Nocardia otitidiscaviarum (GAM-5) induces parkinsonian-like alterations in mouse

Parkinson's disease, a major neurodegenerative disorder in humans whose etiology is unknown, may be associated with some environmental factors. Nocardia otitidiscaviarum (GAM-5) isolated from a patient with an actinomycetoma produced signs similar to Parkinson's disease following iv injection into NMRI mice. NMRI mice were infected intravenously with a non-lethal dose of 5 x 10(6) colony forming units of N. otitidiscaviarum (GAM-5). Fourteen days after bacterial infection, most of the 60 mice injected exhibited parkinsonian features characterized by vertical head tremor, akinesia/bradykinesia, flexed posture and postural instability. There was a peak of nocardial growth in the brain during the first 24 h followed by a decrease, so that by 14 days nocardiae could no longer be cultured. At 24 h after infection, Gram staining showed nocardiae in neurons in the substantia nigra and occasionally in the brain parenchyma in the frontal and parietal cortex. At 21 days post-infection, tyrosine hydroxylase immunolabeling showed a 58% reduction of tyrosine hydroxylase in the substantia nigra, and a 35% reduction of tyrosine hydroxylase in the ventral tegmental region. Dopamine levels were reduced from 110 ± 32.5 to 58 ± 16.5 ng/mg protein (47.2% reduction) in brain from infected mice exhibiting impaired movements, whereas serotonin levels were unchanged (191 ± 44 protein in control and 175 ± 39 ng/mg protein in injected mice). At later times, intraneuronal inclusion bodies were observed in the substantia nigra. Our observations emphasize the need for further studies of the potential association between Parkinson's disease or parkinsonism-like disease and exposure to various nocardial species.

Is avoidant disorder part of the social phobia spectrum in a referred sample of Brazilian children and adolescents?

The diagnosis of avoidant disorder was deleted from the Diagnostic and Statistical Manual of Mental disorders - fourth edition (DSM-IV) based on a `committee decision' suggesting that avoidant disorder is part of the social phobia spectrum. The objective of the present study was to examine the nature of this clinical association in a referred sample of Brazilian children and adolescents. We assessed a referred sample of 375 youths using semi-structured diagnostic interview methodology. Demographic (age at admission to the study and sex) and clinical (level of impairment, age at onset of symptoms and pattern of comorbidity) data were assessed in subsamples of children with avoidant disorder (N = 7), social phobia (N = 26), and comorbidity between both disorders (N = 24). Although a significant difference in the male/female ratio was detected among groups (P = 0.03), none of the other clinical variables differed significantly among subjects that presented each condition separately or in combination. Most of the children with avoidant disorder fulfilled criteria for social phobia. Thus, our findings support the validity of the conceptualization of avoidant disorder as part of the social phobia spectrum in a clinical sample.

Social disability of Brazilian mood disorder patients

Mood disorders cause many social problems, often involving family relationships. Few studies are available in the literature comparing patients with bipolar, unipolar, dysthymic, and double depressive disorders concerning these aspects. In the present study, demographic and disease data were collected using a specifically prepared questionnaire. Social adjustment was assessed using the Disability Adjustment Scale and family relationships were evaluated using the Global Assessment of Relational Functioning Scale. One hundred patients under treatment for at least 6 months were evaluated at the Psychiatric Outpatient Clinic of the Botucatu School of Medicine, UNESP. Most patients were women (82%) more than 50 (49%) years old with at least two years of follow-up, with little schooling (62% had less than 4 years), and of low socioeconomic level. Logistic regression analysis showed that a diagnosis of unipolar disorder (P = 0.003, OR = 0.075, CI = 0.014-0.403) and dysthymia (P = 0.001, OR = 0.040, CI = 0.006-0.275) as well as family relationships (P = 0.002, OR = 0.953, CI = 0914-0.992) played a significant role in social adjustment. Unipolar and dysthymic patients presented better social adjustment than bipolar and double depressive patients (P < 0.001), results that were not due to social class. These patients, treated at a teaching hospital, may represent the severest mood disorder cases. Evaluations were made knowing the diagnosis of the patients, which might also have influenced some of the results. Social disabilities among mood disorder patients are very frequent and intensive.

An empirical comparison of atypical bulimia nervosa and binge eating disorder

The International Classification of Diseases, 10th edition (ICD-10) defines atypical bulimia nervosa (ABN) as an eating disorder that encompasses several different syndromes, including the DSM-IV binge eating disorder (BED). We investigated whether patients with BED can be differentiated clinically from patients with ABN who do not meet criteria for BED. Fifty-three obese patients were examined using the Structured Clinical Interview for DSM-IV and the ICD-10 criteria for eating disorders. All volunteers completed the Binge Eating Scale (BES), the Beck Depression Inventory, and the Symptom Checklist-90 (SCL-90). Individuals fulfilling criteria for both ABN and BED (N = 18), ABN without BED (N = 16), and obese controls (N = 19) were compared and contrasted. Patients with ABN and BED and patients with ABN without BED displayed similar levels of binge eating severity according to the BES (31.05 ± 7.7 and 30.05 ± 5.5, respectively), which were significantly higher than those found in the obese controls (18.32 ± 8.7; P < 0.001 and P < 0.001, respectively). When compared to patients with ABN and BED, patients with ABN without BED showed increased lifetime rates of agoraphobia (P = 0.02) and increased scores in the somatization (1.97 ± 0.85 vs 1.02 ± 0.68; P = 0.001), obsessive-compulsive (2.10 ± 1.03 vs 1.22 ± 0.88; P = 0.01), anxiety (1.70 ± 0.82 vs 1.02 ± 0.72; P = 0.02), anger (1.41 ± 1.03 vs 0.59 ± 0.54; P = 0.005) and psychoticism (1.49 ± 0.93 vs 0.75 ± 0.55; P = 0.01) dimensions of the SCL-90. The BED construct may represent a subgroup of ABN with less comorbities and associated symptoms.

A randomized crossover clinical study showing that methylphenidate-SODAS improves attention-deficit/hyperactivity disorder symptoms in adolescents with substance use disorder

Our objective was to evaluate the effectiveness of a long-acting formulation of methylphenidate (MPH-SODAS) on attention-deficit/hyperactivity disorder (ADHD) symptoms in an outpatient sample of adolescents with ADHD and substance use disorders (SUD). Secondary goals were to evaluate the tolerability and impact on drug use of MPH-SODAS. This was a 6-week, single-blind, placebo-controlled crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD symptoms in 16 adolescents with ADHD/SUD. Participants were randomly allocated to either group A (weeks 1-3 on MPH-SODAS, weeks 4-6 on placebo) or group B (reverse order). The primary outcome measures were the Swanson, Nolan and Pelham Scale, version IV (SNAP-IV) and the Clinical Global Impression Scale (CGI). We also evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating Scale and subject reports of drug use during the study. The sample consisted of marijuana (N = 16; 100%) and cocaine users (N = 7; 43.8%). Subjects had a significantly greater reduction in SNAP-IV and CGI scores (P < 0.001 for all analyses) during MPH-SODAS treatment compared to placebo. No significant effects for period or sequence were found in analyses with the SNAP-IV and CGI scales. There was no significant effect on drug use. MPH-SODAS was well tolerated but was associated with more severe appetite reduction than placebo (P < 0.001). MPH-SODAS was more effective than placebo in reducing ADHD symptoms in a non-abstinent outpatient sample of adolescents with comorbid SUD. Randomized clinical trials, with larger samples and SUD intervention, are recommended.

Anxiety and depression in parents of a Brazilian non-clinical sample of attention-deficit/ hyperactivity disorder (ADHD) students

Higher prevalence rates of anxiety and depression have been reported in parents of children with attention-deficit/hyperactivity disorder (ADHD). The interaction between the burden of ADHD in offspring, a higher prevalence rate of this highly inherited disorder in parents, and comorbidities may explain this finding. Our objective was to investigate levels of ADHD, anxious and depressive symptomatology, and their relationship in parents of ADHD children from a non-clinical sample using a dimensional approach. The sample included 396 students enrolled in all eight grades of a public school who were screened for ADHD using the SNAP IV rating scale. Positive cases were confirmed through a semi-structured interview. Parents of all 26 ADHD students and 31 paired controls were enrolled. A sample of 36 parents of ADHD children (21 mothers, 15 fathers) and 30 parents of control children (18 mothers, 12 fathers) completed the Adult Self Report Scale, State-Trait Anxiety Inventory, and Beck Depression Inventory in order to investigate anxious and depressive symptomatology. Probands' mothers presented a higher level of ADHD symptomatology (with only inattention being a significant cluster). Again, mothers of ADHD children presented higher depressive and anxiety levels; however, these did not correlate with their own ADHD symptomatology. Only trait-anxiety levels were higher in ADHD mothers. Our findings suggest that: 1) anxious and depressive symptoms might be more prevalent in mothers of ADHD students; 2) anxious and depressive symptomatology might be independent of impairment associated with ADHD symptoms; 3) anxious and depressive symptoms are independent of the presence of ADHD.

Effect of auditory training on the middle latency response in children with (central) auditory processing disorder

The purpose of this study was to determine the middle latency response (MLR) characteristics (latency and amplitude) in children with (central) auditory processing disorder [(C)APD], categorized as such by their performance on the central auditory test battery, and the effects of these characteristics after auditory training. Thirty children with (C)APD, 8 to 14 years of age, were tested using the MLR-evoked potential. This group was then enrolled in an 8-week auditory training program and then retested at the completion of the program. A control group of 22 children without (C)APD, composed of relatives and acquaintances of those involved in the research, underwent the same testing at equal time intervals, but were not enrolled in the auditory training program. Before auditory training, MLR results for the (C)APD group exhibited lower C3-A1 and C3-A2 wave amplitudes in comparison to the control group [C3-A1, 0.84 µV (mean), 0.39 (SD - standard deviation) for the (C)APD group and 1.18 µV (mean), 0.65 (SD) for the control group; C3-A2, 0.69 µV (mean), 0.31 (SD) for the (C)APD group and 1.00 µV (mean), 0.46 (SD) for the control group]. After training, the MLR C3-A1 [1.59 µV (mean), 0.82 (SD)] and C3-A2 [1.24 µV (mean), 0.73 (SD)] wave amplitudes of the (C)APD group significantly increased, so that there was no longer a significant difference in MLR amplitude between (C)APD and control groups. These findings suggest progress in the use of electrophysiological measurements for the diagnosis and treatment of (C)APD.

The novel p.E89K mutation in the SRY gene inhibits DNA binding and causes the 46,XY disorder of sex development

Male sex determination in humans is controlled by the SRY gene, which encodes a transcriptional regulator containing a conserved high mobility group box domain (HMG-box) required for DNA binding. Mutations in the SRY HMG-box affect protein function, causing sex reversal phenotypes. In the present study, we describe a 19-year-old female presenting 46,XY karyotype with hypogonadism and primary amenorrhea that led to the diagnosis of 46,XY complete gonadal dysgenesis. The novel p.E89K missense mutation in the SRY HMG-box was identified as a de novo mutation. Electrophoretic mobility shift assays showed that p.E89K almost completely abolished SRY DNA-binding activity, suggesting that it is the cause of SRY function impairment. In addition, we report the occurrence of the p.G95R mutation in a 46,XY female with complete gonadal dysgenesis. According to the three-dimensional structure of the human SRY HMG-box, the substitution of the conserved glutamic acid residue by the basic lysine at position 89 introduces an extra positive charge adjacent to and between the positively charged residues R86 and K92, important for stabilizing the HMG-box helix 2 with DNA. Thus, we propose that an electrostatic repulsion caused by the proximity of these positive charges could destabilize the tip of helix 2, abrogating DNA interaction.

Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine

The objective of the present randomized, open-label, naturalistic 8-week study was to compare the efficacy and safety of treatment with clonazepam (N = 63) and paroxetine (N = 57) in patients with panic disorder with or without agoraphobia. Efficacy assessment included number of panic attacks and clinician ratings of the global severity of panic disorders with the clinical global impression (CGI) improvement (CGI-I) and CGI severity (CGI-S) scales. Most patients were females (69.8 and 68.4% in the clonazepam and paroxetine groups, respectively) and age (mean ± SD) was 35.9 ± 9.6 years for the clonazepam group and 33.7 ± 8.8 years for the paroxetine group. Treatment with clonazepam versus paroxetine resulted in fewer weekly panic attacks at week 4 (0.1 vs 0.5, respectively; P < 0.01), and greater clinical improvements at week 8 (CGI-I: 1.6 vs 2.9; P = 0.04). Anxiety severity was significantly reduced with clonazepam versus paroxetine at weeks 1 and 2, with no difference in panic disorder severity. Patients treated with clonazepam had fewer adverse events than patients treated with paroxetine (73 vs 95%; P = 0.001). The most common adverse events were drowsiness/fatigue (57%), memory/concentration difficulties (24%), and sexual dysfunction (11%) in the clonazepam group and drowsiness/fatigue (81%), sexual dysfunction (70%), and nausea/vomiting (61%) in the paroxetine group. This naturalistic study confirms the efficacy and tolerability of clonazepam and paroxetine in the acute treatment of patients with panic disorder.

The response of social anxiety disorder patients to threat scenarios differs from that of healthy controls

The objective of the present study was to evaluate the response of social anxiety disorder (SAD) patients to threat scenarios. First-choice responses to 12 scenarios describing conspecific threatening situations and mean scores of defensive direction and defensive intensity dimensions were compared between 87 SAD patients free of medication and 87 matched healthy controls (HC). A significant gender difference in the first-choice responses was identified for seven scenarios among HCs but only for two scenarios among SAD patients. A significantly higher proportion of SAD patients chose "freezing" in response to "Bush" and "Noise" scenarios, whereas the most frequent response by HCs to these scenarios was "check out". SAD males chose "run away" and "yell" more often than healthy men in response to the scenarios "Park" and "Elevator", respectively. There was a positive correlation between the severity of symptoms and both defensive direction and defensive intensity dimensions. Factorial analysis confirmed the gradient of defensive reactions derived from animal studies. SAD patients chose more urgent defensive responses to threat scenarios, seeming to perceive them as more dangerous than HCs and tending to move away from the source of threat. This is consistent with the hypothesis that the physiopathology of anxiety disorders involves brain structures responsible for defensive behaviors.

Postural balance in patients with social anxiety disorder

Body stability is controlled by the postural system and can be affected by fear and anxiety. Few studies have addressed freezing posture in psychiatric disorders. The purpose of the present study was to assess posturographic behavior in 30 patients with social anxiety disorder (SAD) and 35 without SAD during presentation of blocks of pictures with different valences. Neutral images consisted of objects taken from a catalog of pictures, negative images were mutilation pictures and anxiogenic images were related to situations regarding SAD fears. While participants were standing on a force platform, similar to a balance, displacement of the center of pressure in the mediolateral and anteroposterior directions was measured. We found that the SAD group exhibited a lower sway area and a lower velocity of sway throughout the experiment independent of the visual stimuli, in which the phobic pictures, a stimulus associated with a defense response, were unable to evoke a significantly more rigid posture than the others. We hypothesize that patients with SAD when entering in a situation of exposure, from the moment the pictures are presented, tend to move less than controls, remaining this way until the experiment ends. This discrete body manifestation can provide additional data to the characterization of SAD and its differentiation from other anxiety disorders, especially in situations regarding facing fear.

Memory mood congruency phenomenon in bipolar I disorder and major depression disorder patients

The objective of the present study was to evaluate memory performance in tasks with and without affective content (to confirm the mood congruency phenomenon) in acutely admitted patients with bipolar I disorder (BD) and major depression disorder (MDD) and in healthy participants. Seventy-eight participants (24 BD, 29 MDD, and 25 healthy controls) were evaluated. Three word lists were used as the memory task with affective content (positive, negative and indifferent). Psychiatric symptoms were also evaluated with rating scales (Young Mania Rating Scale for mania and Hamilton Depression Rating Scale for depression). Patients were selected during the first week of hospitalization. BD patients showed higher scores in the word span with positive tone than MDD patients and healthy controls (P = 0.002). No other difference was observed for tests with affective tone. MDD patients presented significantly lower scores in the Mini-Mental State Exam, logical memory test, visual recognition span, and digit span, while BD patients presented lower scores in the visual recognition test and digit span. Mood congruency effect was found for word span with positive tone among BD patients but no similar effect was observed among MDD patients for negative items. MDD patients presented more memory impairment than BD patients, but BD patients also showed memory impairment

Group cognitive behavior therapy for bipolar disorder can improve the quality of life

Bipolar disorder (BD) can have an impact on psychosocial functioning and quality of life (QoL). Several studies have shown that structured psychotherapy in conjunction with pharmacotherapy may modify the course of some disorders; however, few studies have investigated the results of group cognitive behavior therapy (G-CBT) for BD. Our objective was to evaluate the effectiveness of 14 sessions of G-CBT for BD patients, comparing this intervention plus pharmacotherapy to treatment as usual (TAU; only pharmacotherapy). Forty-one patients with BD I and II participated in this study and were randomly allocated to each group (G-CBT: N = 27; TAU: N = 14). Thirty-seven participants completed the treatment (women: N = 66.67%; mean age = 41.5 years). QoL and mood symptoms were assessed in all participants. Scores changed significantly by the end of treatment in favor of the G-CBT group. The G-CBT group presented significantly better QoL in seven of the eight sub-items assessed with the Medical Outcomes Survey SF-36 scale. At the end of treatment, the G-CBT group exhibited lower scores for mania (not statistically significant) and depression (statistically significant) as well as a reduction in the frequency and duration of mood episodes (P < 0.01). The group variable was significant for the reduction of depression scores over time. This clinical change may explain the improvement in six of the eight subscales of QoL (P < 0.05). The G-CBT group showed better QoL in absolute values in all aspects and significant improvements in nearly all subscales. These results were not observed in the TAU control group.

Attentional bias modulation by reappraisal in patients with generalized anxiety disorder: an event-related potential study

Affective states influence subsequent attention allocation. We evaluated emotional negativity bias modulation by reappraisal in patients with generalized anxiety disorder (GAD) relative to normal controls. Event-related potential (ERP) recordings were obtained, and changes in P200 and P300 amplitudes in response to negative or neutral words were noted after decreasing negative emotion or establishing a neutral condition. We found that in GAD patients only, the mean P200 amplitude after negative word presentation was much higher than after the presentation of neutral words. In normal controls, after downregulation of negative emotion, the mean P300 amplitude in response to negative words was much lower than after neutral words, and this was significant in both the left and right regions. In GAD patients, the negative bias remained prominent and was not affected by reappraisal at the early stage. Reappraisal was observed to have a lateralized effect at the late stage.

Meta-analysis on the efficacy and tolerability of the augmentation of antidepressants with atypical antipsychotics in patients with major depressive disorder

We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.