Search

Depression affects approximately 4 % of the global population and has huge social and economic implications. Social factors, including support, engagement, and stigma, play a crucial role in the development and severity of depression. We provide a synthesis of the consistency and magnitude of the association between measures of social connection and depression. We searched PubMed, PsycINFO, Cochrane Library, and EMBASE and 47 meta-analyses were included in the umbrella review. The strength of the associations was extracted and compared among different populations. The quality/certainty of evidence was assessed using AMSTAR-2 and GRADE tool. Results indicate that social support serves as a protective factor against depression, particularly in peripartum populations, while its impact is weaker in clinical populations. No association was found between social support and depression in post-disaster populations. Stigma and discrimination favour the development and maintenance of depressive symptoms in clinical populations, but have a weaker effect in ethnic minorities. The quality and certainty of evidence should be taken into account when interpreting our findings. Further research with more rigorous methodology and higher-quality evidence is needed to better understand the complex relationship between depression and social connection across various populations and contexts. Our findings confirm the role of social determinants in the emergence and severity of depression, particularly in the case of vulnerable populations. Efforts to counteract disconnection at the societal and individual levels and to reduce stigma should be central to an effective depression prevention agenda. • Social determinants play a significant role in influencing health. • Social connection represents a major protective/risk factors for depression. • Social support is protective against depression, especially in peripartum populations. • Stigma/discrimination represents risk factors for depression in clinical populations. • Social determinants should be central to an effective depression prevention agenda. [ABSTRACT FROM AUTHOR]

CASE DESCRIPTION Two 12-week-old Norwegian Buhunds from a litter of 5 were evaluated because of slowly progressive cerebellar ataxia and fine head tremors. Two other females from the same pedigree had been previously evaluated for similar signs. CLINICAL FINDINGS Findings of general physical examination, CBC, and serum biochemical analysis were unremarkable for all affected puppies. Brain MRI and CSF analysis, including PCR assays for detection of Toxoplasma gondii, Neospora caninum, and canine distemper virus, were performed for 3 dogs, yielding unremarkable results. Urinary organic acid screening, enzyme analysis of fibroblasts cultured from skin biopsy specimens, and brainstem auditoryevoked response testing were performed for 2 puppies, and results were also unremarkable. TREATMENT AND OUTCOME The affected puppies were euthanized at the breeder's request, and their brains and spinal cords were submitted for histologic examination. Histopathologic findings included a markedly reduced expression of calbindin D28K and inositol triphosphate receptor I by Purkinje cells, with only mild signs of neuronal degeneration. Results of pedigree analysis suggested an autosomal recessive mode of inheritance. Candidate-gene analysis via mRNA sequencing for 2 of the affected puppies revealed no genetic variants that could be causally associated with the observed abnormalities. CLINICAL RELEVANCE Findings for the dogs of this report suggested the existence of a hereditary form of ataxia in Norwegian Buhunds with histologic characteristics suggestive of Purkinje cell dysfunction. The presence of hereditary ataxia in this breed must be considered both in clinical settings and for breeding strategies. [ABSTRACT FROM AUTHOR]

Background: Behavioural changes associated with idiopathic epilepsy (IE) have been identified in dogs, with fear and anxiety-related problems seen in both drug-naïve dogs and dogs treated with anti-epileptic drugs (AEDs). Treating anxiety-related behaviour in dogs with IE may be challenging, as seizures are a contraindication for many conventional anxiolytic drugs. In addition, many dogs with IE are already treated with AEDs to reduce their seizure frequency, which may have negative effects if used in polytherapy. Imepitoin is low-affinity partial agonist at the benzodiazepine (BDZ) site of the GABAA receptor, and has been demonstrated to have both anticonvulsant and anxiolytic effects in laboratory rodents. Imepitoin has been developed for the treatment of IE in dogs, with demonstrated anticonvulsant effects and high tolerability and safety. To date, imepitoin's potential to reduce anxiety in dogs with IE has not been investigated. An online survey was conducted to investigate the effect of imepitoin on fear and anxiety-related behaviours in dogs with IE. Eighty-five valid responses were received from owners of dogs with IE currently treated with imepitoin. Anxiety-related behaviour was quantified before and during imepitoin treatment using a validated questionnaire tool (C-BARQ). Results: No differences were observed in the five fear/anxiety-related measures between the two time periods (before vs. during treatment) for dog directed fear, stranger directed fear, non-social fear, pain sensitivity and separation related behaviour. A median 45% reduction in seizure frequency/month was observed following imepitoin treatment; however, imepitoin did not appear effective in reducing seizure frequency in a minority of cases. Polyphagia was the most common chronic side effect, and more side effects were reported in polytherapy cases. Conclusions: Imepitoin does not appear to improve anxiety-related behaviour in dogs with IE treated with this medication for its anti-epileptic effects. Investigating the effects of imepitoin upon the behaviour of dogs with recognised behavioural anxiety-related problems (e.g. specific fears and phobias, separation related behaviours), in both healthy dogs and dogs with epilepsy is required to further explore any potential anxiolytic effects of this medication. [ABSTRACT FROM AUTHOR]

Background Episodic muscular hypertonicity in Norwich terrier dogs was first reported in a brief communication in 1984. Since then, the condition has remained poorly characterized. Objectives The aims of this study were to characterize the phenomenology, clinical course, and family history of paroxysmal dyskinesia in the Norwich terrier and to estimate its prevalence in the United Kingdom. Methods The owners of Norwich terrier dogs born since January 1, 2000 were invited to complete a specifically designed questionnaire aimed at identifying affected and unaffected dogs and investigating the clinical characteristics of this paroxysmal dyskinesia. Pedigrees were collected and reviewed. Results The questionnaire was returned for 198 Norwich terrier dogs. Of these, 26 (13%) were classified as affected by paroxysmal dyskinesia after revision of the questionnaires and after obtaining videos of the episodes, veterinary medical records, and telephone interviews with the owners. All dogs were neurologically normal between episodes. No significant abnormalities were detected on diagnostic investigations. Mean age at the first episode was 3 years. The episodes were characterized by sustained muscular hypertonicity in the pelvic limbs, lumbar region, and thoracic limbs, impairing posture and locomotion without loss of consciousness. Episode frequency varied both between and within individuals. Stress, anxiety, excitement, and variation in daily routine were recognized as episode triggers in 13 dogs. Episode duration generally was from 2 to 5 minutes (range, from < 2 to 30 minutes). The majority of affected dogs were related. Conclusions Paroxysmal dyskinesia segregates in an extended pedigree of Norwich terrier dogs and thus is potentially an inherited disorder in this breed. [ABSTRACT FROM AUTHOR]

Background: Congenital sensorineural deafness (CSD) is the most common type of deafness in dogs and it occurs in numerous canine breeds including the English bull terrier. This study estimates prevalence, heritability and genetic correlations of CSD and coat pigmentation phenotypes in the English bull terrier in England. Results: Hearing status was assessed by brainstem auditory evoked response in 1060 English bull terrier puppies tested at 30-78 (mean 43.60) days of age as complete litters. Gender, coat and iris colour and parental hearing status were recorded. The prevalence of CSD in all 1060 puppies was 10.19 % with 8.21 % unilaterally deaf and 1.98 % bilaterally deaf. The coat was predominately coloured in 49.15 % puppies and white with or without a patch in 50.85 % puppies. The majority (96.29 %) of deaf puppies had a white coat (with or without a patch); 19.29 % of the puppies with a white coat (with or without a patch) were deaf. Heritability and genetic correlations were estimated using residual maximum likelihood. Heritability of hearing status as a trichotomous trait (bilaterally normal/unilaterally deaf/bilaterally deaf) was estimated at 0.15 to 0.16 and was significantly different to zero (P < 0.01). Heritability of coat pigmentation phenotype (all white/white with patches/ coloured) was 0.49 (standard error 0.077). Genetic correlation of CSD with coat pigmentation phenotype was estimated at -0.36 to -0.37 (CSD associated with all white coat), but was not significantly larger than zero (P > 0.05). Analysis of CSD in all white and white patched puppies only estimated the heritability of CSD as 0.25 and was significantly greater than zero (P < 0.01), and the heritability of coat colour (all white/white with patches) as 0.20 (standard error 0.096). The genetic correlation was estimated at -0.53 to -0.54 (CSD associated with all white coat) but was just above the statistical threshold determining significant difference to zero (P = 0.06). Conclusions: These results indicate that CSD occurs predominantly in white English bull terriers and there is genetic variation in CSD beyond that associated with coat colour. [ABSTRACT FROM AUTHOR]

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset <6 months or >6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose. This consensus article represents the basis for a more standardised diagnostic approach to the seizure patient. These recommendations will evolve over time with advances in neuroimaging, electroencephalography, and molecular genetics of canine epilepsy. [ABSTRACT FROM AUTHOR]

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors' experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible. [ABSTRACT FROM AUTHOR]

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset <6 months or >6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose. This consensus article represents the basis for a more standardised diagnostic approach to the seizure patient. These recommendations will evolve over time with advances in neuroimaging, electroencephalography, and molecular genetics of canine epilepsy. [ABSTRACT FROM AUTHOR]

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors' experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible. [ABSTRACT FROM AUTHOR]

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset <6 months or >6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose. This consensus article represents the basis for a more standardised diagnostic approach to the seizure patient. These recommendations will evolve over time with advances in neuroimaging, electroencephalography, and molecular genetics of canine epilepsy. [ABSTRACT FROM AUTHOR]

Background/Aims: Dopamine is an important neurotransmitter involved in the pathophysiology of depression and anhedonia. Dopamine transporters (DAT) may play a crucial role in the pathophysiology of dopaminergic transmission. We investigated the relationship between striatal DAT availability and depression, pointing out possible correlations with anhedonia and treatment outcomes. Methods: Ten depressed patients with anhedonia, 10 depressed patients without anhedonia and 20 healthy controls underwent single photon emission computed tomography using 123I-FP-CIT [123I-N-ω-fluoropropyl-carbomethoxy-3β-(4-iodophenyl)tropane]. Psychometric measures included the Snaith-Hamilton Pleasure Scale and the Hamilton Depression Rating Scale. A further assessment of DAT availability was performed in the 10 patients with marked anhedonia after a 3-month pharmacological treatment. Results: Depressed patients with and without anhedonia showed significantly lower 123I-FP-CIT binding ratios in the bilateral striatum, caudate and putamen. No significant changes were detected after treatment in the 10 patients with marked anhedonia. When considering clinical outcomes, subjects with remission of depression showed a significant reduction of 123I-FP-CIT binding ratios in all regions at baseline, but after treatment no differences were found any longer. Conclusions: We suppose that a hypofunction of the striatal dopaminergic system may be a 'state' feature of a depressive condition as a whole rather than anhedonia itself. On the other hand, some anhedonic features mainly represent an enduring trait that persists independently of mood state. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background The co-occurrence of bipolar disorder (BD) and gambling disorder (GD), though of clinical and public health importance, is still scarcely investigated. Comorbid BD–GD subjects experience a more severe course of illness and poorer treatment outcome, due to a range of clinical and psychosocial factors that collectively impede remission and recovery. The aim of our paper is to review the role of pharmacotherapy in the treatment of comorbid BD–GD, in order to support clinical decisions according to the best available evidence. Methods A qualitative systematic review of studies on pharmacological treatment in comorbid BD–GD was performed. A comprehensive literature search of online databases, bibliographies of published articles and gray literature was conducted. Data on efficacy, safety and tolerability were extracted and levels of evidence were assessed. We also provide a brief overview of current epidemiological, neurobiological and clinical findings, with the intention of proposing a dimensional approach to the choice of available drugs. Results The only drug with a high level of evidence is lithium. Considering the inclusion of GD in DSM-5 ‘Substance-related and Addictive Disorders’ category, we discuss the use of other drugs with a high level of evidence currently used in BD subjects with co-occurring substance use disorders. Limitations Only few clinical trials are available and the population is limited; therefore no conclusive evidence can be inferred. Conclusions Further randomized controlled trials are required to evaluate the efficacy of pharmacological treatment strategies in large samples of patients with comorbid BD–GD. Also, attempts should be made to identify other shared clinical and psychopathological domains that are amenable to treatment. [ABSTRACT FROM AUTHOR]

Pathological gambling or gambling disorder has been defined by the DSM-5 as a behavioral addiction. To date, its pathophysiology is not completely understood and there is no FDA-approved treatment for gambling disorders. Glutamate is the principal excitatory neurotransmitter in the nervous system and it has been recently involved in the pathophysiology of addictive behaviors. In this paper, we review the current literature on a class of drugs that act as modulating glutamate system in PG. A total of 19 studies have been included, according to inclusion and exclusion criteria. Clinical trial and case series using glutamatergic drugs (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, and modafinil) will be presented to elucidate the effectiveness on gambling behaviors and on the related clinical dimensions (craving, withdrawal, and cognitive symptoms) in PG patients. The results have been discussed to gain more insight in the pathophysiology and treatment of PG. In conclusion, manipulation of glutamatergic neurotransmission appears to be promising in developing improved therapeutic agents for the treatment of gambling disorders. Further studies are required. Finally, we propose future directions and challenges in this research area. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia (SCA) in the Parson Russell Terrier (PRT) dog breed is a disease of progressive incoordination of gait and loss of balance. Clinical signs usually become notable between 6 and 12 months of age with affected dogs presenting with symmetric spinocerebellar ataxia particularly evident in the pelvic limbs. The degree of truncal ataxia, pelvic limb hypermetria and impaired balance is progressive, particularly during the initial months of disease. A certain degree of stabilisation as well as intermittent worsening may occur. At the later stages of the disease ambulation often becomes difficult, with owners often electing to euthanise affected dogs on welfare grounds. Using a GWAS approach and target-enriched massively-parallel sequencing, a strongly associated non-synonymous SNP in the CAPN1 gene, encoding the calcium dependent cysteine protease calpain1 (mu-calpain), was identified. The SNP is a missense mutation causing a cysteine to tyrosine substitution at residue 115 of the CAPN1 protein. Cysteine 115 is a highly conserved residue and forms a key part of a catalytic triad of amino acids that are crucial to the enzymatic activity of cysteine proteases. The CAPN1 gene shows high levels of expression in the brain and nervous system and roles for the protein in both neuronal necrosis and maintenance have been suggested. Given the functional implications and high level of conservation observed across species, the CAPN1 variant represents a provocative candidate for the cause of SCA in the PRT and a novel potential cause of ataxia in humans. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim of our study was to assess hedonic capacity in euthymic bipolar subjects, identifying possible differences compared to remitted unipolar depressed patients and healthy controls. Methods: 107 subjects with bipolar disorders, 86 with major depressive disorder and 106 healthy controls, homogeneous with respect to demographic characteristics, were enrolled. The following scales were administered: the Snaith–Hamilton pleasure scale (SHAPS), the subscale for ‘anhedonia/asociality’ of the scale for the assessment of negative symptoms (SANS) and the visual analogue scale (VAS) for hedonic capacity. Results: Scores on SHAPS total, interests and social interactions, SANS ‘anhedonia/asociality’ and VAS were all significantly higher in affective disorder patients compared to healthy controls. No difference was found between clinical groups. 20.5% (n=22) of bipolar disorder subjects and 24.5% (n=21) of major depressed subjects showed a significant reduction in hedonic capacity (SHAPS total score ≥3), compared to 7.5% (n=8) of healthy controls (χ 2=12.03; p=.002). Limitations: Limitations include heterogeneity with respect to pharmacological status and longitudinal course (i.e., ‘single’ vs. ‘recurrent’ affective episodes). Conclusions: The major finding of our study is that euthymic bipolar patients and remitted major depressed patients display residual anhedonic symptoms. This suggests that, in affective disorder patients, altered hedonic capacity could represent an enduring trait and that, possibly, dysfunctions in the neurobiological mechanisms underlying hedonic response and reward processing persist, irrespective of mood state. [Copyright &y& Elsevier]

Objectives: High, normal, or low plasma magnesium (Mg) levels have been observed in depressed patients. The aim of our study was to investigate the relationship of Mg levels with depression severity, specific psychopathological dimensions, and treatment outcome. Methods: A total of 123 outpatients during a major depressive episode were recruited. All patients showed at least two major depressive episodes and did not achieve remission in the former treatment trial. A blood sample was collected to determine total plasma Mg levels. The psychopathological status was assessed using Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression Retardation Rating Scale for psychomotor retardation, and Snaith-Hamilton Pleasure Scale for anhedonia. Hamilton Depression Rating Scale was repeated at 3 months after treatment. Results: All patients showed Mg levels mostly within the normal range. No association between Mg levels and psychopathological severity was reported. Patients who responded to antidepressant treatment showed higher Mg levels and higher retardation scores at basal evaluation in comparison with non-responders. Discussion: Although further studies investigating the relationship between hypomagnesaemia, depression, and treatment outcome are certainly necessary, we have hypothesized that hypomagnesaemia could be an epiphenomenic biochemical trait in less drug-responsive depressed patients. It is also plausible that lower Mg levels and hyperactive traits identify a biological subtype of patients with increased catecholaminergic functioning and a poorer response to aminergic drugs. Moreover, Mg depletion could partly account for the correlation between low Mg levels and poor outcome and this raises the question of Mg's possible therapeutic role in depression. [ABSTRACT FROM AUTHOR]

Background: Neonatal cerebellar cortical degeneration is a neurodegenerative disease described in several canine breeds including the Beagle. Affected Beagles are unable to ambulate normally from the onset of walking and the main pathological findings include Purkinje cell loss with swollen dendritic processes. Previous reports suggest an autosomal recessive mode of inheritance. The development of massively parallel sequencing techniques has presented the opportunity to investigate individual clinical cases using genome-wide sequencing approaches. We used genome-wide mRNA sequencing (mRNA-seq) of cerebellum tissue from a single Beagle with neonatal cerebellar cortical degeneration as a method of candidate gene sequencing, with the aim of identifying the causal mutation. Results: A four-week old Beagle dog presented with progressive signs of cerebellar ataxia and the owner elected euthanasia. Histopathology revealed findings consistent with cerebellar cortical degeneration. Genome-wide mRNA sequencing (mRNA-seq) of RNA from cerebellum tissue was used as a method of candidate gene sequencing. After analysis of the canine orthologues of human spinocerebellar ataxia associated genes, we identified a homozygous 8 bp deletion in the β-III spectrin gene, SPTBN2, associated with spinocerebellar type 5 in humans. Genotype analysis of the sire, dam, ten clinically unaffected siblings, and an affected sibling from a previous litter, showed the mutation to fully segregate with the disorder. Previous studies have shown that β-III spectrin is critical for Purkinje cell development, and the absence of this protein can lead to cell damage through excitotoxicity, consistent with the observed Purkinje cell loss, degeneration of dendritic processes and associated neurological dysfunction in this Beagle. Conclusions: An 8 bp deletion in the SPTBN2 gene encoding β-III spectrin is associated with neonatal cerebellar cortical degeneration in Beagle dogs. This study shows that mRNA-seq is a feasible method of screening candidate genes for mutations associated with rare diseases when a suitable tissue resource is available. [ABSTRACT FROM AUTHOR]

Background: Chiari-like malformation (CM) and syringomyelia is a neurological disease complex with high prevalence in cavalier King Charles spaniels (CKCS). The natural progression of this disease with time has not been described. The objectives of this study were to i) determine if syringomyelia progresses with time ii) determine if features of craniocrebral morphology previously associated with CM are progressive (including caudal cranial fossa volume, caudal cranial fossa parenchymal volume, ventricular dimensions, height of the foramen magnum and degree of cerebellar herniation). A retrospective morphometric analysis was undertaken in 12 CKCS with CM for which repeat magnetic resonance images were available without surgical intervention. Results: The maximal syrinx width, height of the foramen magnum, length of cerebellar herniation and caudal cranial fossa volume increased over time. Ventricular and caudal fossa parenchymal volumes were not significantly different between scans. Conclusions: The results of this study suggest that syringomyelia progresses with time. Increased caudal cranial fossa volume may be associated with active resorption of the supraoccipital bone, which has previously been found in histology specimens from adult CKCS. We hypothesise that active resorption of the supraoccipital bone occurs due to pressure from the cerebellum. These findings have important implications for our understanding of the pathogenesis and variable natural clinical progression of CM and syringomyelia in CKCS. [ABSTRACT FROM AUTHOR]

The objectives of this study were to estimate prevalence, heritability and genetic correlations of congenital sensorineural deafness (CSD) and pigmentation phenotypes in the Border Collie. Entire litters of Border Collies that presented to the Animal Health Trust (1994-2008) for assessment of hearing status by brain stem auditory evoked response (BAER) at 4-10 weeks of age were included. Heritability and genetic correlations were estimated using residual maximum likelihood (REML). Of 4143 puppies that met the inclusion criteria, 97.6g had normal hearing status, 2.0% were unilaterally deaf and 0.4g were bilaterally deaf. Heritability of deafness as a trichotomous trait (normal/unilaterally deaf/bilaterally deaf) was estimated at 0.42 using multivariate analysis. Genetic correlations of deafness with iris colour and merle coat colour were 0.58 and 0.26, respectively. These results indicate that there is a significant genetic effect on CSD in Border Collies and that some of the genes determining deafness also influence pigmentation phenotypes. [ABSTRACT FROM AUTHOR]

Objective—To determine whether clinical signs or magnetic resonance imaging findings were associated with outcome in dogs with presumptive ischemic myelopathy. Design—Retrospective case series. Animals—50 dogs. Procedures—Medical records and magnetic resonance images were reviewed. A neurologic score from 1 (normal) to 5 (most severe degree of dysfunction) was assigned on the basis of neurologic signs at the time of initial examination. Follow-up information was obtained from the medical records and by means of a telephone questionnaire completed by owners and referring veterinarians. Results—Median neurologic score at the time of initial examination was 3 (range, 2 to 5). Median follow-up time was 584 days (range, 4 to 2,090 days). Neurologic score at the time of initial examination and extent of the lesion seen on magnetic resonance images (quantified as the lesion length-to-vertebral length ratio and as the percentage cross-sectional area of the lesion) were significantly associated with outcome. Sensitivity of using a lesion length-to-vertebral length ratio > 2.0 or a percentage cross-sectional area of the lesion ≥ 67% to predict an unsuccessful outcome was 100%. Conclusions and Clinical Relevance—Results suggested that severity of neurologic signs at the time of initial examination and extent of the lesions seen on magnetic resonance images were associated with outcome in dogs with ischemic myelopathy. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of changes in magnetic resonance imaging (MRI) detected after a seizure is not fully understood. Objective: To characterize and describe seizure‐induced changes detected by MRI. Animals Eighty‐one client‐owned dogs diagnosed with idiopathic epilepsy. Methods: Data collected retrospectively from medical records and included anatomical areas affected, T1‐, T2‐weighted and T2‐FLAIR (fluid‐attenuated inversion recovery) appearance, whether changes were unilateral or bilateral, symmetry, contrast enhancement, mass effect, and, gray and white matter distribution. Diffusion‐ and perfusion weighted maps were evaluated, if available. Results: Seizure‐induced changes were T2‐hyperintense with no suppression of signal on FLAIR. Lesions were T1‐isointense (55/81) or hypointense (26/81), local mass effect (23/81) and contrast enhancement (12/81). The majority of changes were bilateral (71/81) and symmetrical (69/71). The most common areas affected were the hippocampus (39/81) cingulate gyrus (33/81), hippocampus and piriform lobes (32/81). Distribution analysis suggested concurrence between cingulate gyrus and pulvinar thalamic nuclei, the cingulate gyrus and parahippocampal gyrus, hippocampus and piriform lobe, and, hippocampus and parahippocampal gyrus. Diffusion (DWI) characteristics were a mixed‐pattern of restricted, facilitated, and normal diffusion. Perfusion (PWI) showed either hypoperfusion (6/9) or hyperperfusion (3/9). Conclusions and Clinical Importance: More areas, than previously reported, have been identified that could incur seizure‐induced changes. Similar to human literature, DWI and PWI changes have been identified that could reflect the underlying metabolic and vascular changes. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location. Hypothesis/Objectives: Identify magnetic resonance imaging (MRI) features predictive of PNST histologic grade. Animals: Forty‐four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation. Methods: A multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board‐certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board‐certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis. Results: Forty‐four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low‐grade), 19 were PNSTs Grade 2 (medium‐grade), and 9 were PNSTs Grade 3 (high‐grade). Large volume (P =.03) and severe peripheral contrast enhancement (P =.04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade. Conclusions and Clinical Importance: Grade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high‐grade PNSTs including tumor size and peripheral contrast enhancement. [ABSTRACT FROM AUTHOR]

Background: Congenital sensorineural deafness (CSD) is the most common type of deafness in Dalmatian dogs. Objectives: To use results of CSD screening in Dalmatian dogs in the United Kingdom in genetic analysis and to determine any changes in the prevalence of CSD in this breed over time. Animals A total of 8955 Dalmatian puppies undergoing hearing function screening using brainstem auditory evoked response (BAER) between July 1992 and February 2019. Methods: Results of BAER testing and pigmentation phenotypic data were linked to the UK Kennel Club Dalmatian pedigree database. Mixed model analysis was used to estimate variance parameters. Results: The overall prevalence of CSD was 17.8% (13.4%, unilateral; 4.4%, bilateral). Heritability of CSD was approximately 0.3 (across models) and significantly >0. Genetic correlations between CSD and blue irises (+0.6) and pigmented head patch (−0.86) were large in magnitude and significantly different form 0. Significant improving phenotypic and genetic trends were identified, likely as the result of selection against deafness, equivalent to avoiding breeding with the 4% to 5% of animals with the highest genetic risk of CSD. Conclusions and Clinical Importance: A decrease in the prevalence and genetic risk of CSD implies breeders have been selecting for hearing dogs. Selective breeding based on estimated breeding values (EBVs) can help further decrease the prevalence of CSD in Dalmatians in the future. [ABSTRACT FROM AUTHOR]

Gambling disorder (GD) is a behavioral addiction, in which dysfunctions in prefrontal activity have been proposed as relevant pathophysiological correlates. The aim of the present study was to preliminarily investigate the feasibility of a noninvasive neuromodulation intervention targeting the prefrontal cortex to treat GD in an open-label setting. We included 8 treatment-seeking patients with GD (7 males; 1 female; mean age: 40.6 ± 11.2). The study consisted of 3 phases: (1) outpatient screening phase, (2) 2-week intensive repetitive transcranial magnetic stimulation (rTMS) treatment phase (twice daily, 5 days/week for 2 weeks); and (3) 3-month maintenance follow-up phase (twice daily, once a week). Each high-frequency (15 Hz) rTMS session was delivered targeting the left dorsolateral prefrontal cortex. GD severity and treatment response were assessed at the baseline and during the follow-up. No relevant side effect was reported. We found a 71.2% Gambling Symptom Assessment Scale mean score reduction after 2 weeks of rTMS treatment; the days spent gambling decreased from 19.63 ± 7.96 to 0.13 ± 0.35 days. Clinical improvements were maintained throughout the study period. The lack of a control group limits the interpretation of these results. In conclusion, these results consolidate the rationale that rTMS interventions deserve further investigation as a potential treatment for GD. These protocols should be tested in larger randomized controlled studies, to determine the real benefits of neuromodulation in the clinical course of patients with GD. Registration Number: ClinicalTrials.gov Identifier NCT03336879. [ABSTRACT FROM AUTHOR]

Background: Abnormal sleep behavior has been reported in 5 dogs during recovery from tetanus. Hypothesis: REM sleep behavior disorder (RBD) is a more common consequence of tetanus than previously reported in veterinary literature and easily confused for epileptic seizures. Animals Sixty‐one client‐owned dogs diagnosed with tetanus at 2 UK referral centers. Methods: A retrospective review of medical records was combined with a questionnaire sent to owners of surviving dogs, to identify cases that developed clinically probable RBD and determine its clinical progression and effect on quality of life of affected dogs and their owners. Descriptive statistical evaluation was performed. Results: Eleven dogs (18%) died or were euthanized before discharge. At least 46% surviving dogs developed abnormal "dream enactment" clinically consistent with RBD. Twitching, running, and vocalization were new sleep behaviors in 53, 80, and 60% of affected dogs. Clinically probable RBD was described as violent or "nightmare"‐like in 36% affected dogs, and like an epileptic seizure in 40% affected dogs. When trialed, antiepileptic medications were ineffective. Onset occurred before discharge in 25% cases. For dogs that developed clinically probable RBD postdischarge, onset occurred within 2 weeks of discharge in 77% dogs. Clinically probable RBD did not worsen in severity or frequency in any dog, and spontaneously resolved within 6 months in 43% cases. Conclusions and Clinical Importance: Clinically probable RBD is a common sequel to canine tetanus with many clinical similarities to epileptic seizure activity. Owners should be made aware of its potential development and care taken to avoid misdiagnosis with epileptic seizure activity. [ABSTRACT FROM AUTHOR]

Punding is a stereotyped behavior characterized by an intense fascination with a complex, excessive, non-goal oriented, repetitive activity, associated with dopaminergic replacement therapy (DRT) in patients affected by Parkinson's disease (PD) and with dopamine agonists in several conditions. We studied 25 PD patients with punding behaviors, and compared them to 130 PD controls. The psychiatric evaluation included: the Snaith-Hamilton Pleasure Scale (SHAPS); the SCales for Outcomes in PArkinson's disease-Psychiatric Complications (SCOPA-PC); the Barratt Impulsiveness Scale, Version 11 (BIS-11); the Mood Disorder Questionnaire; the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS). The occurrence of impulse control disorders (ICDs) was diagnosed through a psychiatric interview. Significantly more punding patients (96% vs. 68%; p < 0.01) were in treatment with DA agonists, receiving significantly higher DA agonists levodopa equivalent daily dose (LEDD). Punding behaviors were found to be associated with psychiatric comorbidity, particularly with psychosis and bipolar disorder. In addition, higher anhedonic symptoms were reported by punders. High rate of co-occurring addictive behaviors (pathological gambling, hedonistic homeostatic dysregulation) and ICDs were found. In conclusion, presented data confirm that DRT, in a subset of PD patients, is strongly associated with addiction-like behavioral issues. Punding shares similarities with addictive behaviors and is associated to other psychiatric symptoms involving dopamine system alterations. [ABSTRACT FROM AUTHOR]

Purpose The aims of the study were to evaluate the occurrence of behavioral addictions (BAs) in alcohol use disorder (AUD) subjects and to investigate the role of impulsivity, personality dimensions and craving. Methods 95 AUD outpatients (DSM-5) and 140 homogeneous controls were assessed with diagnostic criteria and specific tests for gambling disorder, compulsive buying, sexual, internet and physical exercise addictions, as well as with the Barratt Impulsiveness Scale (BIS-11) and Temperamental and Character Inventory–Revised (TCI-R). The Obsessive Compulsive Drinking Scale (OCDS) and Visual Analogue Scale for craving (VASc) were also administered to the AUD sample. Results 28.4% ( n = 27) of AUD subjects had at least one BA, as compared to 15% ( n = 21) of controls ( χ 2 = 6.27; p = .014). In AUD subjects, direct correlations between BIS-11 and Compulsive Buying Scale (CBS), Internet Addiction Disorder test (IAD), Exercise Addiction Inventory-Short Form (EAI-SF) scores ( p < .01), between OCDS obsessive and CBS and VASc and CBS, IAD scores ( p < .003), were found. BIS-11 ( t = −2.36; p = .020), OCDS obsessive ( Z = −4.13; p < .001), OCDS compulsive ( Z = −2.12; p = .034) and VASc ( Z = −4.94; p < .001) scores were higher in AUD subjects with co-occurring BAs. The occurrence of BAs was associated with higher impulsivity traits (BIS-11 scores; OR = 1.08; p = .012) and higher craving levels (VASc scores; OR = 2.48; p < .001). Conclusions Our findings emphasize a significant rate of co-occurrence of BAs in AUD. High levels of impulsivity and craving for alcohol seem to be associated with other addictive behaviors. [ABSTRACT FROM AUTHOR]

Objective: The use of benchtop metabolic profiling technology based on nuclear magnetic resonance (NMR) was evaluated in a small cohort of cats with a view to applying this as a viable and rapid metabolic tool to support clinical decision making. Results: Urinary metabolites were analysed from four subjects consisting of two healthy controls and two chronic kidney disease (CKD) IRIS stage 2 cases. The study identified 15 metabolites in cats with CKD that were different from the controls. Among them were acetate, creatinine, citrate, taurine, glycine, serine and threonine. Benchtop NMR technology is capable of distinguishing between chronic kidney disease case and control samples in a pilot feline cohort based on metabolic profile. We offer perspectives on the further development of this pilot work and the potential of the technology, when combined with sample databases and computational intelligence techniques to offer a clinical decision support tool not only for cases of renal disease but other metabolic conditions in the future. [ABSTRACT FROM AUTHOR]

Background: Avoidance of unnecessary antimicrobial administration is a key tenet of antimicrobial stewardship; knowing the optimal duration of therapy obviates over-treatment. However, little research has been performed to establish course lengths for common canine infections. In clinical practice, antimicrobial therapy is frequently prescribed in dogs presenting lower urinary tract signs (haematuria, pollakiuria and dysuria/stranguria). The proposed length of treatment in International Consensus guidelines has decreased with each iteration, but these recommendations remain arbitrary and largely extrapolated from experience in people. Methods: The objective of this prospective, multi-centre study is to find the shortest course duration that is non-inferior to the standard duration of 7 days of amoxicillin/clavulanate in terms of clinical outcomes for female dogs with lower urinary tract signs consistent with a urinary tract infection. An electronic data capture platform will be used by participating veterinarians working in clinical practice in the United Kingdom. Eligible dogs must be female, aged between 6 months and 10 years and have lower urinary tract signs of up to seven days' duration. Enrolment will be offered in cases where the case clinician intends to prescribe antimicrobial therapy. Automatic pseudo-randomisation to treatment group will be based on the day of presentation (Monday-Friday); all antimicrobial courses will be completed on the Sunday after presentation generating different treatment durations. Follow-up data will be collected 1, 8 and 22–26 days after completion of the antimicrobial course to ensure effective safety netting, and to monitor short-term outcome and recurrence rates. Informed owner consent will be obtained in all cases. The study is approved by the Ethical Review Board of the University of Nottingham and has an Animal Test Certificate from the Veterinary Medicine's Directorate. Discussion: This study has been designed to mirror current standards of clinical management; conclusions should therefore, be widely applicable and guide practising veterinarians in their antimicrobial decision-making process. A duration-response curve will be created allowing determination of the optimal treatment duration for the management of female dogs with lower urinary tract signs. It is hoped that these results will contribute valuable information to improve future antimicrobial stewardship as part of a wider one-health perspective. [ABSTRACT FROM AUTHOR]

Summary: Genotype imputation using a reference panel that combines high‐density array data and publicly available whole genome sequence consortium variant data is potentially a cost‐effective method to increase the density of extant lower‐density array datasets. In this study, three datasets (two Border Collie; one Italian Spinone) generated using a legacy array (Illumina CanineHD, 173 662 SNPs) were utilised to assess the feasibility and accuracy of this approach and to gather additional evidence for the efficacy of canine genotype imputation. The cosmopolitan reference panels used to impute genotypes comprised dogs of 158 breeds, mixed breed dogs, wolves and Chinese indigenous dogs, as well as breed‐specific individuals genotyped using the Axiom Canine HD array. The two Border Collie reference panels comprised 808 individuals including 79 Border Collies and 426 326 or 426 332 SNPs; and the Italian Spinone reference panel comprised 807 individuals including 38 Italian Spinoni and 476 313 SNPs. A high accuracy for imputation was observed, with the lowest accuracy observed for one of the Border Collie datasets (mean R2 = 0.94) and the highest for the Italian Spinone dataset (mean R2 = 0.97). This study's findings demonstrate that imputation of a legacy array study set using a reference panel comprising both breed‐specific array data and multi‐breed variant data derived from whole genomes is effective and accurate. The process of canine genotype imputation, using the valuable growing resource of publicly available canine genome variant datasets alongside breed‐specific data, is described in detail to facilitate and encourage use of this technique in canine genetics. [ABSTRACT FROM AUTHOR]

Background: Avoidance of unnecessary antimicrobial administration is a key tenet of antimicrobial stewardship; knowing the optimal duration of therapy obviates over-treatment. However, little research has been performed to establish course lengths for common canine infections. In clinical practice, antimicrobial therapy is frequently prescribed in dogs presenting lower urinary tract signs (haematuria, pollakiuria and dysuria/stranguria). The proposed length of treatment in International Consensus guidelines has decreased with each iteration, but these recommendations remain arbitrary and largely extrapolated from experience in people. Methods: The objective of this prospective, multi-centre study is to find the shortest course duration that is non-inferior to the standard duration of 7 days of amoxicillin/clavulanate in terms of clinical outcomes for female dogs with lower urinary tract signs consistent with a urinary tract infection. An electronic data capture platform will be used by participating veterinarians working in clinical practice in the United Kingdom. Eligible dogs must be female, aged between 6 months and 10 years and have lower urinary tract signs of up to seven days' duration. Enrolment will be offered in cases where the case clinician intends to prescribe antimicrobial therapy. Automatic pseudo-randomisation to treatment group will be based on the day of presentation (Monday-Friday); all antimicrobial courses will be completed on the Sunday after presentation generating different treatment durations. Follow-up data will be collected 1, 8 and 22–26 days after completion of the antimicrobial course to ensure effective safety netting, and to monitor short-term outcome and recurrence rates. Informed owner consent will be obtained in all cases. The study is approved by the Ethical Review Board of the University of Nottingham and has an Animal Test Certificate from the Veterinary Medicine's Directorate. Discussion: This study has been designed to mirror current standards of clinical management; conclusions should therefore, be widely applicable and guide practising veterinarians in their antimicrobial decision-making process. A duration-response curve will be created allowing determination of the optimal treatment duration for the management of female dogs with lower urinary tract signs. It is hoped that these results will contribute valuable information to improve future antimicrobial stewardship as part of a wider one-health perspective. [ABSTRACT FROM AUTHOR]

• We aimed at providing a synthesis of current knowledge on dopaminergic function in GD. • We adopted a systematic approach encompassing both preclinical and clinical studies. • 67 animal studies using a variety of manipulations of the gambling-like phenotype. • 33 human studies investigating genetic polymorphisms or functional brain imaging data. • DAT, D2, D3, D4 receptor alterations showed strongest translational concordance. Dopamine has a crucial and well-documented role in the development and maintenance of Gambling Disorder (GD). This systematic review adopts a translational approach aimed at providing a comprehensive synthesis of current clinical and preclinical knowledge on dopaminergic function in GD at a neurobiological level. To this end, we present and discuss converging dopaminergic alterations and phenotypes. Preclinical and clinical review protocols were registered on the PROSPERO database (CRD42019124404, CRD42019124405). The literature search was conducted in accordance with PRISMA guidelines using three databases (PubMed, Web of Science, Scopus). We identified 67 preclinical studies using pharmacological and non-pharmacological manipulations of the gambling-like phenotype and 33 human studies investigating either genetic polymorphisms or functional brain imaging data. Dopamine transporter and D2, D3, D4 receptor alterations showed strongest translational concordance. Though no postsynaptic dopaminergic alterations were observed, several studies point at dysfunctions in presynaptic dopamine trafficking in GD, suggestive of hyperdopaminergic states. Developing meaningful translational models is essential to working towards the development of an integrated conceptual framework for GD and neurobiologically-based treatment interventions. [ABSTRACT FROM AUTHOR]

Congenital deafness in the domestic dog is usually related to the presence of white pigmentation, which is controlled primarily by the piebald locus on chromosome 20 and also by merle on chromosome 10. Pigment-associated deafness is also seen in other species, including cats, mice, sheep, alpacas, horses, cows, pigs, and humans, but the genetic factors determining why some piebald or merle dogs develop deafness while others do not have yet to be determined. Here we perform a genome-wide association study (GWAS) to identify regions of the canine genome significantly associated with deafness in three dog breeds carrying piebald: Dalmatian, Australian cattle dog, and English setter. We include bilaterally deaf, unilaterally deaf, and matched control dogs from the same litter, phenotyped using the brainstem auditory evoked response (BAER) hearing test. Principal component analysis showed that we have different distributions of cases and controls in genetically distinct Dalmatian populations, therefore GWAS was performed separately for North American and UK samples. We identified one genome-wide significant association and 14 suggestive (chromosome-wide) associations using the GWAS design of bilaterally deaf vs. control Australian cattle dogs. However, these associations were not located on the same chromosome as the piebald locus, indicating the complexity of the genetics underlying this disease in the domestic dog. Because of this apparent complex genetic architecture, larger sample sizes may be needed to detect the genetic loci modulating risk in piebald dogs. [ABSTRACT FROM AUTHOR]

A form of hereditary cerebellar ataxia has recently been described in the Norwegian Buhund dog breed. This study aimed to identify the genetic cause of the disease. Whole-genome sequencing of two Norwegian Buhund siblings diagnosed with progressive cerebellar ataxia was carried out, and sequences compared with 405 whole genome sequences of dogs of other breeds to filter benign common variants. Nine variants predicted to be deleterious segregated among the genomes in concordance with an autosomal recessive mode of inheritance, only one of which segregated within the breed when genotyped in additional Norwegian Buhunds. In total this variant was assessed in 802 whole genome sequences, and genotyped in an additional 505 unaffected dogs (including 146 Buhunds), and only four affected Norwegian Buhunds were homozygous for the variant. The variant identified, a T to C single nucleotide polymorphism (SNP) (NC_006585.3:g.88890674T>C), is predicted to cause a tryptophan to arginine substitution in a highly conserved region of the potassium voltage-gated channel interacting protein KCNIP4. This gene has not been implicated previously in hereditary ataxia in any species. Evaluation of KCNIP4 protein expression through western blot and immunohistochemical analysis using cerebellum tissue of affected and control dogs demonstrated that the mutation causes a dramatic reduction of KCNIP4 protein expression. The expression of alternative KCNIP4 transcripts within the canine cerebellum, and regional differences in KCNIP4 protein expression, were characterised through RT-PCR and immunohistochemistry respectively. The voltage-gated potassium channel protein KCND3 has previously been implicated in spinocerebellar ataxia, and our findings suggest that the Kv4 channel complex KCNIP accessory subunits also have an essential role in voltage-gated potassium channel function in the cerebellum and should be investigated as potential candidate genes for cerebellar ataxia in future studies in other species. Author summary: Hereditary ataxias, which are a group of disorders characterised by incoordination of movement, are typically incurable and there are often no disease-modifying treatments available. Canine hereditary ataxias are a notable group of movement disorders in dogs, and represent well characterised naturally occurring disease models of ataxia that can help improve our understanding of the underlying biology of the disorder in both dogs and humans. We used the whole genome sequences of two affected siblings to investigate the genetic cause of a slowly progressive form of hereditary ataxia in the Norwegian Buhund dog breed, and identified a single base change within the KCNIP4 gene. We have characterised the expression of KCNIP4 in the dog, and investigated the effect of the identified mutation. This gene has not previously been implicated in inherited ataxia in any species, and our findings suggest that this and related genes represent potential candidates for ataxia in future studies in other species. Our findings will allow dog breeders to avoid producing affected dogs, reduce the disease allele frequency, and eventually eliminate the disease from the breed, through the use of a DNA test. [ABSTRACT FROM AUTHOR]

Background: The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail. Objectives: To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs. Animals: Client‐owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus. Methods: Randomized parallel group clinical trial. Patients were randomly allocated to the IN‐MDZ (n = 21) or IV‐MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for ≥10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at α < .05. Results: IN‐MDZ and IV‐MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P =.34). The median seizure cessation time was 33 and 64 seconds for IN‐MDZ and IV‐MDZ, respectively (P =.63). When the time to place an IV catheter was taken into account, IN‐MDZ (100 seconds) was superior (P =.04) to IV‐MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN‐MDZ and IV‐MDZ, respectively. Conclusions and Clinical Importance: Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account. [ABSTRACT FROM AUTHOR]

Background: Urinary (UI) and fecal (FI) incontinence occur in up to 7.5% and 32% of dogs, respectively, after thoracolumbar acute noncompressive nucleus pulposus extrusion (ANNPE). Hypotheses/Objectives: To investigate clinical, diagnostic, and therapeutic predictors of UI and FI in dogs with ANNPE affecting the T3‐L3 spinal cord segments. Animals: Hundred and eighty‐seven dogs with T3‐L3 ANNPE diagnosed based on clinical and MRI findings. Methods: Multicenter retrospective study. Data were obtained from medical records and telephone questionnaires and analyzed by logistic regression. Results: UI and FI were reported in 17 (9.1%) and 44 (23.5%) dogs, respectively. Paraplegic dogs were 3 times (95% CI = 1.25, 10.87) more likely to develop UI (P =.018) and 4 times (95% CI = 1.94, 12.56) more likely to develop FI (P =.001) compared to nonparaplegic dogs. Dogs with an intramedullary hyperintensity greater than 40% of the cross‐sectional area of the spinal cord at the same level on transverse T2‐weighted MRI images were 4 times more likely to develop UI (95% CI = 1.04, 21.72; P =.045) and FI (95% CI = 1.56, 10.39; P =.004) compared to dogs with smaller lesions. FI was 3 times (95% CI = 1.41, 7.93) more likely in dogs that were not treated with nonsteroidal anti‐inflammatory drugs (NSAIDs) after diagnosis compared to dogs administered NSAIDs (P =.006) and 2 times (95% CI = 1.12, 5.98) more likely in dogs presented with clinical signs compatible with spinal shock compared to dogs without (P =.026). Conclusion and Clinical Importance: The identification of clinical, diagnostic, and therapeutic predictors of UI and FI in dogs with T3‐L3 ANNPE can help to approach these autonomic dysfunctions occurring after spinal cord injury. [ABSTRACT FROM AUTHOR]

Although the involvement of dopamine in gambling disorder (GD) has long been hypothesized, its precise role remains unclear. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We hereinafter present significant differences between a sample of 15 treatment-seeking GD subjects and 17 healthy controls in terms of striatal DAT availability, and we explore its association with reward-based decision making. We performed 123 I-FP-CIT Single-photon emission computed tomography (SPECT) and correlated DAT binding ratios in the bilateral caudate and putamen with gambling symptoms (G-SAS, PG-YBOCS) and behaviors, as well as other psychometric variables (anhedonia and impulsivity). Gambling disorder (GD) subjects were also administered a computerized version of the Iowa gambling task (IGT) to assess reward-based decision making. We found reduced DAT availability in GD subjects compared with healthy controls (-13.30% in right caudate, -11.11% in right putamen, -11.44% in left caudate, and -11.46% in the left putamen). We also found that striatal DAT availability was inversely correlated with days spent gambling and IGT performance in GD subjects. These results provide evidence for a presynaptic dopaminergic dysfunction in striatal regions of GD subjects. Functional DAT down-regulation possibly sustains the transition towards compulsive gambling addiction, characterized both by hyperdopaminergic and hypodopaminergic states in the context of a sensitized dopaminergic system. [ABSTRACT FROM AUTHOR]

Background: Data about congenital sensorineural deafness (CSD) in white blue‐eyed cats derive mainly from research colonies, and information about client‐owned cats is limited. Objectives: To describe the prevalence of CSD in a client‐owned population of white purebred kittens and colored littermates in the United Kingdom. Animals: One hundred thirty‐two solid white client‐owned purebred kittens and 61 colored littermates, 6 to 21 weeks of age. Methods: Retrospective (56 cases) and prospective (137 cases) study. Hearing was assessed by brainstem auditory evoked response testing, and the entire litter was tested. Results: Congenital sensorineural deafness was diagnosed only in solid white kittens, with a prevalence of 30.3% (15.9% bilateral, 14.4% unilateral). The prevalence of CSD was significantly higher in white kittens with 1 (44.4%) or 2 (50%) blue irises than in those without blue irises (22.2%). Kittens with at least 1 blue iris were 3.2 times more likely to have CSD than kittens without blue irises. In solid white kittens, CSD was diagnosed in 7 of 15 (46.7%) Turkish Vankedisi, 8 of 18 (44.0%) Maine Coon, 18 of 41 (43.9%) Norwegian Forest, 3 of 11 (27.3%) British Shorthair, 2 of 12 (16.7%) Devon Rex, 2 of 12 (8.3%) Persian, 1 of 21 (4.8%) Russian, and 0 of 2 Sphinx. The prevalence of CSD was significantly different in Norwegian Forest, Maine Coon, and Turkish Vankedisi kittens compared with Persian or Russian kittens. Conclusion and Clinical Importance: We identified a high prevalence of CSD in a population of client‐owned purebred white kittens in the United Kingdom and suggest differences in breed‐specific prevalence of CSD. [ABSTRACT FROM AUTHOR]

• TRD is a significant health burden, aiming for personalized interventions. • Machine learning approaches may improve precision of treatment strategies. • We trained ML models to predict Esketamine Nasal Spray response in TRD subjects. • Anhedonia, anxious distress and mixed features increase probability of response/remission. • Benzodiazepine use and depression severity may delay treatment response. Treatment-resistant depression (TRD) represents a severe clinical condition with high social and economic costs. Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD by EMA and FDA, but data about predictors of response are still lacking. Thus, a tool that can predict the individual patients' probability of response to ESK-NS is needed. This study investigates sociodemographic and clinical features predicting responses to ESK-NS in TRD patients using machine learning techniques. In a retrospective, multicentric, real-world study involving 149 TRD subjects, psychometric data (Montgomery-Asberg-Depression-Rating-Scale/MADRS, Brief-Psychiatric-Rating-Scale/BPRS, Hamilton-Anxiety-Rating-Scale/HAM-A, Hamilton-Depression-Rating-Scale/HAMD-17) were collected at baseline and at one month/T1 and three months/T2 post-treatment initiation. We trained three different random forest classifiers, able to predict responses to ESK-NS with accuracies of 68.53% at T1 and 66.26% at T2 and remission at T2 with 68.60% of accuracy. Features like severe anhedonia, anxious distress, mixed symptoms as well as bipolarity were found to positively predict response and remission. At the same time, benzodiazepine usage and depression severity were linked to delayed responses. Despite some limitations (i.e., retrospective study, lack of biomarkers, lack of a correct interrater-reliability across the different centers), these findings suggest the potential of machine learning in personalized intervention for TRD. [ABSTRACT FROM AUTHOR]

• Safe and effective treatments for women with PPD is therefore urgently warranted. • Systematic review done in accordance with the PRISMA and PROSPERO guidelines. • Twenty-three rTMS studies were included; none reported side effects for newborns. • rTMS use in PPD shows a good safety profile, even during breastfeeding. Peripartum depression is defined as the onset of depressive symptoms during pregnancy or within 12 months postpartum and affects 11.9% of women. Currently, its treatment often involves psychotherapy and antidepressants, though only one medication has been specifically approved to treat it. In this context, novel, safe non-pharmacological treatment options have gained growing interest. The present review aims to assess current literature on possible side effects on the developing fetus/newborn of Transcranial Magnetic Stimulation (TMS) use in women with peripartum depression. A systematic search was performed using the PubMed, Scopus and Web of Science databases. PRISMA and PROSPERO guidelines were applied. The risk of bias assessment was performed using the Cochrane risk of bias tool version 2.0. Twenty-three studies were included in our systematic review, two were randomized controlled trials. Eleven studies reported mothers experienced mild side effects; none of the included studies reported major side effects for newborns. The present systematic review demonstrated that TMS use in women with peripartum depression is safe, feasible and well-tolerated by the developing fetus/newborn, with a good safety and tolerability profile even during breastfeeding. [ABSTRACT FROM AUTHOR]

Repetitive Transcranial Magnetic Stimulation (rTMS) shows the potential to modulate local brain activity, thus resulting in a modulatory action on neurocircuitries implicated in the pathophysiology of Gambling Disorder (GD). We report the case of a GD patient treated with two weeks of high frequency (15 Hz) rTMS over the dorsolateral prefrontal cortex (DLPFC). At baseline and after rTMS treatment the patient underwent a SPECT examination with (123)I-FP-CIT tracer, to test changes in dopamine transporter (DAT) availability. The patient was followed up for six months, to explore safety and clinical correlates of a weekly high frequency rTMS maintenance treatment. Over the six-month follow-up the patient reported no episodes of gambling relapse. Also, the patient did not report craving for gambling or gambling-related symptoms. After two weeks of left DLPFC-rTMS treatment, we found a decrease in DAT availability in striatal regions, that represents a putative neurobiological substrate of dopaminergic pathways modulation. This study suggests that high frequency DLPFC-rTMS deserves further investigations in larger samples, using controlled study designs, to assess its real potential as a treatment for GD. [ABSTRACT FROM AUTHOR]

Introduction: Gambling disorder (GD) is a major public health concern with currently no validated and efficacious treatments approved. In this single case study, we report the short- and long-term effect of bilateral transcranial direct current stimulation (tDCS) of dorsolateral prefrontal cortex (DLPFC) on craving and impulse control in a subject with GD. Methods: The patient is a 26-year-old Caucasian male with an 8-year history of GD as well as alcohol and cocaine misuse. Treatment consisted of twice-a-day stimulation for 10 days. According to the literature, both the left (to control craving) and the right (to control emotional impulses) DLPFC were stimulated. Patients subsequently received tDCS once a week for 3 months and then once every 2 weeks for another 3 months. Results: After 10 days of treatment, the subject reported improved psychiatric symptoms (depression, anxiety, and impulsivity), as well as reduced gambling craving symptom severity. After 3 and 6 months of treatment, the clinical picture further improved. Discussion: This is the first report of tDCS effectiveness in a single case study of GD. Therapeutic effects, both on the addictive behavior and on psychiatric comorbid symptomatology, were lasting and continued over 6 months of tDCS maintenance treatment. Future case-control studies are required to test the efficacy of this tool in patients with GD. [ABSTRACT FROM AUTHOR]

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog. [ABSTRACT FROM AUTHOR]

A 9-month-old French Bulldog was presented with a chronic history of lateral strabismus and intermittent third eyelid protrusion in the left eye. The neuro-ophthalmological examination revealed mild ptosis of the left upper eyelid, mild lateral strabismus, and external ophthalmoparesis of the left eye. Retraction and ventral deviation of the left eye globe with protrusion of the third eyelid and elevation of the upper eyelid were elicited on attempted voluntary adduction of the left eye. Hematology, serum biochemistry, serology for infectious diseases, magnetic resonance of the head, and cerebrospinal fluid analysis did not reveal significant abnormalities. Forced duction test did not show signs of mechanical restriction in ocular motility. A suspected congenital cranial dysinnervation disorder resembling Duane retraction syndrome in humans was diagnosed based on the typical clinical signs and exclusion of structural abnormalities. The clinical signs remained stable for 9 months until the time of writing this report. [ABSTRACT FROM AUTHOR]

Aims: Gender and psychiatric comorbidity seem to influence patients' inter-individual response to Opioid Substitution Treatments (OST) in Opioid Use Disorder (OUD) management. The aim of the study was to assess psychopathological dimensions in an Italian sample of OUD individuals entering a methadone/buprenorphine maintenance program; secondary, we evaluated the possible gender-specific differences within the psychopathological profiles.Methods: In a cross-sectional study, we recruited 1052 (792 male; 260 female) OUD subjects receiving OST. All patients underwent a clinical and psychometric evaluation assessing demographics, psychiatric history, psychopathological features via the Symptom Checklist-90-Revised (SCL-90-R), and were prescribed psychopharmacological treatments.Results: Our results reveal gender-specific differences in a real-world sample of opioid-maintained OUD individuals attending public addiction services in Italy. Compared to men, women reported higher scores in both General Symptomatic Index (GSI) and in all the SCL-90-R sub-scales. No impact of pharmacological treatment was detected. Finally, regression analysis revealed that being in methadone-maintenance group was significantly associated with high GSI scores in the male, but not female, group.Conclusions: Increasing the knowledge of psychopathological dimensions in patients with OST, with relevance to gender differences, is important for a better understanding of factors that influence the outcome and for further development in gender-tailored strategies. [ABSTRACT FROM AUTHOR]

Decreased cognitive control over the urge to be involved in gambling activities is a core feature of Gambling Disorder (GD). Cognitive control can be differentiated into several cognitive sub-processes pivotal in GD clinical phenomenology, such as response inhibition , conflict monitoring, decision-making, and cognitive flexibility . This article aims to systematically review fMRI studies, which investigated the neural mechanisms underlying diminished cognitive control in GD. We conducted a comprehensive literature search and collected neuropsychological and neuroimaging data investigating cognitive control in GD. We included a total of 14 studies comprising 499 individuals. Our results indicate that impaired activity in prefrontal cortex may account for decreased cognitive control in GD, contributing to the progressive loss of control over gambling urges. Among prefrontal regions, orbital and ventromedial areas seem to be a possible nexus for sensory integration, value-based decision-making and emotional processing, thus contributing to both motivational and affective aspects of cognitive control. Finally, we discussed possible therapeutic approaches aimed at the restoration of cognitive control in GD, including pharmacological and brain stimulation treatments. [ABSTRACT FROM AUTHOR]

Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses neuromuscular diseases in cats.

Among the symptoms of post-traumatic stress disorder (PTSD), impulsiveness has been observed in patients with high levels of hyperarousal. Recent literature reveals the importance of investigating the role of neurotrophins, such as brain-derived neurotrophic factor (BDNF), in several psychiatric disorders. Specifically, contrasting findings have been reported on the levels of serum BDNF in subjects with PTSD. The aim of the present study was to investigate the correlation between BDNF serum levels and impulsiveness in PTSD. To this end, we measured BDNF serum levels in 23 PTSD patients and a control group of 19 trauma-exposed non-PTSD subjects. Results indicate a positive correlation in the PTSD group; that is, the higher the BDNF levels the higher the impulsiveness score, as measured by the Barratt Impulsiveness Scale (BIS-11), suggesting that impulsiveness could be associated with greater BDNF production. Alternatively, it is also possible that high impulsiveness acts as a psychological mechanism that counteracts the negative effects exerted by the traumatic experience and the associated obsessive thoughts. The present paper discusses both hypotheses. [ABSTRACT FROM AUTHOR]