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1.  Disease Biomarkers in Cerebrospinal Fluid of Patients with First-Onset Psychosis 
PLoS Medicine  2006;3(11):e428.
Background
Psychosis is a severe mental condition that is characterized by a loss of contact with reality and is typically associated with hallucinations and delusional beliefs. There are numerous psychiatric conditions that present with psychotic symptoms, most importantly schizophrenia, bipolar affective disorder, and some forms of severe depression referred to as psychotic depression. The pathological mechanisms resulting in psychotic symptoms are not understood, nor is it understood whether the various psychotic illnesses are the result of similar biochemical disturbances. The identification of biological markers (so-called biomarkers) of psychosis is a fundamental step towards a better understanding of the pathogenesis of psychosis and holds the potential for more objective testing methods.
Methods and Findings
Surface-enhanced laser desorption ionization mass spectrometry was employed to profile proteins and peptides in a total of 179 cerebrospinal fluid samples (58 schizophrenia patients, 16 patients with depression, five patients with obsessive-compulsive disorder, ten patients with Alzheimer disease, and 90 controls). Our results show a highly significant differential distribution of samples from healthy volunteers away from drug-naïve patients with first-onset paranoid schizophrenia. The key alterations were the up-regulation of a 40-amino acid VGF-derived peptide, the down-regulation of transthyretin at ~4 kDa, and a peptide cluster at ~6,800–7,300 Da (which is likely to be influenced by the doubly charged ions of the transthyretin protein cluster). These schizophrenia-specific protein/peptide changes were replicated in an independent sample set. Both experiments achieved a specificity of 95% and a sensitivity of 80% or 88% in the initial study and in a subsequent validation study, respectively.
Conclusions
Our results suggest that the application of modern proteomics techniques, particularly mass spectrometric approaches, holds the potential to advance the understanding of the biochemical basis of psychiatric disorders and may in turn allow for the development of diagnostics and improved therapeutics. Further studies are required to validate the clinical effectiveness and disease specificity of the identified biomarkers.
Protein profiles from 179 cerebrospinal fluid samples yield differences between patients with psychotic disorders and healthy volunteers, suggesting that such biomarkers could assist in the early diagnosis of mental illness.
Editors' Summary
Background.
Psychosis is an abnormal mental state characterized by loss of contact with reality, often associated with hallucinations, delusions, personality changes, and disorganized thinking. Psychotic symptoms occur in several psychiatric disorders, including schizophrenia, bipolar disorder, and psychotic depression. It is not clear what the underlying biological abnormalities in the brain are, and whether they are the same for the different psychotic illnesses. The hope is that recent advances in brain imaging and systematic characterization of genetic activity and protein composition in the brain might help to shed light on mental diseases, eventually leading to better diagnosis, treatment, and possibly even prevention.
Why Was This Study Done?
This study was carried out in order to search for biomarkers for psychosis and schizophrenia by comparing the protein composition in the cerebrospinal fluid (the clear body fluid that surrounds the brain and the spinal cord) of patients with different psychotic disorders and normal individuals who served as controls.
What Did the Researchers Do and Find?
The researchers used a technique called surface-enhanced laser desorption ionization mass spectrometry, which allows a comprehensive analysis of the protein composition of a particular sample, on a total of 179 cerebrospinal fluid samples. The samples came from 90 individuals without mental illness who served as controls, 58 people with schizophrenia who were very recently diagnosed and had not yet taken any medication, 16 patients with depression, five patients with obsessive-compulsive disorder, and ten patients with Alzheimer disease. All of the patients gave their informed consent to participate in the study. The researchers found that samples from treatment-naïve schizophrenic patients had a number of characteristic changes compared with samples from control individuals, and that those changes were not found in the patients with other mental illnesses. The researchers then wanted to test whether they would see the same pattern in a separate set of patients with schizophrenia versus controls, which turned out to be the case. Two of the changes in the cerebrospinal fluid that were associated with schizophrenia, namely higher levels of parts of a protein called VGF and lower levels of a protein called transthyretin, were also found in post-mortem brain samples of patients with schizophrenia compared with samples from controls. Lower levels of transthyretin were also found in serum (blood) of first-onset drug naïve schizophrenia patients.
What Do These Findings Mean?
These results suggest that this approach has the potential to find biomarkers for psychosis and, possibly, schizophrenia that might help in the understanding of the molecular basis for these conditions. If shown, in future studies, to be directly involved in causing the disease symptoms, they would be important targets for treatment and prevention efforts, and might also be useful for diagnostic purposes. Overall, there are promising examples, such as this study, suggesting that new molecular techniques can yield fresh insights into psychiatric illnesses such as schizophrenia and other psychotic disorders. Additional studies are needed to confirm the findings presented here and to address many open questions, and would seem well justified given these results.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030428.
MedlinePlus entries on psychosis and schizophrenia
The National Alliance for Research on Schizophrenia and Depression
The National Alliance for the Mentally Ill
The Schizophrenia Society of Canada
Wikipedia entries on psychosis and schizophrenia (note that Wikipedia is an online encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0030428
PMCID: PMC1630717  PMID: 17090210
2.  Psychiatric disorders in 22q11.2 deletion syndrome are prevalent but undertreated 
Psychological medicine  2013;44(6):1267-1277.
Background
Chromosome 22q11.2 deletion syndrome (22q11DS) is a common genetic disorder with high rates of psychosis and other psychopathologies, but few studies discuss treatment. Our aim was to characterize the prevalence and treatment of major psychiatric illnesses in a well-characterized sample of individuals with 22q11DS.
Method
This was a cross-sectional study of 112 individuals aged 8 to 45 years with a confirmed diagnosis of 22q11DS. Each participant was administered a modified Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) and the Structured Interview for Prodromal Syndromes (SIPS). Phenotypes assessed were threshold and subthreshold psychosis, depression, mania, generalized and separation anxiety, obsessions/compulsions, inattention/hyperactivity and substance use. Histories of mental health care and current psychotropic treatment were obtained.
Results
Psychopathology was common, with 79% of individuals meeting diagnostic criteria for a disorder at the time of assessment. Diagnoses of psychosis were made in 11% of cases, attenuated positive symptom syndrome (APS) in 21%, and 47% experienced significant subthreshold symptoms. Peak occurrence of psychosis risk was during adolescence (62% of those aged 12–17 years). Criteria for a mood disorder were met by 14%, for anxiety disorder 34% and for attention deficit hyperactivity disorder (ADHD) 31%. Mental health care had been received by 63% of individuals in their lifetime, but only 40% continued therapy and 39% used psychotropics. Antipsychotics were used by 42% of participants with psychosis and none of the participants with APS. Half of those at risk for psychosis were receiving no mental health care.
Conclusions
Psychopathology is common in 22q11DS but is not adequately treated or clinically followed. Particular attention should be paid to subthreshold psychotic symptoms, especially in adolescents.
doi:10.1017/S0033291713001669
PMCID: PMC4461220  PMID: 24016317
22q11.2 deletion syndrome; psychopathology; psychosis; treatment
3.  Psychotic Illness in First-Time Mothers with No Previous Psychiatric Hospitalizations: A Population-Based Study 
PLoS Medicine  2009;6(2):e1000013.
Background
Psychotic illness following childbirth is a relatively rare but severe condition with unexplained etiology. The aim of this study was to investigate the impact of maternal background characteristics and obstetric factors on the risk of postpartum psychosis, specifically among mothers with no previous psychiatric hospitalizations.
Methods and Findings
We investigated incidence rates and potential maternal and obstetric risk factors of psychoses after childbirth in a national cohort of women who were first-time mothers from 1983 through 2000 (n = 745,596). Proportional hazard regression models were used to estimate relative risks of psychoses during and after the first 90 d postpartum, among mothers without any previous psychiatric hospitalization and among all mothers. Within 90 d after delivery, 892 women (1.2 per 1,000 births; 4.84 per 1,000 person-years) were hospitalized due to psychoses and 436 of these (0.6 per 1,000 births; 2.38 per 1,000 person-years) had not previously been hospitalized for any psychiatric disorder. During follow-up after the 90 d postpartum period, the corresponding incidence rates per 1,000 person-years were reduced to 0.65 for all women and 0.49 for women not previously hospitalized. During (but not after) the first 90 d postpartum the risk of psychoses among women without any previous psychiatric hospitalization was independently affected by: maternal age (35 y or older versus 19 y or younger; hazard ratio 2.4, 95% confidence interval [CI] 1.2 to 4.7); high birth weight (≥ 4,500 g; hazard ratio 0.3, 95% CI 0.1 to 1.0); and diabetes (hazard ratio 0).
Conclusions
The incidence of psychotic illness peaks immediately following a first childbirth, and almost 50% of the cases are women without any previous psychiatric hospitalization. High maternal age increases the risk while diabetes and high birth weight are associated with reduced risk of first-onset psychoses, distinctly during the postpartum period.
Unnur Valdimarsdóttir and colleagues studied the risk factors for psychiatric illness following childbirth and found that, for women who had never previously been hospitalized for a psychiatric illness, the risk of mental illness was greatly increased following childbirth.
Editors' Summary
Background.
The first cries of a new life echo around the delivery suite: this is a time of great joy for most women. Yet, in the following days and weeks (the postpartum period), up to 80% of new mothers experience some sort of mental disturbance. Usually, this is the “baby blues,” a normal reaction to childbirth that is characterized by short-lived mood swings or postnatal depression. However, about one in 1,000 women develop postpartum psychosis, a serious mental disorder that needs immediate medical attention. Postpartum psychosis usually develops suddenly in the first 2–3 weeks after delivery and, like other forms of psychosis, is characterized by a loss of contact with reality. Women with postpartum psychosis may have false ideas about current events and about themselves (delusions) and see and hear things that are not there (hallucinations). They sometimes stop eating or sleeping and may become anxious and agitated. In the worst cases, they can have suicidal thoughts or even threaten their baby's life. Treatment for postpartum psychosis includes antipsychotic drugs, counseling, and hospital admission if the woman is a danger to herself or others.
Why Was This Study Done?
Women with a personal or family history of psychosis have an increased risk of developing postpartum psychosis, but what causes this disorder is unknown. The rapid changes in hormone levels that occur after delivery are likely to be involved—but might social circumstances, stress, other illnesses, or the birth itself also affect whether a woman develops postpartum psychosis? If additional risk factors for postpartum psychosis could be identified, it might be possible to prevent some cases of this serious mental disorder. In this study, the researchers investigate the incidence rate (the rate at which new cases occur in a population) and risk factors for psychotic illnesses diagnosed among first-time mothers registered in the Swedish Medical Birth Registry between 1983 and 2000.
What Did the Researchers Do and Find?
The researchers identified three-quarters of a million first-time mothers and, from the Swedish Hospital Discharge Registry, found that 892 of these women (1.2 per 1,000 births) had been admitted to hospital because of psychosis within 90 days of giving birth. Put another way, the incidence rate of psychosis over the first 90 days postpartum in this population was 4.84 per 1,000 person-years. Almost half of the women who developed postpartum psychosis had not been previously admitted to hospital for any psychiatric disorder. Among this subset of women, the incidence rate of postpartum psychosis was highest during the first month after delivery but dropped to less than a tenth of this initial rate after 90 days postpartum. Furthermore, the risk of developing psychosis during the first 90 days postpartum (but not after) increased with age—women older than 35 years were more than twice as likely to develop psychosis than those aged 19 years or less—but was reduced in women who had large babies or who had diabetes. Many other factors (including smoking and not living with the infant's father) did not affect the risk of psychosis during the first 90 days postpartum in these women.
What Do These Findings Mean?
These findings indicate that the occurrence of psychotic illness severe enough to require hospitalization peaks shortly after giving birth for the first time, even in women with no previous psychiatric illness. Indeed, women with no history of mental disorders account for almost half the women admitted to hospital for postpartum psychosis, at least in Sweden. The timing of the peak of postpartum psychosis supports the idea that either giving birth or the hormonal changes that occur shortly after may trigger the development of psychosis, and the findings that maternal diabetes and high infant birth weight reduce the risk of postpartum psychosis whereas increasing maternal age increases the risk provide new clues about the causes of postpartum psychosis. Most importantly, however, these findings highlight the importance of carefully monitoring women for psychosis during the first month after delivery.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000013.
This paper is further discussed in a PLoS Medicine Perspective by Phillipa Hay
The MedlinePlus Encyclopedia contains a page on MedlinePlus encyclopedia psychosis (in English and Spanish); MedlinePlus also provides links to information on psychotic disorders
The UK National Health Service Direct Health encyclopedia has information on psychosis and on postnatal depression
Mental Health America has a fact sheet on postpartum disorders
doi:10.1371/journal.pmed.1000013
PMCID: PMC2637917  PMID: 19209952
4.  Psychotic symptoms and Gray Matter Deficits In Clinical Pediatric Populations 
Schizophrenia research  2012;140(1-3):149-154.
Background
Neuroanatomic studies have not yet addressed how subtle phenotypic distinctions in psychosis alter the underlying brain changes, and whether there is evidence for psychosis as a dimensional construct. We explored the relationship of cortical GM thickness to psychotic phenotypes in children.
Methods
Cross-sectional comparison of anatomic brain imaging between patients referred as childhood-onset schizophrenia (COS) but ruled out after a drug free inpatient observation. Groups included: patients with no evidence of psychosis (n=22) after drug free observation, patients with psychosis not otherwise specified (PNOS; total n=29) further divided into those without other axis I diagnoses (n=13) and those with other axis I comorbidities (n=16), age/sex matched COS patients (n=48), and 51 matched healthy controls. GM cortical thickness was compared between the groups, and regressed on patients’ SAPS, SANS and GAS scores.
Results
Patients with no evidence of psychosis showed no cortical GM deficits. Presence of psychosis (PNOS with or without co-morbidities) showed some areas of temporal and prefrontal deficits, more subtle compared to the extensive bilateral cortical deficits seen for COS. GAS SAPS and SANS scores showed a relationship with cortical GM thickness although it did not survive adjustment for multiple comparisons.
Conclusions
These results highlight the need for careful phenotypic characterization, as subtle diagnostic distinctions appear to reflect distinct underlying patterns of brain deficits. The incremental nature of cortical deficits from no psychosis to PNOS to COS may further support dimensional model for psychosis.
doi:10.1016/j.schres.2012.07.006
PMCID: PMC3448116  PMID: 22835806
adolescence; psychosis; brain imaging; schizophrenia; gray matter; pediatrics
5.  Hospital Admission With Infection During Childhood and Risk for Psychotic Illness—A Population-based Cohort Study 
Schizophrenia Bulletin  2013;40(6):1518-1525.
A growing body of literature suggests that exposure to infections, particularly maternal infections, during pregnancy confers risk for later development of psychotic disorder. Though brain development proceeds throughout childhood and adolescence, the influence of infections during these ages on subsequent psychosis risk is insufficiently examined. The aim of this study was to investigate the potential association between infections during childhood and nonaffective psychoses in a large population-based birth cohort with follow up long enough to include peak incidence of nonaffective psychosis. We included all individuals born in Sweden between 1973 and 1985, (N = 1172879), with follow up on first time inpatient care with nonaffective psychosis from age 14 years until 2006, (N = 4638). Following adjustment for differences in sex, socioeconomic status, family history of psychosis, and hospital admissions involving noninfectious, nonpsychiatric care, we observed a small but statistically significant association between hospital admissions for infections, in general, throughout childhood (0–13 years) and a later diagnosis of nonaffective psychosis, hazard ratio (HR) = 1.10 (95% CI 1.03–1.18), and this association seemed to be driven by bacterial infection, HR = 1.23 (95% CI 1.08–1.40). Bacterial infections and central nervous system infections during preadolescence (10–13 years) conferred the strongest risk, HR 1.57 (95% CI 1.21–2.05) and HR 1.96 (95% CI 1.05–3.62), respectively. Although preadolescence appeared to be a vulnerable age period, and bacterial infection the most severe in relation to psychosis development, the present findings can also indicate an increased susceptibility to hospital admission for infections among children who will later develop nonaffective psychosis due to social or familial/genetic factors.
doi:10.1093/schbul/sbt195
PMCID: PMC4193695  PMID: 24366719
psychosis; prenatal; schizophrenia;  epidemiology; cohort study
6.  The CCC2000 Birth Cohort Study of Register-Based Family History of Mental Disorders and Psychotic Experiences in Offspring 
Schizophrenia Bulletin  2014;41(5):1084-1094.
Psychotic experiences (PE) in individuals of the general population are hypothesized to mark the early expression of the pathology underlying psychosis. This notion of PE as an intermediate phenotype is based on the premise that PE share genetic liability with psychosis. We examined whether PE in childhood was predicted by a family history of mental disorder with psychosis rather than a family history of nonpsychotic mental disorder and whether this association differed by severity of PE. The study examined data on 1632 children from a general population birth cohort assessed at age 11–12 years by use of a semistructured interview covering 22 psychotic symptoms. The Danish national registers were linked to describe the complete family history of hospital-based psychiatric diagnoses. Uni- and multivariable logistic regressions were used to test whether a family history of any mental disorder with psychosis, or of nonpsychotic mental disorder, vs no diagnoses was associated with increased risk of PE in offspring (hierarchical exposure variable). The occurrence of PE in offspring was significantly associated with a history of psychosis among the first-degree relatives (adjusted relative risk [RR] = 3.29, 95% CI: 1.82–5.93). The risk increased for combined hallucinations and delusions (adjusted RR = 5.90, 95% CI: 2.64–13.16). A history of nonpsychotic mental disorders in first-degree relatives did not contribute to the risk of PE in offspring nor did any mental disorder among second-degree relatives. Our findings support the notion of PE as a vulnerability marker of transdiagnostic psychosis. The effect of psychosis in first-degree relatives may operate through shared genetic and environmental factors.
doi:10.1093/schbul/sbu167
PMCID: PMC4535626  PMID: 25452427
psychosis; schizophrenia; epidemiology; family liability; general population; psychiatric family history
7.  Predictors of Psychosis Remission in Psychotic Disorders That Co-occur With Substance Use 
Schizophrenia Bulletin  2006;32(4):618-625.
Objective: To examine rates and predictors of psychosis remission at 1-year follow-up for emergency admissions diagnosed with primary psychotic disorders and substance-induced psychoses. Method: A total of 319 patients with comorbid psychosis and substance use, representing 83% of the original referred sample, were rediagnosed at 1 year postintake employing a research diagnostic assessment. Remission of psychosis was defined as the absence of positive and negative symptoms for at least 6 months. Likelihood ratio chi-square tests and multivariate logistic regression were the main means of analysis. Results: Of those with a baseline diagnosis of primary psychotic disorder, 50% were in remission at 1 year postintake, while of those with a baseline diagnosis of substance-induced psychosis, 77% were in remission at this time point. Lower Positive and Negative Syndrome Scale (PANSS) symptom levels at baseline, better premorbid functioning, greater insight into psychosis, and a shorter duration of untreated psychosis predicted remission at 1 year in both diagnostic groups. No interaction effects of baseline predictors and diagnosis type were observed. A stepwise multivariate logistic regression holding baseline diagnosis constant revealed the duration of untreated psychosis (odds ratio [OR] = 0.97; 95% confidence interval [CI] = 0.95, 0.997), total PANSS score (OR = 0.98; 95% CI = 0.97, 0.987), Premorbid Adjustment Scale score (OR = 0.13; 95% CI = 0.02, 0.88), and Scale to Assess Unawareness of Mental Disorders unawareness score (OR = 0.84; 95% CI = 0.71, 0.993) as key predictors of psychosis remission. Conclusions: The association of better premorbid adjustment, a shorter duration of untreated psychosis, better insight into psychotic symptoms, and lower severity of psychotic symptoms with improved clinical outcome, reported previously in studies of schizophrenia, generalizes to psychosis remission in psychotic disorders that are substance induced.
doi:10.1093/schbul/sbl007
PMCID: PMC2632269  PMID: 16873441
primary psychosis; substance-induced psychosis; outcome
8.  A Review of Postpartum Psychosis 
Journal of women's health (2002)  2006;15(4):352-368.
Objective
The objective is to provide an overview of the clinical features, prognosis, differential diagnosis, evaluation, and treatment of postpartum psychosis.
Methods
The authors searched Medline (1966–2005), PsycInfo (1974–2005), Toxnet, and PubMed databases using the key words postpartum psychosis, depression, bipolar disorder, schizophrenia, organic psychosis, pharmacotherapy, psychotherapy, and electroconvulsive therapy. A clinical case is used to facilitate the discussion.
Results
The onset of puerperal psychosis occurs in the first 1–4 weeks after childbirth. The data suggest that postpartum psychosis is an overt presentation of bipolar disorder that is timed to coincide with tremendous hormonal shifts after delivery. The patient develops frank psychosis, cognitive impairment, and grossly disorganized behavior that represent a complete change from previous functioning. These perturbations, in combination with lapsed insight into her illness and symptoms, can lead to devastating consequences in which the safety and well-being of the affected mother and her offspring are jeopardized. Therefore, careful and repeated assessment of the mothers’ symptoms, safety, and functional capacity is imperative. Treatment is dictated by the underlying diagnosis, bipolar disorder, and guided by the symptom acuity, patient’s response to past treatments, drug tolerability, and breastfeeding preference. The somatic therapies include antimanic agents, atypical antipsychotic medications, and ECT. Estrogen prophylaxis remains purely investigational.
Conclusions
The rapid and accurate diagnosis of postpartum psychosis is essential to expedite appropriate treatment and to allow for quick, full recovery, prevention of future episodes, and reduction of risk to the mother and her children and family.
doi:10.1089/jwh.2006.15.352
PMCID: PMC3109493  PMID: 16724884
9.  Burden of mental disorders and unmet needs among street homeless people in Addis Ababa, Ethiopia 
BMC Medicine  2014;12:138.
Background
The impact of mental disorders among homeless people is likely to be substantial in low income countries because of underdeveloped social welfare and health systems. As a first step towards advocacy and provision of care, we conducted a study to determine the burden of psychotic disorders and associated unmet needs, as well as the prevalence of mental distress, suicidality, and alcohol use disorder among homeless people in Addis Ababa, the capital of Ethiopia.
Methods
A cross-sectional survey was conducted among street homeless adults. Trained community nurses screened for potential psychosis and administered standardized measures of mental distress, alcohol use disorder and suicidality. Psychiatric nurses then carried out confirmatory diagnostic interviews of psychosis and administered a locally adapted version of the Camberwell Assessment of Needs Short Appraisal Schedule.
Results
We assessed 217 street homeless adults, about 90% of whom had experienced some form of mental or alcohol use disorder: 41.0% had psychosis, 60.0% had hazardous or dependent alcohol use, and 14.8% reported attempting suicide in the previous month. Homeless people with psychosis had extensive unmet needs with 80% to 100% reporting unmet needs across 26 domains. Nearly 30% had physical disability (visual and sensory impairment and impaired mobility). Only 10.0% of those with psychosis had ever received treatment for their illness. Most had lived on the streets for over 2 years, and alcohol use disorder was positively associated with chronicity of homelessness.
Conclusion
Psychoses and other mental and behavioural disorders affect most people who are street homeless in Addis Ababa. Any programme to improve the condition of homeless people should include treatment for mental and alcohol use disorders. The findings have significant implications for advocacy and intervention programmes, particularly in similar low income settings.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-014-0138-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-014-0138-x
PMCID: PMC4147171  PMID: 25139042
Homelessness; Rooflessness; Mental illness; Severe mental disorder; Prevalence; Unmet needs; Low- and middle-income country; Ethiopia
10.  Schizophrenia and Violence: Systematic Review and Meta-Analysis 
PLoS Medicine  2009;6(8):e1000120.
Seena Fazel and colleagues investigate the association between schizophrenia and other psychoses and violence and violent offending, and show that the increased risk appears to be partly mediated by substance abuse comorbidity.
Background
Although expert opinion has asserted that there is an increased risk of violence in individuals with schizophrenia and other psychoses, there is substantial heterogeneity between studies reporting risk of violence, and uncertainty over the causes of this heterogeneity. We undertook a systematic review of studies that report on associations between violence and schizophrenia and other psychoses. In addition, we conducted a systematic review of investigations that reported on risk of homicide in individuals with schizophrenia and other psychoses.
Methods and Findings
Bibliographic databases and reference lists were searched from 1970 to February 2009 for studies that reported on risks of interpersonal violence and/or violent criminality in individuals with schizophrenia and other psychoses compared with general population samples. These data were meta-analysed and odds ratios (ORs) were pooled using random-effects models. Ten demographic and clinical variables were extracted from each study to test for any observed heterogeneity in the risk estimates. We identified 20 individual studies reporting data from 18,423 individuals with schizophrenia and other psychoses. In men, ORs for the comparison of violence in those with schizophrenia and other psychoses with those without mental disorders varied from 1 to 7 with substantial heterogeneity (I2 = 86%). In women, ORs ranged from 4 to 29 with substantial heterogeneity (I2 = 85%). The effect of comorbid substance abuse was marked with the random-effects ORs of 2.1 (95% confidence interval [CI] 1.7–2.7) without comorbidity, and an OR of 8.9 (95% CI 5.4–14.7) with comorbidity (p<0.001 on metaregression). Risk estimates of violence in individuals with substance abuse (but without psychosis) were similar to those in individuals with psychosis with substance abuse comorbidity, and higher than all studies with psychosis irrespective of comorbidity. Choice of outcome measure, whether the sample was diagnosed with schizophrenia or with nonschizophrenic psychoses, study location, or study period were not significantly associated with risk estimates on subgroup or metaregression analysis. Further research is necessary to establish whether longitudinal designs were associated with lower risk estimates. The risk for homicide was increased in individuals with psychosis (with and without comorbid substance abuse) compared with general population controls (random-effects OR = 19.5, 95% CI 14.7–25.8).
Conclusions
Schizophrenia and other psychoses are associated with violence and violent offending, particularly homicide. However, most of the excess risk appears to be mediated by substance abuse comorbidity. The risk in these patients with comorbidity is similar to that for substance abuse without psychosis. Public health strategies for violence reduction could consider focusing on the primary and secondary prevention of substance abuse.
Please see later in the article for Editors' Summary
Editors' Summary
Background
Schizophrenia is a lifelong, severe psychotic condition. One in 100 people will have at least one episode of schizophrenia during their lifetime. Symptoms include delusions (for example, patients believe that someone is plotting against them) and hallucinations (hearing or seeing things that are not there). In men, schizophrenia usually starts in the late teens or early 20s; women tend to develop schizophrenia a little later. The causes of schizophrenia include genetic predisposition, obstetric complications, illegal drug use (substance abuse), and experiencing traumatic life events. The condition can be treated with a combination of antipsychotic drugs and supportive therapy; hospitalization may be necessary in very serious cases to prevent self harm. Many people with schizophrenia improve sufficiently after treatment to lead satisfying lives although some patients need lifelong support and supervision.
Why Was This Study Done?
Some people believe that schizophrenia and other psychoses are associated with violence, a perception that is often reinforced by news reports and that contributes to the stigma associated with mental illness. However, mental health advocacy groups and many mental health clinicians argue that it is a myth that people with mental health problems are violent. Several large, population-based studies have examined this disputed relationship. But, although some studies found no increased risk of violence among patients with schizophrenia compared with the general population, others found a marked increase in violent offending in patients with schizophrenia. Here, the researchers try to resolve this variation (“heterogeneity”) in the conclusions reached in different studies by doing a systematic review (a study that uses predefined search criteria to identify all the research on a specific topic) and a meta-analysis (a statistical method for combining the results of several studies) of the literature on associations between violence and schizophrenia and other psychoses. They also explored the relationship between substance abuse and violence.
What Did the Researchers Do and Find?
By systematically searching bibliographic databases and reference lists, the researchers identified 20 studies that compared the risk of violence in people with schizophrenia and other psychoses and the risk of violence in the general population. They then used a “random effects model” (a statistical technique that allows for heterogeneity between studies) to investigate the association between schizophrenia and violence. For men with schizophrenia or other psychoses, the pooled odds ratio (OR) from the relevant studies (which showed moderate heterogeneity) was 4.7, which was reduced to 3.8 once adjustment was made for socio-economic factors. That is, a man with schizophrenia was four to five times as likely to commit a violent act as a man in the general population. For women, the equivalent pooled OR was 8.2 but there was a much greater variation between the ORs in the individual studies than in the studies that involved men. The researchers then used “meta-regression” to investigate the heterogeneity between the studies. This analysis suggested that none of the study characteristics examined apart from co-occurring substance abuse could have caused the variation between the studies. Importantly the authors found that risk estimates of violence in people with substance abuse but no psychosis were similar to those in people with substance abuse and psychosis and higher than those in people with psychosis alone. Finally, although people with schizophrenia were nearly 20 times more likely to have committed murder than people in the general population, only one in 300 people with schizophrenia had killed someone, a similar risk to that seen in people with substance abuse.
What Do These Findings Mean?
These findings indicate that schizophrenia and other psychoses are associated with violence but that the association is strongest in people with substance abuse and most of the excess risk of violence associated with schizophrenia and other psychoses is mediated by substance abuse. However, the increased risk in patients with comorbidity was similar to that in substance abuse without psychosis. A potential implication of this finding is that violence reduction strategies that focus on preventing substance abuse among both the general population and among people with psychoses might be more successful than strategies that solely target people with mental illnesses. However, the quality of the individual studies included in this meta-analysis limits the strength of its conclusions and more research into the association between schizophrenia, substance abuse, and violence would assist in clarifying how and if strategies for violence reduction are changed.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000120.
The US National Institute of Mental Health provides information about schizophrenia (in English and Spanish)
The UK National Health Service Choices Web site has information for patients and carers about schizophrenia
The MedlinePlus Encyclopedia has a page on schizophrenia; MedlinePlus provides links to other sources of information on schizophrenia and on psychotic disorders (in English and Spanish)
The Schizophrenia and Related Disorders Alliance of America provides information and support for people with schizophrenia and their families
The time to change Web site provides information about an English campaign to reduce the stigma associated with mental illness
The Schizophrenia Research Forum provides updated research news and commentaries for the scientific community
doi:10.1371/journal.pmed.1000120
PMCID: PMC2718581  PMID: 19668362
11.  Association of Serum Interleukin 6 and C-Reactive Protein in Childhood With Depression and Psychosis in Young Adult Life 
JAMA psychiatry  2014;71(10):1121-1128.
IMPORTANCE
Longitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear.
OBJECTIVE
To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis.
DESIGN, SETTING, AND PARTICIPANTS
The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospective general population birth cohort study based in Avon County, England. We have studied a subsample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessments.
MEASUREMENT OF EXPOSURE
Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years.
MAIN OUTCOMES AND MEASURES
Participants were assessed at age 18 years. Depression was measured using the Clinical Interview Schedule–Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ), thus allowing internal replication; psychotic experiences (PEs) and psychotic disorder were measured by a semistructured interview.
RESULTS
After adjusting for sex, age, body mass index, ethnicity, social class, past psychological and behavioral problems, and maternal postpartum depression, participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55; 95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner.
CONCLUSIONS AND RELEVANCE
Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood. Inflammatory pathways may provide important new intervention and prevention targets for these disorders. Inflammation might explain the high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia.
doi:10.1001/jamapsychiatry.2014.1332
PMCID: PMC4561502  PMID: 25133871
12.  Biological and psychosocial risk factors for psychotic major depression 
Aims
Few studies have investigated risk factors for psychotic major depression (PMD). We aimed to investigate the biological and psychosocial risk factors associated with PMD compared with other psychotic disorders.
Methods
Based on the aetiology and ethnicity in schizophrenia and other psychoses (ÆSOP) study, we used a case–control study to identify and recruit, at baseline and 10-year follow-up, all first episode cases of psychosis, presenting for the first time to specialist mental health services in defined catchment areas in the UK. Population-based controls were recruited from the same areas. Data were collected on: sociodemographics; social isolation; childhood adversity; life events; minor physical anomalies; and neurological soft signs.
Results
Living alone (aOR = 2.26, CI = 1.21–4.23), basic level qualification (aOR = 2.89, CI = 1.08–7.74), being unemployed (aOR = 2.12, CI = 1.13–3.96), having contact with friends less than monthly (aOR = 4.24, CI = 1.62–11.14), having no close confidants (aOR = 4.71, CI = 2.08–10.68), having experienced childhood adversity (aOR = 2.57, CI = 1.02–6.44), family history of mental illness (aOR = 10.68, CI = 5.06–22.52), family history of psychosis (aOR = 12.85, CI = 5.24–31.51), and having more neurological soft signs (aOR = 1.15, CI = 1.07–1.24) were all associated with a follow-up diagnosis of PMD and schizophrenia. Few variables associated with PMD were also associated with a diagnosis of bipolar disorder. Minor physical anomalies were associated with a follow-up diagnosis of schizophrenia and bipolar disorder, but not PMD.
Conclusions
Risk factors associated with PMD appear to overlap with those for schizophrenia, but less so for bipolar disorder. Future work on the differential aetiology of PMD, from other psychoses is needed to find the ‘specifier’ between PMD and other psychoses. Future research on aetiology in PMD, and perhaps other psychoses, should account for diagnostic change.
Electronic supplementary material
The online version of this article (doi:10.1007/s00127-015-1131-1) contains supplementary material, which is available to authorized users.
doi:10.1007/s00127-015-1131-1
PMCID: PMC4748002  PMID: 26520449
Depression; Epidemiology; Psychosis; Risk factors
13.  Diagnostic Stability of ICD/DSM First Episode Psychosis Diagnoses: Meta-analysis 
Schizophrenia Bulletin  2016;42(6):1395-1406.
Background:
Validity of current International Classification of Disease/Diagnostic and Statistical Manual of Mental Disorders (ICD/DSM) first episode psychosis diagnoses is essential in clinical practice, research, training and public health.
Method:
We provide a meta-analytical estimate of prospective diagnostic stability and instability in ICD-10 or DSM-IV first episode diagnoses of functional psychoses. Independent extraction by multiple observers. Random effect meta-analysis conducted with the “metaprop,” “metaninf,” “metafunnel,” “metabias,” and “metareg” packages of STATA13.1. Moderators were tested with meta-regression analyses. Heterogeneity was assessed with the I 2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and Egger’s test.
Findings:
42 studies and 45 samples were included, for a total of 14 484 first episode patients and an average follow-up of 4.5 years. Prospective diagnostic stability ranked: schizophrenia 0.90 (95% CI 0.85–0.95), affective spectrum psychoses 0.84 (95% CI 0.79–0.89), schizoaffective disorder 0.72 (95% CI 0.61–0.73), substance-induced psychotic disorder 0.66 (95% CI 0.51–0.81), delusional disorder 0.59 (95% CI 0.47–0.71), acute and transient psychotic disorder/brief psychotic disorder 0.56 (95% CI 0.62–0.60), psychosis not otherwise specified 0.36 (95% CI 0.27–0.45, schizophreniform disorder 0.29 (95% CI 0.22–0.38). Diagnostic stability within schizophrenia spectrum psychoses was 0.93 (95% CI 0.89–0.97); changes to affective spectrum psychoses were 0.05 (95% CI 0.01–0.08). About 0.10 (95% CI 0.05–0.15) of affective spectrum psychoses changed to schizophrenia spectrum psychosis. Across the other psychotic diagnoses there was high diagnostic instability, mostly to schizophrenia.
Interpretation:
There is meta-analytical evidence for high prospective diagnostic stability in schizophrenia spectrum and affective spectrum psychoses, with no significant ICD/DSM differences. These results may inform the development of new treatment guidelines for early psychosis and impact drug licensing from regulatory agencies.
doi:10.1093/schbul/sbw020
PMCID: PMC5049518  PMID: 26980142
schizophrenia; diagnostic stability; psychosis; ICD; DSM
14.  Psychosis 
Continuum : Lifelong Learning in Neurology  2015;21(3 Behavioral Neurology and Neuropsychiatry):715-736.
Purpose of Review:
Psychosis is a common and functionally disruptive symptom of many psychiatric, neurodevelopmental, neurologic, and medical conditions and an important target of evaluation and treatment in neurologic and psychiatric practice. The purpose of this review is to define psychosis, communicate recent changes to the classification of and criteria for primary psychotic disorders described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and summarize current evidence-based approaches to the evaluation and management of primary and secondary psychoses.
Recent Findings:
The DSM-5 classification of and criteria for primary psychotic disorders emphasize that these conditions occur along a spectrum, with schizoid (personality) disorder and schizophrenia defining its mild and severe ends, respectively. Psychosis is also identified as only one of several dimensions of neuropsychiatric disturbance in these disorders, with others encompassing abnormal psychomotor behaviors, negative symptoms, cognitive impairments, and emotional disturbances. This dimensional approach regards hallucinations and delusions as arising from neural systems subserving perception and information processing, thereby aligning the neurobiological framework used to describe and study such symptoms in primary psychotic disorders with those used to study psychosis associated with other neurologic conditions.
Summary:
This article provides practicing neurologists with updates on current approaches to the diagnosis, evaluation, and treatment of primary and secondary psychoses.
doi:10.1212/01.CON.0000466662.89908.e7
PMCID: PMC4455840  PMID: 26039850
15.  Psychiatric Disorders in Youth in Juvenile Detention 
Archives of general psychiatry  2002;59(12):1133-1143.
Background
Given the growth of juvenile detainee populations, epidemiologic data on their psychiatric disorders are increasingly important. Yet, there are few empirical studies. Until we have better epidemiologic data, we cannot know how best to use the system’s scarce mental health resources.
Methods
Using the Diagnostic Interview Schedule for Children (DISC 2.3), interviewers assessed a randomly selected, stratified sample of 1829 African American, non-Hispanic white, and Hispanic youth (1172 males, 657 females, ages 10–18) arrested and detained in Cook County, Illinois (which includes Chicago and surrounding suburbs). We present six-month prevalence estimates by demographic subgroups (gender, race/ethnicity, and age) for the following disorders: affective disorders (major depressive episode, dysthymia, manic episode), anxiety (panic, separation anxiety, overanxious, generalized anxiety, and obsessive-compulsive disorders), psychosis, attention deficit hyperactivity disorder (ADHD), disruptive behavior disorders (oppositional defiant disorder, conduct disorder) and substance use disorders (alcohol and drug).
Results
Nearly two thirds of males and nearly three quarters of females met diagnostic criteria for one or more psychiatric disorders. Excluding conduct disorder (common among detained youth), nearly 60% of males and over two thirds of females met diagnostic criteria and had diagnosis-specific impairment for one or more psychiatric disorders. One half of males and almost one half of females had a substance use disorder, and over 40% of males and females met criteria for disruptive behavior disorders. Affective disorders were also prevalent, especially among females; 20% of females met criteria for a major depressive episode. Rates of many disorders were higher among females, non-Hispanic whites, and older adolescents.
Conclusion
These results suggest substantial psychiatric morbidity among juvenile detainees. Youth with psychiatric disorders pose a challenge for the juvenile justice system and, after their release, for the larger mental health system.
PMCID: PMC2861992  PMID: 12470130
16.  Obsessions and Compulsions in the Community: Prevalence, Interference, Help-Seeking, Developmental Stability, and Co-Occurring Psychiatric Conditions 
The American journal of psychiatry  2009;166(3):10.1176/appi.ajp.2008.08071006.
Objective
It is unclear how many people in the community have obsessions and compulsions and associated levels of interference. It is also unknown what variables predict help-seeking for these symptoms, whether they are developmentally stable, and whether they increase the risk of mental disorders.
Method
The authors analyzed data from the prospective longitudinal Dunedin study of an unselected birth cohort. The presence of obsessions and compulsions and mental disorders was assessed using the Diagnostic Interview Schedule (DIS) at ages 11, 26, and 32. Data on interference and help-seeking were obtained at ages 26 and 32.
Results
Obsessions and compulsions were frequent in individuals with mental disorders other than obsessive-compulsive disorder (OCD) and among people without mental disorders. Even in the latter group, these symptoms caused significant interference. The presence of anxiety/depression and of obsessions (particularly aggressive and shameful thoughts), but not compulsions, was associated with help-seeking. Harm/checking was the most prevalent symptom dimension. Symptom dimensions were temporally stable and associated with increased comorbidity. Obsessive-compulsive symptoms at age 11 predicted a high risk of an adult OCD diagnosis as well as elevated adult symptom dimensions.
Conclusions
Obsessions and compulsions are common in the adult population, have their roots in childhood, and are associated with interference, risk for disorders, and help-seeking. Subclinical obsessions and compulsions should be taken into account in research, intervention, and DSM-V.
doi:10.1176/appi.ajp.2008.08071006
PMCID: PMC3818089  PMID: 19188283
17.  Is schizophrenia disappearing? The rise and fall of the diagnosis of functional psychoses: an essay 
BMC Psychiatry  2016;16:387.
Background
The categories of functional psychoses build on views of influential professionals. There have long been four main categories – affective, schizophrenic, schizoaffective/cycloid/reactive/polymorphic, and delusional/paranoid psychoses. The last three are included in “psychotic disorders”. However, this dichotomy and the distinctions between categories may have been over-estimated and contributed to lack of progress.
Ten topics relevant for the diagnosis of functional psychoses
1. The categories of functional psychoses have varied with time, place and professionals’ views, with moving boundaries, especially between schizophrenia and affective psychoses. 2. Catatonia is most often related to affective and organic psychoses, and paranoia is related to grandiosity and guilt, calling in question catatonic and paranoid schizophrenia. Arguments exist for schizophrenia being a “misdiagnosis”. 3. In some countries schizophrenia has been renamed, with positive consequences. 4. The doctrine of “unitary psychosis”, which included abnormal affect, was left in the second half of the 1800s. 5. This was followed by a dichotomy between schizophrenia and affective psychoses and broadening of the schizophrenia concept, whereas affective symptoms were strongly downgraded. 6. Many homogeneous psychoses with mixtures of schizophrenic and affective symptoms were described and related to “psychotic disorders”, although they might as well be affective disorders. 7. Critique of the extensive schizophrenia concept led to, in DSM-III and ICD-10, affective symptoms being exclusion criteria for schizophrenia and acceptance of mood-incongruent psychotic symptoms in affective psychoses. 8. However, affective symptoms are often difficult to acknowledge, diagnosis is often done on the basis of tradition and previous education, and patients’ affect characterized accordingly. 9. DSM-5 is up-dated with separate chapters for catatonia and psychotic symptoms, and removal of the subtypes of schizophrenia. However, time may be running out for categorical psychosis diagnoses, which may be replaced by continuum, spectrum, dimensional and research domain criteria, in line with new biological data 10. This is supported by treatment responses across categories.
Conclusion
The time-consuming works on diagnosis of psychoses may have hampered progress. Chronic mood disorders may appear as schizophrenic or paranoid psychosis, end-stages like heart failure in heart diseases. This underscores the importance of early and optimal treatment of mood disorders.
doi:10.1186/s12888-016-1101-5
PMCID: PMC5103459  PMID: 27829400
Schizophrenia; Psychosis; Functional; Diagnosis; Category; Mood; Affective
18.  Specificity of Incident Diagnostic Outcomes in Patients at Clinical High Risk for Psychosis 
Schizophrenia Bulletin  2015;41(5):1066-1075.
It is not well established whether the incident outcomes of the clinical high-risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2–45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis.
doi:10.1093/schbul/sbv091
PMCID: PMC4535651  PMID: 26272875
validity; bipolar disorder; nonbipolar mood disorder; anxiety disorder
19.  COMORBID PSYCHIATRIC DISORDERS IN YOUTH IN JUVENILE DETENTION 
Archives of general psychiatry  2003;60(11):1097-1108.
Objective
To estimate six-month prevalence of comorbid psychiatric disorders among juvenile detainees by demographic subgroups (gender, race/ethnicity, and age).
Design
Epidemiologic study of juvenile detainees. Master’s level clinical research interviewers administered the Diagnostic Interview Schedule for Children (DISC 2.3) to randomly selected detainees.
Setting
A large temporary detention center for juveniles in Cook County, Illinois (which includes Chicago and surrounding suburbs).
Participants
Randomly selected, stratified sample of 1829 African American, non-Hispanic white, and Hispanic youth (1172 males, 657 females, ages 10–18) arrested and newly detained.
Main Outcome Measures
Diagnostic Interview Schedule for Children (DISC 2.3).
Results
Significantly more females (56.5%) than males (45.9%) met criteria for 2 or more of the following disorders: major depressive, dysthymic, manic, psychotic, panic, separation-anxiety, overanxious, generalized anxiety, obsessive compulsive, attention deficit-hyperactivity, conduct, oppositional-defiant, alcohol, marijuana, and other substance; 17.3% of females and 20.4% of males had only one disorder. We also examined types of disorder: affective, anxiety, substance use and ADHD/behavioral. The odds of having comorbid disorders were higher than expected by chance for most demographic subgroups, except when base rates of disorders were already high, or when cell sizes were small. Nearly 14% of females and 11% of males had both a major mental disorder (psychosis, manic episode, or major depressive episode) and a substance use disorder. Compared to participants with no major mental disorder (the residual category), those with a major mental disorder had significantly greater odds (1.8–4.1) of having substance use disorders. Nearly 30% of females and over 20% of males with substance use disorders had major mental disorders. Rates of some types of comorbidity were higher among non-Hispanic whites and older adolescents.
Conclusion
Comorbid psychiatric disorders are a major health problem among detained youth. We recommend directions for research and discuss how to improve treatment and reduce health disparities in the juvenile justice and mental health systems.
doi:10.1001/archpsyc.60.11.1097
PMCID: PMC2893728  PMID: 14609885
20.  Physical multimorbidity and psychosis: comprehensive cross sectional analysis including 242,952 people across 48 low- and middle-income countries 
BMC Medicine  2016;14:189.
Background
In people with psychosis, physical comorbidities, including cardiovascular and metabolic diseases, are highly prevalent and leading contributors to the premature mortality encountered. However, little is known about physical health multimorbidity in this population or in people with subclinical psychosis and in low- and middle-income countries (LMICs). This study explores physical health multimorbidity patterns among people with psychosis or subclinical psychosis.
Methods
Overall, data from 242,952 individuals from 48 LMICs, recruited via the World Health Survey, were included in this cross-sectional study. Participants were subdivided into those (1) with a lifetime diagnosis of psychosis (“psychosis”); (2) with more than one psychotic symptom in the past 12 months, but no lifetime diagnosis of psychosis (“subclinical psychosis”); and (3) without psychotic symptoms in the past 12 months or a lifetime diagnosis of psychosis (“controls”). Nine operationalized somatic disorders were examined: arthritis, angina pectoris, asthma, diabetes, chronic back pain, visual impairment, hearing problems, edentulism, and tuberculosis. The association between psychosis and multimorbidity was assessed by multivariable logistic regression analysis.
Results
The prevalence of multimorbidity (i.e., two or more physical health conditions) was: controls = 11.4% (95% CI, 11.0–11.8%); subclinical psychosis = 21.8% (95% CI, 20.6–23.0%), and psychosis = 36.0% (95% CI, 32.1–40.2%) (P < 0.0001). After adjustment for age, sex, education, country-wise wealth, and country, subclinical psychosis and psychosis were associated with 2.20 (95% CI, 2.02–2.39) and 4.05 (95% CI, 3.25–5.04) times higher odds for multimorbidity. Moreover, multimorbidity was increased in subclinical and established psychosis in all age ranges (18–44, 45–64, ≥ 65 years). However, multimorbidity was most evident in younger age groups, with people aged 18–44 years with psychosis at greatest odds of physical health multimorbidity (OR = 4.68; 95% CI, 3.46–6.32).
Conclusions
This large multinational study demonstrates that physical health multimorbidity is increased across the psychosis-spectrum. Most notably, the association between multimorbidity and psychosis was stronger among younger adults, thus adding further impetus to the calls for the early intervention efforts to prevent the burden of physical health comorbidity at later stages. Urgent public health interventions are necessary not only for those with a psychosis diagnosis, but also for subclinical psychosis to address this considerable public health problem.
doi:10.1186/s12916-016-0734-z
PMCID: PMC5118890  PMID: 27871281
Psychosis; Physical health; Multimorbidity; Psychotic experiences; Metabolism
21.  Does Systemic Inflammation Play a Role in Pediatric Psychosis? 
Context
Human and animal studies have suggested an underlying inflammatory mechanism for a variety of neuropsychiatric disorders, including schizophrenia. To date, most available reports focused on adult patients.
Objective
We wished to test the hypothesis that the first psychotic episode in youth is associated with inflammation.
Patients
We studied patients admitted to a pediatric inpatient psychiatric unit. Patients (n=80) had new-onset psychosis diagnosed using DSM-IV TR criteria for Psychosis NOS, Schizophreniform Disorder or Schizoaffective Disorder. Patients were matched for age, race and gender with inpatient controls without psychosis within the same unit (n=66). We also compared these values to normal pediatric hematologic values. To study the role of inflammation in youth with psychosis, we collected serum samples of 28 children presenting with first-episode psychosis and compared their serum cytokine and S100B levels to eight healthy controls.
Main Outcome Measures
In this study, we measured serum markers of systemic inflammation.
Results
Leukocyte counts revealed a statistically significant increase in absolute monocytes compared to patients without psychosis (0.61±0.282 k/ml vs. 0.496±0.14 k/ml; p<0.01) and lymphocytes (2.51±0.84 k/ml vs. 2.24±0.72 k/ml; p<0.05) in patients with psychosis. All other hematologic values were similar between the groups. In addition, psychosis was characterized by increased serum levels of S100B, a peripheral marker of blood-brain barrier (BBB) damage. Several inflammatory mediators (e.g., TNF-α, IL-1β, IL-6, IL-5, IL-10, and IFN-γ) were elevated in children with psychosis.
Conclusions
These results strongly support a link between systemic inflammation, blood-brain barrier disruption and first-episode psychosis in pediatric patients.
doi:10.3371/CSRP.FACA.030813
PMCID: PMC4899842  PMID: 23491967
Pediatric; Blood-Brain Barrier; Markers; Psychosis; Schizophrenia
22.  Obsessive compulsive disorder 
BMJ Clinical Evidence  2012;2012:1004.
Introduction
Obsessions or compulsions that cause personal distress or social dysfunction affect about 1% of adult men and 1.5% of adult women. About half of adults with obsessive compulsive disorder (OCD) have an episodic course, whereas the other half have continuous problems. Prevalence in children and adolescents is 2.7%. The disorder persists in about 40% of children and adolescents at mean follow-up of 5.7 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of initial treatments for obsessive compulsive disorder in adults? What are the effects of initial treatments for obsessive compulsive disorder in children and adolescents? What are the effects of maintenance treatment for obsessive compulsive disorder in adults? What are the effects of maintenance treatment for obsessive compulsive disorder in children and adolescents? What are the effects of treatments for obsessive compulsive disorder in adults who have not responded to initial treatment with serotonin reuptake inhibitors (SRIs)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: addition of antipsychotics to serotonin reuptake inhibitors, behavioural therapy alone or with serotonin reuptake inhibitors, cognitive therapy or cognitive behavioural therapy (CBT) (alone or with serotonin reuptake inhibitors), electroconvulsive therapy, optimum duration of maintenance treatment, psychosurgery, serotonin reuptake inhibitors (citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine, or sertraline), and transcranial magnetic stimulation.
Key Points
Obsessions or compulsions that cause personal distress or social dysfunction affect about 1% of adult men and 1.5% of adult women. Prevalence in children and adolescents is 2.7%. About half of adults with obsessive compulsive disorder (OCD) have an episodic course, whereas the other half have continuous problems. Up to half of adults show improvement of symptoms over time. The disorder persists in about 40% of children and adolescents at mean follow-up of 5.7 years.
In adults, CBT and behavioural therapy improve symptoms of OCD compared with a waiting list control or placebo treatments. Behavioural therapy may be as effective at improving symptoms as CBT, but we don't know how they compare with SRIs (SSRIs and clomipramine).
SRIs improve symptoms of OCD in adults compared with placebo. Abrupt withdrawal of SRIs is associated with adverse effects.
We don't know whether combining SRIs and cognitive therapy or behavioural therapy improves symptoms compared with each treatment alone.
We don't know whether electroconvulsive therapy improves symptoms in adults with OCD.
In children and adolescents, CBT and SRIs improve symptoms of OCD. We don't know whether CBT in combination with SRIs is more effective than CBT alone, but it may be more effective than SRIs alone.
We don't know whether behavioural therapy improves symptoms in children and adolescents with OCD.
We don't know which is the most effective SRI to use, or for how long maintenance treatment should continue in adults or children and adolescents.
Adding antipsychotic drugs to SRIs may improve symptoms in adults who did not respond to SRIs alone, although RCTs have given conflicting results.
We don't know whether psychosurgery improves OCD because we found no studies of sufficient quality to assess its effectiveness.
Transcranial magnetic stimulation (rTMS) is not likely to improve symptoms of OCD. The quality of evidence is limited with trials being small.
CAUTION: SSRIs have been associated with an increase in suicidal ideation in children and adolescents.
PMCID: PMC3285220  PMID: 22305974
23.  Obsessive compulsive disorder 
BMJ Clinical Evidence  2009;2009:1004.
Introduction
Obsessions or compulsions that cause personal distress or social dysfunction affect about 1% of adult men and 1.5% of adult women. About half of adults with obsessive compulsive disorder (OCD) have an episodic course, whereas the other half have continuous problems. Prevalence in children and adolescents is 2.7%. The disorder persists in about 40% of children and adolescents at mean follow-up of 5.7 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of initial treatments for obsessive compulsive disorder in adults? What are the effects of initial treatments for obsessive compulsive disorder in children and adolescents? What are the effects of maintenance treatment for obsessive compulsive disorder in adults? What are the effects of maintenance treatment for obsessive compulsive disorder in children and adolescents? What are the effects of treatments for obsessive compulsive disorder in adults who have not responded to initial treatment with serotonin reuptake inhibitors (SRIs)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 70 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: addition of antipsychotics to serotonin reuptake inhibitors; behavioural therapy alone or with serotonin reuptake inhibitors; cognitive therapy or cognitive behavioural therapy (CBT) (alone or with serotonin reuptake inhibitors); electroconvulsive therapy; serotonin reuptake inhibitors (citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine, or sertraline); and optimum duration of maintenance treatment.
Key Points
Obsessions or compulsions that cause personal distress or social dysfunction affect about 1% of adult men and 1.5% of adult women. Prevalence in children and adolescents is 2.7%. About half of adults with obsessive compulsive disorder (OCD) have an episodic course, whereas the other half have continuous problems. Up to half of adults show improvement of symptoms over time. The disorder persists in about 40% of children and adolescents at mean follow-up of 5.7 years.
In adults,CBT and behavioural therapy improve symptoms of OCD compared with a waiting list control. Behavioural therapy may be as effective at improving symptoms as CBT, but we don't know how they compare with SRIs (SSRIs and clomipramine). Behavioural therapy may be more effective than relaxation.
SRIs improve symptoms of OCD in adults compared with placebo. Abrupt withdrawal of SRIs is associated with adverse effects. SRIs seem more effective at reducing symptoms compared with other antidepressants, including tricyclic antidepressants (other than clomipramine) or MAOIs.We don't know whether SRIs are more effective than venlafaxine.
We don't know whether combining SRIs and cognitive therapy or behavioural therapy improves symptoms compared with each treatment alone.
We don't know whether electroconvulsive therapy improves symptoms in adults with OCD.
In children and adolescents, CBT and SRIs improve symptoms of OCD. We don't know whether CBT in combination with SRIs is more effective than CBT alone, but it may be more effective than SRIs alone.
We don't know whether behavioural therapy improves symptoms in children and adolescents with OCD.
We don't know which is the most effective SRI to use, or for how long maintenance treatment should continue in adults or children and adolescents.
Adding antipsychotic drugs to SRIs may improve symptoms in adults who did not respond to SRIs alone, although RCTs have given conflicting results.
CAUTION: SSRIs have been associated with an increase in suicidal ideation in children and adolescents.
PMCID: PMC2907809
24.  A Review of Executive Function Deficits and Pharmacological Management in Children and Adolescents 
Objective:
To review both the functions and dysfunction of the executive system (ES) focusing on the extent of executive function (EF) deficits in most psychiatric disorders in children and adolescents and the possibility of such deficits acting as markers for pharmacological management.
Method:
A literature review was conducted using MEDLINE, Psychinfo, CINAHL, PsychArticles and PubMed with the following keywords: executive function or dysfunction, pediatric or children or adolescents, psychopharmacology, psychotropic medications, attention deficit hyperactivity disorder (ADHD), depression, obsessive compulsive disorder, anxiety disorders, bipolar disorder, schizophrenia, autism spectrum disorders (ASD), fetal alcohol spectrum disorders (FASD). Due to the limited amount of specific information obtained for some childhood disorders, the search was broadened to include relevant adult literature where information was extrapolated.
Results:
Abundant literature was found on the nature of the ES and the executive dysfunctions in most psychiatric disorders in children and adolescents, but not so much on the use of medication. EF deficits were found to be more consistent in disorders such as ADHD, ASD and FASD than in the other disorders but were not specific enough for use as clinical markers for those disorders. For children with ADHD and ASD there was adequate information on the use of psychotropic medications and impact on some EF domains but information on the impact of medication on EF in the other disorders in children and adolescents was fairly limited. Medications acting on the dopaminergic system also showed positive effects on EF deficits and are commonly used in the treatment of EF disorders such as ADHD, ASD and FASD.
Conclusion:
Existing literature indicates that EF deficits underlie most psychiatric disorders in children and adolescents. However, there are so many executive functions linked to so many activities and circuits in the brain that it is hard to quantify them in a particular disorder for use as specific markers for that disorder. The ES uses dopamine as its main neurotransmitter and this has implications for clinical management. Dopamine agonists (e.g. stimulants) and antagonists (e.g. neuroleptics) are medications that have direct impact on the ES and are commonly used to treat EF disorders in children and adolescents while serotonergic medications e.g. selective serotonin reuptake inhibitors (SSRIs) have not been very successful in treating such disorders. Identifying EF deficits early could be useful in guiding management including the use of medication in those disorders.
PMCID: PMC3413474  PMID: 22876270
executive; function; deficits; children; adolescents; pharmacology
25.  Psychogenic Psychosis Revisited: A Follow up Study 
Background:
Although brief and acute psychoses are usually dramatic in presentation, they usually have benign course. Studies investigating clinical features and changes in diagnosis between psychotic episodes have differed in design. However, some consistent findings have emerged. This study seeks to clarify and extend these features by describing and comparing clinical diagnostic stability in a group of subjects with first episode psychosis diagnosed as acute psychotic disorder (psychogenic psychosis) followed up for 6 years.
Methods:
The study comprises a retrospective evaluation of case records of 161 patients admitted for the first time with first episode psychosis. Among this group a subgroup of 69 psychogenic psychoses were followed up with special reference to stability of diagnosis within a period of 6 years.
Results:
Forty-six patients (67.6%) were male, 22 (32.4%) were female and data were missing in one case-record. There was no significant statistical difference between gender and diagnosis. The mean age was 27.5 years (13–45 years). There were criteria, which distinguish acute psychotic disorder (psychogenic psychosis). These criteria include acute onset with short duration of untreated psychosis, precipitating factors, adjusted pre-morbid personality, no family history of mental disorder, short duration of admission, full recovery in most of cases, with no further admission. Nearly 80% of the patients have never been admitted again in 6 years time.
Conclusions:
Our findings show a high level of agreement with the original concept of psychogenic psychosis; however, these bear little relationship to the DSM-IV (1994) and ICD-10 (WHO, 1993) criteria for brief or acute psychotic disorder.
PMCID: PMC3068793  PMID: 21475510

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