Movement disorder and sensorimotor abnormalities in schizophrenia and other psychoses - European consensus on assessment and perspectives.

Over the last three decades, movement disorder as well as sensorimotor and psychomotor functioning in schizophrenia (SZ) and other psychoses has gained greater scientific and clinical relevance as an intrinsic component of the disease process of psychotic illness; this extends to early psychosis prediction, early detection of motor side effects of antipsychotic medication, clinical outcome monitoring, treatment of psychomotor syndromes (e.g. catatonia), and identification of new targets for non-invasive brain stimulation. In 2017, a systematic cooperation between working groups interested in movement disorder and sensorimotor/psychomotor functioning in psychoses was initiated across European universities. As a first step, the members of this group would like to introduce and define the theoretical aspects of the sensorimotor domain in SZ and other psychoses. This consensus paper is based on a synthesis of scientific evidence, good clinical practice and expert opinions that were discussed during recent conferences hosted by national and international psychiatric associations. While reviewing and discussing the recent theoretical and experimental work on neural mechanisms and clinical implications of sensorimotor behavior, we here seek to define the key principles and elements of research on movement disorder and sensorimotor/psychomotor functioning in psychotic illness. Finally, the members of this European group anticipate that this consensus paper will stimulate further multimodal and prospective studies on hypo- and hyperkinetic movement disorders and sensorimotor/psychomotor functioning in SZ and other psychotic disorders.

Early intervention in psychosis: health economic evaluation using the net benefit approach in a real-world setting.

BACKGROUND: Early intervention in psychosis is a complex intervention, usually delivered in a specialist stand-alone setting, which aims to improve outcomes for people with psychosis. Previous studies have been criticised because the control used did not accurately reflect actual practice. AIMS: To evaluate the cost-effectiveness of early intervention by estimating the incremental net benefit (INB) of an early-intervention programme, delivered in a real-world setting. INB measures the difference in monetary terms between alternative interventions. METHOD: Two contemporaneous incidence-based cohorts presenting with first-episode psychosis, aged 18-65 years, were compared. Costs and outcomes were measured over 1 year. The main outcome was avoidance of a relapse that required admission to hospital or home-based treatment. RESULTS: From the health sector perspective, the probability that early intervention was cost-effective was 0.77. The INB was €2465 per person (95% CI - €4418 to €9347) when society placed a value of €6000, the cost of an in-patient relapse, on preventing a relapse requiring admission or home care. Following adjustment, the probability that early intervention was cost-effective was 1, and the INB to the health sector was €3105 per person (95% CI -€8453 to €14 663). From a societal perspective, the adjusted probability that early intervention was cost-effective was 1, and the INB was €19 928 per person (95% CI - €2075 to €41 931). CONCLUSIONS: Early intervention has a modest INB from the health sector perspective and a large INB from the societal perspective. The perspective chosen is critical when presenting results of an economic evaluation of a complex intervention.

Relationship of suicide rates with climate and economic variables in Europe during 2000-2012.

BACKGROUND: It is well known that suicidal rates vary considerably among European countries and the reasons for this are unknown, although several theories have been proposed. The effect of economic variables has been extensively studied but not that of climate. METHODS: Data from 29 European countries covering the years 2000-2012 and concerning male and female standardized suicidal rates (according to WHO), economic variables (according World Bank) and climate variables were gathered. The statistical analysis included cluster and principal component analysis and categorical regression. RESULTS: The derived models explained 62.4 % of the variability of male suicidal rates. Economic variables alone explained 26.9 % and climate variables 37.6 %. For females, the respective figures were 41.7, 11.5 and 28.1 %. Male suicides correlated with high unemployment rate in the frame of high growth rate and high inflation and low GDP per capita, while female suicides correlated negatively with inflation. Both male and female suicides correlated with low temperature. DISCUSSION: The current study reports that the climatic effect (cold climate) is stronger than the economic one, but both are present. It seems that in Europe suicidality follows the climate/temperature cline which interestingly is not from south to north but from south to north-east. This raises concerns that climate change could lead to an increase in suicide rates. The current study is essentially the first successful attempt to explain the differences across countries in Europe; however, it is an observational analysis based on aggregate data and thus there is a lack of control for confounders.

Are We Really Impacting Duration of Untreated Psychosis and Does It Matter?: Longitudinal Perspectives on Early Intervention from the Irish Public Health Services.

Although early intervention in psychosis is clinically intuitive and theoretically feasible, the reality is that over recent decades the evidence base to support it has not advanced as much as might have been anticipated. Material benefits of early intervention in established psychosis have not been universally demonstrated and much uncertainty continues to surround the field of treatment in the prodromal phase. Undoubtedly methodological differences between studies are relevant and better understanding of different treatment models and the effectiveness of their constituent parts may yield the most benefit, particularly from a public health perspective.

Socioeconomic status at birth and risk for first episode psychosis in rural Ireland: Eliminating the features of urbanicity in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS).

BACKGROUND: There is a paucity of research on the relationship between social environment at birth and risk for psychosis in rural settings. This study examined the relationship between individual- and neighbourhood-level socioeconomic indicators proximal to the time of birth and risk for a first psychotic episode in a rural context using a prospective dataset of unusual epidemiological completeness. METHODS: A matched case-control design was used. 186 cases were identified from the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS) and 679 age- and sex-matched controls from the same rural setting were identified and analysed for relationships with individual and neighbourhood-level socioeconomic indicators at the level of Electoral Divisions. RESULTS: While neither the distribution nor the ordinal scale of parental social class differed between cases and controls, logistic regression revealed both parental social class III and increasing level of rurality to be associated (p≤0.05) with reduced risk for affective psychosis. There was a prominent relationship (p<0.001) between lower parental social class and older age at first presentation [mean age at first presentation for all psychoses: social class I, 22.8; social class VI, 44.3]. CONCLUSIONS: These findings indicate modest effects of individual- and neighbourhood-level socioeconomic indicators and risk for psychosis by place at birth within a rural environment. Thus, these factors are not confined to large urban settings and apply across the urban-rural continuum. The substantive finding in relation to age at first presentation may indicate that a gradient of socioeconomic position is influential on delay in presentation to mental health services.

Relationship of suicide rates to economic variables in Europe: 2000-2011.

BACKGROUND: It is unclear whether there is a direct link between economic crises and changes in suicide rates. AIMS: The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates. METHOD: Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation. RESULTS: There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged. CONCLUSIONS: Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.

Assessment of jaw movements by magnetic sensor in relation to topographies of orofacial behaviour in freely moving rats: Studies with the dopamine D(1)-like receptor agonists SKF 83822 vs SKF 83959.

This study applies new magnetic sensor-electromyographic technology for recording jaw movements in freely moving rats to analyse topographies of orofacial movement that occur in association with individual elements of behaviour under challenge with two dopamine D(1)-like receptor agonists, SKF 83822 ([R/S]-6-chloro-7, 8-dihydroxy-3-allyl-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine) and SKF 83959([R/S]-3-methyl-6-chloro-7, 8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine). Grooming of the snout/face involved primarily dominant-mouth opening jaw movements with small activation of digastric muscles; subsequent grooming of the flank/trunk was characterised by repetitive, uniform jaw movements with small activation of digastric and masseter muscles. In contrast, grooming of the fingers and tail typically involved high-frequency jaw movements with variable vertical jaw movements and/or strong activation of masseter muscles. Vacuous chewing involved two distinct patterns of jaw movements: a dominant-closing pattern, with strong activation of masseter muscles, and a dominant-opening pattern, with slight activation of masseter muscles. SKF 83822 stimulates dopamine D(1)-like receptors and activates adenylate cyclase but not phosphoinositide hydrolysis, while SKF 83959 stimulates dopamine D(1)-like receptors and activates phosphoinositide hydrolysis but not adenylate cyclase. These agonists exerted differential effects on jaw movements, as SKF 83959 induced more jaw movements per episode of syntactic grooming than SKF 83822, while SKF 83822 induced more jaw movements during non-syntactic grooming than SKF 83959. Magnetic sensor technology in freely moving animals resolved distinct topographies of orofacial movement and informs on their relationship to other behaviours in the rodent repertoire and to dopamine D(1)-like receptor function.

Longitudinal assessment of psychopathological domains over late-stage schizophrenia in relation to duration of initially untreated psychosis: 3-year prospective study in a long-term inpatient population.

There remains uncertainty regarding any progressive nature of psychopathology and cognitive dysfunction in late-stage schizophrenia, and whether duration of initially untreated psychosis (DUP) might be associated with such 'progression'. This study examines longitudinally, over 3 years, the psychopathology and neuropsychology in 82 inpatients with DSM-IV schizophrenia, many of whom were admitted in the pre-neuroleptic era. Increase in executive dysfunction exceeded that in general cognitive impairment. Positive but not negative symptom severity decreased modestly; the primary predictor of negative symptom severity was DUP. On index assessment, psychopathology evidenced a three-factor structure; at follow-up, psychomotor poverty evidenced greater prominence and cohesion, and was on both occasions predicted primarily by DUP, while reality distortion was altered and disorganisation disassembled into alternative elements. It would appear that as years of chronic, refractory illness accrue, psychomotor poverty becomes more sharply delineated and dominant within the overall structure of psychopathology, and its prominence is predicted enduringly by DUP.

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 'Knockout'.

Congenic (10 backcrosses into C57BL/6J) mutants with targeted gene deletion of DARPP-32, a neuronal phosphoprotein regarded as an essential mediator of the biological effects of dopamine (DA), were assessed phenotypically using an ethologically based approach that resolves all topographies of behavior in the mouse repertoire. Over initial exploration, female, but not male, DARPP-32 mutants evidenced increased locomotion and decreased grooming, while a decrease in rearing seated was evident in mutants of both genders; continuing assessment over several hours did not reveal additional phenotypic effects. Following challenge with the nonselective DA receptor agonist apomorphine, low doses were associated with reduced levels of sniffing, grooming, total rearing, and rearing seated in DARPP-32 mutants relative to wildtypes; this would suggest some role for DARPP-32 in mediating the biological effects of presynaptic D(2)-like autoreceptor or inhibitory postsynaptic D(2)-like receptor activation. Following challenge with higher doses, while stereotyped sniffing and locomotion with chewing was largely unaltered, the additional murine response of Straub tail was essentially abolished in DARPP-32 mutants, indicating some specific involvement of DARPP-32 in mediating this topography of behavior; additionally, there were overall reductions in levels of sniffing, total rearing, rearing seated, and grooming in DARPP-32 mutants that were unrelated to the dose of apomorphine administered, indicating broader topographical effects following the stress of the injection procedure relative to more naturalistic conditions. The developmental absence of DARPP-32 following targeted gene deletion appears to be associated with compensatory processes that maintain certain topographies of spontaneous and agonist-induced DAergic function, while other topographies remain impaired.

First-episode schizophrenia, bipolar disorder and other psychoses in a rural Irish catchment area: incidence and gender in the Cavan-Monaghan study at 5 years.

BACKGROUND: The potential of first-episode studies in schizophrenia is maximised through systematic epidemiological, clinical and biological comparisons between homogeneous populations of the psychoses. AIMS: To conduct prolonged accrual of 'all' cases of non-affective and affective psychotic illness on an epidemiologically complete basis. METHOD: Within the region covered by Cavan-Monaghan psychiatric service (population 102,810), all putative cases of first-episode psychosis were diagnosed using DSM-IV. RESULTS: From 1995 to 2000, 69 cases of psychosis were ascertained, the incidence being 2.3-fold lower in females than in males. On resolving the 'core' diagnoses of schizophrenia and bipolar disorder, incidence of schizophrenia among women was 7.5-fold lower than among men whereas incidence of bipolar disorder among women was 6.6-fold lower than among men. CONCLUSIONS: This homogeneous population, which eliminates factors associated with urbanicity and minimises confounding factors such as socioeconomic, ethnic and geographical diversity, shows a markedly reduced incidence among females both of schizophrenia and of bipolar disorder.