Neuropsychological performance in OCD: a study in medication-naïve patients

Background

Obsessive-compulsive disorder (OCD) is associated with impairments in multiple neuropsychological domains but the findings are rather inconsistent across studies. One potential reason for poor replication is the confounding influence of medications. There is limited research on neuropsychological performance in medication-naïve, never treated OCD patients.

Methods

In this study, we assessed 31 medication-naïve, never-treated, DSM-IV OCD patients free of comorbid major depression and 31 healthy controls individually matched for age, gender and years of education, with tests of attention, executive function, memory reasoning and visuo-spatial function.

Results

Medication-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Patients performed somewhat poorly only on the highest goal hierarchy of the Tower of London (TOL) test (p = 0.001, effect size = 0.68).

Conclusions

It is intriguing to find that symptomatic, drug-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Our finding of medium effect size on TOL highest goal hierarchy test suggests that brain regions outside the affective orbitofrontal loop may also be perhaps involved in OCD. This finding however needs replication because of modest effect size. Future studies should focus on studying medication-naïve, co-morbidity-free patients and relatives using symptom dimensions for consistent and robust findings.     

Comorbid obsessive-compulsive personality disorder in obsessive-compulsive disorder (OCD): a marker of severity

Introduction

Comorbid obsessive-compulsive personality disorder (OCPD) is well-described in obsessive-compulsive disorder (OCD). It remains unclear, however, whether OCPD in OCD represents a distinct subtype of OCD or whether it is simply a marker of severity in OCD.

Materials and methods

The aim of this study was to compare a large sample of OCD subjects (n = 403) with and without OCPD on a range of demographic, clinical and genetic characteristics to evaluate whether comorbid OCPD in OCD represents a distinct subtype of OCD, or is a marker of severity.

Results

Our findings suggest that OCD with and without OCPD are similar in terms of gender distribution and age at onset of OC symptoms. Compared to OCD − OCPD (n = 267, 66%), those with OCD + OCPD (n = 136, 34%) are more likely to present with the OC symptom dimensions which reflect the diagnostic criteria for OCPD (e.g. hoarding), and have significantly greater OCD severity, comorbidity, functional impairment, and poorer insight. Furthermore there are no differences in distribution of gene variants, or response to treatment in the two groups.

Conclusion

The majority of our findings suggest that in OCD, patients with OCPD do not have a highly distinctive phenomenological or genetic profile, but rather that OCPD represents a marker of severity.     

Association of the ZNF804A gene polymorphism rs1344706 with white matter density changes in Chinese schizophrenia

Background

ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients.

Methods

69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2 × 2 analysis of variance.

Results

1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers.2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group.

Limitation

The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated.

Conclusions

The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia.     

Dimensional correlates of poor insight in obsessive-compulsive disorder

Background

Cross-sectional studies have associated poor insight in patients with obsessive-compulsive disorder (OCD) with increased OCD symptom severity, earlier age of onset, comorbid depression, and treatment response. The goal of this current study was to examine the relationship between dimensions of OCD symptomatology and insight in a large clinical cohort of Brazilian patients with OCD. We hypothesized that poor insight would be associated with total symptom severity as well as with hoarding symptoms severity, specifically.

Methods

824 outpatients underwent a detailed clinical assessment for OCD, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS), the Brown Assessment of Beliefs Scale (BABS), a socio-demographic questionnaire, and the Structured Clinical Interview for axis I DSM-IV disorders (SCID-P). Tobit regression models were used to examine the association between level of insight and clinical variables of interest.

Results

Increased severity of current and worst-ever hoarding symptoms and higher rate of unemployment were associated with poor insight in OCD after controlling for current OCD severity, age and gender. Poor insight was also correlated with increased severity of current OCD symptoms.

Conclusion

Hoarding and overall OCD severity were significantly but weakly associated with level of insight in OCD patients. Further studies should examine insight as a moderator and mediator of treatment response in OCD in both behavioral therapy and pharmacological trials. Behavioral techniques aimed at enhancing insight may be potentially beneficial in OCD, especially among patients with hoarding.     

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls

Background

Similar patterns of subcortical brain abnormalities and neurocognitive dysfunction have been demonstrated in schizophrenia and bipolar disorder, with more extensive findings in schizophrenia. It is unknown whether relationships between subcortical volumes and neurocognitive performance are similar or different between schizophrenia and bipolar disorder.

Methods

MRI scans and neuropsychological test performance were obtained from 117 schizophrenia or 121 bipolar spectrum disorder patients and 192 healthy control subjects. Using the FreeSurfer software, volumes of 18 selected subcortical structures were automatically segmented and analyzed for relationships with results from 7 neurocognitive tests.

Results

In schizophrenia, larger left ventricular volumes were related to poorer motor speed, and bilateral putamen volumes were related to poorer verbal learning, executive functioning and working memory performance. In bipolar disorder, larger left ventricular volumes were related to poorer motor speed and executive functioning. The relationship between left putamen volume and working memory was specific to schizophrenia. The relationships between left inferior lateral ventricles and motor speed and between right putamen volumes and executive functioning were similar in schizophrenia and bipolar disorder, and different from healthy controls. The results remained significant after corrections for use of antipsychotic medication. Significant structure-function relationships were also found when all subjects were combined into one group.

Conclusion

The present findings suggest that there are differences as well as similarities in subcortical structure/function relationships between patients with schizophrenia or bipolar disorder and healthy individuals. The observed differences further suggest that ventricular and putamen volume sizes may reflect severity of cognitive dysfunction in these disorders.     

Verbal learning contributes to cognitive insight in schizophrenia independently of affective and psychotic symptoms

Objective

Patients with schizophrenia exhibit distorted beliefs and experiences, and their own evaluation of this is labeled cognitive insight. We examined the relationship between cognitive insight and neurocognition, as well as the contribution of neurocognition in explaining cognitive insight.

Method

Clinically characterized patients with schizophrenia (n = 102) were assessed with a measure of cognitive insight, Beck Cognitive Insight Scale (BCIS) and a neuropsychological test battery. The contribution of neurocognition to the explained variance in BCIS components self-reflectiveness (i.e. objectivity and reflectiveness) and self-certainty (i.e. overconfidence in own beliefs) was examined controlling for current affective and psychotic symptoms.

Results

A significant negative correlation was found between self-certainty and verbal learning, whereas no associations were found between self-reflectiveness and any of the neuropsychological tests. Verbal learning was added significantly to the explained variance in self-certainty after controlling for potential confounders.

Conclusion

High self-certainty was associated with poor verbal learning. This suggests that overconfidence in own beliefs is associated with cognitive dysfunction in schizophrenia.     

Auditory orienting and inhibition of return in schizophrenia: A functional magnetic resonance imaging study

Background

The brain mechanisms of cognitive-behavioral therapy (CBT), a highly effective treatment for pediatric obsessive-compulsive disorder (OCD), are unknown. Neuroimaging in adult OCD indicates that CBT is associated with metabolic changes in striatum, thalamus, and anterior cingulate cortex. We therefore probed putative metabolic effects of CBT on these brain structures in pediatric OCD using proton magnetic resonance spectroscopic imaging (¹H MRSI).

Method

Five unmedicated OCD patients (4 ♀, 13.5 ± 2.8) and 9 healthy controls (7 ♀, 13.0 ± 2.5) underwent MRSI (1.5 T, repetition-time/echo-time = 1500/30 ms) of bilateral putamen, thalamus and pregenual anterior cingulate cortex (pACC). Patients were rescanned after 12 weeks of exposure-based CBT. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) of OCD symptoms was administered before and after CBT.

Results

Four of 5 patients responded to CBT (mean 32.8% CY-BOCS reduction). Multiple metabolite effects emerged. Pre-CBT, N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (tNAA) in left pregenual anterior cingulate cortex (pACC) was 55.5% higher in patients than controls. Post-CBT, tNAA (15.0%) and Cr (23.9%) in left pACC decreased and choline compounds (Cho) in right thalamus increased (10.6%) in all 5 patients. In left thalamus, lower pre-CBT tNAA, glutamate + glutamine (Glx), and myo-inositol (mI) predicted greater post-CBT drop in CY-BOCS (r = 0.98) and CY-BOCS decrease correlated with increased Cho.

Conclusions

Interpretations are offered in terms of the Glutamatergic Hypothesis of Pediatric OCD. Similar to ¹⁸FDG-PET in adults, objectively measurable regional MRSI metabolites may indicate pediatric OCD and predict its response to CBT.     

Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: comparing vulnerability markers

Background

Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree.

Methods

Three groups (n = 100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2 s & 12 s); sustained attention processing was assessed using the Continuous Performance Task—Identical Pairs version.

Results

SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls.

Conclusions

These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP.     

Source imaging of P300 auditory evoked potentials and clinical correlations in patients with posttraumatic stress disorder

Objective

Posttraumatic stress disorder (PTSD) is associated with abnormal information processing. The P300 component of event-related potentials (ERPs) is known to be a useful marker of information processing. The purposes of this study were to determine the P300 current source density in PTSD patients, and its relationship with symptom severity.

Methods

ERPs were recorded in 30 PTSD patients and 33 healthy controls while participants were performing the auditory oddball task. We compared P300 current source density data - obtained by standardized low-resolution brain electromagnetic tomography (sLORETA) - between the two groups. The correlation between P300 current source density and clinical symptoms (as evaluated using the Korean version of the Structured Interview for PTSD — K-SIPS and Davidson Trauma Scale — K-DTS) was conducted.

Results

In PTSD patients, the current source density of P300 is significantly reduced in the inferior frontal gyrus, precentral gyrus, insula, and anterior cingulate compared to healthy controls. Total K-DTS scores were correlated with the P300 current source density in the posterior cingulate gyrus. The K-SIP B items (re-experiencing) and K-SIB D items (increased arousal) were positively correlated with P300 current source densities in several brain regions located in the frontal, parietal, and temporal lobe (p < 0.05). Conversely, the K-SIP C items (avoidance and numbing) were negatively correlated with P300 current source densities in the superior and middle frontal gyri in the frontal lobes (p < 0.05).

Conclusion

The P300 current source densities reflected the pathophysiology of PTSD patients. PTSD symptoms were related to different neural activities, depending on their symptom characteristics.     

Some stereotypic behaviors in rhesus macaques (Macaca mulatta) are correlated with both perseveration and the ability to cope with acute stressors

Introduction

Literature on the ability of patients with obsessive-compulsive disorder (OCD) to recognize static facial expressions of disgust is not consistent. We aimed to investigate whether OCD is associated with deficits in the recognition of disgust in a dynamic task, and if so, whether the acute administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram would result in the normalization of such deficits.

Methods

OCD patients (n = 20) and matched healthy controls (n = 20) received a single dose of escitalopram 20 mg on one day, and a single dose of placebo on another day, in randomized order, under double-blind conditions. Accuracy (i.e. the percentage of correct answers) and sensitivity to disgust stimuli (defined as the lowest level of emotional intensity expressed on the photo image after which no errors were made in the recognition of disgust for subsequent trials of increasing intensity) were compared in OCD patients and controls, with a repeated measures analysis of variance using a mixed model approach.

Results

On placebo, the accuracy of, and sensitivity to, disgust stimuli were similar across groups. OCD patients had more accurate and more sensitive recognition of disgust after acute SSRI administration than after placebo, while controls had less accurate recognition and less sensitive recognition of disgust after acute SSRI administration than after placebo.

Conclusions

The use of a dynamic facial recognition task demonstrated altered responses to disgust in OCD patients compared to healthy controls after a pharmacological challenge with escitalopram. These findings suggest that the serotonergic system plays a role in disgust recognition.     

Neurological soft signs in obsessive compulsive disorder with good and poor insight

Objective

Obsessive compulsive disorder (OCD) is a clinically heterogeneous disorder; OCD with poor insight has been suggested to be a specific clinical subtype. Neurological soft signs (NSSs) may be helpful to identify the specific subtypes of OCD patients.

Methods

In the present study, we aimed to compare OCD patients with poor insight with OCD patients having good insight, and healthy individuals. Sixty-four OCD patients (38 with good insight and 26 with poor insight), and 32 healthy subjects were enrolled in the present study. The Overvalued Ideas Scale (OVIS) was used to determine OCD patients with poor insight. NSSs were assessed by using the Neurological Evaluation Scale (NES).

Results

Two OCD groups had significantly higher total NES scores compared to controls (p = .000). Compared to healthy controls, OCD patients with poor insight performed significantly worse on all NES subscales, and they had significantly more NSSs on motor coordination, and sensory integration subscales compared to the OCD with good insight group.

Conclusion

Our results suggested that OCD patients with poor insight exhibit more extensive neurodevelopmental impairments compared to OCD patients with good insight.     

Shared impairment in associative learning in schizophrenia and bipolar disorder

Background

Schizophrenia (SCZ) and bipolar disorder (BD) share some cognitive commonalities. However, the role of associative learning, which is a cornerstone of human cognition mainly relying on hippocampus, has been under-investigated. We assessed behavioral performance during associative learning in a group of SCZ, BD and healthy controls (HC).

Methods

Nineteen patients with SCZ (36 ± 8.1 years; 13 males, 6 females; all Caucasians), 14 patients with BD (41 ± 9.6 years; 5 males, 9 females; all Caucasians) and 45 HC (27.7 ± 6.9 years; 18 males, 27 females; all Caucasians) were studied. Learning was assessed using an established object-location paired-associative learning paradigm. Subjects learned associations between nine equi-familiar common objects and locations in a nine-location grid. Performance data were analyzed in a repeated measures analysis of variance with time (repeated) and group as factors.

Results

Learning curves (performance = 1−e^−k?time) fitted to average performance data in the three groups revealed lower learning rates in SCZ and BD (k = 0.17 and k = 0.34) than HC (k = 0.78). Significant effects of group (F = 11.05, p < 0.001) and time (F = 122.06, p < 0.001) on learning performance were observed.

Conclusions

Our study showed that associative learning is impaired in both SCZ and BD, being potentially not affected by medication. Future studies should investigate the neural substrates of learning deficits in SCZ and BD, particularly focusing on hippocampus function and glutamatergic transmission.     

Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial

Rationale

Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.

Objectives

We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.

Method

Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥ 20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50 mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100 mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥ 50% improvement in the MADRS) at week 8.

Results

Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n = 20) showed a higher rate of responders than the Continuing group (n = 21) (75% vs. 19%: p = 0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤ 10 in the MADRS) (60% vs. 14%: p = 0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p < 0.001).

Conclusions

Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.     

A clinical comparison of pathologic skin picking and obsessive-compulsive disorder

Background

It has been hypothesized that pathologic skin picking (PSP) shares many of the same biological and phenomenological characteristics as obsessive-compulsive disorder (OCD). This study sought to examine the clinical similarities between PSP and OCD.

Method

Demographic and clinical characteristic data were examined in a treatment-seeking sample of 53 PSP (mean age, 34.2 ± 13.1 years; 86.8% female) and 51 OCD (mean age, 36.5 ± 11.7 years; 35.3% female) subjects. Psychiatric comorbidity and family history data were also obtained.

Results

The PSP subjects were more likely to be female (P < .001), report higher rates of co-occurring compulsive nail biting (P < .001), and have a first-degree relative with a grooming disorder (P < .001). The OCD subjects spent significantly more time on their thoughts and behaviors (P < .001) and were more likely to have co-occurring body dysmorphic disorder (P = .001).

Conclusion

Although PSP and OCD share some clinical similarities, important differences exist and cast doubt on the conceptualization of PSP as simply a variant of OCD.     

Disrupted regional homogeneity in treatment-resistant depression: a resting-state fMRI study

Background

Using a newly developed regional homogeneity (ReHo) approach, we were to explore the features of brain activity in patients with treatment-resistant depression (TRD) in resting state, and further to examine the relationship between abnormal brain activity in TRD patients and specific symptom factors derived from ratings on the Hamilton Rating Scale for Depression (HRSD).

Methods

24 patients with TRD and 19 gender-, age-, and education-matched healthy subjects participated in the fMRI scans.

Results

1.

Compared with healthy controls, decreased ReHo were found in TRD patients in the left insula, superior temporal gyrus, inferior frontal gyrus, lingual gyrus and cerebellum anterior lobe (culmen) (p < 0.05, corrected).

2.

Compared with healthy controls, increased ReHo were found in the left superior temporal gyrus, cerebellum posterior lobe (tuber), cerebellum anterior lobe (culmen), the right cerebellar tonsil and bilateral fusiform gyrus (p < 0.05, corrected).

3.

There was no correlation between the ReHo values in any brain region detected in our study and the patients' age, years of education, illness duration, HRSD total score and its symptom factors.

Limitation

The influence of antidepressants to the brain activity in TRD patients was not fully eliminated.

Conclusions

The pathogenesis of TRD may be attributed to abnormal neural activity in multiple brain regions.     

Role of serotonergic-related systems in suicidal behavior: Data from a case-control association study

Objective

To investigate whether functional polymorphisms directly (HTR2A and SLC6A4 genes) or indirectly (IL-1 gene complex, APOE and ACE genes) related with serotonergic neurotransmission were associated with suicidal behavior.

Subjects and methods

227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods.

Results

There were no differences in genotype frequencies between the three groups. The −1438A/G [χ² (df) = 9.80 (2), uncorrected p = 0.007] and IL-1α −889C/T [χ² (df) = 8.76 (2), uncorrected p = 0.013] genotype frequencies between impulsive and planned suicide attempts trended toward being different (not significant after Bonferroni correction). Suicide attempts were more often impulsive in the presence of −1438G/G or IL-1α −889C/T or C/C genotypes. There was interaction between the polymorphism 5-HTTLPR and age [LRT (df) = 6.84 (2), p = 0.033] and between the polymorphisms APOE and IL-1RA (86 bp)_n [LRT (df) = 12.21 (4), p = 0.016] in relation to suicide attempt lethality.

Conclusion

These findings further evidence the complexity of the association between genetics and suicidal behavior, the need to study homogenous forms of the behavior and the relevance of impulsive and aggressive traits as endophenotypes for suicidal behavior.     

Aggression and psychopharmacological treatments in major psychosis and personality disorders during hospitalisation

Background

A number of large-scale studies have shown that there is a relationship between many psychiatric disorders and aggression or violence. As no medication is currently approved for the treatment of aggression, pharmacotherapy (often involving drug combinations) is used on a trial-and-error basis with various degrees of response.

Method

The study involved 244 in-patients aged 19-83 years (mean 41.9 ± 11.3 SD). The Modified Overt Aggression Scale (MOAS) was used to assess any aggressive or violent behaviors occurring in the week before admission and upon discharge.Psychopathology was assessed using the Brief Psychiatric Rating Scales (BPRS).

Results

All of the patients showed a significant improvement (p < 0.001) in mean weighted total MOAS scores at the end of the study, with no significant differences between the various drugs or combination therapies. The patients who received combination treatments including antidepressants showed a worsening in the weighted total MOAS score (18.46% ± 114.31% SD); the patients who did not receive antidepressants had an improvement (13.61% ± 257.36% SD) (p = 0.0069).

Conclusions

Multivariate testing of the variables age, gender, substance/alcohol abuse, the duration of hospitalisation, the administration of mood stabilisers, and the use of typical or atipical antipsychotics showed that the severity of the psychopathological picture correlated significantly with the presence of violence, whereas the effect of combined antidepressant treatment on violent behavior was only relative.     

Disturbed functional connectivity within brain networks subserving domain-specific subcomponents of working memory in schizophrenia: Relation to performance and clinical symptoms

Introduction

Disturbed interregional functional connectivity has been hypothesized to be a promising marker of schizophrenia. The relationship between working memory (WM) impairment, disturbed functional connectivity, and the characteristic symptoms of schizophrenia, however, remains elusive.

Methods

We used functional MRI (fMRI) to investigate in patients with schizophrenia and matched controls the patterns of functional connectivity during the performance of different tasks selectively engaging subcomponent processes of working memory.

Results

Compared with controls, patients showed reduced connectivity of the prefrontal cortex with the intraparietal cortex and the hippocampus and abnormal negative interactions between the ventrolateral and dorsolateral prefrontal cortex during the non-articulatory maintenance of phonological information. During the maintenance of visuospatial information, patients presented reduced connectivity between regions in the superior parietal and occipital cortex, as well as enhanced positive connectivity of the frontal eye field with visual processing areas.

Discussion

Our findings suggest complex dysregulations within the networks supporting working memory functions in schizophrenia, which manifest as decreased positive and abnormal negative interactions. Correlations between the connection strength and WM performance suggest that these dysregulations may be neurofunctional correlates of the WM deficits seen in schizophrenia. Altered prefronto-hippocampal and parieto-occipital connectivity was further found to be associated with higher positive symptoms, providing a possible explanation for the development of delusions and disorganization symptoms.

Conclusion

The present findings can help to better understand the relationship between altered patterns of synchronized brain activity and the cognitive and clinical symptoms of schizophrenia.     

Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects

Objective

Aim of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of Acetyl-l-Carnitine (ALC), at different dosages, on specific anhedonic symptoms in detoxified alcohol dependent subjects. Secondary endpoints were the effect of ALC on melancholic and negative symptoms.

Method

Sixty-four anhedonic alcohol dependent patients with minor or absent withdrawal symptoms were randomized: 23 received ALC at a dosage of 3 g/day, 21 received ALC at a dosage of 1 g/day, and 20 were given placebo. ALC was given intravenously for 10 days, followed by 80 days of oral treatment plus a follow-up period of 45 days. The presence of anhedonic symptoms was determined by the SHAPS (Snaith-Hamilton Pleasure Scale) and the VASa (Visual Analogue Scale for Anhedonia); negative and melancholic symptoms were evaluated by the SANS (Scale for the Assessment of Negative Symptoms), and the BRMS (Bech-Rafaelsen Melancholia Scale).

Results

The natural course of anhedonia in the placebo group showed a decline until day 30 and remains stable for the rest of the study. Intravenously ALC accelerated the improvement of anhedonia reaching constant low levels early, on day 10. At this step levels of anhedonia (SHAPS, VASa) and melancholic symptoms (BRMES) resulted significantly reduced (p < 0.05) in both the ALC 3 g and ALC 1 g groups with respect to placebo; SANS scores significantly reduced only in the ALC 1 g respect to placebo (p = 0.014). During oral treatment with ALC, anhedonia scores did not differ from placebo.

Conclusion

Intravenously ALC was effective in accelerating the abstinence-associated improvement of anhedonia, melancholic and negative symptoms, whereas oral ALC treatment starting on day 10 showed no further improvements. Accordingly, in alcohol dependent subjects, ALC may be considered as a new potentially useful drug for the treatment of anhedonia.     

Development of a computer-based behavioral assessment of checking behavior in obsessive-compulsive disorder

Objective

The goal of the current study was to develop and obtain preliminary psychometric data for a computer-based behavioral measure of compulsive checking behavior in a sample of patients with obsessive-compulsive disorder (OCD).

Method

We examined performance on a novel behavioral measure in 30 patients with OCD and 27 matched healthy controls. In the computerized assessment, participants navigated through two virtual environments (home and office) using a joystick and head-mounted display. The experiment consisted of three phases: training, distraction, and the main task. After the training and distraction phases, participants were instructed to check the virtual environments freely as if they were in their natural environment. Primary dependent variables in the current study included several indices of frequency and duration of checking behaviors. We examined construct validity for the task by comparing the novel behavioral measures with standardized self-report and interviewer-rated measures.

Results

Results indicated that (1) OCD patients demonstrated significantly greater problems with compulsive checking compared to controls, and (2) performance on the task was positively correlated with both self-reported symptoms and interviewer-rated measures associated with OCD.

Conclusions

This study provides preliminary data to support the use of this task as a new possible behavioral measure of compulsive checking behavior in OCD. If we merge the traditional behavioral research with this novel and ecologically valid method, it could improve the assessment of OCD in both clinical and research setting.