Does comorbid anxiety or depression affect clinical outcomes in patients with post-traumatic stress disorder and alcohol use disorders?

Post-traumatic stress disorder (PTSD) is commonly comorbid with other psychiatric disorders, including substance use disorders. In spite of this, pharmacologic treatment trials for PTSD often exclude individuals with significant psychiatric comorbidity. This study is a post hoc analysis of a 12-week double-blind placebo-controlled trial investigating sertraline in the treatment of patients with comorbid PTSD and an alcohol use disorder. Individuals with additional anxiety and affective disorders were included. Patients (N = 93) were stratified into four groups depending on presence or absence of additional anxiety or depressive disorders and evaluated for the effects of comorbidity on PTSD symptoms, depressive symptoms, and drinking behaviors. We hypothesized that additional comorbidity would be associated with poorer outcomes. Patients in all four subgroups showed marked and clinically significant improvement in alcohol drinking behaviors over the course of the study. For the entire sample, over the course of the 12 weeks, mean drinks per drinking day fell from 13.0 +/- 8.4 (SD) to 3.0 +/- 5.0 (SD); t = 10.2, df = 92, P <.000. There were, however, no significant differences among groups. Patients in all four groups showed moderate improvement in Hamilton Depression Rating Scale (HAMD) scores and Clinician-Administered PTSD scale (CAPS) scores at endpoint. For the entire sample, mean CAPS scores fell from 59.3 +/- 19.4 (SD) to 40.8 +/- 26.0, t = 8.9, df = 92, P <.000. Mean HAMD scores fell from 17. 9 +/- 6.7 (SD) at baseline to 11.8 +/- 9.4 (SD) at endpoint; t = 6.7, df = 92, P <.000. There were, however, no significant differences among groups for change in HAM-D or CAPS scores. Hence, contrary to our hypothesis, having additional anxiety or mood disorder comorbidity did not decrease treatment response in individuals with comorbid PTSD and an alcohol use disorder.     

Does fatigue in Parkinson’s disease correlate with autonomic nervous system dysfunction?

Background

Despite its negative impact on quality of life, fatigue in Parkinson’s disease (PD) remains an under-recognized issue and the underlying pathology is undetermined.

Objective

To contribute at understanding the pathogenesis of fatigue in a naturalistic cohort of cognitively intact PD patients.

Methods

In a Caucasian population of PD patients (n?=?27), we evaluated to what extent fatigue (quantified as PFS-16 score) is associated with PD duration and with autonomic dysfunction, studied by both MIBG scintigraphy and autonomic nervous system testing. The latter included the head-up tilt test, Valsalva maneuver, deep breathing, and handgrip tests.

Results

PFS-16 score correlated with disease duration (R?=?0.57, p?=?0.002). Fatigue showed a clear correlation with deep breathing test (R?=???0.53, p?=?0.004) but not with the MIBG H/M ratios.

Conclusions

Our data are consistent with a multifactorial pathogenesis of fatigue and with effects of dopamine depletion in PD-related fatigue; on the other hand, our findings do not support a role for sympathetic denervation in PD-related fatigue.

     

Does continuous positive airway pressure treatment affect autonomic nervous system in patients with severe obstructive sleep apnea?

ObjectiveThis study is aimed at evaluating whether Continuous Positive Airway Pressure treatment (CPAP) may affect autonomic nervous system (ANS) in male patients with severe obstructive sleep apnea (OSAS).MethodsWe compared autonomic symptoms of de novo severe OSAS patients, OSAS patients on chronic CPAP treatment and healthy controls, using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire. All groups underwent cardiovascular function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, hand grip and cold face tests. Statistical significance was set at p < 0.05.ResultsTwelve de novo severe OSAS patients, 17 male OSAS on CPAP and 14 controls were studied. The mean SCOPA-AUT total score was significantly higher in de novo OSAS patients compared with controls. Regarding the distinct domains, both de novo OSAS and CPAP group had abnormalities in respect of controls in urinary sphere. In supine rest condition the baseline values of systolic blood pressure were significantly increased in untreated OSAS patients compared with controls, whereas the basal values of diastolic blood pressure were significantly higher in CPAP patients with respect to controls. After ten min of HUTT, diastolic blood pressure changes were significantly higher in controls compared to both OSAS groups. Untreated OSAS patients showed significant different responses at deep breathing compared to controls. Both OSAS groups had a significant reduction of reflex bradycardia at cold face test.ConclusionsOur study shows that both treated and untreated OSAS patients complain of subjective autonomic symptoms like other sleep disorders reinforcing the close relationship between sleep and autonomic activity. Furthermore, cardiovascular reflexes indicate a tendency to hypertension and a reduced sensitivity to stimuli during wakefulness even in OSA patients on CPAP treatment, suggesting potentially permanent autonomic function deficits.     

Does anxiety increase impulsivity in patients with bipolar disorder or major depressive disorder?

The objective of this study was to examine whether anxiety increases impulsivity among patients with bipolar disorder (BPD) and major depressive disorder (MDD). Subjects comprised 205 BPD (mean age ± SD 36.6 ± 11.5 y; 29.3% males) and 105 with MDD (mean age ± SD 38 ± 13.1 y; 29.5% males) diagnosed using the DSM-IV-SCID. Impulsivity was assessed with the Barratt Impulsivity Scale and anxiety with the Hamilton Anxiety Rating Scale. Comorbid anxiety disorders were present in 58.9% of the BPD and 29.1% of MDD. BPD were significantly more impulsive than MDD (p < 0.001), and both BPD and MDD subjects showed significantly higher impulsivity when anxiety was present either as a comorbidity (p = 0.010) or as a symptom (p = 0.011). Impulsivity rose more rapidly with increasing anxiety symptoms in MDD than in BPD. The presence of anxiety, either as a comorbid disorder or as current anxiety symptoms, is associated with higher impulsivity in subjects with either BPD or MDD.     

Does ADHD moderate the manifestation of anxiety disorders in children?

The main aim of this study was to examine the moderating effects of attention deficit hyperactivity disorder (ADHD) on anxiety disorders in children. Data were analyzed from a large referred sample of children with anxiety disorder without comorbid ADHD (anxiety disorder, N = 253), anxiety disorder plus comorbid ADHD (anxiety disorder + ADHD, N = 704), and ADHD without comorbid anxiety disorder (ADHD, N = 511). Children were comprehensively assessed, including by structured diagnostic interview (K-SADS-E). Overall rates of individual anxiety disorders, as well as age of onset and severity of illness were not significantly different in the presence of comorbid ADHD. School functioning in children with anxiety disorders was negatively impacted by the presence of comorbid ADHD. Frequency of mental health treatment in children with anxiety disorders was significantly increased in the presence of comorbid ADHD. ADHD had a limited impact on the manifestation of anxiety disorder in children suggesting that ADHD and anxiety disorders are independently expressed.     

Do depression and anxiety converge or diverge in their association with suicidality?

Depressive disorders have been strongly linked to suicidality, but the association with anxiety disorders is less well established. This exploratory study aims to examine whether anxiety and depressive disorders are both independent risk factors for suicidal ideation and attempted suicide, and additionally examined the role of specific clinical characteristics (disorder type, severity, duration, onset age) in suicidality. Data are from 1693 persons with a current (6-month) CIDI based depressive or anxiety disorder and 644 healthy controls participating in the baseline measurement of the Netherlands Study of Depression and Anxiety, which is an existing dataset. Suicidal ideation in the week prior to baseline and attempted suicide ever in life were assessed. Results showed that compared to persons with only an anxiety disorder, persons with a depressive disorder were at significantly higher risk to have current suicidal ideation or a history of attempted suicide. When examining the association between type of disorder and suicidality the odds ratio for MDD was significantly higher than those for the separate anxiety disorders. Although depression and anxiety severity were univariate risk indicators for suicidal ideation and attempted suicide, only depression severity remained a risk indicator for suicidal ideation and attempted suicide in multivariate analyses. Additional risk indicators were an early age at disorder onset for both suicidal ideation and attempted suicide, male gender for suicidal ideation and lower education for attempted suicide. These findings suggest that although anxiety and depression tend to converge in many important areas, they appear to diverge with respect to suicidality.     

The role of the sympathetic nervous system in anxiety: Is it possible to relieve anxiety with endoscopic sympathetic block?

The function of the autonomic nervous system is divided so that the parasympathetic system spares central nervous system energy and the sympathetic system makes extra energy available and consumes it. The sympathetic nervous system then prepares our body for emergency and it always functions when our conscious or even unconscious mind notices a need for defence or to provide energy. A surgical procedure, where the upper thoracic sympathetic ganglions are ablated, either with cauterization or clamping with metallic clips, has been used to treat sweating of the hands and facial blushing for decades. Instead of ablating large areas of sympathetic trunk, which can cause severe side-effects such as reflex sweating of the body, the surgical procedure is nowadays carried out in a more precise symptom-mediating level of uppermost thoracic sympathetic ganglia. Blushing, hyperhidrosis of palms and head, and trembling are common in social phobia, and they seem to be provoked by the activation of the sympathetic nervous system. Preliminary studies show that some social phobia patients may benefit from the endoscopic sympathetic block (ESB). If the patient with generalized social phobia has not received help with adequate medication or psychotherapy, the ESB may be a new possible treatment of choice.     

Does a coexisting anxiety disorder predict persistence of depressive illness in primary care patients with major depression?

We assessed whether a coexisting anxiety disorder predicts risk for persistent depression in primary care patients with major depression at baseline. Patients with major depression were identified in a 12-month prospective cohort study at a University-based family practice clinic. Presence of an anxiety disorder and other potential prognostic factors were measured at baseline. Persistent depressive illness (major depression, minor depression, or dysthymia) was determined at 12 months. Of 85 patients with major depression at baseline, 43 had coexisting anxiety disorder (38 with social phobia). The risk for persistent depression at 12 months was 44% greater [Risk Ratio (RR) = 1.44, 95% confidence interval (CI) 1.02-2.04] in those with coexisting anxiety. This risk persisted in stratified analysis controlling for other prognostic factors. Patients with coexisting anxiety had greater mean depressive severity [repeated measures analysis of variance (ANOVA), p < 0.04] and total disability days (54.9 vs 19.8, p < 0.02) over the 12-month study. Patients with social phobia had similar increased risk for persistent depression (RR = 1.40, 95% CI 0.98-2.00). A coexisting anxiety disorder indicates risk for persistent depression in primary care patients with major depression. Social phobia may be important to recognize in these patients. Identifying anxiety disorders can help primary care clinicians target patients needing more aggressive treatment for depression.     

Does depression in patients with known or suspected cerebral disease contribute to impairment on the Luria-Nebraska Neuropsychological Battery?

Both the Luria-Nebraska Neuropsychological Battery (LNNB) and the Beck Depression Inventory (BDI) were administered to 48 consecutively referred patients. These consecutively seen patients comprised 25 cases of confirmed brain damage and 23 cases of "suspected" or questionable damage. Product-moment correlations were calculated between the BDI and three LNNB-derived indices of impairment. No relationship was found between depression and any of the LNNB performance indicators, indicating that the battery may be robust in the presence of depression. Necessary constraints on this implication were discussed and explicated in light of the concurrent need to evaluate new neuropsychological instruments in realistic clinical contexts.     

Is disgust associated with psychopathology? Emerging research in the anxiety disorders

Recent evidence indicates that the propensity towards experiencing disgust may contribute to the development and maintenance of some anxiety disorders. This article summarizes the empirical evidence with emphasis on illuminating potential mediators, moderators, and mechanisms of the disgust–anxiety disorder association that may inform the development of an integrative conceptual model. Early research using neuroimaging methods suggest that disgust processing is associated with activation of the insula. This research has the potential to facilitate progress in developing an empirically informed psychobiological theory on the causal role of disgust in the anxiety disorders.     

Does akathisia influence psychopathology in psychotic patients treated with clozapine?

BACKGROUND: Akathisia has been reported to predict more severe symptoms and poorer treatment response to typical neuroleptics among patients with schizophrenia. Akathisia has also been associated with symptom exacerbation. This study addressed four questions: 1) Does akathisia predict greater severity in global psychopathology? 2) Is this effect global or specific? 3) Does clozapine treatment alter this relationship? 4) Does severity of psychopathology covary with the level of akathisia? METHODS: Akathisia and clinical symptoms were examined in 33 "treatment refractory" schizophrenic patients treated with clozapine across 16 weeks. Weekly ratings were Barnes Akathisia Rating Scale, Abbreviated Dyskinesia Rating Scale, and Brief Psychiatric Rating Scale (BPRS). Patients were classified as "with" (n = 15) or "without" (n = 18) akathisia. Data analyses involved independent t-test comparisons of selected variables, between-group multivariate analyses of variance across time for BPRS Total scores and Guy's five factors, and partial correlations to assess covariation between BPRS scores and level of akathisia. RESULTS: Akathisia predicted more severe global psychopathology, specific to the Activation (AC) and Thought Disturbance (TH) factors. These relationships did not change with clozapine treatment even when akathisia declined. Interestingly, level of akathisia did not covary with severity of psychopathology. CONCLUSIONS: In this sample, akathisia predicted more severe psychopathology, specific to AC and TH BPRS factor scores. Clozapine treatment did not alter this relationship. Although the presence of akathisia predicted more severe symptoms, the level of akathisia did not covary across time with severity of psychopathology, suggesting an "uncoupling" of these symptom domains.     

Is autonomic nervous system involved in restless legs syndrome during wakefulness?

ObjectiveTo investigate cardiovascular autonomic function in patients with restless leg syndrome (RLS) by means of cardiovascular reflexes and heart rate variability (HRV) during wakefulness.MethodsTwelve RLS patients and 14 controls underwent cardiovascular function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, hand grip, and cold face. HRV analysis was performed in the frequency domain using both autoregressive (AR) and fast Fourier transform algorithms in rest supine condition and during HUTT.ResultsThere was a significant increase in systolic blood pressure values in supine rest condition and a trend toward a lower Valsalva ratio in RLS patients with respect to controls. The significant and physiological changes of HRV at HUTT detected in healthy subjects were not found in RLS patients.ConclusionRLS patients exhibit a tendency toward hypertension, reduced amplitude of both sympathetic and parasympathetic responses at HUTT, as well as blunted parasympathetic drive to blood pressure changes. These findings, if confirmed by more controlled studies, might support the hypothesis of autonomic nervous system involvement during wakefulness and consequently an enhanced cardiovascular risk in RLS.     

Autonomic nervous system activity associated with postural disturbances in patients with perilymphatic fistula: sympathetic or vagal origin?

The study focused on patients suffering from perilymphatic fistula (PLF), whether they had undergone surgery or not. Vestibular disturbances can be harmless but are associated with varying symptoms, demonstrating disorders within the autonomic nervous system (ANS). The aim was to test whether the orthosympathetic is involved as the vagal part is often suspected of eliciting a feeling of sickness. Non-invasive and uninterrupted recording of ANS activity represents an objectivation technique to evidence such disturbances. Electrodermal activity, thermovascular variables, instantaneous cardiac rate and blood pressure were recorded. Discomfort was triggered experimentally by applying various stimulations successively to the intact ear then to the PLF (or operated) side. Twelve subjects took part in the experiment. Two types of ANS activity were distinguished: (1) phasic responses during stimulation and (2) tonic evolution thereafter. Results show strong activation in orthosympathetic variables when the PLF side was stimulated. No further significant difference between the two sides was to be observed following surgery. After stimulation, a sudden increase in skin resistance was observed, associated with slight bradycardia. No vagal signs having been evidenced, actual nausea may result from brief inhibition of sympathetic activation resulting, in turn from primary over-activation of this system.     

Generalized anxiety disorder in patients with major depression: is DSM-IV's hierarchy correct?

OBJECTIVE: DSM-III imposed a hierarchical relationship in the diagnosis of anxiety disorders in depressed patients, stipulating that anxiety disorders could not be diagnosed if their occurrence was limited to the course of a mood disorder. In the subsequent versions of the DSM this hierarchy was eliminated for all anxiety disorders except generalized anxiety disorder. The authors examined the validity of this remaining hierarchical relationship between mood and anxiety disorders. METHOD: Psychiatric outpatients with major depressive disorder (N=332) were evaluated with a semistructured diagnostic interview and completed paper-and-pencil questionnaires on presentation for treatment. To study the validity of the DSM-IV hierarchical relationship between generalized anxiety disorder and mood disorders, the authors made a diagnosis of modified generalized anxiety disorder for patients with major depressive disorder who met all the criteria for generalized anxiety disorder except for the exclusion criterion. The analyses compared the characteristics of three nonoverlapping groups of patients with DSM-IV major depressive disorder: 1) those with coexisting DSM-IV generalized anxiety disorder, 2) those with coexisting modified generalized anxiety disorder, and 3) those with neither DSM-IV nor modified generalized anxiety disorder. RESULTS: Compared to the depressed patients without generalized anxiety disorder, the depressed patients with DSM-IV and modified generalized anxiety disorder had higher levels of suicidal ideation; poorer social functioning; a greater frequency of other anxiety disorders, eating disorders, and somatoform disorders; higher scores on most subscales of a multidimensional self-report measure of DSM-IV axis I disorders; a greater level of pathological worry; and a higher morbid risk for generalized anxiety disorder in first-degree family members. The two generalized anxiety disorder groups did not differ from each other. CONCLUSIONS: The findings question the validity of the DSM-IV hierarchical relationship between major depressive disorder and generalized anxiety disorder and suggest that the exclusion criterion should be eliminated.     

Glutamate receptors in the enteric nervous system: ionotropic or metabotropic?

Intracellular recording methods were used to investigate actions of glutamate on morphologically identified neurones in the myenteric and submucous plexuses of guinea-pig small intestine. Glutamate evoked a tetrodotoxin-resistant, slowly activating depolarizing response in most of the submucous neurones (86 of 125, 69%) and a smaller number of myenteric neurones (6 of 60, 10%). The depolarizing responses were restricted to S-type neurones with uniaxonal morphology. The group I metabotropic glutamate receptor (mGluRs) agonists quisqualate, 1S, 3R-ACPD and DHPG mimicked the depolarizing action of glutamate. A group I mGluRs antagonist, S-4-carboxyphenylglycine (S-4CPG), suppressed the glutamate responses with an IC50 of 357 microM at 30 microM glutamate. Group II or III mGluRs agonists did not produce depolarizing responses and group II or III mGluRs antagonists did not alter glutamate-evoked depolarization. The ionotropic glutamate receptor (iGluRs) agonists NMDA, AMPA, or kainate did not evoke depolarizing responses and glutamate-evoked depolarization was unaffected by the iGluRs antagonists D-APV, MK-801, or DNQX. No rapidly activating fast depolarizing responses reminiscent of fast excitatory postsynaptic potentials (EPSPs) were ever observed during application of glutamate or AMPA and stimulus-evoked fast EPSPs were unaffected by DNQX. The results suggest that the excitatory action of glutamate on enteric neurones is mediated by group I metabotropic glutamate receptors and that ionotropic glutamate receptors are not involved. The results also suggest that glutamate-mediated fast EPSPs may not be present in myenteric and submucous neurones in guinea-pig small bowel.     

Chronic dopaminergic treatment in restless legs syndrome: does it affect the autonomic nervous system?

ObjectiveThe link between the autonomic nervous system and restless legs syndrome (RLS) has been recently postulated. Since dopaminergic agents are used as first-line treatment for RLS, the purpose of our study is to verify whether chronic pramipexole treatment could influence the autonomic control of cardiovascular reflexes and heart rate variability (HRV) in RLS during wakefulness.MethodsConsecutive drug naive RLS patients underwent polysomnography (PSG), subjective scales, and cardiovascular function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, handgrip and cold face before and after 3-month pramipexole therapy. HRV analysis was performed in the frequency domain using both autoregressive and fast Fourier transform algorithms in rest supine condition and during HUTT.ResultsTwenty RLS patients reported a significant reduction of RLS symptoms after pramipexole treatment, while PSG did not show significant improvements except for periodic limb movement index. Pramipexole induced a trend to a lower systolic blood pressure and a significant higher variation of systolic and diastolic blood pressure at HUTT. Cardiovascular responses to the other tests were unchanged. No significant differences in HRV spectral analysis between drug naive and treated patients were observed. Moreover, the within-group analysis of HRV between orthostatic and supine position did not show any significant change in sympathetic and parasympathetic components both in the drug naive and pramipexole groups.ConclusionsChronic pramipexole treatment does not seem to affect autonomic balance during wakefulness. Considering that neither PSG data nor autonomic parameters are significantly modified by pramipexole, we hypothesize a non-dopaminergic autonomic dysfunction in RLS.     

The enteric nervous system: another forgotten autonomic target in viral infections?

Clinical Autonomic Research -