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1.  Psychiatric, Behavioral, and Attitudinal Correlates of Avoidant and Obsessive-Compulsive Personality Pathology in Patients with Binge-Eating Disorder 
Comprehensive psychiatry  2010;51(5):531-537.
Objective
We examined correlates of avoidant and obsessive-compulsive personality pathology—with respect to psychiatric comorbidity, eating disorder psychopathology, and associated psychological factors—in patients with binge-eating disorder (BED).
Method
Three hundred forty-seven treatment-seeking patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) research criteria for BED were reliably assessed with semistructured interviews to evaluate DSM-IV axis I disorders, personality disorders, and behavioral and attitudinal features of eating disorder psychopathology.
Results
Fifteen percent of subjects had avoidant personality disorder features, 12% had obsessive-compulsive personality disorder features, 8% had features of both disorders, and 66% had features of neither. These groups differed significantly in the frequencies of depressive and anxiety disorders, as well as on measures of psychological functioning (negative/depressive affect and self-esteem) and eating disorder attitudes (shape and weight concerns). There were no group differences on measures of eating behaviors. The avoidant and obsessive-compulsive groups had more psychiatric comorbidity than the group without these personality features, but less than the combined group. The group without these features scored significantly lower than all other groups on negative/depressive affect, and significantly higher than the avoidant and combined groups on self-esteem. The combined group had the greatest severity on shape and weight concerns.
Conclusions
Avoidant and obsessive-compulsive personality features are common in patients with BED. Among BED patients, these forms of personality psychopathology—separately and in combination—are associated with clinically meaningful diagnostic, psychological, and attitudinal differences. These findings have implications for the psychopathological relationship between BED and personality psychopathology, and may also have implications for assessment and treatment.
doi:10.1016/j.comppsych.2009.11.005
PMCID: PMC2927363  PMID: 20728012
2.  Neurocognitive Dysfunction in Bipolar and Schizophrenia Spectrum Disorders Depends on History of Psychosis Rather Than Diagnostic Group 
Schizophrenia Bulletin  2009;37(1):73-83.
Objectives: Neurocognitive dysfunction is milder in bipolar disorders than in schizophrenia spectrum disorders, supporting a dimensional approach to severe mental disorders. The aim of this study was to investigate the role of lifetime history of psychosis for neurocognitive functioning across these disorders. We asked whether neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders depends more on history of psychosis than diagnostic category or subtype. Methods: A sample of individuals with schizophrenia (n = 102), schizoaffective disorder (n = 27), and bipolar disorder (I or II) with history of psychosis (n = 75) and without history of psychosis (n = 61) and healthy controls (n = 280), from a large ongoing study on severe mental disorder, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery. Results: Compared with controls, all 3 groups with a history of psychosis performed poorer across neurocognitive measures, while the bipolar group without a history of psychosis was only impaired on a measure of processing speed. The groups with a history of psychosis did not differ from each other but performed poorer than the group without a history of psychosis on a number of neurocognitive measures. These neurocognitive group differences were of a magnitude expected to have clinical significance. In the bipolar sample, history of psychosis explained more of the neurocognitive variance than bipolar diagnostic subtype. Conclusions: Our findings suggest that neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders is determined more by history of psychosis than by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic category or subtype, supporting a more dimensional approach in future diagnostic systems.
doi:10.1093/schbul/sbp034
PMCID: PMC3004191  PMID: 19443616
neurocognition; verbal memory; working memory; verbal fluency; interference control; schizoaffective disorder
3.  Life threatening self starvation; a case report 
BMC Research Notes  2013;6:36.
Background
Obsessive compulsive disorders are a complex group that can have a variety of manifestations. Many authors now describe an obsessive compulsive spectrum disorder where many other specific diagnostic entities such as trichotillomania, tic disorders and body dysmorphic disorder are considered to be related and linked disorders.
Case presentation
We report a case of a twenty two year old Sri Lankan male who presented with life threatening self starvation due to severe obsessive compulsive disorder. The diagnosis was not considered till late due to the atypical presentation of the patient. While his symptoms bordered on a delusional psychosis, a decision was made to treat him as for obsessive compulsive disorder with behavioural therapy which was successful in the end.
Conclusions
In analysis of a patient with severe anorexia, the psychological causes should not be forgotten. In fact, if the feeding pattern of the patient was observed at the beginning, unnecessary investigating and life threatening worsening of the condition could have been avoided.
doi:10.1186/1756-0500-6-36
PMCID: PMC3598395  PMID: 23369616
4.  Kiddie-SADS Reveals High Rates of DSM-IV Disorders in Children and Adolescents with Autism Spectrum Disorders 
Prevalence of current comorbid DSM-IV disorders was assessed in a special school population of children and adolescents with ASD (N = 71, age 6.0–17.9 years), representing all cognitive levels and main ASD subgroups. Symptoms were assessed through parent interview and association to child characteristics was explored. Seventy-two percent was diagnosed with at least one comorbid disorder. Anxiety disorders (41%) and attention deficit/hyperactivity disorder (31%) were most prevalent. Obsessive–compulsive disorder was more common in older children, and oppositional defiant disorder/conduct disorder more prevalent in pervasive developmental disorder, not otherwise specified. Our results show high rates of comorbid DSM-IV disorders and underscore the importance of such evaluation in children ASD. However, diagnostic challenges are present and future research on the diagnostic validity of comorbid psychiatric disorders is needed.
doi:10.1007/s10803-010-1095-7
PMCID: PMC3094530  PMID: 20824493
ASD; Children–adolescents; Comorbid psychiatric disorders
5.  Birth Order and Sibling Gender Ratio of a Clinical Sample of Children and Adolescents Diagnosed with Attention Deficit Hyperactivity Disorder 
Iranian Journal of Psychiatry  2012;7(3):109-113.
Objective
It is not clear whether sibling's gender ratio is associated with attention deficit hyperactivity disorder (ADHD). This study examines whether inattentiveness severity and hyperactivity/impulsivity severity are associated with birth order of children with ADHD.
Method
Participants are a clinical sample of 173 children and adolescents with ADHD and 43 ones without ADHD. Diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders forth edition-Text Revision (DSM-IV-TR), diagnostic criteria according to face-to-face interview with the children and their parents. ADHD DSM-IV checklist was used to measure inattentiveness and hyperactivity/impulsivity scores.
Results
The association of birth order and diagnosis of ADHD was not statistically significant after adjusting for covariate factors. The gender ratio of siblings is not associated with ADHD.
Conclusion
Birth order and siblings gender ratio are independent of ADHD diagnosis. The results of this study support the fact that genetic factors rather than environmental factor of birth order is associated with ADHD. Moreover, contrary to autism, the current results do not suggest the androgen theory for ADHD.
PMCID: PMC3488865  PMID: 23139691
Attention deficit disorder with hyperactivity; Birth order; Sex ratio
6.  Relationship of Neurocognitive Deficits to Diagnosis and Symptoms across Affective and Non-Affective Psychoses 
Schizophrenia research  2011;133(1-3):212-217.
Introduction
Neurocognitive dysfunction is believed to be a core feature of schizophrenia and is increasingly recognized as a common symptom dimension in bipolar disorder. Despite a copious literature on neurocognition in these disorders, the relationship amongst neurocognition, symptoms, and diagnosis remains unclear. We examined neurocognitive functioning in a cross-diagnostic sample of patients with psychotic disorders. Based on previous findings, it was hypothesized that neurocognitive functioning would be impaired in all three patient groups, and that groups would be similarly impaired on all neuropsychological measures. Additionally, we predicted that negative symptoms but not positive, general, or mood symptoms, would be associated with neurocognitive functioning.
Method
Neurocognitive functioning and symptoms were assessed in participants with schizophrenia (n=25), schizoaffective disorder (n=29), or bipolar disorder with psychosis (n=31), and in healthy controls (n=20).
Results
Neurocognitive functioning was significantly impaired in all patient groups, and groups did not differ by diagnosis on most measures. A series of linear regressions revealed that negative symptoms (but no other clinical symptom) predicted poorer executive functioning across groups. Diagnosis was not a significant predictor of any neurocognitive variable.
Discussion
Neurocognitive deficits were pronounced in this cross-diagnostic sample of patients with psychotic disorders, and did not differ by diagnosis. Neurocognitive dysfunction may represent a symptom dimension that spans diagnostic categories, and may reflect shared pathogenic processes. As neurocognitive dysfunction is among the strongest predictors of outcome in patients, efforts to treat these deficits, which have shown promise in schizophrenia, should be extended to all patients with psychosis.
doi:10.1016/j.schres.2011.09.004
PMCID: PMC3225688  PMID: 21996265
Bipolar; Schizophrenia; Schizoaffective; neurocognitive; comparative
7.  Tourette’s disorder and other tic disorders in DSM-5: a comment 
Classification of tic disorders will be revised in the forthcoming edition of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5). We do not support the suggestion to move tic disorders to “Anxiety and Obsessive–Compulsive Disorders”, if the section “Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence” is not retained. Other than that, most proposed changes of the criteria for tic disorders contain a number of welcome improvements, e.g., the more unified definition of tics including the removal of the term “stereotyped” and the better capture of the temporal pattern of tics (e.g., removal of the maximum 3 months criterion for a tic-free period in chronic tic disorders). But, unfortunately there are some inconsistencies in detail, e.g., the unification of diagnostic criteria for tic disorders had not been consistently pursued in transient tic disorder. In sum, the proposed DSM-5 criteria could be seen as an important step forward particularly in clinical routine. However, continued research is needed to justify the existing and proposed classification of tic disorders as well as to better clarify what other changes should be made in the DSM-5 and beyond.
doi:10.1007/s00787-010-0143-3
PMCID: PMC3038221  PMID: 21076848
DSM-5; Tic disorders; Tourette syndrome
8.  Increased Number of Subcortical Hyperintensities on MRI in Children and Adolescents With Tourette's Syndrome, Obsessive-Compulsive Disorder, and Attention Deficit Hyperactivity Disorder 
The American journal of psychiatry  2006;163(6):1106-1108.
Objective
To investigate whether cerebral hyperintensities on T2-weighted magnetic resonance images (MRI) are associated with childhood neuropsychiatric disorders.
Method
The authors compared the frequency of cortical and subcortical cerebral hyperintensities in 100 children and adolescents with Tourette's syndrome, obsessive-compulsive disorder (OCD), or attention deficit hyperactivity disorder (ADHD) and 32 healthy comparison subjects.
Results
The frequency of cerebral hyperintensities was significantly higher in subjects with Tourette's syndrome, OCD, or ADHD than in healthy comparison subjects; each diagnostic group seemed to contribute to this effect. Among the patient groups, the likelihood of detecting cerebral hyperintensities in the subcortex (primarily the basal ganglia and thalamus) was significantly greater than in the cortex.
Conclusions
A childhood diagnosis of Tourette's syndrome, OCD, or ADHD significantly increased the likelihood of detecting cerebral hyperintensities, particularly in the subcortex, supporting the notion that subcortical injury may play a role in the pathophysiology of these conditions.
doi:10.1176/appi.ajp.163.6.1106
PMCID: PMC2367225  PMID: 16741215
9.  Obsessive Compulsive Symptoms in the Psychosis Prodrome: Correlates of Clinical and Functional Outcome 
Schizophrenia research  2008;108(1-3):170-175.
Objectives
Obsessive-Compulsive Disorder (OCD) is a common co-morbid condition in schizophrenia, associated with poor prognosis. However, the prevalence of obsessive compulsive symptomatology (OCS) and its relationship to outcome has not been evaluated in adolescents at ultra high-risk for psychosis (UHR).
Methods
Sixty-four UHR and 26 non-prodromal comparison (NPC) youth were ascertained using the Structured Interview for Prodromal Syndromes (SIPS). Participants completed diagnostic interviews and the Padua Inventory (Sanavio, 1988), a self-report measure of OCS.
Results
UHR youth reported significantly higher rates of OCS on the Padua Inventory compared to NPC youth. Clinical diagnosis of OCD (20% of sample) was associated with lower risk of conversion to psychosis over the follow-up period, but was unrelated to clinical severity or psychosocial functioning. However, dimensional ratings of OCS were significantly associated with positive symptom severity, self-reported depression, and a trend toward increased suicidal ideation within the UHR sample.
Conclusions
OCS rates in UHR youth are well above estimated prevalence rates in normal populations, and commensurate with rates of comorbidity observed in schizophrenia. Although clinical diagnosis of OCD was not associated with later conversion to psychosis, OCS severity in UHR youth was associated with more acute symptomatic presentation, including more severe depression and suicidality.
doi:10.1016/j.schres.2008.11.023
PMCID: PMC2670932  PMID: 19097751
Prodrome; Ultra-High-risk; Psychosis; Obsessive-Compulsive; Anxiety; Psychosocial Functioning
10.  Long term functioning in early onset psychosis: Two years prospective follow-up study 
Background
There were few studies on the outcome of schizophrenia in developing countries. Whether the outcome is similar to or different from developed world is still a point for research. The main aim of the current study was to know if patients with early onset non affective psychosis can behave and function properly after few years from start of the illness or not. Other aims included investigation of possible predictors and associated factors with remission and outcome.
Method
The study prospectively investigated a group of 56 patients with onset of psychosis during childhood or adolescence. Diagnosis made according to DSM-IV criteria and included; schizophrenia, psychotic disorder not otherwise specified and acute psychosis. Severity of psychosis was measured by PANSS. Measures of the outcome included; remission criteria of Andreasen et al 2005, the children's global assessment scale and educational level.
Results
Analysis of data was done for only 37 patients. Thirty patients diagnosed as schizophrenia and 7 with Psychotic disorder not otherwise specified. Mean duration of follow up was 38.4 +/- 16.9 months. At the end of the study, 6 patients (16.2%) had one episode, 23(62.1%) had multiple episodes and 8 (21.6%) continuous course. Nineteen patients (51.4%) achieved full remission, and only 11(29.7%) achieved their average educational level for their age. Twenty seven percent of the sample had good outcome and 24.3% had poor outcome. Factors associated with non remission and poor outcome included gradual onset, low IQ, poor premorbid adjustment, negative symptoms at onset of the illness and poor adherence to drugs. Moreover, there was tendency of negative symptoms at illness start to predict poor outcome.
Conclusion
Some patients with early onset non affective psychosis can behave and function properly after few years from the start of the illness. Although remission is a difficult target in childhood psychosis, it is still achievable.
doi:10.1186/1744-9081-7-28
PMCID: PMC3162891  PMID: 21801438
11.  Neurocognitive impairment and psychosis in bipolar disorder during early remission from an acute episode of mood disturbance 
Objective
Recent studies have reported greater neurocognitive impairment in euthymic bipolar disorder patients with a history of psychosis relative to patients without such a history. To further explore the relation between psychosis and cognitive dysfunction in bipolar disorder, the current study examined the cognitive functioning of patients during early remission from a discrete episode of mood disturbance. The study aimed to determine whether the presence of psychosis during inpatient hospitalization was associated with greater cognitive impairment at the time of hospital discharge.
Method
Fifty-nine inpatients who met DSM-IV criteria for bipolar disorder (24 admitted with psychosis, 35 admitted without psychosis), ages 18–59, completed a neuropsychological battery and mood measures 24–48 hours before discharge. The cognitive battery included standardized tests of IQ, attention and working memory, visual memory, verbal memory and executive functioning.
Results
A multivariate analysis of variance detected group differences on measures of verbal memory (p<0.001) and executive functioning (p<0.003), using mood measures and previous number of psychiatric admissions as covariates. Post-hoc analysis of between-subjects effects revealed significantly poorer performance on the California Verbal Learning Test–Second Edition, Logical Memory test from Wechsler Memory Scale–Revised, Stroop–Word/Color Interference test and the Wisconsin Card Sorting Test for patients who were admitted to the hospital with psychosis. These results remained significant after matching the groups for past psychosis, with the exception of the Logical Memory test.
Conclusions
The results of this study indicate that patients with bipolar disorder who were admitted to the hospital due to psychosis exhibited significantly more severe cognitive impairment at the time of discharge than patients admitted for an acute mood disturbance without psychosis. These findings may be important for improving discharge planning and the development of more effective outpatient services.
doi:10.4088/JCP.08m04663yel
PMCID: PMC3143061  PMID: 19925749
bipolar disorder; cognitive impairment; psychosis; inpatients
12.  Consistency of the Diagnosis of Major Depression with Psychosis Across 10 Years 
The Journal of clinical psychiatry  2011;72(9):1207-1213.
Objective
The present study investigates how consistently DSM-IV major depression (MDD) with psychosis was diagnosed by research consensus across 10 years and the association of clinical characteristics with diagnostic consistency.
Method
The sample included 146 participants, part of a larger first admission cohort (N=628) presenting with psychosis, who were diagnosed with psychotic depression at least once across 4 assessments spanning 10 years (after first admission, at 6-month, 24-month, and 10-year follow-ups). Diagnoses at each assessment were determined from semi-structured interviews, medical records, and informant reports.
Results
Fifty-five (37.7%) of the 146 were diagnosed with psychotic depression at each available assessment, 13(8.9%) switched from MDD to bipolar disorder, 24 (16.4%) switched from MDD to schizophrenia or schizoaffective disorder, and the remaining 54 (37.0%) had other patterns of diagnostic change. Only 47 (58.8%) of 80 participants diagnosed with MDD at baseline retained a mood disorder diagnosis 10 years later (36 or 45.0% had MDD and 11 or 13.8% had bipolar disorder), while 16 (30.8%) of 52 participants who ended the study with MDD were initially misdiagnosed. Those switching from MDD to bipolar disorder had better premorbid adjustment, more first degree relatives with MDD, better functioning, and fewer negative symptoms at baseline, whereas those shifting to the schizophrenia spectrum had a more insidious onset, longer initial hospital stays, worse functioning, and more negative symptoms.
Conclusions
The diagnosis of MDD with psychosis among inpatients showed poor long-term consistency. For clinicians, results indicate that the diagnosis of MDD with psychosis based on a single assessment should be considered provisional.
doi:10.4088/JCP.10m06774
PMCID: PMC3589602  PMID: 21903033
13.  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
14.  Transgenic Mouse Models of Childhood Onset Psychiatric Disorders 
Childhood onset psychiatric disorders, such as Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Mood Disorders, Obsessive Compulsive Spectrum Disorders (OCSD), and Schizophrenia (SZ), affect many school age children leading to a lower quality of life, including difficulties in school and personal relationships that persists into adulthood. Currently, the causes of these psychiatric disorders are poorly understood resulting in difficulty diagnosing affected children, and insufficient treatment options. Family and twin studies implicate a genetic contribution for ADHD, ASD, Mood Disorders, OCSD, and SZ. Identification of candidate genes and chromosomal regions associated with a particular disorder provide targets for directed research, and understanding how these genes influence the disease state will provide valuable insights for improving the diagnosis and treatment of children with psychiatric disorders. Animal models are one important approach in the study of human diseases, allowing for the use of a variety of experimental approaches to dissect the contribution of a specific chromosomal or genetic abnormality in human disorders. While it is impossible to model an entire psychiatric disorder in a single animal model, these models can be extremely valuable in dissecting out the specific role of a gene, pathway, neuron subtype, or brain region in a particular abnormal behavior. In this review we discuss existing transgenic mouse models for childhood onset psychiatric disorders. We compare the strength and weakness of various transgenic animal models proposed for each of the common childhood onset psychiatric disorders, and discuss future directions for the study of these disorders using cutting-edge genetic tools.
doi:10.1111/j.1469-7610.2011.02380.x
PMCID: PMC3075087  PMID: 21309772
15.  Childhood Psychosis or Mental Retardation: A Diagnostic Dilemma 
Canadian Medical Association Journal  1963;89(20):1015-1019.
A relatively large percentage of children seen at a mental retardation clinic demonstrated psychotic symptoms. The entire group with psychotic manifestations, 62 in all, were reviewed in order to clarify the diagnosis of childhood psychosis or mental retardation. The 1961 British criteria for childhood psychosis were used and are advocated by the authors. Childhood psychosis was the primary diagnosis in 38 cases, and psychosis secondary to brain damage in 24 cases. Onset of the condition under the age of three years and a poor prognosis for social recovery were characteristic of the entire group.
Obvious emotional disorder was present in 21 mothers and 14 fathers. There was a continuum in terms of number of psychotic symptoms, level of intelligence and presence of organic signs. It is concluded that there is an overlap between the entities of childhood psychosis and mental retardation.
PMCID: PMC1922122  PMID: 14081785
16.  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
17.  Stability/Change of DSM Diagnoses among Children and Adolescents Assessed at a University Hospital: A Cross-sectional Cohort Study 
Objectives:
This study’s aim was to examine changes or stability of DSM diagnoses in children and adolescents over the period from childhood to young adulthood and to discuss the instability in DSM diagnoses from a developmental perspective.
Method:
We used cross-sectional cohort design to assess the congruence of DSM diagnoses in children and adolescents who had a diagnostic assessment at least twice as inpatient and/or outpatient at a university hospital from age 5 to 22. Data analysis was conducted using kappa statistics
Results:
The hospital computerized database consisted of 264 patients who were born from 1983 to 1985 and had had a diagnostic assessment at least twice over a 17-year period. The highest percentages of stable cases were of Mood disorders and Psychosis. Behavioural disorders and Anxiety disorders had lower percentages of stable cases but significant Kappa values suggesting fewer cases were stable but also fewer new cases were added. Substance related disorders had very low percentages and non-significant Kappa value. When divided into three groups based on the delay between first and second diagnosis, stability of diagnosis degraded sharply with time.
Conclusions:
The results of this study show poor stability for all diagnoses, however the trend seemed to follow that reported in previous literature where moods disorders and schizophrenia showed more stability than other diagnoses. Explanations are provided for the results. A well-designed prospective longitudinal study utilizing structured diagnostic interviews to assign DSM-IV TR diagnosis from child hood to adulthood would improve the reliability of diagnoses and perhaps time for crystallization of psychopathology and clarification into more discrete diagnostic entities.
PMCID: PMC2765380  PMID: 19881937
stability of diagnosis; DSM diagnosis; child and adolescent psychiatry
18.  Outpatient Diagnosis and Clinical Presentation of Bipolar Youth 
Introduction:
Many children and adolescents in the community do not fit the classic Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria for Bipolar Disorder, Type I., and bipolar disorder, not otherwise specified (BPNOS) is often the “catch all” diagnosis. Significant research has been conducted to better understand the phenomenology of the spectrum of bipolar disorder; however, there are presently different operational definitions for bipolar disorder, in both clinical and research settings. A recent study, The Course and Outcome of Bipolar Youth (COBY) provided preliminary validation for diagnosing BPNOS. Using these COBY research definitions for BPNOS, we examined the clinical presentation and the prior history of psychotropic medication usage of youth with BPI vs. BPNOS presenting to an outpatient clinic.
Methods:
The initial evaluation consisted of a direct clinical interview with the parent(s) and the patient. Standardized rating scales such as the Young Mania Rating Scale and the Quick Inventory of Depressive Symptoms were used to assess current mood states. The Clinical Global Impressions Scale-Severity was used to assess the overall functioning of bipolar youth.
Results:
Age, comorbidities, and family histories of 68 bipolar youth in the clinic are similar to what other studies have reported. BPNOS youth have significant functional impairment which is comparable to the BPI youth. Both bipolar groups are equally likely to have similar prior exposure to psychotropic medications.
Discussion:
BPNOS is a serious illness the diagnostic guidelines for which are still debatable. Until further clarification of this diagnosis, the COBY definitions for BPNOS can be used in a clinic. The use of stringent criteria for diagnosing the bipolar spectrum disorders allows for careful differential diagnoses of psychiatric illnesses.
PMCID: PMC2732727  PMID: 19718422
bipolar; outpatient; diagnosis
19.  Response to methylphenidate by adult and pediatric patients with attention-deficit/hyperactivity disorder: the Spanish multicenter DIHANA study 
Background:
The purpose of this multicenter Spanish study was to evaluate the response to immediate-release methylphenidate by children and adults diagnosed with attention-deficit/hyperactivity disorder (ADHD), as well as to obtain information on current therapy patterns and safety characteristics.
Methods:
This multicenter, observational, retrospective, noninterventional study included 730 patients aged 4–65 years with a diagnosis of ADHD. Information was obtained based on a review of medical records for the years 2002–2006 in sequential order.
Results:
The ADHD predominantly inattentive subtype affected 29.7% of patients, ADHD predominantly hyperactive-impulsive was found in 5.2%, and the combined subtype in 65.1%. Overall, a significant lower Clinical Global Impression (CGI) score and mean number of DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision) symptoms by subtype were found after one year of treatment with immediate-release methylphenidate; CGI decreased from 4.51 to 1.69, symptoms of inattention from 7.90 to 4.34, symptoms of hyperactivity from 6.73 to 3.39, and combined subtype symptoms from 14.62 to 7.7. Satisfaction with immediate-release methylphenidate after one year was evaluated as “very satisfied” or “satisfied” by 86.90% of the sample; 25.75% of all patients reported at least one adverse effect. At the end of the study, 41.47% of all the patients treated with immediate-release methylphenidate were still receiving it, with a mean time of 3.80 years on therapy.
Conclusion:
Good efficacy and safety results were found for immediate-release methylphenidate in patients with ADHD.
doi:10.2147/NDT.S35836
PMCID: PMC3573811  PMID: 23430373
attention deficit hyperactivity disorder; ADHD; pharmacologic treatment; methylphenidate; satisfaction
20.  Psychiatric Comorbidity in Children with Autism Spectrum Disorders: A Comparison with Children with ADHD 
The present study was conducted with the aim to identify comorbid psychiatric disorders in children with autism spectrum disorders (ASD) (n = 40) and to compare those comorbidity rates to those in children with attention deficit hyperactivity disorder (ADHD) (n = 40). Participants were clinically referred children aged 7–18 years. DSM-IV classifications were used for the primary diagnosis (ASD/ADHD), while comorbid psychiatric disorders were assessed using a structured diagnostic interview, the structured clinical interview for DSM-IV, childhood diagnoses (KID-SCID). Twenty-three children with ASD (57.5 %) had at least one comorbid disorder, whereas 16 children with ADHD (40.0 %) were classified as having at least one comorbid disorder. No group differences were found with respect to this comorbidity rate or for the rate of comorbid externalizing disorders (ODD and/or CD). However, children with ASD had more comorbid internalizing disorders compared to children with ADHD. More specifically, children with ASD had higher rates of anxiety disorders, but not mood disorders. No associations between comorbidity and age or between comorbidity and the intelligence quotient was found. It is important for clinicians to always be aware of, and screen for, comorbidity, and to consider treatment for these comorbid disorders. In addition, research should focus on establishing valid and reliable screening tools as well as effective treatment options for these comorbid disorders.
doi:10.1007/s10826-012-9587-z
PMCID: PMC3602612
ASD; ADHD; Children; Psychiatric comorbidity
21.  Prevalence of Tourette Syndrome and Chronic Tics in the Population-Based Avon Longitudinal Study of Parents and Children Cohort 
Objective
Recent epidemiologic studies have demonstrated that Tourette syndrome (TS) and chronic tic disorder (CT) are more common than previously recognized. However, few population-based studies have examined the prevalence of co-occurring neuropsychiatric conditions such as obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). We evaluated the prevalence of TS, CT, and their overlap with OCD and ADHD in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.
Method
A total of 6,768 children were evaluated using longitudinal data from mother-completed questionnaires. DSM-IV-TR diagnoses of TS and CT were derived using three levels of diagnostic stringency (Narrow, Intermediate, and Broad). Validity of the case definitions was assessed by comparing gender ratios and rates of co-occurring OCD and ADHD using heterogeneity analyses.
Results
Age 13 prevalence rates for TS (0.3% for Narrow; 0.7% for Intermediate) and CT (0.5% for Narrow; 1.1% for Intermediate) were consistent with rates from other population-based studies. Rates of co-occurring OCD and ADHD were higher in TS and CT Narrow and Intermediate groups compared with controls but lower than has been previously reported. Only 8.2% of TS Intermediate cases had both OCD and ADHD; 69% of TS Intermediate cases did not have either co-occurring OCD or ADHD.
Conclusions
This study suggests that co-occurring OCD and ADHD is markedly lower in TS cases derived from population-based samples than has been reported in clinically ascertained TS cases. Further examination of the range of co-occurring neuropsychiatric disorders in population-based TS samples may shed new perspective on the underlying shared pathophysiology of these three neurodevelopmental conditions.
doi:10.1016/j.jaac.2011.11.004
PMCID: PMC3314954  PMID: 22265365
Tourette syndrome; prevalence; ALSPAC; obsessive-compulsive disorder; attention-deficit/hyperactivity disorder
22.  Adaptive, Emotional, and Family Functioning of Children With Obsessive-Compulsive Disorder and Comorbid Attention Deficit Hyperactivity Disorder 
The American journal of psychiatry  2005;162(6):1125-1132.
Objective
The purpose of the study was to examine adaptive, emotional, and family functioning in a well-characterized group of children and adolescents with obsessive-compulsive disorder (OCD) and to evaluate the influence of comorbid attention deficit hyperactivity disorder (ADHD) on the levels of impairment in various functional domains.
Method
The study group included 287 children and adolescents (191 boys, 96 girls) ages 7–18 years. Fifty-six subjects had a diagnosis of OCD only, 43 had both OCD and ADHD, 95 had ADHD, and 93 were unaffected comparison children. Best estimate DSM-IV diagnoses were assigned on the basis of structured interviews and clinical ratings. The children's functioning was evaluated with a comprehensive battery of well-established, standardized measures, including the Vineland Adaptive Behavior Scales, parents' ratings of social and family functioning, and children's self-reports of emotional adjustment.
Results
The children with OCD only were more impaired than were unaffected comparison subjects in most areas of adaptive functioning and emotional adjustment. Children with OCD plus ADHD had additional difficulties in social functioning, school problems, and self-reported depression. Impairment in daily living skills, reduced number of activities, and self-reported anxiety were uniquely associated with the diagnosis of OCD. Family dysfunction was associated with ADHD but not with OCD.
Conclusions
Children and adolescents with OCD are impaired in multiple domains of adaptive and emotional functioning. When comorbid ADHD is present, there is an additional burden on social, school, and family functioning.
doi:10.1176/appi.ajp.162.6.1125
PMCID: PMC2291297  PMID: 15930061
23.  Phenomenology of Early Childhood Onset Obsessive Compulsive Disorder 
This paper describes the phenomenological features of early childhood onset obsessive compulsive disorder (OCD; defined as children meeting DSM-IV criteria for OCD with age of onset <8 years). Fifty-eight children (ages 4–8) were included in the sample. OCD and comorbid diagnoses were determined by structured interview, and OCD severity was measured using the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Mean age of OCD onset was almost five, and mean age of presentation was between 6 and 7. Mean symptom severity was in the moderately severe range. Comorbidity and family history of OCD were common. Contamination and aggressive/catastrophic obsessions and washing and checking compulsions were endorsed most frequently. Results indicate that early childhood onset OCD may have a lower boy to girl ratio and lower rates of depressive disorders, but may be similar to later childhood onset OCD in terms of OCD symptom presentation and severity.
doi:10.1007/s10862-008-9094-0
PMCID: PMC2830071  PMID: 20198131
Child; OCD; Phenomenology
24.  Obsessionality & compulsivity: a phenomenology of obsessive-compulsive disorder 
Progress in psychiatry depends on accurate definitions of disorders. As long as there are no known biologic markers available that are highly specific for a particular psychiatric disorder, clinical practice as well as scientific research is forced to appeal to clinical symptoms. Currently, the nosology of obsessive-compulsive disorder is being reconsidered in view of the publication of DSM-V. Since our diagnostic entities are often simplifications of the complicated clinical profile of patients, definitions of psychiatric disorders are imprecise and always indeterminate. This urges researchers and clinicians to constantly think and rethink well-established definitions that in psychiatry are at risk of being fossilised. In this paper, we offer an alternative view to the current definition of obsessive-compulsive disorder from a phenomenological perspective.
Translation
This article is translated from Dutch, originally published in [Handbook Obsessive-compulsive disorders, Damiaan Denys, Femke de Geus (Eds.), (2007). De Tijdstroom uitgeverij BV, Utrecht. ISBN13: 9789058980878.]
doi:10.1186/1747-5341-6-3
PMCID: PMC3041996  PMID: 21284843
25.  Three-Year Follow-up of a Randomized Controlled Trial of Cognitive Therapy for the Prevention of Psychosis in People at Ultrahigh Risk 
Schizophrenia Bulletin  2006;33(3):682-687.
There have been recent advances in the ability to identify people at high risk of developing psychosis. This has led to interest in the possibility of preventing the development of psychosis. A randomized controlled trial compared cognitive therapy (CT) over 6 months with monthly monitoring in 58 patients meeting criteria for ultrahigh risk of developing a first episode of psychosis. Participants were followed up over a 3-year period. Logistic regression demonstrated that CT significantly reduced likelihood of being prescribed antipsychotic medication over a 3-year period, but it did not affect transition to psychosis defined using the Positive and Negative Syndrome Scale (PANSS) or probable Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis. However, exploratory analyses revealed that CT significantly reduced the likelihood of making progression to psychosis as defined on the PANSS over 3 years after controlling for baseline cognitive factors. Follow-up rate at 3 years was 47%. There appear to be enduring benefits of CT over the long term, suggesting that it is an efficacious intervention for people at high risk of developing psychosis.
doi:10.1093/schbul/sbl042
PMCID: PMC2526150  PMID: 16973786
cognitive therapy; psychosis; prevention; early intervention

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