Volumetric analysis of the diagonal band of Broca in patients with schizophrenia and affective disorders: A post‐mortem study

The human diagonal band of Broca is connected to other parts of the limbic system, such as the hippocampus, that are involved in the pathology of schizophrenia. This study aimed to characterize the volume and anterior‐to‐posterior distance of the human diagonal band of Broca (vertical limb) from post‐mortem brains obtained from three groups: healthy control subjects (N = 17), patients with schizophrenia (N = 26), and patients with affective disorders (N = 12). There were no significant differences in the volume or anterior‐to‐posterior distance in the patients with schizophrenia or affective disorders compared with the healthy control subjects. To date, this is the first post‐mortem investigation measuring the volume and the anterior‐to‐posterior distance of the diagonal band of Broca (vertical limb) in patients with schizophrenia or affective disorders compared with healthy control subjects. Clin. Anat. 29:466–472, 2016. © 2015 Wiley Periodicals, Inc.     

Discriminating Dissociative Identity Disorder from Schizophrenia and Feigned Dissociation on Psychological Tests and Structured Interview

ABSTRACT

Objective: The purpose of this study was to evaluate the relative efficacy of a number of psychological tests and interviews in discriminating dissociative identity disorder (DID) from feigned dissociation and schizophrenia.

Method: Three measures of dissociation (SCID-D, DES, SDQ-5) two personality measures (MMPI-2, Millon-III) and a brief measure of hypnotic susceptibility (Spiegel & Spiegel's Eye-Roll Sign) were assessed for their ability to differentiate these diagnostic groups.

Results: Results indicate that the SCID-D was clearly the most efficacious instrument in discriminating DID from schizophrenia and from feigned dissociation. The DES-Taxon and the SDQ-5 were adequate in screening pathological dissociation from schizophrenia but were less discriminative of feigned dissociation. The commonly used personality inventories were unable to detect feigned dissociation and the DID group tended to have higher elevations on scales measuring psychotic symptoms than did the schizophrenic group. The Eye-Roll Sign discriminated feigned dissociation from those with dissociative disorders.

Conclusions: Structured interviews such as the SCID-D, although resource consuming, are essential in comprehensive assessment of dissociative disorders. Comprehensive assessment of psychotic disorders should include some measure of dissociation.     

Validation of the Edinburgh Postnatal Depression Scale in an Iranian sample

Summary Background: Considering the adverse effects of postpartum depression on both mother and infant, a screening instrument for early diagnosis seems to be of importance. Aims: To assess the psychometric properties of the Persian version of Edinburgh Postnatal Depression Scale (EPDS) on a sample of Iranian postpartum women. Method: The EPDS was translated and back-translated in the standard method. The questionnaire was completed by 600 postpartum women. Hundred cases with an EPDS score of ≥9 and 100 cases with an EPDS of <9 were randomly selected for interview. Sensitivity, specificity, positive likelihood ratio, and receiver operating characteristics were calculated by comparing the EPDS sum score against the DSM-IV diagnoses. The correlation coefficient of the EPDS score with GHQ-12 score was calculated. Principal component analysis and internal consistency were assessed. Results: The best cutoff scores for major depression were 12/13 with a sensitivity and specificity of 95.3% and 87.9%, respectively. The correlation coefficient of the total score of the Persian version of EPDS with the GHQ-12 total score was 0.76 (P < 0.001). A two-factor solution was selected as the most appropriate model based on both values and the score plot. The coefficient alpha for the whole scale was 0.83. Conclusion: The Persian version of EPDS is a reliable and valid measure for detecting postpartum depression. Furthermore, it seems acceptable to patients and a valid screening instrument for depression in postpartum women. Correspondence: Shahrzad Mazhari, M.D., Neuroscience Department, Research Center of Kerman University of Medical Sciences, Jomhoori Islamic Blvd, P.O. Box 67175-113, Kerman, Iran     

Reliability and Validity of the Turkish Version of the Structured Clinical Interview for DSM–IV Dissociative Disorders (SCID-D): A Preliminary Study

A total of 34 consecutive patients with dissociative identity disorder or dissociative disorder not otherwise specified were evaluated using the Turkish version of the Structured Clinical Interview for DSM–IV Dissociative Disorders (SCID-D). They were compared with a matched control group composed of 34 patients who had a nondissociative psychiatric disorder. Interrater reliability was evaluated by 3 clinicians who assessed videotaped interviews conducted with 5 dissociative and 5 nondissociative patients. All subjects who were previously diagnosed by clinicians as having a dissociative disorder were identified as positive, and all subjects who were previously diagnosed as not having a dissociative disorder were identified as negative. The scores of the main symptom clusters and the total score of the SCID-D differentiated dissociative patients from the nondissociative group. There were strong correlations between the SCID-D and the Dissociative Experiences Scale total and subscale scores. These results are promising for the validity and reliability of the Turkish version of the SCID-D. However, as the present study was conducted on a predominantly female sample with very severe dissociation, these findings should not be generalized to male patients, to dissociative disorders other than dissociative identity disorder, or to broader clinical or nonclinical populations.     

Dopamine receptor D4 gene is not associated with major psychoses

We previously reported an association between dopamine receptor D4 (DRD4) gene exon 1 variants and delusional disorder. The aim of this investigation was to study the DRD4 gene exon 1 and 3 variants in schizophrenia, delusional, bipolar, and unipolar disorders. We studied 651 inpatients affected by schizophrenia (n = 229), delusional (n = 86), bipolar (n = 210), and unipolar (n = 126) disorders (DSM III-R) and 471 healthy controls; these were typed for DRD4 variants at the first and third exon using polymerase chain reaction techniques. DRD4 variants were not associated with schizophrenic and delusional subjects even when possible confounders like gender and onset were considered. A marginal association between DRD4 exon 3 variants with unipolar (excess of DRD4*2/4, p = 0.004) and bipolar (excess of DRD4*2/4, p = 0.001) disorders was observed, both associations drop to insignificance when corrected for multiple testing. Our results exclude that coding variants of the DRD4 exon 1 and 3 may play a major role in conferring susceptibility to major psychoses; moreover, we could not replicate the association of DRD4 exon 1 variant with delusional disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:486–491, 1999. © 1999 Wiley-Liss, Inc.     

Resting EEG in first-episode schizophrenia patients, bipolar psychosis patients, and their first-degree relatives

We evaluated the resting electroencephalogram (EEG) of 50 first-episode schizophrenia patients and 55 of their relatives, 31 first-episode bipolar patients and 35 of their relatives, and 113 nonpsychiatric subjects and 42 of their relatives. The frequency characteristics of the EEG showed moderate stability for a subgroup of these subjects (n= 106) who were tested twice, approximately 9 months apart. Both the schizophrenia and bipolar patients showed a generalized pattern of increased delta and theta and decreased alpha activity. The bipolar patients demonstrated additional right hemisphere activity that was not present among the schizophrenia patients and nonpsychiatric subjects, a finding consistent with hypotheses concerning nondominant hemisphere involvement in the regulation of elated mood. The schizophrenia patients' female relatives and/or relatives with affective disorders and the bipolar patients had significantly reduced peak alpha frequencies. This finding may be related to reduced information processing capacity among these subjects.     

Diagnostic Efficiency of the Child and Adolescent Symptom Inventory (CASI-4R) Depression Subscale for Identifying Youth Mood Disorders

This study examined the diagnostic and clinical utility of the Child and Adolescent Symptom Inventory–4 R (CASI-4 R) Depressive and Dysthymia subscale for detecting mood disorders in youth (ages 6–12; M = 9.37) visiting outpatient mental health clinics. Secondary analyses (N = 700) utilized baseline data from the Longitudinal Assessment of Manic Symptoms study. Semistructured interviews with youth participants and their parents/caregivers determined psychiatric diagnoses. Caregivers and teachers completed the CASI-4 R. CASI-4 R depressive symptom severity and symptom count scores each predicted mood disorder diagnoses. Both caregiver scores (symptom severity and symptom count) of the CASI-4 R subscale significantly identified youth mood disorders (areas under the curve [AUCs] = .78–.79, ps < .001). The symptom severity version showed a small but significant advantage. Teacher symptom severity report did not significantly predict mood disorder diagnosis (AUC = .56, p > .05), whereas the teacher symptom count report corresponded to a small effect size (AUC = .61, p < .05). The CASI-4 R Depression scale showed strong incrememental validity even controlling for the other CASI-4 R scales. Caregiver subscale cutoff scores were calculated to assist in ruling in (diagnostic likelihood ratio [DLR] = 3.73) or ruling out (DLR = 0.18) presence of a mood disorder. The CASI-4 R Depressive subscale caregiver report can help identify youth mood disorders, and using DLRs may help improve diagnostic accuracy.     

Dissociation and Schizophrenia

Abstract

Comorbidity of psychotic and dissociative disorders often is not reported. This 38 year-old female with a history of schizophrenic symptoms displayed evidence of dissociative identity disorder (DID) during admission to an inpatient psychiatric unit. The case illustrates how the presence of a dissociative disorder may influence the presentation of a co-morbid psychosis. The historical association and differential diagnosis between DID and schizophrenia is described. Implications of various treatment approaches for patients exhibiting dissociation in the context of psychosis are discussed.     

Examining the relationship between object relations and interpersonal distress in a clinical sample

The goal of the present study was to explore the relationship between patients' object relational functioning (Social Cognition and Object Relations Scale‐Global Ratings) as rated by clinicians during the course of outpatient psychodynamic psychotherapy in a university‐based clinic and patient self‐reported interpersonal vulnerabilities (Inventory of Interpersonal Problems‐64). Participants (n = 112) were outpatients entering treatment at a university‐based psychotherapy clinic and were diagnosed primarily with mood disorders as well as Axis II relational problems and features. Participants completed the IIP‐64 prior to receiving therapy, and SCORS‐G ratings were based on patients' level of relational functioning during the evaluation process (i.e., the semistructured interview, follow‐up and feedback) and across the first two psychotherapy sessions. Results showed a significant relationship between the IIP‐64 Total score with SCORS‐GSelf‐Esteem (r = ?.21, p < .05) and Affective Quality of Representations (r = ?.20, p < .05), wherein self‐reported interpersonal dysfunction was greater among patients who had lower self‐worth and perceived others as more malevolent. These findings suggest that patients who rated themselves as having more significant interpersonal difficulty reported more negative expectations and experiences of relationships in their psychotherapy narratives. The utility of the SCORS‐G and the IIP‐64 as two different avenues of assessing patient relational functioning is explored.     

Region‐specific insular volumetric decreases in drug‐naive,first‐episode schizophrenia and their unaffected siblings

Decreased insular volume may be one of the anatomical alterations caused by schizophrenia. The possibility of region‐specific insular volumetric reduction as an endophenotype and/or a possible treatment predictor is a critical issue with great implications for the diagnosis and prognosis of the disease. The sample of the current study comprised 44 drug‐naive and first‐episode patients, 42 unaffected siblings, and 44 healthy controls. A computational anatomy toolbox (CAT12) was applied to analyze the structural images with a fine‐grained, cross‐validated brainnetome atlas. Correlation analysis and support vector regression (SVR) were used to determine the relationship between insular deficits and symptomatic severity among patients. The gray matter volume (GMV) values in the left hypergranular insula (G) exhibited the following pattern: patients < siblings < controls. GMV values in the right ventral agranular insula (vIa) and baseline Positive and Negative Syndrome Scale negative symptoms subscale scores among patients showed a positive correlation (r = 0.384, p = .010). Further SVR analysis exhibited a significantly positive correlation between GMV values in the right vIa and negative symptomatic improvement among patients (r = 0.537, p < .001). Results suggested the presence of region‐specific insular volumetric decreases in first‐episode schizophrenia. Thus, volumetric decrease in left G might be a potential endophenotype for schizophrenia, and GMV values in right vIa might be used to predict negative symptomatic improvement in schizophrenia.     

Association between TLR2 polymorphisms (− 196–174 Ins/Del,R677W,R753Q,and P631H) and schizophrenia in a Tunisian population

Since immune dysregulation has been well studied in schizophrenia pathophysiology, recent studies showed a potent role of TLR2 in neuroinflammation process underlying schizophrenia pathogenesis. However, the genetic predisposition is still unclear. Thus, we hypothesized that TLR2 polymorphisms − 196–174 Ins/Del (rs111200466), R753Q (rs5743708), R677W (rs121917864), and P631H (rs5743704) could be involved in schizophrenia predisposition. A case–control study was performed on a Tunisian population composed of 250 healthy controls and 250 patients genotyped by PCR–RFLP. Genotype and allele distribution were evaluated with sex, schizophrenia subtypes, and other clinical features. We also assessed a haplotype analysis for TLR2 polymorphisms with schizophrenia. Our results showed higher ins/del genotype frequency in healthy women compared to patients (p = 0.006; OR = 0.2). In the other hand, logistic regression showed higher ins/del genotype frequency in controls compared to paranoid patients (p = 0.05; OR = 0.48, adjusted). Frequencies of CT and T allele of R677W were significantly higher in patients compared to controls (p < 10⁻⁴, OR = 10.39; p < 10⁻⁴, OR = 4, adjusted, respectively). R753Q polymorphism was exclusively detected in patients (GA + AA = 2.5%) particularly in men with disorganized subtype. P631H did not show any association with schizophrenia. Finally, haplotype analysis showed that InsGTC and delGTC were associated with higher risk of schizophrenia (p = 0.0001, OR = 8.58; p = 0.04, OR = 5.01, respectively). In the Tunisian population, our results suggested that TLR2 R677W could be associated with susceptibility for schizophrenia, while − 196–174 Ins/Del suggested a trend of protection in women. Otherwise, R753Q could have an effect on schizophrenia especially for disorganized subgroup.

     

Association between a Synaptosomal Protein (SNAP-25) Gene Polymorphism and Verbal Memory and Attention in Patients with Endogenous Psychoses and Mentally Healthy Subjects

Synaptosomal protein SNAP-25 is involved in the process of transmitting nerve spikes in the CNS and in the consolidation of memory traces in the hippocampus. Two independent studies have demonstrated associations between SNAP-25 gene polymorphisms and intellectual functions in a group of mentally healthy subjects and patients with schizophrenia. The aim of the present work was to perform a comparative study of the association between the MnlI polymorphism of SNAP-25 and cognitive functions (verbal memory, attention/executive functions) in 66 patients with endogenous psychoses, 75 of their mentally healthy relatives, and 136 healthy control subjects. Statistical analysis showed that the effectiveness of performing cognitive tests was significantly affected by group assignment (p = 0.00001) and genotype (p = 0.012). The interaction between genotype and group assignment also had an influence (p = 0.02). In all groups, carriers of the TT genotype had worse measures than carriers of other genotypes. The similar nature of the influences of the MnlI polymorphism on variations in measures in all groups indicates that this gene is related to overall intellect.     

Association of the IFN-γ (+874A/T) Genetic Polymorphism with Paranoid Schizophrenia in Tunisian Population

Since growing evidence suggests a significant role of chronic low-grade inflammation in the physiopathology of schizophrenia, we have hypothesized that functional genetic variant of the IFN gamma (IFN-γ; +874A/T; rs2430561) gene may be involved in the predisposition to schizophrenia. This research is based on a case–control study which aims to identify whether polymorphism of the IFN-γ gene is a risk factor for the development of schizophrenia. The RFLP-PCR genotyping of the IFN-γ gene was conducted on a Tunisian population composed of 218 patients and 162 controls. The IFN-γ (+874A/T) polymorphism analysis showed higher frequencies of minor homozygous genotype (TT) and allele (T) in all patients compared with controls (11.5 vs. 4.9%; p = 0.03, OR = 2.64 and 30.7 vs. 24.1%, p = 0.04, OR = 1.4, respectively). This correlation was confirmed for male but not for female patients. Also, the T allele was significantly more common among patients with paranoid schizophrenia when compared with controls (25.8 vs. 4.9%, p = 0.0001; OR = 6.7). Using the binary regression analysis to eliminate confounding factors as age and sex, only this last association remained significant (p = 0.03; OR = 1.76, CI = 1.05–2.93). In conclusion, our results showed a significant association between +874A/T polymorphism of IFN-γ and paranoid schizophrenia, suggesting that this single nucleotide polymorphism (SNP) or another at proximity could predispose to paranoid schizophrenia. Since the minor allele of this polymorphism was correlated with an increased expression of their product, our study validates the hypothesis of excessive pro-inflammatory cytokine in the physiopathology of paranoid schizophrenia.     

Norms,reliability, and concurrent validity measures of the Portuguese version of the depression adjective check lists

This study reports normative data of depressive mood in Brazil, using a Portuguese version of the Depression Adjective Check Lists (DACL; Lubin, 1981, in press). Participants (N = 1,063) were college students drawn from randomly selected courses in 10 Brazilian universities. Cross-cultural comparisons showed that this Brazilian sample had significantly higher depressive scores compared to Hispanic (p < .01), American (p < .01), and Israeli (p < .05) samples. The results also indicated that Brazilian females (p < .05) and young adults (p < .05) reported significantly more depressive mood than males and older adults, respectively. All reliability (internal consistency, split-half, and alternate form) and concurrent validity measures were found to be appropriate and compared well to other cross-cultural samples.     

Tumor necrosis factor‐alpha −1031T/C polymorphism is associated with cognitive deficits in chronic schizophrenia patients versus healthy controls

Recent compelling research has demonstrated a pathophysiologic role for proinflammatory cytokines of microglial origin in decreasing neurocognitive function. Psychiatric diseases are already known to have reduced cognitive function and are also associated with increased inflammation. To elaborate on these data, our study aims to investigate how a particular polymorphism of the tumor necrosis factor gene, TNF‐α ?1031T/C, affects neurocognitive performance in patients with schizophrenia. We recruited 905 patients with schizophrenia and 571 healthy control subjects. We employed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to test for neurocognitive function and the positive and negative syndrome scale to evaluate schizophrenia severity. The ?1031T/C polymorphism was genotyped in both healthy controls and schizophrenic patients. Our results demonstrate that patients with the C allele (either T/C or C/C) possessed increased immediate memory index, visuospatial/constructional index, and RBANS total scores as compared to patients without it (p < .05). In healthy controls, there was no significant difference across genotypes (p > .05). Our findings demonstrate that the TNF‐α ?1031T/C polymorphism may not play a role in the susceptibility of schizophrenia itself, but may be involved in the cognitive deficits of schizophrenia. This suggests an important role for cytokine signaling in mediating the severity of cognitive dysfunction in schizophrenia.     

P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts

We investigated the effect of nine candidate genes on risk for mood disorders, hypothesizing that predisposing gene variants not only elevate the risk for mood disorders but also result in clinically significant differences in the clinical course of mood disorders. We genotyped 178 DSM‐IV bipolar I and II and 272 major depressive disorder patients from three independent clinical cohorts carefully diagnosed with semistructured interviews and prospectively followed up with life charts for a median of 60 (range 6–83) months. Healthy control subjects (n = 1322) were obtained from the population‐based national Health 2000 Study. We analyzed 62 genotyped variants within the selected genes (BDNF, NTRK2, SLC6A4, TPH2, P2RX7, DAOA, COMT, DISC1, and MAOA) against the presence of mood disorder, and in post‐hoc analyses, specifically against bipolar disorder or major depressive disorder. Estimates for time ill were based on life charts. The P2RX7 gene variants rs208294 and rs2230912 significantly elevated the risk for a familial mood disorder (OR = 1.35, P = 0.0013, permuted P = 0.06, and OR = 1.44, P = 0.0031, permuted P = 0.17, respectively). The results were consistent in all three cohorts. The same risk alleles predicted more time ill in all cohorts (OR 1.3, 95% CI 1.1–1.6, P = 0.0069 and OR 1.7, 95% CI 1.3–2.3, P = 0.0002 with rs208294 and rs2230912, respectively), so that homozygous carriers spent 12 and 24% more time ill. P2RX7 and its risk alleles predisposed to mood disorders consistently in three independent clinical cohorts. The same risk alleles resulted in clinically significant differences in outcome of patients with major depressive and bipolar disorder. © 2011 Wiley‐Liss, Inc.     

Objective measures of sleep duration and continuity in major depressive disorder with comorbid hypersomnolence: a primary investigation with contiguous systematic review and meta‐analysis

Hypersomnolence plays an important role in the presentation, treatment and course of mood disorders. However, there has been relatively little research that examines objective measures of sleep duration and continuity in patients with depression and hypersomnolence, despite the use of these factors in sleep medicine nosological systems. This study compared total sleep time and efficiency measured by naturalistic actigraphic recordings followed by ad libitum polysomnography (PSG; without prescribed wake time) in 22 patients with major depressive disorder and co‐occurring hypersomnolence against age‐ and sex‐matched healthy sleeper controls. The major depressive disorder and co‐occurring hypersomnolence group demonstrated significantly longer sleep duration compared with healthy sleeper controls quantified by sleep diaries, actigraphy and ad libitum PSG. No between‐group differences in sleep efficiency (SE), latency to sleep or wake after sleep onset were observed when assessed using objective measures. To further contextualize these findings within the broader scientific literature, a systematic review was performed to identify other comparable investigations. A meta‐analysis of pooled data demonstrated patients with mood disorders and co‐occurring hypersomnolence have significantly greater sleep duration and similar SE compared with healthy controls when assessed using ad libitum PSG. These results suggest current sleep medicine nosology that distinguishes hypersomnia associated with psychiatric disorders primarily as a construct characterized by low SE and increased time in bed may not be accurate. Future studies that establish the biological bases hypersomnolence in mood disorders, as well as clarify the accuracy of nosological thresholds to define excessive sleep duration, are needed to refine the diagnosis and treatment of these disorders.     

Differentiating Dissociative Disorders from Other Diagnostic Groups Through Somatoform Dissociation in Turkey

Abstract

This study aimed to assess the reliability, validity, and psychometric characteristics of the Turkish version of the Somatoform Dissociation Questionnaire (SDQ-20). In this context, it investigated whether somatoform dissociation differentiates dissociative disorders from other diagnostic groups and non-clinical individuals. The Turkish Version of the SDQ-20 was administered to 50 patients with a dissociative disorder, 94 patients with psychiatric disorders other than dissociative disorder, and 175 non-clinical participants. To confirm the clinical diagnosis, all patients in the dissociative disorder group had been evaluated using the Structured Clinical Interview for DSM-IV Dissociative Disorders. The internal consistency and the test-retest correlation of the SDQ-20 were excellent. The scale had strong correlations with the DES and the DIS-Q. There was a statistically significant difference between dissociative patients and other diagnostic groups on the SDQ-20 total score. The discriminative power of the SDQ-20 was as robust as that of the DES. There was no significant difference between the mean SDQ-20 total scores of Turkish and Dutch patients, but Turkish dissociative patients reported pseudoseizures more frequently than Dutch patients. The specificity of the short version of the scale (SDQ-5) was weak among Turkish patients. Dissociative disorders can be differentiated from other diagnostic groups through somatoform dissociation. The good psychometric characteristics of the SDQ-20 among Turkish participants support its cross-cultural validity.