Comorbidity rates of autism spectrum disorder and functional neurological disorders: A systematic review, meta-analysis of proportions and qualitative synthesis.

LAY ABSTRACT: Autism spectrum disorder (ASD) and functional neurological disorders (FND) are relatively common conditions, and there has been recent interest in the overlap between them. Both conditions share core features of alexithymia, impaired interoception and deficits in attentional focus. To date, relatively little is known about the comorbidity rates between ASD and FND. This is the first meta-analysis and qualitative synthesis on the subject. We found that around 10% of children presenting with functional seizures have a comorbid ASD diagnosis. People with ASD are more likely than the neurotypical population to have functional somatic disorders, and there is also evidence that ASD rates are higher for other FNDs such as functional motor disorders. Since FND comes with risks of unnecessary medical procedures and investigations, it is important to recognize the potential for people with ASD to have an FND comorbidity.

Deep brain stimulation for treatment-refractory obsessive-compulsive disorder should be an accepted therapy in Australia.

Deep brain stimulation has shown promise for the treatment of severe, treatment-refractory obsessive-compulsive disorder. With the recent publication of the first Australian, randomised, sham-controlled trial of deep brain stimulation for obsessive-compulsive disorder, there are now four placebo-controlled trials demonstrating the efficacy of this therapy. Together with recent data identifying a biological substrate of effective stimulation that can predict response and that has been successfully reproduced, studies comparing and finding equivalent efficacy among different targets, as well as recent, large, open trials supporting the long-term effectiveness of deep brain stimulation, we argue that this should now be considered an accepted therapy for a select group of patients in the Australasian setting. We call on the Royal Australian and New Zealand College of Psychiatrists to revise their memorandum describing deep brain stimulation for obsessive-compulsive disorder as an 'experimental' treatment and recognise that it has proven efficacy. We stress that this should remain a therapy offered only to those with high treatment-refractory illnesses and only at specialised centres where there is an experienced multidisciplinary team involved in work-up, implantation and follow-up and also where frameworks are in place to provide careful clinical governance and ensure appropriate fully informed consent.

Defining Atypical Anxiety in Parkinson's Disease.

BACKGROUND: Anxiety is a major complication in Parkinson's disease (PD). Many PD patients experience clinically significant anxiety not meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) anxiety disorder criteria. This atypical anxiety (anxiety disorder not otherwise specified [NOS]) is often under-recognized and its diagnosis is underdeveloped. OBJECTIVES: This study aimed to identify the demographic, psychiatric, and clinical characteristics of anxiety disorder NOS in PD. METHODS: A cross-sectional design studied a convenience sample of 184 PD patients without dementia recruited from neurology outpatient clinics. A semi-structured interview using DSM-IV criteria categorized PD patients into current anxiety disorder NOS (n = 28), DSM-IV anxiety disorders (n = 42) or no anxiety (n = 86) groups. Logistic regression modeling identified characteristics associated with the anxiety disorder NOS group compared to DSM-IV anxiety and no anxiety groups. RESULTS: The anxiety disorder NOS group was associated with motor complications of PD therapy, episodic, persistent and social anxiety symptoms, depression, non-motor experiences of daily living, poor quality of life, and female sex compared to the no anxiety group. Compared to DSM-IV anxiety, those with anxiety disorder NOS demonstrated greater global cognitive impairment, more severe motor complications of PD therapy, a greater severity and functional impact of dyskinesias, and greater complexity of motor fluctuations. Persistent, episodic, and social anxiety symptoms did not significantly differ between anxiety disorder NOS and DSM-IV anxiety groups. CONCLUSIONS: These findings suggest that PD-specific symptoms characterize anxiety in a subgroup of PD patients who do not fulfill DSM-IV criteria for anxiety disorders.

A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ± 10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ± 1.9 points (χ2 (11) = 39.8, p = 3.8 × 10-5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ± 3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no serious psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant's individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS in the region of the BNST for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.

A Pilot Trial of Cognitive Behavioral Therapy for Caregivers After Deep Brain Stimulation for Parkinson's Disease.

Subthalamic deep brain stimulation for Parkinson's disease may not ameliorate burden among caregivers. An 8-session, manualized program of cognitive-behavioral therapy (CBT) was delivered to a pilot sample of 10 caregivers (6 females, mean age: 60, age range: 34-79). Primary outcome measures were caregiver burden (Zarit Burden Interview) and caregiver quality of life (Parkinson's Disease Questionnaire-Carer). Secondary outcome measures comprised ratings of depression and anxiety in the caregiver, in addition to relationship quality. Caregiver burden (t = 2.91 P = .017) and caregiver anxiety (t = 2.82 P = .020) symptoms were significantly reduced at completion of the program, and these benefits were maintained 3 months later. Caregiver quality of life had significantly improved by the end of the intervention (t = 3.02 P = .015), but this effect was not sustained after 3 months. The longitudinal influence of participation in the program on caregiver burden was confirmed in a linear, mixed-effects model, χ2 (3) = 15.1, P = .0017). The intervention was well received by participants, and qualitative feedback was obtained. These results indicate that caregiver burden is modifiable in this cohort with a short course of CBT, that benefits are maintained after termination of the program, and that psychological treatment is acceptable to participants. Larger, controlled trials are justified.

The CuePed Trial: How Does Environmental Complexity Impact Cue Effectiveness? A Comparison of Tonic and Phasic Visual Cueing in Simple and Complex Environments in a Parkinson's Disease Population with Freezing of Gait.

BACKGROUND: The optimal prescription of cueing for the treatment of freezing of gait (FoG) in Parkinson's disease (PD) is currently a difficult problem for clinicians due to the heterogeneity of cueing modalities, devices, and the limited comparative trial evidence. There has been a rise in the development of motion-sensitive, wearable cueing devices for the treatment of FoG in PD. These devices generally produce cues after signature gait or electroencephalographic antecedents of FoG episodes are detected (phasic cues). It is not known whether these devices offer benefit over simple (tonic) cueing devices. METHODS: We assembled 20 participants with PD and FoG and familiarized them with a belt-worn, laser-light cueing device (Agilitas™). The device was designed with 2 cueing modalities-gait-dependent or "phasic" cueing and gait-independent or "tonic" cueing. Participants used the device sequentially in the off, phasic, or tonic modes, across 2 tasks-a 2-minute walk and an obstacle course. RESULTS: A significant improvement in mean distance walked during the 2-minute walk test was observed for the tonic mode (127.3 m) compared with the off (111.4 m) and phasic (116.1 m) conditions. In contrast, there was a nonsignificant trend toward improvement in FoG frequency, duration, and course time when the device was switched from off to tonic and to phasic modes for the obstacle course. CONCLUSIONS: Parkinson's disease patients with FoG demonstrated an improvement in distance walked during the two-minute walk test when a cueing device was switched from off to phasic and to tonic modes of operation. However, this benefit was lost when patients negotiated an obstacle course.

Depression symptomatology correlates with event-related potentials in Parkinson's disease: An affective priming study.

BACKGROUND: Depression is a predominant non-motor symptom of Parkinson's disease (PD), which is often under recognised and undertreated. To improve identification of depression in PD it is imperative to examine objective brain-related markers. The present study addresses this gap by using electroencephalography (EEG) to evaluate the processing of emotionally valanced words in PD. METHODS: Fifty non-demented PD patients, unmedicated for depression or anxiety, completed an affective priming task while EEG was simultaneously recorded. Prime and target word pairs of negative or neutral valence were presented at a short 250 ms stimulus onset asynchrony. Participants were asked to evaluate the valence of the target word by button press. Depression was measured using an established rating scale. Repeated measures analysis of covariance and correlational analyses were performed to examine whether event-related potentials (ERP) varied as a function of depression scores. RESULTS: Key ERP findings reveal reduced responses in parietal midline P300, N400 and Late Positive Potential (LPP) difference waves between congruent and incongruent neutral targets in patients with higher depression scores. LIMITATIONS: Comparisons of ERPs were limited by insufficient classification of participants with and without clinical depression. A majority of PD patients who had high depression scores were excluded from the analysis as they were receiving antidepressant and/or anxiolytic medications which could interfere with ERP sensitivity. CONCLUSIONS: The present study suggests that the Pz-P300, N400 and LPP are ERP markers relates to emotional dysfunction in PD. These findings thus advance current knowledge regarding the neurophysiological markers of a common neuropsychiatric deficit in PD.

How Well Do Caregivers Detect Depression and Anxiety in Patients With Parkinson Disease?

Depression and anxiety are prevalent in Parkinson disease (PD) yet underrecognized in clinical practice. Caregiver reports are frequently utilized to aid in the assessment of neuropsychiatric symptoms but little is known about caregivers' ability to recognize them in patients with PD. This study sought to examine the accuracy of caregiver reports. Eighty patient-caregiver dyads were involved. Accuracy of caregiver recognition was assessed by examining the level of agreement between caregiver ratings on the Neuropsychiatric Inventory and patients' diagnosis of depression and anxiety on the Mini-International Neuropsychiatric Interview (MINI)-Plus. The agreement between caregiver report and MINI-Plus diagnosis was low for both depression (6.3%) and anxiety (17.5%). The presence of depression was overreported, while anxiety was largely underestimated by caregivers. Caregiver distress significantly predicted inaccurate caregiver identification of depression ( R2 = .51, P < .001) and anxiety ( R2 = .08, P < .05). Results indicate that caregivers may be poor at recognizing depression and anxiety in patients with PD. Utilization of caregiver report should take into account potential biases that affect caregiver judgment.

Cognitive Behavior Therapy for Anxiety in Parkinson's Disease: Outcomes for Patients and Caregivers.

OBJECTIVE: Anxiety negatively impacts the quality of life of Parkinson's disease (PD) patients and caregivers. Despite high prevalence, there is a paucity of trials investigating effective treatments for anxiety in PD. This uncontrolled study investigated the use of a manualized and tailored Cognitive Behavior Therapy (CBT) for anxiety in PD. METHODS: Participants completed 6 weekly CBT sessions. Pre-, post- and follow-up (3 and 6 months) assessments were made. Change in outcomes were analysed using t-tests and Reliability Change Index. Of 17 PD patients who agreed to CBT, 12 completed the intervention. RESULTS: This study showed a significant reduction in Hamilton Anxiety Rating Scale scores in PD immediately post CBT (t(11) = 3.59, p < .01), maintained at 3-month (t(8) = 2.83, p = .02) and 6-month (t(7) = 2.07, p = .04) follow-up. A reduction in caregiver burden (t(11) = 2.68, p = .03) was observed post intervention. Improvements in motor disability (t(11) = 2.41, p = .04) and cognitive scores (t(11) = -2.92, p = .01) were also observed post intervention and at follow-up. CONCLUSIONS: Tailored CBT can be used to treat anxiety in PD. CLINICAL IMPLICATIONS: This study provides preliminary evidence suggesting that tailored CBT reduces anxiety in PD with persisting benefits, and lowers caregiver burden.

N400 and emotional word processing in Parkinson's disease.

OBJECTIVE: Emotional and cognitive disturbances are common complications in Parkinson's disease (PD). N400 is an event related potential (ERP) strongly linked to lexical-semantic processing and has demonstrated alterations in amplitude and latency when PD patients performed semantic priming tasks. The present study investigated the role of N400 in an automatic affective priming paradigm in PD. Other ERP components relevant to emotion processing were also examined. METHOD: Twenty-two PD patients and 17 healthy adults performed an automatic affective priming task while ERPs were recorded using 128 channels. Prime-target word pairs of negative or neutral valence were presented at a stimulus onset asynchrony of 250 ms. Participants were asked to evaluate the valence of the target word by button press. RESULTS: A larger N400 amplitude for incongruent compared with congruent neutral targets was observed at right central and parietal regions and did not differ between PD and controls. PD and controls also displayed larger P300 and late positive potential (LPP) amplitudes for negative compared with neutral targets at central parietal and right frontal regions. In contrast, whereas controls showed a larger slow negative wave (SNW) for negative targets compared with neutral targets at left frontal and left central regions, PD group demonstrated a significant reduction in SNW amplitude difference at the left central region. CONCLUSION: N400 is intact in PD when processing evaluative judgments of emotional words. P300 and LPP were also intact in PD. The altered left central SNW in PD suggests an ERP marker for emotional dysfunction in PD. (PsycINFO Database Record

Mindfulness for Motor and Nonmotor Dysfunctions in Parkinson's Disease.

Background. Motor and nonmotor symptoms negatively influence Parkinson's disease (PD) patients' quality of life. Mindfulness interventions have been a recent focus in PD. The present study explores effectiveness of a manualized group mindfulness intervention tailored for PD in improving both motor and neuropsychiatric deficits in PD. Methods. Fourteen PD patients completed an 8-week mindfulness intervention that included 6 sessions. The Five Facet Mindfulness Questionnaire (FFMQ), Geriatric Anxiety Inventory, Hamilton Depression Rating Scale, PD Cognitive Rating Scale, Unified PD Rating Scale, PD Quality of Life Questionnaire, and Outcome Questionnaire (OQ-45) were administered before and after the intervention. Participants also completed the FFMQ-15 at each session. Gains at postassessment and at 6-month follow-up were compared to baseline using paired t-tests and Wilcoxon nonparametric tests. Results. A significant increase in FFMQ-Observe subscale, a reduction in anxiety, depression, and OQ-45 symptom distress, an increase in PDCRS-Subcortical scores, and an improvement in postural instability, gait, and rigidity motor symptoms were observed at postassessment. Gains for the PDCRS were sustained at follow-up. Conclusion. The mindfulness intervention tailored for PD is associated with reduced anxiety and depression and improved cognitive and motor functioning. A randomised controlled trial using a large sample of PD patients is warranted.

Disease-specific anxiety symptomatology in Parkinson's disease.

BACKGROUND: Symptoms of anxiety relating to Parkinson's disease (PD) occur commonly and include symptomatology associated with motor disability and complications arising from PD medication. However, there have been relatively few attempts to profile such disease-specific anxiety symptoms in PD. Consequently, anxiety in PD is underdiagnosed and undertreated. The present study characterizes PD-related anxiety symptoms to assist with the more accurate assessment and treatment of anxiety in PD. METHODS: Ninety non-demented PD patients underwent a semi-structured diagnostic assessment targeting anxiety symptoms using relevant sections of the Mini International Neuropsychiatric Interview (MINI-plus). In addition, they were assessed for the presence of 30 PD-related anxiety symptoms derived from the literature, the clinical experience of an expert panel and the PD Anxiety-Motor Complications Questionnaire (PDAMCQ). The onset of anxiety in relation to the diagnosis of PD was determined. RESULTS: Frequent (>25%) PD-specific anxiety symptoms included distress, worry, fear, agitation, embarrassment, and social withdrawal due to motor symptoms and PD medication complications, and were experienced more commonly in patients meeting DSM-IV criteria for an anxiety disorder. The onset of common anxiety disorders was observed equally before and after a diagnosis of PD. Patients in a residual group of Anxiety Not Otherwise Specified had an onset of anxiety after a diagnosis of PD. CONCLUSION: Careful characterization of PD-specific anxiety symptomatology provides a basis for conceptualizing anxiety and assists with the development of a new PD-specific measure to accurately assess anxiety in PD.

Deep brain stimulation for depression: Scientific issues and future directions.

OBJECTIVE: Deep brain stimulation is an experimental intervention for treatment-resistant depression. Open trials have shown a sustained response to chronic stimulation in many subjects. However, two recent randomised, double-blind, placebo-controlled trials failed to replicate these results. This article is a conceptual paper examining potential explanations for these discrepant findings. METHOD: We conducted a systematic review of the published studies obtained from PubMed and PsycINFO. Studies were selected if they directly examined the impact of deep brain stimulation on depressive symptoms. We excluded case reports and papers re-describing the same cohort of patients. We compared them with data from the placebo-controlled trials, available from Clinicaltrials.gov and abstracts of the American Society for Stereotactic and Functional Neurosurgery. We supplemented our investigation by reviewing additional publications by the major groups undertaking deep brain stimulation for mood disorders. RESULTS: We selected 10 open studies reporting on eight cohorts of patients using four different operative targets. All published studies reported positive results. This was not replicated in data available from the randomised, placebo-controlled trials. Many studies reported suicide or suicide attempts in the postoperative period. CONCLUSION: We consider the placebo effect, the pattern of network activation, surgical candidacy and design of a blinded trial including the length of a crossover period. We suggest a greater focus on selecting patients with melancholia. We anticipate that methodological refinements may facilitate further investigation of this technology for intractable depression. We conclude by noting the psychiatric adverse events that have been reported in the literature to date, as these will also influence the design of future trials of deep brain stimulation for depression.

The psychiatric and neuropsychiatric symptoms after subthalamic stimulation for Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for the motor symptoms of Parkinson's disease (PD). Nonmotor features of PD, however, may not improve with STN DBS, and a specific constellation of neuropsychiatric symptoms may emerge in the postoperative period. Mania, impulsivity, depression, and apathy may curtail the potential gains from surgery. In this paper, the authors discuss surgical candidacy, postoperative management of neuropsychiatric issues, and clinical dilemmas for the psychiatrist at the DBS center. A paradigm that considers stimulation effects and dopamine replacement therapy to be key drivers of postoperative neuropsychiatric problems is presented.

Characteristics and Treatment of Anxiety Disorders in Parkinson's Disease.

Background: Anxiety disorders are common in Parkinson's disease (PD) and are undertreated. The current study investigates demographic and PD-specific factors associated with Diagnostic and Statistical Manual (DSM-IV) anxiety disorders and subsyndromal anxiety in PD. It also examines the use of pharmacological and nonpharmacological treatments for anxiety in PD. Methods: Ninety nondemented PD patients completed a semistructured interview. Logistic regression models were constructed examining associations between several demographic, disease-specific, and treatment factors, as well as both current syndromal, DSM-IV anxiety disorders, and subsyndromal anxiety. Results: Associations were found between current DSM-IV anxiety disorder, as well as female gender, younger age, more severe stages of PD, and poor activities of daily living. Subsyndromal anxiety was related to a younger onset age of PD. Relationships were also found between both anxiety groups and more complications of PD therapy, as well as higher depression scores. There were no associations between anxiety and levodopa equivalent daily dosage, motor disability, and cognition. In our sample, 57% of patients with current DSM-IV anxiety disorders or subsyndromal anxiety were not currently treated with pharmacotherapy. Of those who currently received such treatment, 83% still experienced current anxiety disorders. Results suggest that anxiety is poorly recognized and treated in PD. Conclusions: Clinical trials investigating the efficacy of pharmacotherapy, tailored psychotherapy, and combination therapy primarily focusing on anxiety are much needed, with the aim of establishing novel targeted treatment protocols for the management of subtypes of anxiety disorders in PD.

The clinical spectrum of anxiety in Parkinson's disease.

Anxiety is common in Parkinson's disease (PD), and contributes to increased disability and poorer quality of life. In spite of its significant impact, the symptomatology, chronology, and neurobiology of anxiety in PD are all poorly understood, and this hinders accurate diagnosis and development of effective treatment strategies. This review investigates and updates literature related to the clinical spectrum of anxiety in PD. The reported prevalence of anxiety in PD varies considerably, with emerging interest in the frequency of the DSM-IV residual category of "Anxiety disorder, not otherwise specified" (Anxiety disorder NOS), which is observed in up to 25% of PD patients. By design, there are no standardized diagnostic criteria for Anxiety disorder NOS, because this is the category applied to individuals who do not meet diagnostic criteria for any other current anxiety disorder. Anxiety rating scales incompletely capture anxiety symptoms that relate specifically to PD symptoms and the complications arising from PD therapy. Consequently, these scales have been deemed inappropriate for use in PD, and there remains a need for the development of a new PD-specific anxiety scale. Research establishing accurate symptom profiles of anxiety in PD is sparse, although characterizing such symptomatology would likely improve clinical diagnosis and facilitate targeted treatment strategies. Research into the neurobiological and psychological underpinnings of anxiety in PD remains inconclusive. Anxiety can precede the onset of PD motor symptoms or can develop after a diagnosis of PD. Further investigations focused on the chronology of anxiety and its relationship to PD diagnosis are required.

Clinical issues in the treatment of anxiety and depression in older adults with Parkinson's disease.

A significant proportion of persons affected by Parkinson's disease (PD) are over age 65 years. Mental health issues are often less a focus of treatment in this population than physical manifestations of the illness. Anxiety or depression alone, as well as comorbid depression and anxiety, are underrecognized in patients with PD and are associated with deleterious effects on physical and interpersonal functioning, negatively impacting quality of life and well-being. We offer a brief overview of salient clinical points with respect to assessment and treatment approaches to enhance efficacy of the treatment of mental health symptoms in older adults with PD. Cognitive behavior therapy involves the patient learning to overcome behavioral avoidance associated with anxiety and challenge unhelpful negative cognitions. It is suggested that cognitive behavior therapy is an effective approach to treatment of anxiety and depression in PD and should be offered as a treatment to patients.

Validity and reliability of the Geriatric Anxiety Inventory in Parkinson's disease.

AIM: To examine the psychometric properties of a novel anxiety rating scale, the Geriatric Anxiety Inventory (GAI) in Parkinson's disease (PD). METHOD: The predictive validity of the GAI was tested against the presence of any DSM-IV anxiety disorders in 58 PD patients using receiver operating curve analysis. The concurrent validity of this scale was also studied against the state half of the Spielberger State Trait Anxiety Inventory (STAI). The internal consistency and test-retest reliability of the GAI were also examined. RESULTS: The GAI displayed good concurrent validity against the STAI and the DSM-IV. It also showed good internal consistency and test-retest reliability. CONCLUSIONS: This study suggested that the GAI is an appropriate scale to use in non-demented PD patients.