In this community physician-based sample, lifetime prevalence was 49%and current prevalence was 43% for anxiety disorders in individuals with PD. This high prevalence of anxiety disturbances in PD underscores its prominence as a significant psychiatric co-morbidity in PD. Previous estimates have ranged from 28%-40%,(1
) lower than observed in our study but still elevated over the rate in the general population or in medically ill groups with comparable physical disability.(2
) The high prevalence rate in our study, despite ascertainment in a community sample in which lower rates of psychiatric comorbidity might be expected,(22
) is likely the result of the comprehensive assessment strategies used in this study, including informant input, and the inclusion of all anxiety diagnoses, including Anxiety Disorder, NOS. We tentatively conclude that the nearly 50% rate of anxiety reported provides the best available estimate of the true rate of anxiety associated with community-based PD populations. The high rate of anxiety sufficiently severe to merit diagnosis as a disorder underscores the prominence of anxiety as a significant co-morbid feature of PD.
The most common diagnosis in our sample was Anxiety Disorder NOS, with a lifetime prevalence of 30%. In DSM-IV-TR, the Anxiety Disorder, NOS category is used for “disorders with prominent anxiety or phobic avoidance that do not meet criteria for any specific Anxiety Disorder.” Previous smaller studies describing anxiety in PD that did not fit into specific DSM categories found similar rates to our study (21-40%).(6
) but the atypical nature of the anxiety in these subjects was not delineated. We found that over half of the subjects with the Anxiety Disorder NOS had anxiety related to motor fluctuations in the form of ‘wearing-off’ panic attacks or situational anxiety with phobic avoidance related to fear of experiencing off-periods or freezing.
The reason for the correlation between motor fluctuation and atypical forms of anxiety is not clear. In PD patients with motor fluctuations, anxiety could be a conditioned phenomenon in which “off periods” become associated with a fear of the inability to move. Alternatively, excessive anxiety or an underlying pathology associated with both anxiety and PD causes subjects to have a higher frequency of motor fluctuations. Regardless of the mechanism, the DSM-IV-TR diagnostic criteria do not consistently capture episodic anxiety associated with motor fluctuations because the episodes do not fit into preexisting diagnostic categories. Fluctuation-associated anxiety has previously been shown to correlate with level of disability, emphasizing the importance of recognition of this form of anxiety.(3
) This is of particular importance as fluctuation associated anxiety, and other PD-specific forms of anxiety, may be related to dopamine,(24
) and may not respond to the anxiety treatments used in the general population.
Specific phobia (19%), panic disorder (10%), and social phobia (9%) were the next most prevalent anxiety disorders in our sample, consistent with some previous studies.(1
) One study found much higher rates (50%) of social phobia in PD patients.(25
) As compared to prevalence estimates in the general population elderly (>60 years),(22
) panic disorder, agoraphobia, specific phobia, and social phobia are more prevalent in our sample whereas PTSD is less prevalent; rates of OCD are similar across samples. These differential prevalence rates support our hypothesis that select anxiety disorders are associated with the etiology or neurodegenerative process of PD. Previous epidemiological studies show that anxiety, without specification of subtype, increases the risk of developing PD;(10
) our results suggest that specific forms of anxiety may be most correlated with future PD. For example, 8 of 11 with social phobia had symptoms many years before the onset of PD (). By contrast, median age onset of specific phobia was 40 years in our sample, which is relatively later than the childhood onset of specific phobia in the general population. This later appearance of specific phobias may be related to emerging autonomic dysfunction, which is present in PD and regarded as integral to the pathophysiology of specific phobias.(27
Panic disorder, of the anxiety subtypes frequent enough for statistical analysis in our study, was uniquely associated with an earlier age of PD onset and fluctuations in motor function. Earlier age of PD onset has been associated with a greater degree of genetic influence and subjects with young-onset genetic causes of PD are typically more prone to motor complications of treatment.(28
) One possible implication of our findings is that panic disorder may be a marker for a discrete phenotype in PD. Consistent with this interpretation, panic disorder, including cases with panic onset before clinical motor symptoms, have been reported in PD associated with mutations in parkin
) From the standpoint of pathophysiology, the association of panic disorder with locus coeruleus and noradrenergic dysfunction in both PD and the general population (27
) is consistent with Braak's theory (35
) that the earliest pathological processes in PD involve non-dopaminergic systems in the lower brainstem. Specifically, damage to the locus coeruleus could account for a variety of non-motor manifestations of PD, including sleep disturbances, autonomic symptoms, and anxiety.(36
) In addition, locus coeruleus dysfunction and anxiety-attacks have been associated with dyskinesia, on-off motor fluctuations, and other complications of antiparkinsonian treatment.(4
) Whether PD subjects with panic disorder represent a subgroup with disproportionate involvement of the locus coeruleus and noradrenergic system is unclear.
The high lifetime and current co-occurrence of anxiety and depressive disorders in PD that we detected is consistent with previous findings.(1
) Interestingly, we did not find a higher prevalence of anxiety in women, in contrast with the general population in which women have a higher prevalence of anxiety disorders than men.(1
) While needing replication, this result supports the hypothesis that anxiety disorders are uniquely associated with PD, and may differ from anxiety disorders in the general population. As in previous investigations of PD, we found evidence that quality of life is worse for patients with anxiety disorders.(5
) What our evidence indicates, however, is that this association is specific to particular subtypes of anxiety (Anxiety Disorder NOS and panic disorder), additional support for utility of distinguishing among different subtypes of anxiety disorder in PD.
Several limitations of this study are worth noting. First, individuals with psychiatric symptoms may have been more likely to participate in our study, thus yielding higher prevalence rates. In addition, exclusion of the 10 subjects who screened negative for mood symptoms and did not progress to a diagnostic interview could lead to overestimation of prevalence ranging from 0.11% to 3.62%, depending upon the number of screen-negative cases that would have been diagnosed with an anxiety disorder. Recall bias could also influence the information subjects or informants provided during the clinical interviews, affecting lifetime prevalence. We attempted to limit this bias by reaching consensus diagnoses using a combination of a semi-structured interview, medical records, and an outside informant. Also, because of the exploratory nature of this study, we have reported associations without correcting for multiple comparisons; thus, replication of our findings in other samples is necessary. Finally, sample size limited comparisons of all identified anxiety subgroups or resulted in insufficient power in analyses. As this was a cross-sectional study, we were also unable to draw conclusions regarding the significance of higher rates of dopamine agonist use in the non-anxious group.
In conclusion, this investigation supports and extends previous findings demonstrating the high prevalence of anxiety in PD and the prominence of anxiety diagnoses in PD that do not fall into discrete DSM diagnostic categories. This study provides preliminary data suggesting that certain anxiety diagnoses are uniquely associated with PD and may be clinically useful as a marker associated with disease impact. Specifically, our study presents evidence suggesting that panic disorder and its association with younger age of PD onset and fluctuations in motor function represents an important anxiety subtype in this population. Anxiety disorders that do not meet DSM criteria have been overlooked in the literature and may be unrecognized in clinical practice despite their impact on quality of life and likely impact on disability.