Relationships between cognitive appraisals of adolescents with OCD and their mothers

Objective

Our aim was to investigate cognitive models of OCD via the influence of mothers’ cognitive appraisals on children's cognitions and OCD symptoms.

Method

Our sample consisted of 21 adolescents with OCD, their mothers and 27 parent–child dyads for control group without OCD. Subjects with OCD and their mothers were administered The Beck Depression Inventory (BDI), The Thought–Action Fusion Scale (TAFS), The White Bear Suppression Inventory (WBSI), The Padua Inventory-Revised (PI-R) and The Penn Inventory of Scrupulosity (PIOS).

Results

While the BDI (t = 2.18, p < 0.05) and TAF Morality (t = 2.18, p < 0.05) scores of the mothers of OCD subjects were significantly higher than the mothers of control subjects, the comparisons for the PI, TAF likelihood and PIOS scores of groups were not significant. Intradyadic correlation revealed significant relationships for PI-Rumination, PI-Checking and WBSI scales between the scores of parent and child in OCD dyads, (respectively, r = 0.49, P = 0.11; r = 0.37, P = 0.045; and r = 0.47, P = 0.014). There was no significant relationship in the control group.

Conclusion

Our results partially supported that mothers’ cognitive appraisals are associated with the cognitive appraisal of adolescents. A cognitive intradyadic interaction between mother and child might be more likely in the presence of OCD in adolescents.     

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study

Objectives

We evaluated the efficacy of bimodal repetitive transcranial magnetic stimulation (rTMS) in treating pharmacologically non-responsive patients with schizophrenia.

Methods

Ten patients with DSM-IV schizophrenia, unresponsive to pharmacological treatment, underwent treatment with 15 rTMS sessions, as an adjunctive therapy, for three weeks. Each session comprised 40 trains, beginning every 30 s: 20 trains of 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC) with a 3-s duration and 20 trains of 1 Hz rTMS to the left temporoparietal cortex (TPC) with a 30-s duration. We assessed patients via the Positive and Negative Syndrome Scale (PANSS) and Korean Version of the Calgary Depression Scale for Schizophrenia (K-CDSS), at five time points: baseline, Days 8, 15, and 22, and 1 week after final treatment (Day 29). Patients who agreed to take neurocognitive tests underwent neurocognitive function evaluations at baseline and 1 week after final treatment.

Results

At Day 29, all PANSS subscale scores in had decreased significantly compared to baseline (Z = − 2.214, p = 0.027, positive; Z = − 2.132, p = 0.033, negative; Z = − 2.023, p = 0.043, general pathology; Z = − 2.371, p = 0.018, total). Effect over time was significant for the PANSS positive and negative subscale scores and total score (χ² = 13.35, p = 0.010; χ² = 10.27, p = 0.036; and χ² = 16.50, p = 0.002, respectively) but not for the general pathology subscale. Among the neurocognitive tests, the fourth and fifth trials and total K-AVLT scores showed significant increases (Z = − 2.041, p = 0.041; Z = − 2.251, p = 0.024; and Z = − 2.201, p = 0.028, respectively), suggesting improvement in short-term auditory verbal memory.

Conclusions

Bimodal rTMS stimulation of left DLPFC and left TPC induced clinical improvement in pharmacologically non-responsive schizophrenia patients and may have improved their short-term verbal memories.     

Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response

Tryptophan hydroxylase-2 (TPH2) is the rate-limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of antidepressant action. This study aimed to investigate whether common genetic variation in the TPH2 gene is associated with MDD and therapeutic response to antidepressants in a Chinese population. A total of 508 MDD patients and 463 unrelated controls were recruited. Among the MDD patients, 187 accepted selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressant treatment for 8 weeks with therapeutic evaluation before and after treatment. Five TPH2 polymorphisms were genotyped and their association with MDD or treatment response was assessed by haplotype and single-marker analysis. In single-marker-based analysis, the rs17110747-G homozygote polymorphism was found to be more frequent in the MDD patients than in the controls (P = 0.002). Genotype analysis in responders (defined as those with a 50% reduction in baseline Hamilton score) and non-responders after 8 weeks of antidepressant treatment showed that the proportion of rs2171363 heterozygote carriers was higher in the responders than the non-responders (P = 0.009). No significant association with MDD or antidepressant therapeutic response was discovered in haplotype analyses. Our findings show that TPH2 genetic variants may play a role in MDD susceptibility and in acute therapeutic response to selective serotonin reuptake inhibitors.     

Exploring soluble urokinase plasminogen activator receptor and its relationship with arterial stiffness in a bi-ethnic population: the SAfrEIC-study

Introduction

Elevated soluble urokinase-type plasminogen activator receptor (suPAR) indicates an inflammatory state caused by conditions such as HIV and cancer. Recently suPAR was identified as an indicator of cardiovascular disease (CVD). CVD is highly prevalent in black South Africans, but the potential role of suPAR is unknown. We investigated suPAR as a possible marker of arterial stiffness in Africans and Caucasians.

Methods

This study involved 207 Africans and 314 Caucasians (aged 20-70 yrs). C-reactive protein (CRP) and suPAR were determined in fasting blood samples. We measured blood pressure, pulse wave velocity (PWV) and Windkessel arterial compliance (Cwk).

Results

Africans displayed higher suPAR, CRP, PWV and lower Cwk (p < 0.001) compared to Caucasians. SuPAR was elevated in Africans irrespective of gender and smoking. We found strong relationships between PWV and suPAR (r = 0.27; p < 0.001) and Cwk and suPAR (r = − 0.39; p < 0.001) in the whole group, but found no independent relationship of any arterial stiffness measure and suPAR in Africans after adjustment for confounders. Caucasian men indicated a weak significant independent association between Cwk and suPAR (β = − 0.09; p = 0.028).

Conclusion

Africans had higher levels of suPAR and arterial stiffness than Caucasians (p < 0.001), but there was no independent relationship between arterial stiffness and suPAR in the Africans. It is speculated that due to the inflammatory role of suPAR, it will have stronger relationships with atherosclerosis, which has not yet manifested in this relatively young population group. SuPAR may therefore not be an ideal early marker of cardiovascular dysfunction, but may rather indicate established CVD.     

Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression

Background

Ketamine rapidly improves depressive symptoms in patients with treatment-resistant major depressive disorder (MDD) who do not respond to multiple standard antidepressants. However, it remains unknown whether ketamine is equally effective in patients with MDD who previously also did not respond to electroconvulsive therapy (ECT).

Methods

This study compared 17 patients with treatment-resistant MDD who previously did not respond to ECT and 23 patients with treatment-resistant MDD who had not previously received ECT. All subjects received a single open-label infusion of ketamine (0.5 mg/kg). Patients were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline (60 min before the infusion), as well as at 40, 80, 120, and 230 min after infusion.

Results

Depressive symptoms were significantly improved in the ECT-resistant group at 230 minutes with a moderate effect size (p < .001, d = 0.50, 95% C.I.: 0.21-0.80). At 230 minutes, the non-ECT exposed group showed significant improvement with a large effect size (p < .001, d = 1.00, 95% C.I.: 0.71-1.29).

Conclusion

Ketamine appears to improve depressive symptoms in patients with MDD who had previously not responded to ECT. These preliminary results encourage further investigation with a larger sample size to determine effectiveness compared to other treatment-resistant patients with MDD.     

Effects of venlafaxine and fluoxetine on lymphocyte subsets in patients with major depressive disorder: A flow cytometric analysis

Background

Studies have yielded conflicting results concerning flow cytometric lymphocyte analyses in patients with depression. Data about the effect of antidepressants on lymphocyte subsets are also contradictory. The aim of this study was to determine effects of venlafaxine versus fluoxetine on lymphocyte subsets in depressive patients.

Methods

Sixty-nine patients diagnosed with major depressive disorder (MDD) according to DSM-IV and 36 healthy controls are included in the study. Sixty-nine patients were randomized to take fluoxetine (FLX) (n = 33) or venlafaxine (VEN) (n = 36). Serum lymphocyte subsets included CD3, CD4, CD8, CD16/56, CD19, CD45, Anti-HLA-DR which were measured by flow cytometric analyses at baseline and 6 weeks after the start of treatment. The severity of depression was evaluated with Hamilton rating scale for depression.

Results

At baseline, patients with MDD had significantly lower CD16/56 ratio and higher CD45 ratio compared to the controls. Although numerically higher in the VEN treated patients, treatment response rates between the FLX (53%) and the VEN (75%) groups were not different statistically. CD45 values decreased significantly in the VEN group at the end of the 6 week treatment period whereas no difference was observed in the FLX group. By the 6th week, treatment responders showed a significantly higher CD16/56 ratio than non-responders. Baseline severity of depression and anxiety was positively correlated with baseline CD45 ratio and negatively correlated with baseline CD16/56 ratio. We did not observe consistent changes in the absolute number of circulating B or T cells, nor in the helper/inducer (CD4) or suppressor/cytotoxic (CD8) subsets.

Conclusions

CD16/56 was lower in patients with MDD and increased in treatment responders at 6th week. CD45 ratio was higher in patients with MDD than healthy subjects; it decreased with antidepressant treatment and was positively correlated with the severity of depression. Antidepressant treatment contributes to immune regulation in patients with major depressive disorder.     

Endogenous thrombin potential (ETP) in plasma from patients with AMI during antithrombotic treatment

Background

The beneficial impact of warfarin in preventing new events after AMI is well established. Decrease in thrombin generation seems to be the key element in anticoagulant treatment.

Objectives

The aims were to investigate the effect of warfarin and platelet inhibition on thrombin generation, assessed by the endogenous thrombin potential (ETP), and study the relation between coagulation parameters and ETP in patients with AMI.

Patients/Methods

In the present sub-study of the WARIS II trial, patients with AMI were randomly assigned to treatment with aspirin 160 mg/d (n = 57), aspirin 75 mg/d and warfarin (INR 2.0-2.5) (n = 68) or warfarin (INR 2.8-4.2) (n = 61). Fasting blood samples were collected from patients at discharge from hospital and after 6 weeks treatment.

Results

Correlation analyses showed that both ETP and peak thrombin levels were significantly correlated with Factor VII Ag (r = 0.38 and 0.36 respectively, p < 0.01 for both) and with F1+2 (r = 0.26 and 0.23 respectively, p = 0.01 for both) at baseline. Antithrombotic treatment for 6 weeks caused a highly significant inhibition of ETP in patients treated with warfarin (− 28% ± 5%, p < 0.001), and patients treated with aspirin/warfarin (− 24% ± 8%, p = 0.04). Similarly, peak thrombin levels were reduced in patients treated with warfarin (− 18% ± 7%, p = 0.049) and aspirin/warfarin (− 19% ± 5%, p = 0.029), whereas an increase (12% ± 4%, p = 0.029) occurred during aspirin treatment alone. F1+2 levels decreased by 64% and 58% in the warfarin and aspirin/warfarin groups, respectively (p = 0.001 for both).

Conclusions

In patients with AMI, warfarin significantly reduced the endogenous thrombin generation and the potential to generate thrombin in plasma ex vivo, whereas aspirin alone had no effect on thrombin generation in vivo or ex vivo, assessed by ETP.     

CVD risk factors are related to plasma fibrin clot properties independent of total and or γ’ fibrinogen concentration

Introduction

Cardiovascular disease (CVD) risk factors are associated with total fibrinogen concentration and/or altered clot structure. It is however, unclear whether such associations with clot structure are ascribed to fibrinogen concentration or other independent mechanisms. We aimed to determine whether CVD risk factors associated with increased total and/or γ’ fibrinogen concentration, were also associated with altered fibrin clot properties and secondly whether such associations were due to the fibrinogen concentration or through independent associations.

Materials and methods

In a plasma setting CVD risk factors (including total and γ’ fibrinogen concentration) were cross-sectionally analysed in 2010 apparently healthy black South African participants. Kinetics of clot formation (lag time, slope and maximum absorbance) as well as clot lysis times were calculated from turbidity curves.

Results

Of the measured CVD risk factors age, metabolic syndrome, C-reactive protein (CRP), high density lipoprotein (HDL)-cholesterol and homocysteine were significantly associated with altered fibrin clot properties after adjustment for total and or γ’ fibrinogen concentration. Aging was associated with thicker fibres (p = 0.004) while both metabolic syndrome and low HDL-cholesterol levels were associated with lower rates of lateral aggregation (slope), (p = 0.0004 and p = 0.0009), and the formation of thinner fibres (p = 0.007 and p = 0.0004). Elevated CRP was associated with increased rates of lateral aggregation (p = 0.002) and consequently thicker fibres (p < 0.0001). Hyperhomocysteinemia was associated with increased rates of lateral aggregation (p = 0.0007) without affecting fibre thickness.

Conclusion

Final clot structure may contribute to increased CVD risk in vivo through associations with other CVD risk factors independent from total or γ’ fibrinogen concentration.     

The relationship between impulsivity and lipid levels in bipolar patients: does temperament explain it?

Background

The aim of this study was to investigate whether there was a relationship between impulsivity and lipid levels in patients with bipolar disorder (BD) and to examine the correlation of impulsivity and lipid levels with temperament subtypes.

Methods

For this purpose, one hundred patients who were admitted to our out-patient unit for routine controls, had been in remission for at least 8 weeks, and diagnosed as BD according to the DSM-IV were evaluated consecutively. Impulsivity and temperament were evaluated with the BIS-11 and the TEMPS-A. Blood samples were obtained to measure levels of lipids (cholesterol, triglyceride, high density lipoprotein-HDL, low density lipoprotein-LDL).

Results

A weak correlation was found between impulsivity scores and triglyceride levels (r = 0.190, p = 0.050). Correlation was found between impulsivity scores and depressive, anxious, cyclothymic, and irritable temperaments (r = 0.371, p < 0.001; r = 0.458, p < 0.001; r = 0.541, p < 0.001; r = 0.530, p < 0.001), while triglyceride levels were only related with depressive and anxious temperaments (r = 0.485, p = 0.001 and r = 0.391, p = 0.006).

Conclusions

Temperament is an important mediator of the relationship between lipid levels and trait impulsivity in patients with BD.     

Impulsivity in children and adolescents with mood disorders and unaffected offspring of bipolar parents

Objective

Increased impulsivity seems to be present across all phases of bipolar disorder (BD). Impulsivity may therefore represent an endophenotype for BD, if it is also found among normal individuals at high genetic risk for mood disorders. In this study, we assessed impulsivity across four different groups of children and adolescents: patients with BD, major depressive disorder (MDD) patients, unaffected offspring of bipolar parents (UO), and healthy controls (HC).

Subjects and Methods

52 patients with BD, 31 with MDD, 20 UO, and 45 HC completed the Barratt Impulsiveness Scale (BIS-11), an instrument designed to measure trait impulsivity.

Results

UO displayed significantly higher total BIS-11 impulsivity scores than HC (p = 0.02) but lower scores than BD patients (F = 27.12, p < 0.01). Multiple comparison analysis revealed higher BIS-11 total scores among BD patients when compared to HC (p < 0.01) and UO (p < 0.01). MDD patients had higher BIS-11 scores when compared to HC (p < 0.01). Differences between MDD patients and UO, as well as between MDD and BD patients, were not statistically significant.

Conclusion

Our findings suggest that trait impulsivity is increased among children and adolescents with mood disorders, as well as in unaffected individuals at high genetic risk for BD.     

Changes in cognitive symptoms after a buspirone–melatonin combination treatment for Major Depressive Disorder

Cognitive deficits are often associated with acute depressive episodes and contribute to the functional impairment seen in patients with Major Depressive Disorder (MDD). Many patients sustain residual cognitive deficits after treatment that may be independent of the core MDD disorder. We tracked changes in cognitive deficits relative to antidepressant treatment response using the patient self-rated Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) during a 6-week, double-blind trial of a combination antidepressant treatment (buspirone 15 mg with melatonin-SR 3 mg) versus buspirone (15 mg) monotherapy versus placebo in MDD patients with acute depressive episodes. The CPFQ includes distinct cognitive and physical functioning dimension subscales. Treatment response was determined using the Inventory of Depressive Symptomatology (IDSc30). Treatment responders improved significantly more on the total CPFQ than non-responders (p < 0.0001) regardless of treatment assignment. The cognitive dimension of the CPFQ score favored the combination treatment over the other two groups (ANCOVA: p = 0.050). Among the treatment non-responders, the effect size for the CPFQ cognitive dimension was 0.603 favoring the combination treatment over the over two groups and 0.113 for the CPFQ physical dimension. These preliminary findings suggest that a combination of buspirone with melatonin may benefit cognitive function distinct from mood symptoms and that some aspects of cognition may be specific targets for treatment within a population of patients with MDD.     

Plasma fibrin clot properties in arterial hypertension and their modification by antihypertensive medication

Background

We sought to determine plasma fibrin clot properties in hypertensive subjects and to evaluate potential effects of antihypertensive therapy on these parameters.

Patients and Methods

Sixty-one patients (30 men, 31 women) with essential arterial hypertension stage 1 or 2 (aged 46.6 ± 14.4 years), free of clinically evident vascular disease, were randomly allocated for monotherapy with one of the 5 antihypertensive agents, i.e. quinapril, losartan, amlodipine, hydrochlorothiazide, or bisoprolol. Plasma fibrin clot permeability, turbidimetry and efficiency of fibrinolysis were investigated at baseline and after 6 months of therapy.

Results

Baseline systolic blood pressure in a 24-hour ambulatory monitoring was correlated with clot permeability (r = − 0.37, p < 0.05), lysis time (r = 0.42, p < 0.05) and maximal D-dimer concentration released from clots (r = 0.45, p < 0.05). Antihypertensive treatment resulted in reduction of systolic/diastolic blood pressure in office measurements and 24-hour monitoring (all p < 0.001), accompanied by an increase in clot permeability, reduction in clot lysis time and lower maximal D-dimer concentration released from fibrin clots (all p < 0.05). No changes were observed in turbidimetric variables. Posttreatment changes in plasma fibrin clot properties were related to reductions in systolic blood pressure, complement component C3 and total cholesterol.

Conclusions

Reduction in systolic blood pressure during antihypertensive treatment leads to increased plasma fibrin clot permeation and susceptibility to lysis, which might be a novel antithrombotic mechanism of blood pressure lowering therapy.     

Cognitive dysfunction and mental fatigue in childhood chronic fatigue syndrome--a 6-month follow-up study

Objectives: Cognitive function was investigated in patients with childhood type chronic fatigue syndrome (CCFS) using the modified advanced trail making test (mATMT). Methods: mATMT was performed on 19 patients with CCFS and 25 healthy controls of comparable age and sex. The effectiveness of combined treatment with cognitive behavioral therapy (CBT) and pharmacotherapy and its relationship to cognitive function was investigated by evaluation of Chalder’s fatigue scale and behavior state before and after treatment for 6 consecutive months. Results: All three tasks (motor skill, selective and alternative attention, and spatial working memory) of the mATMT, especially the difference in reaction time of the alternative attention task, could discriminate CCFS patients from control subjects with 70.5% accuracy (P = 0.007). CCFS patients showed significantly lower alternative attention and Chalder’s fatigue score before treatment (P = 0.037 and 0.002, respectively). A significant improvement in performance status scores was found during the 6 months follow-up period with combined treatment with CBT and medication (P < 0.001). Improvement of their cognitive symptoms was significantly correlated with improvement of alternative attention (r = 0.653, P = 0.002). Conclusions: Higher-order level cognitive dysfunction affects CCFS pathogenesis. Alternative attention performance evaluated by the mATMT may be used to monitor improvement in patients with CCFS. Combined treatment with CBT and medication may be effective to improve poor attention characteristics associated with CCFS.     

Reduced platelet BDNF level in patients with major depression

Serum and plasma brain-derived neurotrophic factor (BDNF) levels as well as brain BDNF have previously been shown to be decreased in patients with major depressive disorder (MDD). We explored whether platelet BDNF levels, circulating stored BDNF, would be lower in MDD patients than in normal controls. BDNF levels were examined in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) in 20 hospitalized non-suicidal MDD patients, 20 recent-suicidal MDD patients, and 20 normal controls. Platelet BDNF content was calculated by subtracting PPP BDNF level from PRP BDNF level, and dividing the result by the total platelet count, and it was expressed as pg/10⁶ platelets. Individuals were evaluated using a Structured Clinical Interview for DSM-IV and a Hamilton Depression Rating Scale. Platelet BDNF contents were significantly lower in non-suicidal patients (3.09 ± 2.53 pg/10⁶ platelets) and recent-suicidal MDD patients (3.16 ± 1.99 pg/10⁶ platelets) than in healthy controls (6.17 ± 2.64 pg/10⁶ platelets) (p < 0.01). However, platelet BDNF contents had no significant differences between non-suicidal and recent-suicidal patients. PRP BDNF levels were also significantly lower in non-suicidal and suicidal MDD patients than in healthy controls (p = 0.029), while PPP BDNF had no significant difference between 3 groups (p = 0.971). Our findings suggest that there is a decrease in the platelet BDNF of patients with major depression. Reduced platelet BDNF contents as circulating stored BDNF could be associated with lower serum BDNF level in patients with major depression.     

Cross-cultural comparisons on Wisconsin Card Sorting Test performance in euthymic patients with bipolar disorder

We compared executive dysfunction with the Wisconsin Card Sorting Test (WCST) among distinct national and ethnic patients with bipolar disorder in euthymia. Bipolar patients, aged 16-45 years, from the United States (n = 25) and Taiwan (n = 30) did not differ significantly on any measure. The WCST score for number Failure to Maintain Set was significantly positively correlated with residual affective symptoms in Taiwanese and US patients. Selective executive dysfunction in euthymia is inherent to bipolar disorder. Euthymic bipolar patients of various ethnic groups may exhibit similar executive dysfunction.     

Déficits des fonctions exécutives dans la schizophrénie selon les dimensions positive, négative et de désorganisation

The aim of this study was to examine whether executive deficits underlie positive, negative and disorganisation of schizophrenia. The sample comprised 34 patients (30 males, 4 females) diagnosed with DSM-IV criteria (mean age = 35 ± 9.5 years; mean duration of illness since first psychotic symptoms = 10.2 ± 7 years; mean years of education = 11.7 ± 2.6). Evaluation of patients was performed after achieved sufficient remission (clinically stable for 4 weeks at least, no depressive symptoms at moment of cognitive testing and no medication change during the three last weeks). Symptom dimensions were evaluated using items drawn from the Positive And Negative Symptoms Scale (PANSS). The Negative factor comprised N1 (blunted affect), N2 (emotional withdrawal), N3 (poor contact), N4 (passive, apathetic), N6 (lack of spontaneity), G7 (stereotyped thinking) and G16 (active social avoidance). The Positive factor comprised P1 (delusions), P3 (hallucinatory behaviour), P5 (grandiosity), P6 (suspiciousness) and G9 (unusual thought content). The Disorganisation factor comprised P2 (conceptual disorganisation), N5 (difficulty in abstract thinking), G10 (disorientation) and G11 (poor attention). The mean total PANSS score was 63.3 ± 16 (mean of positive score = 14.3 ± 4.7; mean of negative score = 18.1 ± 6.3; mean of general score = 30.9 ± 8.5). Executive functions were examined through the Wisconsin Card Sorting Test (WCST), the Hayling Test (Tunisian version) and two semantic verbal fluency tasks (simple with one category “animals” and alternating with two categories “fruits and clothes”). Partial correlations between syndrome scores and cognitive scores were examined while holding the effects of other symptoms, age and education level constant. Severity of disorganisation symptoms correlated with high number of perseverative errors (r = 0.47, P < 0.05) and total errors in the WCST (r = 0.37, P < 0.05) and with reduced score of alternating semantic verbal fluency (r = -0.39, P < 0.05). Severity of both negative and positive dimensions uncorrelated with performance of any of the executive tasks. Also, scores of the Hayling Test (time part B minus time part A; errors part B) and semantic simple verbal fluency (total of correct words) were uncorrelated with symptoms. The present study provides evidence that disorganisation dimension of the PANSS correlates specifically with impaired cognitive flexibility as reflected by high number of perseveration in the WCST and reduced set-shifting in semantic alternating verbal fluency.     

Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder

Accumulating evidence suggests that N-methyl-d-aspartate receptor (NMDAR) antagonists (e.g. ketamine) may exert rapid antidepressant effects in MDD patients. In the present study, we evaluated the rapid antidepressant effects of ketamine compared with the electroconvulsive therapy (ECT) in hospitalized patients with MDD. In this blind, randomized study, 18 patients with DSM-IV MDD were divided into two groups which received either three intravenous infusions of ketamine hydrochloride (0.5 mg/kg over 45 min) or ECT on 3 test days (every 48 h). The primary outcome measure was the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS), which was used to rate overall depressive symptoms at baseline, 24 h after each treatment, 72 h and one week after the last (third) ketamine or ECT. Within 24 h, depressive symptoms significantly improved in subjects receiving the first dose of ketamine compared with ECT group. Compared to baseline level, this improvement remained significant throughout the study. Depressive symptoms after the second dose ketamine was also lower than the second ECT. This study showed that ketamine is as effective as ECT in improving depressive symptoms in MDD patients and have more rapid antidepressant effects compared with the ECT.     

Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on memory and mental processing speed in patients with major depressive disorder

Patients with major depressive disorder (MDD) usually suffer from altered cognitive functions of episodic memory, working memory, mental processing speed and motor response. Diverse studies suggest that different antidepressant agents may improve cognitive functions in patients with MDD. The aim of this work is to study the effects of serotonergic reuptake inhibitors (SSRIs) and serotonergic-noradrenergic reuptake inhibitors (SNRIs) treatments to improve the performance on memory tasks and mental processing speed in MDD. Seventy-three subjects meeting criteria for major depressive disorder were assessed with the Hamilton depression rating scale and a neuropsychological battery. The subjects were medicated with escitalopram (n = 36) or duloxetine (n = 37) for 24 weeks. At the end of the trial, the subjects were assessed again with the same neuropsychological battery used prior to the treatment. Both treatments improved importantly the episodic memory and to a lesser extent, working memory, mental processing speed and motor performance. Our results suggest that cognition is partially independent from improvement in clinical symptoms. Both groups achieved remission rates in the HAM-D-17 after 24 weeks of treatment, but SNRI was superior to SSRI at improving episodic and working memory. Our work indicates that the superiority of SNRI over the SSRI at episodic memory improvement is clinically relevant.     

The kynurenine pathway in adolescent depression: Preliminary findings from a proton MR spectroscopy study

Background

Cytokine induction of the enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in the development of major depressive disorder (MDD). IDO metabolizes tryptophan (TRP) into kynurenine (KYN), thereby decreasing TRP availability to the brain. KYN is further metabolized into several neurotoxins. The aims of this pilot were to examine possible relationships between plasma TRP, KYN, and 3-hydroxyanthranilic acid (3-HAA, neurotoxic metabolite) and striatal total choline (tCho, cell membrane turnover biomarker) in adolescents with MDD. We hypothesized that MDD adolescents would exhibit: i) positive correlations between KYN and 3-HAA and striatal tCho and a negative correlation between TRP and striatal tCho; and, ii) the anticipated correlations would be more pronounced in the melancholic subtype group.

Methods

Fourteen adolescents with MDD (seven with melancholic features) and six healthy controls were enrolled. Minimums of 6 weeks MDD duration and a severity score of 40 on the Children's Depression Rating Scale-Revised were required. All were scanned at 3 T with MRI, multi-voxel 3-dimensional, high, 0.75 cm³, spatial resolution proton magnetic resonance spectroscopic imaging. Striatal tCho concentrations were assessed using phantom replacement. Spearman correlation coefficients were Bonferroni-corrected.

Results

Positive correlations were found only in the melancholic group, between KYN and 3-HAA and tCho in the right caudate (r = 0.93, p = 0.03) and the left putamen (r = 0.96, p = .006), respectively.

Conclusions

These preliminary findings suggest a possible role of the KYN pathway in adolescent melancholic MDD. Larger studies should follow.     

Activated inflammatory cells participate in thrombus size through tissue factor and plasminogen activator inhibitor-1 in acute coronary syndrome: Immunohistochemical analysis

Introduction

Recent studies have suggested that circulating inflammatory cells augment the growth of thrombus in acute coronary syndrome (ACS). We therefore immunohistochemically analyzed thrombi in aspirates obtained from patients immediately after the onset of ACS.

Materials and Methods

Two hundred twenty samples were studied. Total thrombus area, white thrombus area, and red thrombus area were measured. As antibodies in immunohistochemical staining, myeloperoxidase (MPO), CD66b, CD68, p-selectin, tissue factor (TF) and PAI-1were employed respectively.

Results

The ratios of areas of red and white thrombi correlated with whole sample areas of enlarged thrombi (r = 0.48, p < 0.001). The immunohistochemical findings revealed granulocytes and macrophages aggregated around p-selectin-positive platelets that shared the boundary between white and red thrombi, a region where MPO and CD66b expression was abundant in neutrophils. The ratios (%) of MPO- and CD66b-positive cells significantly correlated with whole sample areas (r = 0.50; p < 0.001 and r = 0.49; p < 0.001, respectively). Neutrophils and macrophages within thrombi were positive for TF and PAI-1. Along the boundary between red and white thrombi, TF and PAI-1 positivity coincided with MPO-, CD66b- and CD68-positive cells. The ratios of cells positive for both TF and PAI-1 in this area significantly correlated with the whole sample area (r = 0.43, p < 0.001 and r = 0.60, p < 0.001, respectively).

Conclusions

These results suggested that enhanced activation of peripheral neutrophils together with increased TF and PAI-1 expression might comprise a considerable portion of thrombus enlargement.