Risk of first-episode psychosis in migrants to the Republic of Ireland.

BACKGROUND: Migration is an established risk factor for developing a psychotic disorder in countries with a long history of migration. Less is known for countries with only a recent history of migration. This study aimed to determine the risk for developing a psychotic disorder in migrants to the Republic of Ireland. METHODS: We included all presentations of first-episode psychosis over 8.5 years to the DETECT Early Intervention for psychosis service in the Republic of Ireland (573 individuals aged 18-65, of whom 22% were first-generation migrants). Psychotic disorder diagnosis relied on SCID. The at-risk population was calculated using census data, and negative binomial regression was used to estimate incidence rate ratios. RESULTS: The annual crude incidence rate for a first-episode psychotic disorder in the total cohort was 25.62 per 100000 population at risk. Migrants from Africa had a nearly twofold increased risk for developing a psychotic disorder compared to those born in the Republic of Ireland (IRR = 1.83, 95% CI 1.11-3.02, p = 0.02). In contrast, migrants from certain Asian countries had a reduced risk, specifically those from China, India, Philippines, Pakistan, Malaysia, Bangladesh and Hong Kong (aIRR = 0.36, 95% CI 0.16-0.81, p = 0.01). CONCLUSIONS: Further research into the reasons for this inflated risk in specific migrant groups could produce insights into the aetiology of psychotic disorders. This information should also be used, alongside other data on environmental risk factors that can be determined from census data, to predict the incidence of psychotic disorders and thereby resource services appropriately.

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.

Cadexomer iodine effectively reduces bacterial biofilm in porcine wounds ex vivo and in vivo.

Biofilms are prevalent in non-healing chronic wounds and implicated in delayed healing. Tolerance to antimicrobial treatments and the host's immune system leave clinicians with limited interventions against biofilm populations. It is therefore essential that effective treatments be rigorously tested and demonstrate an impact on biofilm across multiple experimental models to guide clinical investigations and protocols. Cadexomer iodine has previously been shown to be effective against biofilm in various in vitro models, against methicillin-resistant Staphylococcus aureus biofilm in mouse wounds, and clinically in diabetic foot ulcers complicated by biofilm. Similarities between porcine and human skin make the pig a favoured model for cutaneous wound studies. Two antiseptic dressings and a gauze control were assessed against mature biofilm grown on ex vivo pig skin and in a pig wound model. Significant reductions in biofilm were observed following treatment with cadexomer iodine across both biofilm models. In contrast, silver carboxymethylcellulose dressings had minimal impact on biofilm in the models, with similar results to the control in the ex vivo model. Microscopy and histopathology indicate that the depth of organisms in wound tissue may impact treatment effectiveness. Further work on the promising biofilm efficacy of cadexomer iodine is needed to determine optimal treatment durations against biofilm.

Cadexomer iodine provides superior efficacy against bacterial wound biofilms in vitro and in vivo.

Examination of clinical samples indicates bacterial biofilms are present in the majority of chronic wounds, and substantial evidence suggests biofilms contribute significantly to delayed healing. Bacteria in biofilms are highly tolerant of antimicrobials, and little data exist to guide the choice of anti-biofilm wound therapy. Cadexomer iodine (CI) was recently reported to have superior efficacy compared to diverse wound dressings against Pseudomonas aeruginosa biofilms in an ex vivo model. In the current study, the strong performance of CI vs. P. aeruginosa biofilm was confirmed using colony and colony drip-flow in vitro wound biofilm models. Similar in vitro efficacy of CI was also demonstrated against mature Staphylococcus aureus biofilms using the same models. Additionally, the rapid kill of mature S. aureus and P. aeruginosa colony biofilms was visualized by confocal microscopy using Live/Dead fluorescent stains. Superior in vitro efficacy of CI vs. staphylococcal biofilms was further demonstrated against methicillin-resistant S. aureus (MRSA) using multiple biofilm models with log reduction, Live/Dead, and metabolic endpoints. Comparator antimicrobial dressings, including silver-based dressings used throughout and other active agents used in individual models, elucidated only limited effects against the mature biofilms. Given the promising in vitro activity, CI was tested in an established mouse model of MRSA wound biofilm. CI had significantly greater impact on MRSA biofilm in mouse wounds than silver dressings or mupirocin based on Gram-stained histology sections and quantitative microbiology from biopsy samples (>4 log reduction in CFU/g vs. 0.7-1.6, p < 0.0001). The superior efficacy for CI in these in vitro and in vivo models suggests CI topical products may represent a better choice to address established bacterial biofilm in chronic wounds.

Neighbourhood level social deprivation and the risk of psychotic disorders: a systematic review.

PURPOSE: The incidence of psychotic disorders varies according to the geographical area, and it has been investigated whether neighbourhood level factors may be associated with this variation. The aim of this systematic review is to collate and appraise the literature on the association between social deprivation and the incidence or risk for psychotic disorders. METHOD: A systematic review was conducted, and studies were included if they were in English, provided a measure of social deprivation for more than one geographically defined area and examined either the correlation, rate ratio or risk of psychotic disorder. A defined search strategy was undertaken with Medline, CINAHL Plus and PsychInfo databases. RESULTS: A total of 409 studies were identified in the search, of which 28 fulfilled the inclusion criteria. Of these, four examined the association between social deprivation at the time of birth, three examined the putative prodrome of psychosis or those at ultra-high risk (UHR) for psychosis, and 23 examined the time at presentation with a first episode of psychosis (FEP) (one study examined two time points and one study included both UHR and FEP). Three of the studies that examined the level of social deprivation at birth found an association with a higher risk for psychotic disorders and increased social deprivation. Seventeen of the 23 studies found that there was a higher risk or rate of psychotic disorders in more deprived neighbourhoods at the time of presentation; however, adjusting for individual factors tended to weaken this association. Limited research has been conducted in the putative prodromal stage and has resulted in conflicting findings. CONCLUSIONS: Research conducted to date has not definitively identified whether the association is a result of social causation or social drift; however, the findings do have significant implications for service provision, such as the location and access of services.

The therapeutic relationship after psychiatric admission.

The therapeutic relationship is one of the most central and important factors in the treatment of mental health disorders. A better therapeutic relationship is associated with service engagement, medication adherence, and satisfaction with services. This study aimed to compare the demographic and clinical factors associated with the therapeutic relationship in voluntarily and involuntarily admitted psychiatric service users. We found that individuals who had been admitted involuntarily, who had a diagnosis of a psychotic disorder, and who reported higher levels of perceived pressures on admission were more likely to have a poorer therapeutic relationship with their consultant psychiatrist. Greater levels of insight and treatment satisfaction, together with higher levels of procedural justice experienced on admission, were associated with a better therapeutic relationship. We found that the level of perceived coercion on admission was not related to the therapeutic relationship. Targeted interventions to improve the therapeutic relationship, particularly for involuntarily admitted service users, are discussed.

Satisfaction with services following voluntary and involuntary admission.

BACKGROUND: Service user perspectives are essential for the evaluation and development of mental health services. Service users expressing less satisfaction with services subsequently have poorer treatment outcomes. AIMS: To measure satisfaction with services following psychiatric admission, and to explore its relationship with a number of clinical and service factors. METHODS: A multi-centre observational study was conducted across three mental health services in Ireland. Service users were interviewed and provided with self-report questionnaires. The Client Satisfaction Questionnaire (CSQ-8) was used to measure treatment satisfaction. RESULTS: The overall level of satisfaction with services was good (CSQ-8 mean score 24.5). Service users who were admitted involuntarily, who experienced physical coercion and lower levels of procedural justice were less satisfied. A better therapeutic relationship, improved insight and better functioning were associated with higher levels of treatment satisfaction. CONCLUSION: Mental health services should implement strategies to ameliorate the effects of factors associated with lower levels of treatment satisfaction.

Payment of research participants: current practice and policies of Irish research ethics committees.

BACKGROUND: Payment of research participants helps to increase recruitment for research studies, but can pose ethical dilemmas. Research ethics committees (RECs) have a centrally important role in guiding this practice, but standardisation of the ethical approval process in Ireland is lacking. AIM: Our aim was to examine REC policies, experiences and concerns with respect to the payment of participants in research projects in Ireland. METHOD: Postal survey of all RECs in Ireland. RESULTS: Response rate was 62.5% (n=50). 80% of RECs reported not to have any established policy on the payment of research subjects while 20% had refused ethics approval to studies because the investigators proposed to pay research participants. The most commonly cited concerns were the potential for inducement and undermining of voluntary consent. CONCLUSIONS: There is considerable variability among RECs on the payment of research participants and a lack of clear consensus guidelines on the subject. The development of standardised guidelines on the payment of research subjects may enhance recruitment of research participants.

Outcomes 1 year after a first episode of psychosis in migrants to the Republic of Ireland.

BACKGROUND: Migration is a robust risk factor for developing a psychotic disorder, yet there is a paucity of research on the outcomes of migrants who develop a psychotic disorder. Identifying sub-groups within FEP cohorts who have a poorer outcome, could assist in the development and delivery of more targeted interventions. AIMS: There is a paucity of research on the outcomes of migrants who develop a psychotic disorder. This study aimed to evaluate a broad range of outcomes for those with a FEP who migrated to the Republic of Ireland, including: (i) symptomatic; (ii) functional; (iii) hospitalisation and (iv) engagement with psychosocial services. METHODS: All individuals with a FEP aged 18 to 65 who presented between 01.02.2006 and 01.07.2014 were included. Structured and validated instruments were used to measure positive, negative, depressive symptoms and insight. RESULTS: Of the 573 individuals with a FEP, 22.3% were first-generation migrants and 63.4% (n = 363) were followed up at 1 year. At this time, 72.4% of migrants were in remission of positive psychotic symptoms compared to 78.5% of the Irish born (OR = 0.84, 95% CI [0.50-1.41], p = .51). In relation to negative symptoms, 60.5% of migrants were in remission compared to 67.2% of the Irish born (OR = 0.75, 95% CI [0.44-1.27], p = .283). There was no difference in the severity of positive, negative or depressive symptoms between groups and there was a trend for the Irish born to have better insight (p = .056). The functional outcomes were similar across groups. One third of migrants were admitted to hospital compared to 28.7% of the Irish born (OR = 1.24, 95% CI [0.73-2.13], p = .426). Just over half of both groups attended CBT and 46.2% of caregivers for migrants attended the psychoeducation programme, compared to 39.7% for the Irish born (OR = 1.30, 95% CI [0.79-2.16], p = .306). CONCLUSIONS: These findings demonstrate that migrants have broadly similar outcomes to the native-born populations, however there is still considerable scope for the outcomes for all individuals affected by psychotic disorders to be improved.

A model for evaluating topical antimicrobial efficacy against methicillin-resistant Staphylococcus aureus biofilms in superficial murine wounds.

A wound biofilm model was created by adapting a superficial infection model. Partial-thickness murine wounds were inoculated with methicillin-resistant Staphylococcus aureus (MRSA). Dense biofilm communities developed at the wound surface after 24 h as demonstrated by microscopy and quantitative microbiology. Common topical antimicrobial agents had reduced efficacy when treatment was initiated 24 h after inoculation compared to 4 h after inoculation. This model provides a rapid in vivo test for new agents to treat wound biofilm infections.

Increasing the presence of biofilm and healing delay in a porcine model of MRSA-infected wounds.

Data supporting the concept that microbial biofilms are a major cause of non-healing ulcers remain limited. A porcine model was established where delayed healing resulted from methicillin-resistant Staphylococcus aureus (MRSA) infection in full-thickness wounds. At the end of one study a wound remaining open was sampled and a MRSA strain was isolated. This pig-passaged strain was used as the inoculating strain in several subsequent studies. The resulting MRSA wound infections exhibited a greater, more stable tissue bioburden than seen in studies using the parent strain. Furthermore, wounds infected with the passaged strain experienced a greater delay in healing. To understand whether these changes corresponded to an increased biofilm character of the wound infection, wound biopsy samples from studies using either the parent or passaged MRSA strains were examined microscopically. Evidence of biofilm was observed for both strains, as most samples at a minimum had multiple isolated, dense microcolonies of bacteria. However, the passaged MRSA resulted in bacterial colonies of greater frequency and size that occurred more often in concatenated fashion to generate extended sections of biofilm. These results provide a model case in which increasing biofilm character of a wound infection corresponded with a greater delay in wound healing.

Audit of thrice- versus twice-weekly ECT.

BACKGROUND: There is a lack of knowledge regarding some basic differences between different electroconvulsive therapy (ECT) treatment schedules. OBJECTIVES: To examine differences, including ECT technical parameters and length of stay, between thrice- and twice-weekly ECT treatment schedules. METHODS: Prospective audit of the changeover period of administering thrice- to twice-weekly ECT in a Dublin psychiatric hospital. RESULTS: Twice-weekly ECT was associated with significantly lower total electricity dosage administered, a tendency toward shorter overall hospital stay and fewer ECT treatments compared to thrice-weekly ECT. CONCLUSIONS: Our results support the current international trend toward giving ECT twice weekly.

Sarcoid-like granulomatosis and testicular germ cell tumor: the 'Great Imitator'.

OBJECTIVES: Only a few case reports and small case series of patients with sarcoidosis or sarcoid-like reaction and testicular germ cell tumors (GCT) have been reported in the literature. We performed a retrospective study of patients with testicular GCT managed at the Centre Léon-Bérard, who presented granulomatosis. METHODS: We performed a computerized search to identify all male patients with both a diagnosis of sarcoidosis or granuloma and testicular tumors seen at the Centre Léon-Bérard between 1992 and 2008. RESULTS: A total of 13 patients were identified among the 1,182 patients with testicular tumors. The median age at diagnosis of testicular GCT was 25.5 years. Six patients had stage I disease, 2 patients had stage IIb and 5 patients had stage III. Sarcoid-like granulomatosis was found in 9 patients at the time of initial diagnosis and in 4 patients during follow-up. Sarcoidosis presented mainly as pulmonary disease without severe organ involvement, with a benign evolution. CONCLUSION: We advise caution in the interpretation of clinical and histological findings in these patients. Sarcoid-like granulomatosis, a condition that can be combined with testicular cancer, should always be considered in the differential diagnosis of metastatic testicular tumors.

Pleural metastasis of atypical meningioma: a novel therapeutic approach.

Meningiomas are the most common intracranial tumours in adults and they are infrequently associated with a metastasis clinical course. Pleural metastases are extremely rare and no guidelines on a specific treatment have been established. When localized, surgical resection is the mainstay of treatment, but there is a high risk of pleural recurrence. We aimed to describe a novel surgical approach in pleural metastasis of meningiomas. We report the case of a 41-year-old man with the medical history of surgically resected intracranial atypical meningioma. Nine years after diagnosis of atypical meningioma, a CT scan of the chest disclosed 10 pleural implants gathered in the fissure, in the paramediastinal pleura and at the base of the left hemithorax. Surgical resection was decided. Parietal and mediastinal pleura resection with visceral pleural lesions removal were performed. Cytoreductive surgery was associated with intrathoracic hyperthermic chemotherapy. Postoperative course was uneventful and no adjuvant therapy was undertaken. The patient is free of pleural recurrence 12 months post operatively. The present case report suggests that cytoreductive surgery with intrathoracic hyperthermic chemotherapy is feasible and safe in pleural metastasis from meningioma. Prolonged follow-up and prospective studies are mandatory to assess its oncological benefit.

[Lung metastases of epithelioid sarcoma revealed by bilateral spontaneous pneumothorax: a pathological diagnosis]. / Métastases pulmonaires d'un sarcome épithélioïde révélées par un pneumothorax spontané bilatéral : un diagnostic anatomopathologique exclusif.

Spontaneous pneumothorax may be one of the presenting manifestation of metastatic epithelioid sarcoma even if imaging does not show evident metastatic nodules. We report the case of a 24-year-old man presenting a bilateral spontaneous pneumothorax in association with an epithelioid sarcoma developed in the right foot. CT-scan revealed bilateral microcystic lesions with no evidence of metastatic disease. A left thoracoscopy and a pleurodesis were performed. Persistent air leakage led to a thoracotomy during which lung biopsies were carried out. Histopathological examination of the pulmonary biopsies revealed rare millimetric nodules, composed of very atypical epithelioid cells, growing along alveolar walls reminiscent of a bronchiolo-alveolar carcinoma. However, these cells and primary neoplastic cells of the foot tumour were morphologically and immunohistochemically similar and the atypical pulmonary cells were TTF1 negative. All these constatations allowed a diagnosis of pulmonary metastases of the epithelioid sarcoma. This very unusual case underlines that sarcomatous metastases may be a clinical and pathological pitfall.

Higher rates of disengagement among young adults attending a general adult community mental health team: Time to consider a youth-specific service?

AIM: The initial onset of mental illness occurs most frequently in adolescence or early adulthood. In order to inform the development of mental health services tailored for youth, we sought to compare the characteristics of young (18-25 years old) and older (over 25 years old) adults following referral to a general adult community mental health team. METHODS: All individuals referred to a Dublin-based community mental health team and offered an appointment between January 1 and December 31, 2016 were included in the study. Information in relation to engagement patterns, demographic characteristics and clinical characteristics was collected. RESULTS: A total of 298 appointments were offered during the study period among which 94 (31.6%) were for young adults. Significant differences in demographic and clinical characteristics between the two age groups were evident. Young adults were significantly less likely to have been prescribed psychotropic medication at the point of referral (63% vs. 82% respectively, χ2 = 12.30, p < .001). Older adults were four times more likely to demonstrate a good level of early engagement in treatment than young adults (AOR 4.00, 95% CI 1.11-14.37, p = .03). CONCLUSIONS: Young adults had distinct clinical needs and a lower level of engagement in the early stage of treatment compared with their older counterparts in this community team. Further research and stakeholder consultation is needed to more clearly identify the issues in relation to patient engagement. These insights will help to inform the development of youth-specific community mental health services.

Enzymatic Debridement of Porcine Burn Wounds via a Novel Protease, SN514.

Necrotic tissue generated by a thermal injury is typically removed via surgical debridement. However, this procedure is commonly associated with blood loss and the removal of viable healthy tissue. For some patients and contexts such as extended care on the battlefield, it would be preferable to remove devitalized tissue with a nonsurgical debridement agent. In this paper, a proprietary debridement gel (SN514) was evaluated for the ability to debride both deep-partial thickness (DPT) and full-thickness burn wounds using an established porcine thermal injury model. Burn wounds were treated daily for 4 days and visualized with both digital imaging and laser speckle imaging. Strip biopsies were taken at the end of the procedure. Histological analyses confirmed a greater debridement of the porcine burn wounds by SN514 than the vehicle-treated controls. Laser speckle imaging detected significant increases in the perfusion status after 4 days of SN514 treatment on DPT wounds. Importantly, histological analyses and clinical observations suggest that SN514 gel treatment did not damage uninjured tissue as no edema, erythema, or inflammation was observed on intact skin surrounding the treated wounds. A blinded evaluation of the digital images by a burn surgeon indicated that SN514 debrided more necrotic tissue than the control groups after 1, 2, and 3 days of treatment. Additionally, SN514 gel was evaluated using an in vitro burn model that used human discarded skin. Treatment of human burned tissue with SN514 gel resulted in greater than 80% weight reduction compared with untreated samples. Together, these data demonstrate that SN514 gel is capable of debriding necrotic tissue and suggest that SN514 gel could be a useful option for austere conditions, such as military multi-domain operations and prolonged field care scenarios.

In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: microbiology profiling studies with staphylococci and streptococci.

We present data from antimicrobial assays performed in vitro that pertain to the potential clinical utility of a novel rifamycin-quinolone hybrid antibiotic, CBR-2092, for the treatment of infections mediated by gram-positive cocci. The MIC(90)s for CBR-2092 against 300 clinical isolates of staphylococci and streptococci ranged from 0.008 to 0.5 mug/ml. Against Staphylococcus aureus, CBR-2092 exhibited prolonged postantibiotic effects (PAEs) and sub-MIC effects (SMEs), with values of 3.2, 6.5, and >8.5 h determined for the PAE (3x MIC), SME (0.12x MIC), and PAE-SME (3x MIC/0.12x MIC) periods, respectively. Studies of genetically defined mutants of S. aureus indicate that CBR-2092 is not a substrate for the NorA or MepA efflux pumps. In minimal bactericidal concentration and time-kill studies, CBR-2092 exhibited bactericidal activity against staphylococci that was retained against rifampin- or intermediate quinolone-resistant strains, with apparent paradoxical cidal characteristics against rifampin-resistant strains. In spontaneous resistance studies, CBR-2092 exhibited activity consistent with balanced contributions from its composite pharmacophores, with a mutant prevention concentration of 0.12 mug/ml and a resistance frequency of <10(-12) determined at 1 mug/ml in agar for S. aureus. Similarly, CBR-2092 suppressed the emergence of preexisting rifamycin resistance in time-kill studies undertaken at a high cell density. In studies of the intracellular killing of S. aureus, CBR-2092 exhibited prolonged bactericidal activity that was superior to the activities of moxifloxacin, rifampin, and a cocktail of moxifloxacin and rifampin. Overall, CBR-2092 exhibited promising activity in a range of antimicrobial assays performed in vitro that pertain to properties relevant to the effective treatment of serious infections mediated by gram-positive cocci.

In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus.

Rifamycins have proven efficacy in the treatment of persistent bacterial infections. However, the frequency with which bacteria develop resistance to rifamycin agents restricts their clinical use to antibiotic combination regimens. In a program directed toward the synthesis of rifamycins with a lower propensity to elicit resistance development, a series of compounds were prepared that covalently combine rifamycin and quinolone pharmacophores to form stable hybrid antibacterial agents. We describe mode-of-action studies with Staphylococcus aureus of CBR-2092, a novel hybrid that combines the rifamycin SV and 4H-4-oxo-quinolizine pharmacophores. In biochemical studies, CBR-2092 exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant. Macromolecular biosynthesis studies confirmed that CBR-2092 has rifampin-like effects on RNA synthesis in rifampin-susceptible strains and quinolone-like effects on DNA synthesis in rifampin-resistant strains. Studies of mutant strains that exhibited reduced susceptibility to CBR-2092 further substantiated RNA polymerase as the primary cellular target of CBR-2092, with DNA gyrase and DNA topoisomerase IV being secondary and tertiary targets, respectively, in strains exhibiting preexisting rifampin resistance. In contrast to quinolone comparator agents, no strains with altered susceptibility to CBR-2092 were found to exhibit changes consistent with altered efflux properties. The combined data indicate that CBR-2092 may have potential utility in monotherapy for the treatment of persistent S. aureus infections.

Negative symptoms of psychosis: A life course approach and implications for prevention and treatment.

AIM: Negative symptoms are a cause of enduring disability in serious mental illness. In spite of this, the development of effective treatments for negative symptoms has remained slow. The challenge of improving negative symptom outcomes is compounded by our limited understanding of their aetiology and longitudinal development. METHODS: A literature search was conducted for life course approach of negative symptoms using PubMed. Further articles were included following manual checking of reference lists and other search strategies. The paper contains a theoretical synthesis of the literature, summarized using conceptual models. RESULTS: Negative symptom definitions are compared and considered within a context of the life course. Previous studies suggest that several illness phases may contribute to negative symptoms, highlighting our uncertainty in relation to the origin of negative symptoms. CONCLUSIONS: Similar to other aspects of schizophrenia, negative symptoms likely involve a complex interplay of several risk and protective factors at different life phases. Concepts suggested in this article, such as "negative symptom reserve" theory, require further research, which may inform future prevention and treatment strategies.