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1.  Auditory evoked potentials in panic disorder. 
Neuroimaging studies of behavioral-induced anxiety in non-patients and of lactate-induced anxiety in panic disorder patients have indicated that normal and pathological anxiety may share a common pathway involving the temporal poles. As panic-related anxiety may reflect faulty temporopolar evaluative processing of input, the objective of this study was to examine sensory reactivity in panic disorder patients via scalp recordings of the late auditory evoked 'vertex' potential (LAEP) which appears to have a predominantly temporal lobe origin. Twelve patients diagnosed according to DSM-III criteria as panic disorder and ten normal controls served as subjects in this study. EEG was recorded from 16 scalp sites using a monopolar fronto-occipital derivation and LAEPs were separately averaged in response to four acoustic intensities. Analysis focused on group and electrode-site differences in the negative (N1) and positive (P2) component amplitudes of the LAEPs. Panic disorder patients were found to exhibit significantly larger N1 amplitudes across all stimulus intensities and across all recording sites. No significant group differences were observed with P2. Although the results provide indirect support for a temporal focus, other modulating influences must be considered in data interpretation.
PMCID: PMC1188339  PMID: 1786264
2.  Panic attacks and supraventricular tachycardias: the chicken or the egg? 
Netherlands Heart Journal  2012;21(2):74-77.
Panic attacks occur in about 2 % of the population. Symptoms include a racing or pounding heart beat, chest pain, dizziness, light-headedness, nausea, difficulty in breathing, tingling or numbness in the hands, flushes or chills, dreamlike sensations or perceptual distortions. The symptoms of paroxysmal supraventricular tachycardia (PSVT) may be similar. A PSVT is often difficult to document on the ECG since it has often ceased before the patient comes to medical attention. Besides, a tachycardia may still be present and even be documented but interpreted as a phenomenon secondary to the panic attack. In addition, ECG abnormalities between episodes can often not be identified. The evidence that in some patients paroxysmal SVT is the cause, but not the consequence of a panic attack, is based on observations that catheter ablation was able to cure patients presenting with panic disorders. To better establish the prevalence of SVT as the underlying mechanism of a panic attack, there is a need for prospective studies and/or registries. Whereas gastric ulcer has in some patients changed from a psychosomatic disorder to an infectious disease, we may hypothesise that a certain proportion of panic disorders may mutate into an underlying arrhythmia rather than a primary psychiatric disorder.
PMCID: PMC3547429  PMID: 23179613
Panic attacks; Panic disorder; Paroxysmal supraventricular tachycardia
3.  Overgeneralization of Conditioned Fear as a Pathogenic Marker of Panic Disorder 
Classical conditioning features prominently in many etiological accounts of panic disorder. According to such accounts, neutral conditioned stimuli present during panic attacks acquire panicogenic properties. Conditioned stimuli triggering panic symptoms are not limited to the original conditioned stimuli but are thought to generalize to stimuli resembling those co-occurring with panic, resulting in the proliferation of panic cues. The authors conducted a laboratory-based assessment of this potential correlate of panic disorder by testing the degree to which panic patients and healthy subjects manifest generalization of conditioned fear.
Nineteen patients with a DSM-IV-TR diagnosis of panic disorder and 19 healthy comparison subjects were recruited for the study. The fear-generalization paradigm consisted of 10 rings of graded size presented on a computer monitor; one extreme size was a conditioned danger cue, the other extreme a conditioned safety cue, and the eight rings of intermediary size created a continuum of similarity from one extreme to the other. Generalization was assessed by conditioned fear potentiating of the startle blink reflex as measured with electromyography (EMG).
Panic patients displayed stronger conditioned generalization than comparison subjects, as reflected by startle EMG. Conditioned fear in panic patients generalized to rings with up to three units of dissimilarity to the conditioned danger cue, whereas generalization in comparison subjects was restricted to rings with only one unit of dissimilarity.
The findings demonstrate a marked proclivity toward fear overgeneralization in panic disorder and provide a methodology for laboratory-based investigations of this central, yet understudied, conditioning correlate of panic. Given the putative molecular basis of fear conditioning, these results may have implications for novel treatments and prevention in panic disorder.
PMCID: PMC2806514  PMID: 19917595
4.  Cognitive-behavioral treatment of panic attacks in chronic schizophrenia 
Although panic attacks have been described as relatively common in schizophrenia, few studies have examined treatments for this problem. Because cognitive-behavioral therapy (CBT) has demonstrated efficacy for panic disorder without schizophrenia, the authors conducted an open clinical trial of CBT for the treatment of panic attacks in schizophrenic patients. Eight patients meeting DSM-III-R criteria for schizophrenia and panic disorder were given a 16-week clinical trial of CBT. Ratings after treatment demonstrated both a statistically significant reduction in panic symptoms and a diminution in the number of panic attacks compared with baseline ratings. These results suggest use of CBT in the integrated treatment of patients with a diagnosis of schizophrenia and panic disorder is a promising approach that merits further investigation.
PMCID: PMC3330456  PMID: 9071665
5.  Abdominal epilepsy in chronic recurrent abdominal pain 
Abdominal epilepsy (AE) is an uncommon cause for chronic recurrent abdominal pain in children and adults. It is characterized by paroxysmal episode of abdominal pain, diverse abdominal complaints, definite electroencephalogram (EEG) abnormalities and favorable response to the introduction of anti-epileptic drugs (AED). We studied 150 children with chronic recurrent abdominal pain and after exclusion of more common etiologies for the presenting complaints; workup proceeded with an EEG. We found 111 (74%) children with an abnormal EEG and 39 (26%) children with normal EEG. All children were subjected to AED (Oxcarbazepine) and 139 (92%) children responded to AED out of which 111 (74%) children had an abnormal EEG and 27 (18%) had a normal EEG. On further follow-up the patients were symptom free, which helped us to confirm the clinical diagnosis.
Recurrent chronic abdominal pain is a common problem encountered by pediatricians. Variety of investigations are done to come to a diagnosis but a cause is rarely found. In such children diagnosis of AE should be considered and an EEG will confirm the diagnosis and treated with AED.
To find the incidence of AE in children presenting with chronic recurrent abdominal pain and to correlate EEG findings and their clinical response to empirical AEDs in both cases and control.
Settings and Design:
Krishna Institute of Medical Sciences University, Karad, Maharashtra, India. Prospective analytical study.
Materials and Methods:
A total of 150 children with chronic recurrent abdominal pain were studied by investigations to rule out common causes of abdominal pain and an EEG. All children were then started with AED oxycarbamezepine and their response to the treatment was noted.
111 (74%) of the total 150 children showed a positive EEG change suggestive of epileptogenic activity and of which 75 (67.56%) were females and 36 (32.43%) were male, majority of children were in the age of group of 9-12 years. Temporal wave discharges were 39 (35.13%) of the total abnormal EEG's. All the children were started on AEDs and those with abnormal EEG showed 100% response to treatment while 27 (18%) children with normal EEG also responded to treatment. Twelve (8%) children did not have any improvement in symptoms.
A diagnosis of AE must be considered in children with chronic recurrent abdominal pain, especially in those with suggestive history, and an EEG can save a child from lot of unnecessary investigations and suffering.
PMCID: PMC3611899  PMID: 23559997
Abdominal epilepsy; chronic recurrent abdominal pain; electroencephalogram
6.  Fear of memories: the nature of panic in posttraumatic stress disorder 
European Journal of Psychotraumatology  2012;3:10.3402/ejpt.v3i0.19084.
Although there is increasing evidence that panic attacks are common in posttraumatic stress disorder (PTSD), little is known if posttraumatic panic is comparable to panic attacks observed in panic disorder (PD).
This study examined the cognitive responses to panic attacks in participants with PD and PTSD.
Participants with PD (n=22) and PTSD (n=18) were assessed on the Anxiety Disorder Interview Schedule for DSM-IV and subsequently administered the Agoraphobic Cognitions Questionnaire and a measure of fears related to trauma memories.
Although participants did not differ in terms of catastrophic appraisals about somatic sensations, PTSD participants were more likely to experience fears about trauma memories and being harmed by trauma again during their panic attacks than PD participants.
These findings suggest that although PTSD participants fear somatic outcomes during panic attacks, their panic attacks are distinguished by a marked fear of trauma memories.
PMCID: PMC3488113  PMID: 23130094
Panic attack; posttraumatic stress disorder; panic disorder; trauma memories
Indian Journal of Psychiatry  2002;44(3):246-252.
In a sample of 94 panic patients, 43 patients (45.7%) had comorbid depression. In majority of patients, the comorbid depression was severe enough to be diagnosed as major depression. Panic patients with depression were more severely functionally impaired and had more generalized anxiety symptoms as compared to pure panic patients. There were no significant differences between panic patients with primary and secondary depression on any of the clinical variables. Findings from the present study are in agreement with earlier studies in that panic disorder comorbid with depression is a much more severe illness than pure panic disorder.
PMCID: PMC2954395  PMID: 21206579
Panic disorder; depression
8.  Panic Disorder Among Cambodian Refugees Attending a Psychiatric Clinic 
General hospital psychiatry  2000;22(6):437-444.
This study surveys Khmer refugees attending two psychiatric clinics to determine both the prevalence of panic disorder as well as panic attack subtypes in those suffering panic disorder. A culturally valid adaptation of the SCID-panic module, the Cambodian Panic Disorder Survey (CPDS), was administered to 89 consecutive Cambodian refugees attending these psychiatric clinics. Utilizing culturally sensitive panic probes, the CPDS provides information regarding both the presence of panic disorder and panic-attack subtypes during the month prior to interview. Of 89 patients surveyed at two psychiatric clinics, 53 (60%) currently suffered panic disorder. Among the 53 patients suffering panic disorder, the most common panic attack subtypes during the previous month were the following: “sore neck” [51% of the 53 panic disorder patients (PDPs)], orthostatic dizziness (49% of PDPs), gastro-intestinal distress (26% of PDPs), effort induced (21% of PDPs), olfactory induced (21% of PDPs), and “while-sitting dizziness” (16% of PDPs).
PMCID: PMC2749726  PMID: 11072060
9.  Sensitization of catastrophic cognition in cognitive-behavioral therapy for panic disorder 
BMC Psychiatry  2007;7:70.
Cognitive model of panic disorder have proposed that panic attacks result from the catastrophic misinterpretation of certain bodily sensations. Cognitive-Behavioral Therapy (CBT) for panic disorder aims to change these catastrophic cognitions. CBT intervention successfully caused reduction of catastrophic cognitions and symptomatic improvement in the majority of cases. However there are some patients who fail to modify their catastrophic cognitions or rather experience an increase in them during CBT treatment. It is clinically and theoretically important to understand about cognitive sensitization of panic disorder during CBT sessions. The purpose of the present study is 1) to clarify the baseline characteristics of panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment, and 2) to examine the course of symptomatic changes for them.
Of ninety-five outpatients with panic disorder started the group CBT program for treatment of panic disorder, seventy-nine completer were classified as "cognitively sensitized (CS)" or "cognitive responding (CR)" or "no-responder" according to the difference of the Agoraphobic Cognitions Questionnaire score across treatment. We compared the CS and CR patients in terms of their baseline clinical characteristics. Then we assessed the symptomatic and functional changes for both groups.
At the start of the CBT program, despite of the same degree of panic disorder severity, CS scored significantly lower on ACQ score than CR. CS also showed significantly lower score on anticipatory anxiety compared to CR. At the end of treatment CS showed significant improvement in severity of panic disorder, although the degree of improvement was smaller than that for CR. Then CS would progressively reduce their agoraphobic fear and avoidance, and would improve their functional impairment up to three month of follow-up.
Panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment could nonetheless gradually improve. They showed a relatively low level of catastrophic cognition and anticipatory anxiety before starting the CBT program. We might conclude that temporary sensitization of catastrophic cognition may be necessary before improvement especially among those with initially low catastrophic body sensation fears and that we need not be concerned too much with temporary increase in catastrophic cognition in the process of CBT for panic disorder.
PMCID: PMC2211294  PMID: 18067686
10.  Brainstem evoked potentials in panic disorder. 
Patient reports and laboratory tests support the notion that panic attacks are generated by stimulation of brainstem nuclei. Scalp-recorded brainstem auditory evoked potentials may serve as a unique measurement strategy for the noninvasive assessment of the role of brainstem functioning in panic disorder. Ipsilateral and contralateral BSAEP recordings were examined in response to separate left and right ear click stimulation in 28 patients with a diagnosis of panic disorder and in 18 normal controls. Latency measures did not differentiate between the patient and control groups but amplitudes of wave III and V were found to be larger in patients. These findings are discussed in relation to pathophysiological and neurochemical theories of panic and specific emphasis is placed on serotonergic function.
PMCID: PMC1188612  PMID: 7918353
11.  Smoking Behavior and Alcohol Consumption in Individuals With Panic Attacks 
Individuals with anxiety often report greater smoking and drinking behaviors relative to those without a history of anxiety. In particular, smoking and alcohol use have been directly implicated among individuals experiencing panic attacks, diagnosed with panic disorder, or high on panic-relevant risk factors such as anxiety sensitivity. Less is known, however, about specific features of panic that may differentiate among those who do or do not use cigarettes or alcohol. The purpose of the current study was to replicate previous research findings of an association between panic symptomatology, cigarette smoking, and alcohol consumption, as well as extend findings by examining whether specific symptoms of panic attacks differentiated among those who do or do not use cigarettes or alcohol. Participants (n = 489) completed the Panic Attack Questionnaire-IV, a highly detailed assessment of panic attacks and symptoms, as well as self-report measures of smoking history and alcohol use. Consistent with previous research, participants who reported a history of panic attacks (n = 107) were significantly more likely to report current daily or lifetime daily cigarette smoking, and significantly greater hazardous or harmful alcohol use than participants with no panic history (n = 382). Although smoking and hazardous alcohol use were highly associated regardless of panic status, participants with panic attacks showed elevated hazardous alcohol use after controlling for daily or lifetime smoking. Surprisingly, although participants who reported having had at least one panic attack were more likely to smoke, panic attack symptoms, intensity, or frequency did not differentiate panickers who did or did not smoke. Furthermore, panic-related variables were not shown to differentially relate to problematic drinking among panickers. Implications for understanding the complex relationship between panic attacks and smoking and drinking behaviors are discussed.
PMCID: PMC3170754  PMID: 21915160
smoking; alcohol; panic attacks; comorbidity
12.  Duloxetine in panic disorder with somatic gastric pain 
Panic disorder is the most common type of anxiety disorder, and its most common expression is panic attacks characterized with sudden attacks of anxiety with numerous symptoms, including palpitations, tachycardia, tachypnea, nausea, and vertigo: ie, cardiovascular, gastroenterologic, respiratory, and neuro-otologic symptoms. In clinical practice, panic disorder manifests with isolated gastroenteric or cardiovascular symptoms, requiring additional clinical visits after psychiatric intervention. The first-line treatment for anxiety disorders, and in particular for panic disorder, is the selective serotonin reuptake inhibitors. However, these drugs can have adverse effects, including sexual dysfunction, increased bodyweight, and abnormal bleeding, that may be problematic for some patients. Here we report the case of a 29-year-old Caucasian woman affected by panic disorder with agoraphobia who was referred to our clinic for recurrent gastroenteric panic symptoms. The patient reported improvement in her anxiety symptoms and panic attacks while on a selective serotonin reuptake inhibitor, but not in her gastric somatic problems, so the decision was taken to start her on duloxetine, a serotonin-norepinephrine reuptake inhibitor. After 6 months of treatment, the patient achieved complete remission of her gastric and panic-related symptoms, and was able to stop triple gastric therapy. Other authors have hypothesized and confirmed that duloxetine has greater initial noradrenergic effects than venlafaxine and is effective in patients with panic disorder. This case report underscores the possibility of tailoring therapeutic strategies for the gastroenteric expression of panic disorder.
PMCID: PMC3842215  PMID: 24294001
anxiety disorder; panic attacks; palpitations; tachycardia; tachypnea; nausea; vertigo
13.  Carbon Dioxide Inhalation Induces Dose-Dependent and Age-Related Negative Affectivity 
PLoS ONE  2007;2(10):e987.
Carbon dioxide inhalation is known to induce an emotion similar to spontaneous panic in Panic Disorder patients. The affective response to carbon dioxide in healthy subjects was not clearly characterized yet.
Methodology/Principal Findings
Sixty-four healthy subjects underwent a double inhalation of four mixtures containing respectively 0, 9, 17.5 and 35% CO2 in compressed air, following a double blind, cross-over, randomized design. Affective responses were assessed according to DSM IV criteria for panic, using an Electronic Visual Analogue Scale and the Panic Symptom List. It was demonstrated that carbon dioxide challenges induced a dose dependent negative affect (p<0.0001). This affect was semantically identical to the DSM IV definition of panic. Older individuals were subjectively less sensitive to Carbon Dioxide (p<0.05).
CO2 induced affectivity may lay on a continuum with pathological panic attacks. Consistent with earlier suggestions that panic is a false biological alarm, the affective response to CO2 may be part of a protective system triggered by suffocation and acute metabolic distress.
PMCID: PMC1991589  PMID: 17912364
14.  Cognitive behavior therapy in the treatment of panic disorder 
Indian Journal of Psychiatry  2009;51(2):108-116.
Comprehensive cognitive behavior therapies have been proved to be more effective than behavioral interventions. However, the efficacy of CBT is not studied in the Indian context and also, the amount of change brought about by CBT is not known. Aims: This study aims to examine the efficacy of cognitive behavioral intervention (CBI) in the treatment of panic disorder. Our specific objectives were to assess the effectiveness of CBI in reducing symptom severity as well as cognitions related to panic and panic-related behaviors. Design: The study adopted a two-group comparison with pre- and postassessments design.
Materials and Methods:
The sample consisted of 30 patients sequentially allotted to the CBI (n = 15) and behavioral intervention (BI, n = 15) groups. Assessment was done using a semistructured interview schedule, panic disorder severity scale, Texas panic attack record form, Anxiety Sensitivity Index, Agoraphobic cognitions questionnaire, Behavioral avoidance checklist, and Panic appraisal inventory. The CBI group was provided with comprehensive cognitive behavior therapy and the BI group with psycho-education and applied relaxation.
CBI was found to be superior to BI in the reduction of panic symptoms, behavioral avoidance, safety behaviors, and cognitions. A large percentage of the CBI group patients met the criteria for clinically significant change with a large magnitude of change.
Multicomponent CBI is superior to BI in terms of the amount of change it brings about with respect to panic symptoms, avoidance, safety behaviors, and cognitions.
PMCID: PMC2755166  PMID: 19823629
Clinically significant change; magnitude of change; multicomponent cognitive behavioral intervention
15.  Somatic panic-attack equivalents in a community sample of Rwandan widows who survived the 1994 genocide 
Psychiatry research  2003;117(1):1-9.
The present study is the first to attempt to determine rates of panic attacks, especially ‘somatically focused’ panic attacks, panic disorder, symptoms of post-traumatic stress disorder (PTSD), and depression levels in a population of Rwandans traumatized by the 1994 genocide. The following measures were utilized: the Rwandan Panic-Disorder Survey (RPDS); the Beck Depression Inventory (BDI); the Harvard Trauma Questionnaire (HTQ); and the PTSD Checklist (PCL). Forty of 100 Rwandan widows suffered somatically focused panic attacks during the previous 4 weeks. Thirty-five (87%) of those having panic attacks suffered panic disorder, making the rate of panic disorder for the entire sample 35%. Rwandan widows with panic attacks had greater psychopathology on all measures. Somatically focused panic-attack subtypes seem to constitute a key response to trauma in the Rwandan population. Future studies of traumatized non-Western populations should carefully assess not only somatoform disorder but also somatically focused panic attacks.
PMCID: PMC2772881  PMID: 12581815
Panic disorder; Stress disorders; post-traumatic; Depression; Rwanda; Holocaust
16.  A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study 
BMC Psychiatry  2009;9:25.
Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication, it is important to identify additional therapeutic strategies for the management of panic symptoms. This article describes a randomized, rater-blind study comparing low-dose risperidone to standard-of-care paroxetine for the treatment of panic attacks.
Fifty six subjects with a history of panic attacks were randomized to receive either risperidone or paroxetine. The subjects were then followed for eight weeks. Outcome measures included the Panic Disorder Severity Scale (PDSS), the Hamilton Anxiety Scale (Ham-A), the Hamilton Depression Rating Scale (Ham-D), the Sheehan Panic Anxiety Scale-Patient (SPAS-P), and the Clinical Global Impression scale (CGI).
All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received. Statistically significant improvements in rating scale scores for both groups were identified for the PDSS, the Ham-A, the Ham-D, and the CGI. There was no difference between treatment groups in the improvement in scores on the measures PDSS, Ham-A, Ham-D, and CGI. Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine.
We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks. Low-dose risperidone appears to be tolerated equally well as paroxetine. Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component.
Trial Registration Identifier: NCT100457106
PMCID: PMC2696444  PMID: 19470174
17.  Respiratory and Cognitive Mediators of Treatment Change in Panic Disorder: Evidence for Intervention Specificity 
There are numerous theories of panic disorder, each proposing a unique pathway of change leading to treatment success. However, little is known about whether improvements in proposed mediators are indeed associated with treatment outcomes and whether these mediators are specific to particular treatment modalities. Our purpose in this study was to analyze pathways of change in theoretically distinct interventions using longitudinal, moderated mediation analyses.
Forty-one patients with panic disorder and agoraphobia were randomly assigned to receive 4 weeks of training aimed at altering either respiration (capnometry-assisted respiratory training) or panic-related cognitions (cognitive training). Changes in respiration (PCO2, respiration rate), symptom appraisal, and a modality-nonspecific mediator (perceived control) were considered as possible mediators.
The reductions in panic symptom severity and panic-related cognitions and the improvements in perceived control were significant and comparable in both treatment groups. Capnometry-assisted respiratory training, but not cognitive training, led to corrections from initially hypocapnic to normocapnic levels. Moderated mediation and temporal analyses suggested that in capnometry-assisted respiratory training, PCO2 unidirectionally mediated and preceded changes in symptom appraisal and perceived control and was unidirectionally associated with changes in panic symptom severity. In cognitive training, reductions in symptom appraisal were bidirectionally associated with perceived control and panic symptom severity. In addition, perceived control was bidirectionally related to panic symptom severity in both treatment conditions.
The findings suggest that reductions in panic symptom severity can be achieved through different pathways, consistent with the underlying models.
PMCID: PMC3327286  PMID: 20873904
mediation; respiration; cognitions; panic; treatment
18.  Vestibular testing in patients with panic disorder and chronic dizziness 
In order to investigate the relationship between chronic dizziness and vestibular function in patients with panic disorder, in the present study neurotologic findings in 15 patients with panic disorder and chronic dizziness were compared with those in 15 patients with chronic dizziness, without panic disorder. All underwent neurotologic screening for spontaneous, positional and positioning nystagmus with head-shaking and head-thrust tests, an audiometric examination and electronystagmography with bithermal stimulation according to Freyss. A significantly higher number of patients with panic disorder and chronic dizziness showed pathological neurotologic findings in comparison to subjects with chronic dizziness only (9 and 2 patients, respectively; p < 0.05). Most patients with panic disorder showed signs of peripheral vestibular disorders. These results suggest that the complaint of dizziness in patients with panic disorder may be linked to a malfunction of the vestibular system and vestibular disorders may play a role in the pathophysiology of panic disorder. Possible mechanisms underlying this finding are discussed. In patients with panic disorder and chronic dizziness between panic attacks, a careful neurotologic examination is warranted.
PMCID: PMC2640032  PMID: 18198754
Dizziness; Panic disorder; Vestibular function; Electronystagmography
19.  Improved Diagnosis in Children with Partial Epilepsy Using a Multivariable Prediction Model Based on EEG Network Characteristics 
PLoS ONE  2013;8(4):e59764.
Electroencephalogram (EEG) acquisition is routinely performed to support an epileptic origin of paroxysmal events in patients referred with a possible diagnosis of epilepsy. However, in children with partial epilepsies the interictal EEGs are often normal. We aimed to develop a multivariable diagnostic prediction model based on electroencephalogram functional network characteristics.
Methodology/Principal Findings
Routinely performed interictal EEG recordings at first presentation of 35 children diagnosed with partial epilepsies, and of 35 children in whom the diagnosis epilepsy was excluded (control group), were used to develop the prediction model. Children with partial epilepsy were individually matched on age and gender with children from the control group. Periods of resting-state EEG, free of abnormal slowing or epileptiform activity, were selected to construct functional networks of correlated activity. We calculated multiple network characteristics previously used in functional network epilepsy studies and used these measures to build a robust, decision tree based, prediction model. Based on epileptiform EEG activity only, EEG results supported the diagnosis of with a sensitivity and specificity of 0.77 and 0.91 respectively. In contrast, the prediction model had a sensitivity of 0.96 [95% confidence interval: 0.78–1.00] and specificity of 0.95 [95% confidence interval: 0.76–1.00] in correctly differentiating patients from controls. The overall discriminative power, quantified as the area under the receiver operating characteristic curve, was 0.89, defined as an excellent model performance. The need of a multivariable network analysis to improve diagnostic accuracy was emphasized by the lack of discriminatory power using single network characteristics or EEG's power spectral density.
Diagnostic accuracy in children with partial epilepsy is substantially improved with a model combining functional network characteristics derived from multi-channel electroencephalogram recordings. Early and accurate diagnosis is important to start necessary treatment as soon as possible and inform patients and parents on possible risks and psychosocial aspects in relation to the diagnosis.
PMCID: PMC3614973  PMID: 23565166
20.  The effects of an Internet based self-help course for reducing panic symptoms - Don't Panic Online: study protocol for a randomised controlled trial 
Trials  2011;12:75.
Internet based self-help for panic disorder (PD) has proven to be effective. However, studies so far have focussed on treating a full-blown disorder. Panic symptoms that do not meet DSM-IV criteria are more prevalent than the full-blown disorder and patients with sub-clinical panic symptoms are at risk of developing PD. This study is a randomised controlled trial aimed to evaluate an Internet based self-help intervention for sub-clinical and mild PD compared to a waiting list control group.
Participants with mild or sub-clinical PD (N = 128) will be recruited in the general population. Severity of panic and anxiety symptoms are the primary outcome measures. Secondary outcomes include depressive symptoms, quality of life, loss of production and health care consumption. Assessments will take place on the Internet at baseline and three months after baseline.
Results will indicate the effectiveness of Internet based self-help for sub-clinical and mild PD. Strengths of this design are the external validity and the fact that it is almost completely conducted online.
Trial registration
Netherlands Trial Register (NTR): NTR1639 The Netherlands Trial Register is part of the Dutch Cochrane Centre.
PMCID: PMC3062612  PMID: 21396089
21.  Main and Interactive Effects of a Nonclinical Panic Attack History and Distress Tolerance in Relation to PTSD Symptom Severity 
Journal of anxiety disorders  2010;25(2):185-191.
The current study investigated the main and interactive effects of a nonclinical panic attack history and distress tolerance in relation to PTSD symptoms. The sample consisted of 91 adults (62.6% women; Mage = 23.45, SD = 9.56) who met DSM-IV criteria for trauma exposure, 53.8% of whom met criteria for a recent (past two years) history of nonclinical panic attacks. Results indicated that distress tolerance, as measured by the Distress Tolerance Scale (Simons & Gaher, 2005), was significantly related to all PTSD symptom clusters, and a nonclinical panic attack history was significantly related to PTSD re-experiencing and hyperarousal symptoms. The interaction of a nonclinical panic attack history and distress tolerance significantly predicted unique variance in only PTSD hyperarousal symptoms. Implications and future directions are discussed for the role of nonclinical panic attacks and distress tolerance in PTSD symptom expression.
PMCID: PMC3017224  PMID: 20888732
PTSD; distress tolerance; panic attacks; anxiety
22.  The Role of Panic-fear in Comorbid Asthma and Panic Disorder 
Journal of anxiety disorders  2008;23(2):178-184.
We examined mediational models of panic-fear, panic disorder (PD), and asthma outcomes among adult asthma patients. PD was assessed by the Anxiety Disorders Interview Schedule. Twenty-one asthma-PD patients and 27 asthma-only patients completed spirometry and questionnaires. Asthma-PD patients reported greater illness-specific and generalized panic-fear than asthma-only patients, despite no differences in asthma severity or physical symptoms during asthma attacks. Illness-specific panic-fear mediated the relationship between PD and poorer health-related quality of life, including emotional disturbance due to asthma. Illness-specific panic-fear was associated with more primary care office visits for asthma. Asthma-PD patients reported greater irritability during asthma attacks than asthma-only patients. Generalized panic-fear was directly associated with restriction of activities due to asthma and use of rescue medication for asthma. Neither measure of panic-fear was associated with asthma severity. Panic-fear experienced during asthma attacks may be an important area to target for improving health-related quality of life among asthma-PD patients.
PMCID: PMC2661851  PMID: 18667290
asthma; generalized panic-fear; illness-specific panic-fear; panic disorder; quality of life
23.  The Experience of Panic Symptoms across Racial Groups in a Student Sample 
Journal of anxiety disorders  2010;24(8):873-878.
While there is general agreement that, across cultures, panic disorder appears to be characterized by sudden onset of bodily sensations, such as dizziness and heart palpitations, followed by catastrophic misinterpretations of these symptoms, there remains a need for research investigating ethnic/cultural differences in the experience of panic attacks. In addition to investigating ethnic differences in the experience of panic, it is important to assess whether increased endorsement of panic symptoms translates into increased dysfunction. The present study investigated differences in the experience of panic attacks and examined the relation between symptom endorsement and overall distress and impairment in a large multiracial/ethnic student population. Preliminary analyses indicated that although overall endorsement of panic symptoms was similar across groups, differences did emerge on specific symptoms. Participants identifying as Asian tended to endorse symptoms such as dizziness, unsteadiness, choking, and feeling terrified more frequently than those identifying as Caucasian, and individuals identifying as African American reported feeling less nervous than those identifying as Caucasian. Participants of Hispanic/Latino(a) descent showed no differences from any other group on symptom endorsement. Panic symptom severity was not found to differ across racial/ethnic groups; however, the correlation between panic symptoms and panic severity was stronger for Asian and Caucasian participants than for African Americans. These results suggest that symptoms of panic may be experienced differently across racial/ethnic groups, and highlight the need for clinicians and researchers to assess panic symptoms within the context of culture.
PMCID: PMC2956784  PMID: 20621442
24.  Fluoxetine in panic disorder: pharmacologic and tritiated platelet imipramine and paroxetine binding study. 
Serotonergic implication in panic disorder has been demonstrated by the efficacy of serotonin reuptake blockers in treatment. Fluoxetine, a potent 5-HT reuptake blocker, has been suggested to have anti-panic efficacy. This open study examines 30 patients (eight males and 22 females) with an average age of 36.9 years, ranging from 18 to 62, who were treated for eight weeks with fluoxetine (mean dose 20 mg per day). All patients fulfilled DSM-III-R criteria of panic disorder with agoraphobia as determined in a SCID interview schedule. Out of 28 patients who started medication, 64% of the patients completed the clinical trial and 36% of the patients dropped out of treatment because of increased anxiety or a lack of efficacy. Thirty-two percent of the patients had zero panic attacks by week 3. By the end of eight weeks of treatment, 48% of the patients had zero panic attacks. There was a significant reduction in anxiety and phobic avoidance and panic attacks. Tritiated platelet imipramine and paroxetine bindings revealed significantly lower maximal binding for patients with panic disorder in comparison with controls. Paroxetine Bmax showed a trend to increase in the direction of control values by the end of the trial.
PMCID: PMC1188684  PMID: 7786880
25.  Effects of citalopram treatment on behavioural, cardiovascular and neuroendocrine response to cholecystokinin tetrapeptide challenge in patients with panic disorder. 
Eight patients with panic disorder were administered 20 micrograms of cholecystokinin tetrapeptide (CCK-4) before and after 8 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram. All patients responded to treatment by showing a significant general improvement and reaching a panic-free state for 2 weeks. At the rechallenge with CCK-4, patients displayed a marked reduction in the intensity and number of panic symptoms. The frequency of panic attacks induced with CCK-4 decreased by 50% after treatment. Citalopram treatment had no substantial effect on cardiovascular (heart rate and blood pressure) or hormonal (cortisol, prolactin and growth hormone) responses to CCK-4. Patients who still had panic attacks after treatment demonstrated a blunted growth hormone response to CCK-4 that was not seen in those who did not have panic attacks. This study suggests that treatment with an SSRI can reduce an enhanced sensitivity to CCK-4 without modifying cardiovascular and neuroendocrine responses to CCK-4 in patients with panic disorder.
PMCID: PMC1188881  PMID: 9401314

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