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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.
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).
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.
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.
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.
PMCID: PMC2927363  PMID: 20728012
2.  DSM-5: a collection of psychiatrist views on the changes, controversies, and future directions 
BMC Medicine  2013;11:202.
The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders.
PMCID: PMC3846446  PMID: 24229007
DSM-5; Psychiatry; Autism; PTSD; Mood disorders; Bipolar; Obsessive-compulsive disorders; Depression; Schizophrenia
3.  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.
PMCID: PMC3004191  PMID: 19443616
neurocognition; verbal memory; working memory; verbal fluency; interference control; schizoaffective disorder
4.  Life threatening self starvation; a case report 
BMC Research Notes  2013;6:36.
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.
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.
PMCID: PMC3598395  PMID: 23369616
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.
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.
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.
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.
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.  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.
PMCID: PMC3094530  PMID: 20824493
ASD; Children–adolescents; Comorbid psychiatric disorders
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.
PMCID: PMC3038221  PMID: 21076848
DSM-5; Tic disorders; Tourette syndrome
8.  Relationship of Neurocognitive Deficits to Diagnosis and Symptoms across Affective and Non-Affective Psychoses 
Schizophrenia research  2011;133(1-3):212-217.
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.
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).
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.
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.
PMCID: PMC3225688  PMID: 21996265
Bipolar; Schizophrenia; Schizoaffective; neurocognitive; comparative
9.  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.
To investigate whether cerebral hyperintensities on T2-weighted magnetic resonance images (MRI) are associated with childhood neuropsychiatric disorders.
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.
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.
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.
PMCID: PMC2367225  PMID: 16741215
10.  Association between Obsessive Compulsive Disorder and Tumor Necrosis Factor-α Gene −308 (G>A) and −850 (C>T) Polymorphisms in Turkish Children 
Obsessive compulsive disorder (OCD) is a neurobiological disease characterized with obsessions and compulsions. Obsessive compulsive disorder occurs with an autoimmune mechanism after Group A β hemolytic streptococcus (GABHS) infection. Tumor necrosis factor (TNF) is an important cytokine, as well as having an important role in the apoptosis mechanism of autoimmune diseases. It is expressed by the TNF-α gene. The aim of this study was to examine the relationship between the TNF-α gene promoter region −308 (G>A) and −850 (C>T) polymorphisms and OCD. In this study, ages of the OCD patients and the control group ranged between 4 and 12 years. We studied two patient groups, one included childhood onset OCD patients (n = 49) and the control group was composed of healthy children (n = 58). Patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria and with Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (KSAD-S-PL) version. For identifying the polymorphisms, polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and polyacrylamide gel electrophoresis (PAGE) methods were used.
For the −308 polymorphism, 45 of 49 OCD patients’ results were completed, and for the −850 polymorphism, 47 of 49 OCD patients’ results were completed. According to our statistical results, there is a positive relationship between OCD and the −308 polymorphism (p <0.001) but no association between OCD and the −850 polymorphism (p = 0.053). There is no positive relationship between antistreptolysin O (ASO) titers and the −308 polymorphism (p = 0.953) but there is an important significance between the −850 polymorphism and ASO (p = 0.010). There is no positive relationship between gender of patients and OCD (p = 0.180) and no positive association between ASO and gender (p = 0.467). According to our results, we hypothesize that we can propose the mutant AA genotype for the −308 polymorphism, and that the mutant CT genotype for the −850 polymorphism may be used as molecular indicators for OCD.
PMCID: PMC3776664  PMID: 24052733
Child; Genetic; Obsessive compulsive disorder (OCD); Polymorphism
11.  Obsessive Compulsive Symptoms in the Psychosis Prodrome: Correlates of Clinical and Functional Outcome 
Schizophrenia research  2008;108(1-3):170-175.
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).
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.
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.
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.
PMCID: PMC2670932  PMID: 19097751
Prodrome; Ultra-High-risk; Psychosis; Obsessive-Compulsive; Anxiety; Psychosocial Functioning
12.  Long term functioning in early onset psychosis: Two years prospective follow-up study 
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.
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.
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.
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.
PMCID: PMC3162891  PMID: 21801438
13.  Consistency of the Diagnosis of Major Depression with Psychosis Across 10 Years 
The Journal of clinical psychiatry  2011;72(9):1207-1213.
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.
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.
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.
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.
PMCID: PMC3589602  PMID: 21903033
14.  Neurocognitive impairment and psychosis in bipolar disorder during early remission from an acute episode of mood disturbance 
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.
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.
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.
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.
PMCID: PMC3143061  PMID: 19925749
bipolar disorder; cognitive impairment; psychosis; inpatients
15.  The Coexistence of Psychiatric Disorders and Intellectual Disability in Children Aged 3–18 Years in the Barwani District, India 
ISRN Psychiatry  2013;2013:875873.
Background. The coexistence of psychiatric disorders in people with intellectual disability (ID) is common. This study determined the prevalence of psychiatric disorders in children with ID in Barwani, India. Method. A total of 262 children with ID were evaluated for psychiatric disorders using the diagnostic criteria outlined in the International Classification of Diseases (ICD-10). Results. Psychiatric disorders appeared in study participants at the following rates: attention deficit hyperactivity disorder (ADHD), 6.5%; autism, 4.2%; anxiety, 2.7%; bipolar disorder, 1.1%; delusional disorder, 0.8%; depression, 2.3%; obsessive-compulsive disorder, 0.8%; schizophrenia, 1.9%; enuresis, 10.3%; epilepsy, 23.7%; and behavioral problems, 80.9%. The prevalence of psychiatric disorders was statistically higher in severely intellectually disabled children (IQ ≤ 49) than mildly intellectually disabled children (IQ ≥ 50). Conclusions. There is a higher prevalence of psychiatric disorders in children with ID when their IQ ≤ 49 compared with ID children whose IQ ≥ 50.
PMCID: PMC3664507  PMID: 23738223
16.  A Review of Executive Function Deficits and Pharmacological Management in Children and Adolescents 
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.
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.
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.
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
17.  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.
PMCID: PMC3075087  PMID: 21309772
18.  Neurocognitive features in subgroups of bipolar disorder 
Bipolar Disorders  2013;15(3):272-283.
To examine which subgroups of DSM-IV bipolar disorder (BD) [BD type I (BD-I) or BD type II (BD-II), and subgroups based on history of psychosis, presenting polarity, and age at onset] differentiate best regarding neurocognitive measures.
A total of 199 patients with BD were characterized by clinical and neurocognitive features. The distribution of subgroups in this sample was: BD-I, 64% and BD-II, 36%; 60% had a history of psychosis; 57% had depression as the presenting polarity; 61% had an early onset of BD, 25% had a mid onset, and 14% had a late onset. We used multivariate regression analyses to assess relationships between neurocognitive variables and clinical subgroups.
Both BD-I diagnosis and elevated presenting polarity were related to impairments in verbal memory, with elevated presenting polarity explaining more of the variance in this cognitive domain (22.5%). History of psychosis and BD-I diagnosis were both related to impairment in semantic fluency, with history of psychosis explaining more of the variance (11.6%).
Poor performance in verbal memory appears to be associated with an elevated presenting polarity, and poor performance in semantic fluency appears to be associated with a lifetime history of psychosis.
PMCID: PMC3660782  PMID: 23521608
age at onset; bipolar I disorder; bipolar II disorder; neurocognition; polarity of presenting episode; psychosis
19.  HFE Gene Polymorphisms and the Risk for Autism in Egyptian Children and Impact on the Effect of Oxidative Stress 
Disease markers  2011;31(5):289-294.
Background: Autism is among the commonest neurodevelopmental childhood disorders worldwide; its aetiology is still unknown. Iron metabolism alteration in the central nervous system is recently implicated as a risk factor for several neurodegenerative disorders.
Haemochromatosis HFE gene polymorphisms (p.H63D and p.C282Y) have shown significant association with several neurological diseases. Some evidences show altered iron related proteins in serum of autistic children. The aim of this work is to conduct a preliminary pilot study for the association of HFE polymorphisms and autism.
Methods: All cases were referred from the clinic of special needs, National Research Centre, Cairo. Clinical diagnosis was based on the criteria for autistic disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR).
Whole genome DNA was extracted; p.H63D and p.C282Y genotyping was studied using specific sequence amplification followed by restriction enzyme digestion on a sample of autism patients (25 cases) and twenty controls.
Results: The p.H63D is more abundant than the C282Y among both autism and control samples. No significant association of p.H63D nor p.C282Y polymorphism and autism was revealed.
Conclusion: We here report on the first pilot study of the possible genetic association between autism and HFE gene polymorphisms among Egyptians. Although our results do not prove the role of HFE polymorphisms as risk factors for autism, yet this does not exclude the role of iron in this prevalent disorder. Further extended studies are recommended to include other iron metabolism genes.
PMCID: PMC3826890  PMID: 22048270
Neurodevelopmental disorders; Iron; haemochromatosis; genes; polymorphisms
20.  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
21.  Shared or induced obsessive compulsive disorder: Is it a reality? 
Indian Journal of Psychiatry  2014;56(1):72-75.
Shared or induced obsessive compulsive disorder (OCD) is not yet a distinct diagnosis in classification of psychiatric disorders. In fact, though recognized as a diagnostic category, shared or induced psychotic disorders are rare and most of the literature is based on the case reports.
Materials and Methods:
We are reporting three case studies manifested with shared or induced OCD (cases with obsessive symptoms that were shared from the primary case in their family).
All the cases were treated considering shared or induced OCD as psychopathology. Response to treatment modalities in first and second case and poor response to treatment in third case is suggestive of shared or induced OCD as a distinct entity. It is different from shared psychosis in many ways.
Shared or induced OCD is a distinct diagnosis. Greater awareness about this entity among mental health professionals is needed.
PMCID: PMC3927249  PMID: 24574562
Induced obsessive compulsive disorder; obsessive compulsive disorder; shared obsessive compulsive disorder
22.  Disease Biomarkers in Cerebrospinal Fluid of Patients with First-Onset Psychosis 
PLoS Medicine  2006;3(11):e428.
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.
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
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
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)
PMCID: PMC1630717  PMID: 17090210
23.  Stability/Change of DSM Diagnoses among Children and Adolescents Assessed at a University Hospital: A Cross-sectional Cohort Study 
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.
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
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.
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
24.  Outpatient Diagnosis and Clinical Presentation of Bipolar Youth 
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.
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.
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.
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
25.  Response to methylphenidate by adult and pediatric patients with attention-deficit/hyperactivity disorder: the Spanish multicenter DIHANA study 
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.
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.
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.
Good efficacy and safety results were found for immediate-release methylphenidate in patients with ADHD.
PMCID: PMC3573811  PMID: 23430373
attention deficit hyperactivity disorder; ADHD; pharmacologic treatment; methylphenidate; satisfaction

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