0), and the effects of an injection of either a dopamine agonist [cabergoline (CAB); Velactis, Ceva Santé Animale; labeled for use only with abrupt dry-off; i.e., no reduction in feeding level or milking frequency before the last milking] or saline (SAL) following the last milking on d 0 (2 × 2 × 2 factorial arrangement), on automatically monitored feeding behavior and rumination time in 119 clinically healthy, loose-housed, pregnant, lactating Holstein cows during the week before and after d 0. From d 0, all cows were fed the same dry-cow diet ad libitum. Data were analyzed in R using mixed-effects models. Over the days before d 0, REDU cows spent 30% more time feeding at a 50% lower feeding rate, visited both assigned and unassigned feed bins more frequently, and spent more time ruminating than NORM cows. No clear behavioral effects of reduced milking frequency were found. Within 24 h following injection, CAB cows spent approximately 40% less time feeding at a lower feeding rate, visited their feed bin 28% less often, and spent 40% less time ruminating than SAL cows, irrespective of treatment before dry-off. The current study demonstrates that reducing diet energy density for 1 wk before dry-off led to clear behavioral changes in high-yielding cows. Administering CAB after the last milking induced decreased feeding behavior lasting approximately 24 h, indicating collateral effects other than reduced prolactin secretion.

Effects on feed intake, milk production, and methane emission in dairy cows fed silage or fresh grass with concentrate or fresh grass harvested at early or late maturity stage without concentrate.

The objective of the study was to quantify the effects on dry matter intake (DMI), nutrient digestibility, gas exchange, milk production, and milk quality in dairy cows fed fresh grass harvested at different maturity stages. Sixteen Danish Holstein cows in mid-lactation were divided into 4 blocks and used in 4 incomplete 4 × 2 Latin squares with 2 periods of 21 d. The cows received 1 of 4 treatments in each period, resulting in 8 cows per treatment, as follows: grass-clover silage supplemented with 6 kg/d concentrate pellets (SILc), fresh grass harvested at late maturity stage supplemented with 6 kg/d concentrate pellets (LATc), fresh grass harvested at late maturity stage (LAT), and fresh grass harvested at early maturity stage (ERL). The cows were housed in tiestalls and milked twice daily. The cows had ad libitum access to the forage, and concentrate pellets were divided into equal amounts and fed separately in the morning and afternoon. Fecal samples were collected to determine apparent total-tract digestibility, and samples of rumen fluid were collected for determination of short chain fatty acid composition. Halters were used for measuring eating and rumination time. Gas exchange was measured in open-circuit respiration chambers. Total DMI was higher in LATc and ERL (16.9 ± 0.45 and 15.5 ± 0.39 kg/d, respectively) compared with LAT (14.1 ± 0.42 kg/d). Relative to SILc, cows fed fresh grass experienced a convex pattern in DMI during the experiment. The changes in DMI were related to changes in leaf to stem ratio, fiber concentration, and organic matter digestibility determined in vitro in samples of the fresh grass harvested throughout the experiment. The apparent total-tract digestibility of organic matter was higher in SILc and LAT compared with LATc. Methane yield was lower for LATc compared with LAT (19.5 ± 0.61 vs. 22.6 ± 0.55 g of CH4/kg of DMI), and was not different between LAT and ERL. Compared with LAT, milk yield was higher for ERL (21.1 ± 1.14 vs. 23.4 ± 1.11 kg/d) and energy-corrected milk (ECM) yield was higher for LATc (21.5 ± 0.99 vs. 25.3 ± 1.03 kg/d). We detected no differences in milk or ECM yield between SILc and LATc. Milk protein yield was higher and milk fat concentration was lower in LATc compared with LAT. The fatty acid percentages of ∑C4-C14:1 and ∑C16 in milk were higher for SILc compared with LATc, signifying pronounced de novo synthesis. The n-6:n-3 ratio in milk fatty acids was lower for SILc and LAT compared with LATc, indicating improved nutritional quality for SILc and LAT. However, retinol concentration in milk was lower in SILc compared with all other treatments. The study implies that feeding silage instead of fresh grass has no effect on DMI, ECM yield, or CH4 yield, and that concentrate supplementation can increase milk production, affects milk quality, and reduces the effect on climate, whereas feeding less mature grass increases DMI and milk yield, but has no effect on CH4 yield.

Commercial layer hybrids kept under organic conditions: a comparison of range use, welfare, and egg production in two layer strains.

Outdoor range areas provide laying hens with improved opportunities to perform natural behaviors and increase the available space per bird, however, birds are also exposed to potentially stressful factors including weather and predators. Ability to cope with challenging environments varies between different strains and must be considered to ensure good welfare. The aim of this study was to determine how suitable 2 hybrids, the Dekalb White (DW) and the Bovans Brown (BB), are for organic production with special emphasis on ranging behavior. A total of 1,200 hens were housed according to organic regulations across 12 flocks of 100 birds. Range and shelter use, effect of weather, vegetation cover, egg production and quality, and mortality were assessed in addition to a range of clinical welfare indicators. Initially a greater proportion of DW hens accessed the range. However, after approximately 2 mo, a greater proportion of BB were using the range and venturing further from the house. DW hens were more likely to use the shelters than BB hens (P < 0.001). Vegetation was also worn away to a greater extent in the BB ranges. Weather affected the proportion of hens that went outside, the distance ranged from the popholes, and shelter use. BB hens were found to have better plumage condition (P < 0.001), fewer footpad lesions (P < 0.001), fewer comb wounds (P < 0.001), and lower mortality rates (P = 0.013). Both hybrids experienced keel bone fractures, though DW hens had more at the cranial portion (P < 0.001) and BB at the caudal portion (P < 0.001). DW hens had an earlier onset of lay and higher egg production than BB hens (P < 0.001), though BB hens laid heavier eggs (P < 0.001) with thicker shells (P = 0.001). Overall, BB hens seemed to perform superiorly or equivalently to the DW hens for all variables apart from egg production. These results demonstrate the importance of considering the strain of bird selected for organic production systems in order for the birds to reap the potential benefits that are offered by outdoor access.

Effects of dietary and milking frequency changes and administration of cabergoline on clinical udder characteristics in dairy cows during dry-off.

We investigated the effects of 2 diet energy densities [normal lactation diet (NORM) vs. energy-reduced diet (REDU), both fed for ad libitum intake] and 2 daily milking frequencies [twice (2×) vs. once (1×)] during 1 week before the dry-off day, as well as effects of an injection of either a dopamine agonist [cabergoline (CAB); Velactis, Ceva Santé Animale, Libourne, France; labelled for use only with abrupt dry-off, e.g. no reduction in diet energy density or milking frequency before the last milking] or saline (SAL) following the last milking, on clinical udder characteristics of Holstein cows. During a week before and after the last milking, the following measures were recorded: palpation-based udder firmness and soreness; image-based hock-hock distance; responsiveness to mechanical udder stimulation and degree of udder fill measured with a dynamometer. Before the last milking, REDU cows displayed lower odds of having a firm udder and lower degree of udder fill, as well as lower responsiveness to mechanical udder stimulation, than NORM cows. After the last milking, REDU cows displayed shorter hock-hock distance compared with NORM cows. The effects of milking frequency on the clinical udder characteristics were unclear. Within 24 h following injection, CAB cows showed lower odds of having a firm udder, shorter hock-hock distance, and lower degree of udder fill than SAL cows, irrespective of treatment group before dry-off. In this study, reducing diet energy density prior to dry-off, and to some extent administering the dopamine agonist cabergoline after the last milking, resulted in fewest clinical udder changes.

Status of claw recordings and claw health in Danish dairy cattle from 2013 to 2017.

Since 2009, Danish claw trimmers have been able to record claw health digitally during trimming. The records are owned by the farmer and can be used locally in the herd and on a large scale by breeding organisations to improve claw health. The objective of this study was to describe data on claw recording routines and describe the prevalence of digital dermatitis (DD), interdigital hyperplasia (IH), sole ulcer (SU) and white line abscess (WLA) recorded by claw trimmers (TrimmerID) at trimming. More than 5.18 million records of cows with claw recordings and 2.75 million records of claw trimming with 2.4 million concurrent claw diseases from 62 TrimmerIDs from 705,803 animals from 1635 herds over a 5-year period from 2013 to 2017 were included in the dataset. Data on cow level was used for the descriptive statistics. The data was restricted to, and grouped by, heifers from 12 months of age, first, second and third or older parity cows from the breeds Holstein, Danish Red Dairy, Jersey and crossbreds. The number of recorded trimmings per TrimmerID per year varied from 132 to 48,040 with a mean of 9556 and increased during the period studied. The overall prevalence across breed and parity groups of DD, IH, SU and WLA was 21%, 6%, 7% and 3%, respectively. The prevalence of the lesions remained quite constant during the 5-year period. DD was recorded in 95% of the herds in 2017. The prevalence of IH, SU and WLA increased with increasing parity. Digital recording of claw lesions may be a good indicator of claw health. However, the recording routines and quality of the recordings must be considered.

Potential of milk mid-infrared spectra to predict nitrogen use efficiency of individual dairy cows in early lactation.

Improving nitrogen use efficiency (NUE) at both the individual cow and the herd level has become a key target in dairy production systems, for both environmental and economic reasons. Cost-effective and large-scale phenotyping methods are required to improve NUE through genetic selection and by feeding and management strategies. The aim of this study was to evaluate the possibility of using mid-infrared (MIR) spectra of milk to predict individual dairy cow NUE during early lactation. Data were collected from 129 Holstein cows, from calving until 50 d in milk, in 3 research herds (Denmark, Ireland, and the UK). In 2 of the herds, diets were designed to challenge cows metabolically, whereas a diet reflecting local management practices was offered in the third herd. Nitrogen intake (kg/d) and nitrogen excreted in milk (kg/d) were calculated daily. Nitrogen use efficiency was calculated as the ratio between nitrogen in milk and nitrogen intake, and expressed as a percentage. Individual daily values for NUE ranged from 9.7 to 81.7%, with an average of 36.9% and standard deviation of 10.4%. Milk MIR spectra were recorded twice weekly and were standardized into a common format to avoid bias between apparatus or sampling periods. Regression models predicting NUE using milk MIR spectra were developed on 1,034 observations using partial least squares or support vector machines regression methods. The models were then evaluated through (1) a cross-validation using 10 subsets, (2) a cow validation excluding 25% of the cows to be used as a validation set, and (3) a diet validation excluding each of the diets one by one to be used as validation sets. The best statistical performances were obtained when using the support vector machines method. Inclusion of milk yield and lactation number as predictors, in combination with the spectra, also improved the calibration. In cross-validation, the best model predicted NUE with a coefficient of determination of cross-validation of 0.74 and a relative error of 14%, which is suitable to discriminate between low- and high-NUE cows. When performing the cow validation, the relative error remained at 14%, and during the diet validation the relative error ranged from 12 to 34%. In the diet validation, the models showed a lack of robustness, demonstrating difficulties in predicting NUE for diets and for samples that were not represented in the calibration data set. Hence, a need exists to integrate more data in the models to cover a maximum of variability regarding breeds, diets, lactation stages, management practices, seasons, MIR instruments, and geographic regions. Although the model needs to be validated and improved for use in routine conditions, these preliminary results showed that it was possible to obtain information on NUE through milk MIR spectra. This could potentially allow large-scale predictions to aid both further genetic and genomic studies, and the development of farm management tools.

Between- and within-herd variation in blood and milk biomarkers in Holstein cows in early lactation.

Both blood- and milk-based biomarkers have been analysed for decades in research settings, although often only in one herd, and without focus on the variation in the biomarkers that are specifically related to herd or diet. Biomarkers can be used to detect physiological imbalance and disease risk and may have a role in precision livestock farming (PLF). For use in PLF, it is important to quantify normal variation in specific biomarkers and the source of this variation. The objective of this study was to estimate the between- and within-herd variation in a number of blood metabolites (ß-hydroxybutyrate (BHB), non-esterified fatty acids, glucose and serum IGF-1), milk metabolites (free glucose, glucose-6-phosphate, urea, isocitrate, BHB and uric acid), milk enzymes (lactate dehydrogenase and N-acetyl-ß-D-glucosaminidase (NAGase)) and composite indicators for metabolic imbalances (Physiological Imbalance-index and energy balance), to help facilitate their adoption within PLF. Blood and milk were sampled from 234 Holstein dairy cows from 6 experimental herds, each in a different European country, and offered a total of 10 different diets. Blood was sampled on 2 occasions at approximately 14 days-in-milk (DIM) and 35 DIM. Milk samples were collected twice weekly (in total 2750 samples) from DIM 1 to 50. Multilevel random regression models were used to estimate the variance components and to calculate the intraclass correlations (ICCs). The ICCs for the milk metabolites, when adjusted for parity and DIM at sampling, demonstrated that between 12% (glucose-6-phosphate) and 46% (urea) of the variation in the metabolites' levels could be associated with the herd-diet combination. Intraclass Correlations related to the herd-diet combination were generally higher for blood metabolites, from 17% (cholesterol) to approximately 46% (BHB and urea). The high ICCs for urea suggest that this biomarker can be used for monitoring on herd level. The low variance within cow for NAGase indicates that few samples would be needed to describe the status and potentially a general reference value could be used. The low ICC for most of the biomarkers and larger within cow variation emphasises that multiple samples would be needed - most likely on the individual cows - for making the biomarkers useful for monitoring. The majority of biomarkers were influenced by parity and DIM which indicate that these should be accounted for if the biomarker should be used for monitoring.

Prediction of metabolic clusters in early-lactation dairy cows using models based on milk biomarkers.

The aim of this study was to describe metabolism of early-lactation dairy cows by clustering cows based on glucose, insulin-like growth factor I (IGF-I), free fatty acid, and ß-hydroxybutyrate (BHB) using the k-means method. Predictive models for metabolic clusters were created and validated using 3 sets of milk biomarkers (milk metabolites and enzymes, glycans on the immunogamma globulin fraction of milk, and Fourier-transform mid-infrared spectra of milk). Metabolic clusters are used to identify dairy cows with a balanced or imbalanced metabolic profile. Around 14 and 35 d in milk, serum or plasma concentrations of BHB, free fatty acids, glucose, and IGF-I were determined. Cows with a favorable metabolic profile were grouped together in what was referred to as the "balanced" group (n = 43) and were compared with cows in what was referred to as the "other balanced" group (n = 64). Cows with an unfavorable metabolic profile were grouped in what was referred to as the "imbalanced" group (n = 19) and compared with cows in what was referred to as the "other imbalanced" group (n = 88). Glucose and IGF-I were higher in balanced compared with other balanced cows. Free fatty acids and BHB were lower in balanced compared with other balanced cows. Glucose and IGF-I were lower in imbalanced compared with other imbalanced cows. Free fatty acids and BHB were higher in imbalanced cows. Metabolic clusters were related to production parameters. There was a trend for a higher daily increase in fat- and protein-corrected milk yield in balanced cows, whereas that of imbalanced cows was higher. Dry matter intake and the daily increase in dry matter intake were higher in balanced cows and lower in imbalanced cows. Energy balance was continuously higher in balanced cows and lower in imbalanced cows. Weekly or twice-weekly milk samples were taken and milk metabolites and enzymes (milk glucose, glucose-6-phosphate, BHB, lactate dehydrogenase, N-acetyl-ß-d-glucosaminidase, isocitrate), immunogamma globulin glycans (19 peaks), and Fourier-transform mid-infrared spectra (1,060 wavelengths reduced to 15 principal components) were determined. Milk biomarkers with or without additional cow information (days in milk, parity, milk yield features) were used to create predictive models for the metabolic clusters. Accuracy for prediction of balanced (80%) and imbalanced (88%) cows was highest using milk metabolites and enzymes combined with days in milk and parity. The results and models of the present study are part of the GplusE project and identify novel milk-based phenotypes that may be used as predictors for metabolic and performance traits in early-lactation dairy cows.

Potential of milk mid-IR spectra to predict metabolic status of cows through blood components and an innovative clustering approach.

Unbalanced metabolic status in the weeks after calving predisposes dairy cows to metabolic and infectious diseases. Blood glucose, IGF-I, non-esterified fatty acids (NEFA) and ß-hydroxybutyrate (BHB) are used as indicators of the metabolic status of cows. This work aims to (1) evaluate the potential of milk mid-IR spectra to predict these blood components individually and (2) to evaluate the possibility of predicting the metabolic status of cows based on the clustering of these blood components. Blood samples were collected from 241 Holstein cows on six experimental farms, at days 14 and 35 after calving. Blood samples were analyzed by reference analysis and metabolic status was defined by k-means clustering (k=3) based on the four blood components. Milk mid-IR analyses were undertaken on different instruments and the spectra were harmonized into a common standardized format. Quantitative models predicting blood components were developed using partial least squares regression and discriminant models aiming to differentiate the metabolic status were developed with partial least squares discriminant analysis. Cross-validations were performed for both quantitative and discriminant models using four subsets randomly constituted. Blood glucose, IGF-I, NEFA and BHB were predicted with respective R 2 of calibration of 0.55, 0.69, 0.49 and 0.77, and R 2 of cross-validation of 0.44, 0.61, 0.39 and 0.70. Although these models were not able to provide precise quantitative values, they allow for screening of individual milk samples for high or low values. The clustering methodology led to the sharing out of the data set into three groups of cows representing healthy, moderately impacted and imbalanced metabolic status. The discriminant models allow to fairly classify the three groups, with a global percentage of correct classification up to 74%. When discriminating the cows with imbalanced metabolic status from cows with healthy and moderately impacted metabolic status, the models were able to distinguish imbalanced group with a global percentage of correct classification up to 92%. The performances were satisfactory considering the variables are not present in milk, and consequently predicted indirectly. This work showed the potential of milk mid-IR analysis to provide new metabolic status indicators based on individual blood components or a combination of these variables into a global status. Models have been developed within a standardized spectral format, and although robustness should preferably be improved with additional data integrating different geographic regions, diets and breeds, they constitute rapid, cost-effective and large-scale tools for management and breeding of dairy cows.

Does hut climate matter for piglet survival in organic production?

Piglet mortality in outdoor production systems varies across the year, and a reason for this variation could be fluctuations in hut climate, as ambient temperature might influence piglet survival, both directly and indirectly. Therefore, the aim of the current study was to investigate the impact of farrowing hut climate and year variation on stillbirth and liveborn mortality. A large-scale observational study was conducted at five commercial organic pig-producing herds in Denmark from June 2015 to August 2016. Both year variation (F 3,635=4.40, P=0.004) and farrowing hut temperature (F 2,511=6.46, P=0.002) affected the rate of stillbirths. The risk of stillborn piglets was lowest in winter and during this season larger changes in hut temperature between day 1 prepartum and the day of farrowing increased the risk of stillbirths (F 1,99=6.39, P=0.013). In addition, during the warm part of the year stillbirth rate increased at temperatures ⩾27°C. Year variation also affected liveborn mortality (F 3,561=3.86, P=0.009) with a lower rate of liveborn deaths in spring. However, the hut climate did not influence liveborn deaths. Consequently, other factors than hut climate may explain the influence of year variation on liveborn mortality. These could be light differences causing seasonality in reproduction and lactation.

The validity and sensitivity of PANSS-6 in treatment-resistant schizophrenia.

OBJECTIVE: To test the validity and sensitivity of the six-item version (PANSS-6) of the 30-item Positive and Negative Syndrome Scale (PANSS-30) in treatment-resistant schizophrenia (TRS). METHOD: Using data from the clozapine phase (2E) of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, we investigated the following: (i) The scalability of PANSS-6 and PANSS-30; (ii) The correlation between PANSS-6 and PANSS-30 total scores; (iii) Whether PANSS-6 could identify cross-sectional symptom remission; and (iv) The efficacy of clozapine, olanzapine, risperidone and quetiapine in TRS using the 'speed of change' on PANSS-6 and PANSS-30 (change in total score per week) as outcome measures. RESULTS: We found that (i) only PANSS-6 and not PANSS-30 was scalable; (ii) The correlation between PANSS-6 and PANSS-30 total scores was high (Spearman coefficient: 0.85), (iii) PANSS-6 accurately identified cross-sectional symptom remission as defined by the Andreasen et al. criteria; and (iv) The only antipsychotic that caused improvement (speed of change significantly lower than 0 during the first three months of treatment) was clozapine, both when using PANSS-6 (speed of change: -0.50 points/week; 95%CI: -0.84, -0.17) and PANSS-30 (speed of change: -1.41 points/week; 95%CI: -2.80, -0.02) as outcome measures. CONCLUSION: PANSS-6 validly measures severity, remission and antipsychotic efficacy in TRS.

Early-adult outcome of child and adolescent mental disorders as evidenced by a national-based case register survey.

BACKGROUND: Mental disorders show varying degrees of continuity from childhood to adulthood. This study addresses the relationship of child and adolescent mental disorders to early adult psychiatric morbidity. METHODS: From a population at risk of 830,819 children and adolescents aged 6-16 years, we selected all those (n=6043) who were enrolled for the first time in the Danish Psychiatric Register with an ICD-10 F00-99 diagnosis in 1995-1997, and identified any mental disorder for which they received treatment up to 2009. RESULTS: Neurodevelopmental and conduct disorders were the principal diagnostic groups at 6-16 years and exhibited a characteristic male preponderance; while affective, eating, neurotic, stress-related and adjustment disorders were more common in girls. Over a mean follow-up period of 10.1 years, 1666 (27.6%) cases, mean age 23.4 years, were referred for treatment to mental health services, and they had a markedly higher risk than the general population (RR 5.1; 95% CI 4.9-5.4). Affective, eating, neurodevelopmental, obsessive-compulsive and psychotic disorders had the strongest continuity. Heterotypic transitions were observed for affective, eating, neurodevelopmental, personality and substance use disorders. CONCLUSIONS: These findings suggest that individuals with psychiatric antecedents in childhood and adolescence had a high risk of being referred for treatment in early adulthood, and many mental disorders for which they required treatment revealed both homotypic and heterotypic continuity.

Plasma brain-derived neurotrophic factor and prefrontal white matter integrity in late-onset depression and normal aging.

OBJECTIVE: To explore the relationship between brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), cerebral deep white matter lesions (DWMLs), and measures of white matter integrity in patients with late-onset depression, with respect to vascular risk factors. METHOD: We examined 22 patients with late-onset depression and 22 matched controls. Quantification of plasma BDNF and VEGF levels were performed with enzyme-linked immunosorbent assay (ELISA) kits. Measures of white matter integrity comprised apparent diffusion coefficient (ADC) and fractional anisotropy (FA), obtained by diffusion tensor imaging (DTI). Effects of DWMLs, FA, ADC, and vascular risk factors on BDNF and VEGF were assessed using multiple linear regression. RESULTS: The BDNF and VEGF levels did not differ significantly between groups. With pooled data for patients and controls, the BDNF level was positively associated with both number (t = 2.14, P = 0.039) and volume (t = 2.04, P = 0.048) of prefrontal DWMLs and negatively associated with FA in prefrontal normal-appearing white matter (t = -2.40, P = 0.02), adjusted for age and gender. Smoking and hypercholesterolemia was positively associated with the BDNF (t = 2.36, P = 0.023) and VEGF levels (t = 2.28, P = 0.028), respectively. CONCLUSION: Our results suggest a role for BDNF in the complex pathophysiologic mechanisms underlying DWMLs in both normal aging and late-onset depression.

Excess mortality of acute and transient psychotic disorders: comparison with bipolar affective disorder and schizophrenia.

OBJECTIVE: To investigate mortality and causes of death of short-lived psychotic disorders, by carrying out a comparison with bipolar disorder and schizophrenia. METHOD: Record linkage study to the official register of causes of death of all cases aged 15-64 years who were listed for the first time in the Danish Psychiatric Register between 1995 and 2008 with an ICD-10 diagnosis of 'acute and transient psychotic disorders' (ATPDs; n = 4157), bipolar disorder (n = 3200) and schizophrenia (n = 4576). RESULTS: A total of 232 patients (5.6%) with ATPDs, 172 (5.4%) with bipolar disorder and 233 (5.1%) with schizophrenia had died over a mean follow-up period of 6.6 years. The standardized mortality ratio for all causes, natural causes and unnatural causes was significantly high for the three conditions. Mortality of ATPDs was greater in men, with about two-thirds of all deaths resulting from natural causes mainly cardiovascular, digestive, neoplastic and respiratory diseases. Suicide was the major cause of premature death in patients with ATPDs. CONCLUSION: These findings suggest that ATPDs are associated with an increased mortality from both natural causes and suicide.

The association between physical illness and major depressive episode in general practice.

OBJECTIVE: Physical illness and depression are associated. However, it remains unclear whether this association is sufficiently strong to merit systematic screening for depression among primary care patients suffering from physical illness. In the present study, we investigated the strength of the association between physical illness and depression among patients in general practice. METHOD: Four thousand two hundred and seventy-one consecutive primary care patients completed a diagnostic depression questionnaire. The general practitioner evaluated the patients' physical health, which was then compared to their diagnostic status of depression. RESULTS: Physical illness was associated with the presence of depression. Two hundred and thirty-six patients (5.5%) fulfilled diagnostic criteria for depression. Fourteen of these suffered from extreme physical illness, 27 from at least severe physical illness and 96 from at least moderate physical illness. The number needed to screen decreased with increasing severity and chronicity of the physical illness. CONCLUSIONS: Depression is relatively common in primary care patients suffering from physical illness, particularly if the illness is severe and chronic. However, relatively few depressed patients suffer from a comorbid physical illness. Screening for depression among patients with physical illness may therefore only have a modest impact on the under-recognition of depression in general practice.

10-year trends in the treatment and outcomes of patients with first-episode schizophrenia.

OBJECTIVE: The first episode of schizophrenia is a critical period for illness course and outcomes. We aimed to investigate treatments and outcomes during the first year after the diagnosis of schizophrenia. METHOD: Pharmacoepidemiologic inception cohort study of all newly diagnosed patients with schizophrenia in Denmark (n = 13,600) 1996-2005. RESULTS: From 1996 to 2005, the mean age at first diagnosis decreased significantly (29.2-26.1 years), more patients received antipsychotics (67.2-80.7%, annual OR = 1.07, CI: 1.06-1.09, P < 0.001) and antipsychotic polypharmacy for >4 months (16.7-37.1%, OR = 1.14, CI: 1.12-1.57, P < 0.001). The antipsychotic defined daily dosage (DDD) doubled (150-332 DDD, P < 0.001), use of antidepressants (24.3-40.6%, P < 0.001). Bed days [89.9 days (CI: 81.8-98.8) to 71.8 days, CI: 63.7-80.8, P < 0.0001] decreased, whereas outpatient contacts [10.2 (CI: 9.5-11.0) to 21.4 (CI: 19.9-21.0), P < 0.0001] doubled. CONCLUSION: Between 1996 and 2005, there was an earlier recognition of schizophrenia, intensified outpatient treatment, increased use and dosing of antipsychotics and antidepressants, but also more antipsychotic polypharmacy.