Differential effects of childhood abuse and neglect: mediation by posttraumatic distress in neurotic disorder and negative symptoms in schizophrenia?

Dissociation, though understood as a response to trauma, lacks a proven etiology. The assumption of a dose-response relationship between trauma, dissociation and Schneiderian symptoms led to the proposal of a dissociative subtype of schizophrenia characterized by severe child maltreatment, dissociation and psychosis. Child maltreatment and dissociation are common features of neurotic disorders as well, and the link between trauma, dissociation, and hallucinations is not specific for schizophrenia. This study compares childhood abuse and neglect, posttraumatic distress and adult dissociation in patients with psychotic vs. non-psychotic disorder. Thirty-five participants with non-psychotic disorder and twenty-five with schizophrenia were analyzed using the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery-Åsberg Depression Rating Scale (MADRS), the Posttraumatic Stress Diagnostic Scale PDS (PDS), the Childhood Trauma Questionnaire (CTO) and the Arbeitsgemeinschaft Methodik und Dokumentation in der Psychiatrie (AMDP)-module on dissociation. Trauma and clinical syndromes were compared by means of T-testing and logistic regression between 1) the diagnoses and 2) groups with and without post-traumatic stress disorder (PTSD), marked dissociation and psychotic symptoms. While non-psychotic disorder was related to abuse, schizophrenia showed an association with neglect. Childhood trauma predicted posttraumatic symptomatology and negative symptoms. Childhood abuse and neglect may effectuate different outcomes in neurotic and psychotic disorder. The underlying mechanisms, including dissociation, dovetail with cognitive, emotional and behavioural changes involved in depression, posttraumatic distress and chronic schizophrenia symptoms rather than being directly linked to trauma.     

A gene–environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder

While an interactive effect of genes with adverse life events is increasingly appreciated in current concepts of depression etiology, no data are presently available on interactions between genetic and environmental (G × E) factors with respect to personality and related disorders. The present study therefore aimed to detect main effects as well as interactions of serotonergic candidate genes (coding for the serotonin transporter, 5-HTT; the serotonin autoreceptor, HTR1A; and the enzyme which synthesizes serotonin in the brain, TPH2) with the burden of life events (#LE) in two independent samples consisting of 183 patients suffering from personality disorders and 123 patients suffering from adult attention deficit/hyperactivity disorder (aADHD). Simple analyses ignoring possible G × E interactions revealed no evidence for associations of either #LE or of the considered polymorphisms in 5-HTT and TPH2. Only the G allele of HTR1A rs6295 seemed to increase the risk of emotional-dramatic cluster B personality disorders (p = 0.019, in the personality disorder sample) and to decrease the risk of anxious-fearful cluster C personality disorders (p = 0.016, in the aADHD sample). We extended the initial simple model by taking a G × E interaction term into account, since this approach may better fit the data indicating that the effect of a gene is modified by stressful life events or, vice versa, that stressful life events only have an effect in the presence of a susceptibility genotype. By doing so, we observed nominal evidence for G × E effects as well as main effects of 5-HTT-LPR and the TPH2 SNP rs4570625 on the occurrence of personality disorders. Further replication studies, however, are necessary to validate the apparent complexity of G × E interactions in disorders of human personality.     

Is reduction of symptoms in eating disorder patients after 1 year of treatment related to attachment security and mentalization?

In a sample of 38 eating disorder (ED) patients who received psychotherapeutic treatment, changes in attachment security, and mentalization in relation to symptoms reduction were investigated. Attachment security improved in 1 year but was unrelated to improvement of ED or comorbid symptoms. Mentalization did not change significantly in 1 year. Pretreatment mentalization was negatively related to the severity of ED symptoms, trait anxiety, psycho-neuroticism, and self-injurious behavior after 1 year of treatment. We conclude that for ED patients, improving mentalization might increase the effect of treatment on core and comorbid symptoms.     

Effects of a synbiotic on symptoms,and daily functioning in attention deficit hyperactivity disorder – A double-blind randomized controlled trial

Some prebiotics and probiotics have been proposed to improve psychiatric symptoms in children with autism. However, few studies were placebo-controlled, and there is no study on persons with an attention deficit hyperactivity disorder (ADHD) diagnosis. Our aim was to study effects of Synbiotic 2000 on psychiatric symptoms and functioning in children and adults with ADHD without an autism diagnosis. Children and adults (n = 182) with an ADHD diagnosis completed the nine weeks randomized double-blind parallel placebo-controlled trial examining effects of Synbiotic 2000 on the primary endpoints ADHD symptoms, autism symptoms and daily functioning, and the secondary endpoint emotion regulation, measured using the questionnaires SNAP-IV, ASRS, WFIRS, SCQ, AQ and DERS-16. Levels at baseline of plasma C-reactive protein and soluble vascular cell adhesion molecule-1 (sVCAM-1), central to leukocyte-endothelial cell adhesion facilitating inflammatory responses in tissues, were measured using Meso Scale Discovery. Synbiotic 2000 and placebo improved ADHD symptoms equally well, and neither active treatment nor placebo had any statistically significant effect on functioning or sub-diagnostic autism symptoms. However, Synbiotic 2000, specifically, reduced sub-diagnostic autism symptoms in the domain restricted, repetitive and stereotyped behaviors in children, and improved emotion regulation in the domain of goal-directed behavior in adults. In children with elevated sVCAM-1 levels at baseline as well as in children without ADHD medication, Synbiotic 2000 reduced both the total score of autism symptoms, and the restricted, repetitive and stereotyped behaviors. In adults with elevated sVCAM-1 at baseline, Synbiotic 2000 significantly improved emotion regulation, both the total score and four of the five subdomains. To conclude, while no definite Synbiotic 2000-specific effect was detected, the analysis of those with elevated plasma sVCAM-1 levels proposed a reduction of autism symptoms in children and an improvement of emotion regulation in adults with ADHD.Trial registration number: ISRCTN57795429.     

Prevalence and predictors of posttraumatic stress disorder and depressive symptoms among child survivors 1 year following the Wenchuan earthquake in China

The purpose of this study was to estimate the prevalence rates of probable posttraumatic stress disorder (PTSD) and depression and to explore potential risk factors among child and adolescent survivors 1 year following the 2008 Wenchuan earthquake. 3052 participants were administered the Child PTSD Symptom Scale, the Center for Epidemiologic Studies Depression Scale for Children, and the earthquake experience scale. Results indicated that the prevalence rates of probable PTSD and depression were 8.6 and 42.5 %, respectively. Demographic variables (i.e., age and gender) and most aspects of earthquake experiences (i.e., direct exposure, close ones’ exposure, fear for the safety of close ones, prior exposure to trauma, living location, and house damage, with the exception of type of housing) made unique contributions to PTSD and depressive symptoms. In addition, the moderating effect of gender on the relationships between age and PTSD and depressive symptoms was significant. In conclusion, depression was a more common psychological response than was PTSD among child survivors 1 year following the Wenchuan earthquake. Age and gender were risk factors for both PTSD and depressive symptoms. Furthermore, older female survivors exhibit more severe PTSD and depressive symptoms. Additionally, several aspects of earthquake experiences (i.e., direct exposure, close ones’ exposure, fear for the safety of close ones, prior exposure to trauma, living location, and house damage) was also important for the development and maintenance of PTSD and depressive symptoms.     

Differential, size-dependent sensory neuron involvement in the painful and ataxic forms of primary Sjögren's syndrome-associated neuropathy

Primary Sj?gren's syndrome (pSS)-associated neuropathy manifests a wide variety of peripheral neuropathies that may show overlap among the neuropathic forms. In this report, we describe histopathological findings of two autopsy cases with pSS-associated neuropathy; one of them manifested the painful form and another showed ataxic form. The population of dorsal root ganglion (DRG) neurons and the density of myelinated fibers in the dorsal spinal root were variably reduced among spinal segments in both forms. In the painful form, there was a prominent reduction of small neurons, while in the ataxic form, large neurons were predominately lost. In accordance with the degree of the DRG cell loss, the modality of nerve fiber loss in the dorsal spinal roots and sural nerve correlated well with the corresponding DRG neuron loss. Prominent CD8+ T lymphocyte infiltration was present in the DRG, sympathetic ganglion, epineurial and perineurial space throughout the peripheral nerve trunks, and visceral organs, including the submandibular gland of both forms. Although the size of affected DRG neurons is different, these two forms share a similar causal mechanism, namely, cytotoxic autoimmunity to ganglion neurons, which may be one of a continuum of etiological factors. This hypothesis may have an impact on therapeutic approach.     

The characteristics of a discrete mood episode, neuro-cognitive impairment and re-hospitalization in bipolar disorder

This longitudinal study examined characteristics of a discrete mood episode that predict re-hospitalization for bipolar disorder, highlighting associated cognitive dysfunction as a potential mechanism linking episode severity and relapse. Eighty-two inpatients meeting DSM-IV-TR diagnostic criteria for bipolar I disorder completed the study. Twenty-two of the patients were readmitted to the hospital within 3 months of discharge. The study compared these patients to the remaining 60 patients who were not readmitted to the hospital during this period. Patients were compared on several factors related to the severity of the mood episode and the course of illness more generally. Analysis also compared the groups on measures of mood and neuro-cognitive functioning, assessed 24-48 h before initial hospitalization discharge. Re-hospitalized patients had longer initial hospital stays (t = −3.10, p < 0.01), higher rates of psychosis while in the hospital (Chi square = 5.1, p < 0.02), and lower GAF scores on discharge (t = 2.37, p < 0.05). The groups did not differ in age of illness onset or number of previous psychiatric hospitalizations. With respect to neuro-cognitive functioning, analysis indicated poorer performance for re-hospitalized patients on measures of executive functioning (Wilks’ Lambda, F (7, 71) = 9.0, p < 0.001), IQ (Wilks’ Lambda, F (2, 76) = 5.06, p < 0.01), and memory (Wilks’ Lambda, F (6,72) = 4.19, p < 0.001). Trends in the expected direction emerged for attention/working memory tests (Wilks’ Lambda, F (7, 71) = 1.79, p < 0.10). Results highlight features of a discrete mood episode associated with increased rates of re-hospitalization. This study observed connections among episode severity, cognitive dysfunction at hospital discharge and re-hospitalization.     

An examination of the factor structure of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, narcissistic personality disorder criteria: one or two factors?

A growing body of research has suggested that narcissistic personality disorder (NPD) contains 2 factors or types: overt/grandiose and covert/vulnerable. A recent factor analysis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), NPD symptoms supported a similar 2-factor model. The present research tested this proposed 2-factor solution against a 1-factor solution (N = 289; 72% patients) using both confirmatory factor analysis and an examination of associations between the resultant factors and theoretically relevant criteria (other personality disorders; depression, anxiety). The results of the confirmatory factor analysis supported a 1-factor solution. Likewise, the 2 factors each yielded a similar pattern of correlations with relevant criteria. Together, these results argue against a 2-factor structure for the current DSM-IV NPD symptoms. Given the broader research literature suggesting a 2-factor structure of narcissism, strategies for assessing both overt/grandiose and covert/vulnerable forms of narcissism in DSM-V are discussed.     

The auditory P200 is both increased and reduced in schizophrenia? A meta-analytic dissociation of the effect for standard and target stimuli in the oddball task

ObjectiveConflicting reports of P200 amplitude and latency in schizophrenia have suggested that this component is increased, reduced or does not differ from healthy subjects. A systematic review and meta-analysis were undertaken to accurately describe P200 deficits in auditory oddball tasks in schizophrenia.MethodsA systematic search identified 20 studies which were meta-analyzed. Effect size (ES) estimates were obtained: P200 amplitude and latency for target and standard tones at midline electrodes.ResultsThe ES obtained for amplitude (Cz) for standard and target stimuli indicate significant effects in opposite directions: standard stimuli elicit smaller P200 in patients (d = ?0.36; 95% CI [?0.26, ?0.08]); target stimuli elicit larger P200 in patients (d = 0.48; 95% CI [0.16, 0.82]). A similar effect occurs for latency at Cz, which is shorter for standards (d = ?0.32; 95% CI [?0.54, ?0.10]) and longer for targets (d = 0.42; 95% CI [0.23, 0.62]). Meta-regression analyses revealed that samples with more males show larger ES for amplitude of target stimuli, while the amount of medication was negatively associated with the ES for the latency of standards.ConclusionsThe results obtained suggest that claims of reduced or augmented P200 in schizophrenia based on the sole examination of standard or target stimuli fail to consider the stimulus effect.SignificanceQuantification of effects for standard and target stimuli is a required first step to understand the nature of P200 deficits in schizophrenia.     

Trends in bipolar disorder or depression as a cause of death on death certificates of US residents, 1999–2009

Background

Temporal trends in mortality from bipolar disorder (BD) or depression in the US population, based on multiple causes (MC) rather than underlying cause (UC) alone on death certificates, apparently have not been examined.

Method

The annual US age-standardized rate (ASR) for deaths per 100,000 US residents age 15+ years, and age-specific rates, for BD or depression using MC versus UC alone was examined for 1999–2009; percentage change (PC) from 1999 to 2009 was calculated.

Results

The ASRs at age 15+ years were much higher using MC than UC alone. For BD using MC, the ASR increased from 1999 to 2009 (PC +69.2 %) with larger increases in age groups within 15–64 years (PCs about 200 %). For depression using MC, the ASR rose from 1999 to 2003 and then declined, but the decline was restricted to age 65+ years; the ASR at age 15–64 years increased from 1999 to 2009 (PC +55.5 %). For deaths at age 15–64 years with BD or depression as other than UC, the ASRs increased for external causes, cardiovascular diseases, external causes, and neoplasms as UC.

Conclusion

The large increases in mortality from BD using MC are consistent with reported increases in BD prevalence rates in the US population. The temporal increases in death rates related to mood disorders at age 15–64 years may provide further support for the need for interventions to address the mediators of excess mortality identified from cohort studies.     

Do hyperactivity,impulsivity and inattention have an impact on the ability of facial affect recognition in children with autism and ADHD?

Psychopathological, genetic and neuropsychological findings indicate an association between autism and attention deficit/hyperactivity disorder (ADHD). The goal of this study was to assess possible differences in facial affect recognition in children with autism (with and without comorbid ADHD), with ADHD and healthy controls. Children aged 6–18 years old with DSM-IV-diagnosis ADHD (n = 30) or autism (n = 40) were included consecutively in the study. Facial affect recognition was assessed with a computer-based program used for teaching emotion processing called the Frankfurt Test and Training of Social Affect (FEFA) using faces and eye-pairs as target material. Additionally three attention-tasks (Sustained attention, Inhibition, Set-Shifting) were administered. Approximately 52% of the autistic children met the criteria for the comorbid diagnosis of ADHD. A MANOVA with post-hoc Scheffé tests revealed a significant difference in the recognition of faces and eye pairs between the group ADHD and controls (P = 0.009). Children with autism and ADHD also differed significantly from healthy participants in the recognition of eye-pairs (P = 0.009). Neither correlations with PDD nor with ADHD symptom scores were able to explain these results. Sustained attention and inhibition deficits had a significant influence on emotion recognition in children with ADHD. Our findings imply that the ability of facial affect recognition is reduced in children suffering from ADHD symptoms, both in autistic and pure ADHD children. ADHD symptoms need to be taken into account in future studies assessing emotion recognition in autistic children and adolescents. Supported by the Koeln Fortune Program/Faculty of Medicine, University of Cologne     

Serum concentrations of CRP, IL-6, TNF-α and cortisol in major depressive disorder with melancholic or atypical features

The aim of the present study was to explore possible differences between serum C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and cortisol concentration in patients with major depressive disorder (MDD) with melancholic features, and MDD with atypical features. As secondary aim, we investigated possible associations with clinical features such as suicidal ideation, number of episodes, duration of depression and symptomatology severity. We included 55 MDD patients (32 with melancholic features and 23 with atypical features) and 18 healthy controls. When compared to healthy controls, MDD with melancholic or atypical features showed higher CRP and IL-6, but not TNF-α. Cortisol concentration was higher in MDD with melancholic type, in comparison to the atypical type of MDD or controls. A positive correlation was found between the severity of depressive symptoms, concentrations of IL-6 and cortisol in the MDD group with melancholic features, while a negative correlation was observed between IL-6 and CRP in the MDD group with atypical feature. Also, in the MDD group with atypical features, there was a correlation between the severity of anxiety symptoms based on the Hamilton Rating Scale for Anxiety (HARS), concentration of CRP, and the duration of symptoms. In conclusion, we observed several differences in serum CRP, IL-6, and cortisol concentrations in MDD patients considering clinical features as well.     

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, paranoid personality disorder diagnosis: a unitary or a two-dimensional construct?

Objective

This article examines reliability and validity aspects of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) paranoid personality disorder (PPD) diagnosis.

Method

Patients with personality disorders (n = 930) from the Norwegian network of psychotherapeutic day hospitals, of which 114 had PPD, were included in the study. Frequency distribution, χ², correlations, reliability statistics, exploratory, and confirmatory factor analyses were performed.

Results

The distribution of PPD criteria revealed no distinct boundary between patients with and without PPD. Diagnostic category membership was obtained in 37 of 64 theoretically possible ways. The PPD criteria formed a separate factor in a principal component analysis, whereas a confirmatory factor analysis indicated that the DSM-IV PPD construct consists of 2 separate dimensions as follows: suspiciousness and hostility. The reliability of the unitary PPD scale was only 0.70, probably partly due to the apparent 2-dimensionality of the construct. Persistent unwarranted doubts about the loyalty of friends had the highest diagnostic efficiency, whereas unwarranted accusations of infidelity of partner had particularly poor indicator properties.

Conclusions

The reliability and validity of the unitary PPD construct may be questioned. The 2-dimensional PPD model should be further explored.     

Clinically related or predictive factors and impacts on long-term treatment outcomes of involvement behaviors in patients with obsessive–compulsive disorder

BackgroundPatients with obsessive–compulsive disorder (OCD) frequently exhibit involvement behaviors (IBs) in which they accommodate their caregivers to their OCD symptoms by 1) asking them for reassurance, 2) forcing them to participate in their rituals, or 3) forcing them to assist in avoidance according to the patients’ rules or demands. Such behaviors correspond to those of their caregivers, and are referred to as family accommodation (FA).MethodsWe performed multifactorial comparisons between 256 OCD patients with and without IBs in order to examine the clinical characteristics and long-term treatment outcomes of OCD patients with IBs. A multiple logistic regression analysis was also performed to identify the related and predictive factors of IBs.ResultsA total of 108 out of the 256 OCD patients examined (42%) were determined to exhibit IBs. OCD patients with IBs were differentially characterized by demographic and phenomenological characteristics (e.g. female predominance and poorer insight), more severe psychopathological features (e.g. lower GAFS, higher anxiety, or a depressive status), and poorer treatment outcomes. Furthermore, the predictive factors of IBs such as being female, having a higher compulsive score, and lower GAFS were identified by logistic analyses and structural equation modeling.ConclusionThe presence of IBs correlated with the severe clinical features, treatment refractoriness, and poorer long-term outcome of OCD. The severity of compulsions, being female, and lower GAFS were identified as predictive factors for the presence of IBs. Similar to FA, these findings appear to support the effectiveness of early identification and family-focused intervention in the treatment of OCD patients with IBs.     

Executive functions in 7-year-old children of parents with schizophrenia or bipolar disorder compared with controls: The Danish High Risk and Resilience Study—VIA 7, a population-based cohort study

Cognitive impairments are strongly associated with schizophrenia (SZ) and bipolar disorder (BP) with executive functions (EF) impairments as a likely key feature. Studies of everyday behavior rated EF in young children at familial high risk of SZ (FHR-SZ) are scarce and, to our knowledge, non-existent in young children at familial high risk of BP (FHR-BP). We aimed to compare everyday behavior-rated EF of FHR-SZ, FHR-BP, and control children. A nationwide population-based cohort of 522 7-year-old children with parents diagnosed with either SZ (N = 202) or BP (N = 120) and matched controls (N = 200) were recruited using the Danish national registries. The children’s EF were assessed with the Behavior Rating Inventory of Executive Functions questionnaire rated by primary caregivers and teachers. According to primary caregiver assessments, FHR-SZ children displayed widespread EF impairments and had an odds ratio of 3.7 (2.0–6.9) of having clinically significant global EF impairments compared to controls. FHR-BP children were most severely impaired regarding EF related to emotional control and had an odds ratio of 2.5 (1.2–5.1) of clinically significant global EF impairments compared to controls. Teacher assessments were overall comparable to primary caregiver assessments but teachers rated more difficulties in the FHR-SZ group than primary caregivers. Already at age 7, children with a parental history of SZ or BP displayed significant impairments of EF in everyday-life situations. FHR-SZ children displayed widespread significant impairments of EF, whereas FHR-BP children were most severely impaired on emotional control. Clinicians should be aware of potential EF impairments in FHR children.

     

Effects of 3,N,N′-trimethyl-2-phenyl-1,4-piperazine diastereomers on monoamine uptake and monoamine oxidase in rat brain

Summary The diastereomers of 3,N,N-trimethyl-2-phenyl-1,4-piperazine dihydrochloride (TPP) were tested for their effects on NA, DA and 5-HT uptake in synaptosomes prepared from hypothalamus, corpus striatum, and frontal cortex, respectively. The diastereomers differed with respect to their inhibitory properties. (2R, 3R)-TPP was more potent than the other diastereomers on NA and DA uptake, whereas (2S, 3S)-TPP was least potent. In contrast, the (2S, 3S)- and (2 S, 3R)-diastereomers of TPP were more potent than (2R, 3R)- and (2R, 3S)-TPP as inhibitors of 5-HT uptake. None of the diastereomers affected monoamine oxidase activity. The findings show that the diastereomers of TPP interact stereoselectively with neuronal mechanisms for monoamine uptake, and that the (S)-configuration at the 2 carbon is important for inhibitory actions of TPP on 5-HT uptake.