Clinical Correlates of Schizotypy in Patients With Epilepsy

We analyzed data from 89 patients with epilepsy (42 men). Their mean age was 42.5 years (SD=14.6), age at onset of the epilepsy was 23.6 years (SD=20.2), 77.5% had a diagnosis of partial epilepsy (n=69), and 69.7% had temporal lobe epilepsy (n=62) ( Table 1 ). Almost half of the patients (49.4%) were taking carbamazepine (n=44), 19.1% valproate (n=17), 14.6% barbiturates (n=13), 11.2% lamotrigine (n=10), 10.1% oxcarbazepine (n=9), 9% topiramate (n=8), 3.4% levetiracetam (n=3), and 2.2% phenytoin (n=2). In previous psychiatric history, 21.3% had a diagnosis of mood disorders (n=19), 18% of anxiety disorders (n=16), and 3.4% of psychoses (n=3).

The Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI) Y1 and Y2, Schizotypal Personality Questionnaire (SPQ) totals and SPQ subscales scores are shown in Table 2 . There was no relation between SPQ total and subscales scores and EEG laterality or seizure frequency. Age at onset of epilepsy did not correlate with BDI or STAI-Y1 and Y2, while significant correlations were found for SPQ total score (ρ=−0.247, p=0.019), disorganized (ρ=−0.214, p=0.044), interpersonal (ρ=−0.248, p=0.019), cognitive-perceptual (ρ=−0.233, p=0.028), odd belief (ρ=−0.249, p=0.019), unusual perceptions (ρ=−0.214, p=044), odd speech (ρ=−0.239, p=0.24), constricted affect (ρ=−0.421, p<0.001), and suspiciousness (ρ=−0.215, p=0.043). However, linear regression models including total SPQ score, the three factors (disorganized, interpersonal, cognitive-perceptual), and the subscales odd belief, unusual perceptions, odd speech, constricted affect, and suspiciousness showed that only constricted affect scores significantly correlated with age at onset of the epilepsy (OR=−3.04; 95% confidence interval [CI]=−5.32 to −1.48, p=0.001). Constricted affect scores showed also a significant correlation with STAI-Y1 (ρ=0.458, p<0.001), STAI-Y2 (ρ=0.364, p<0.001), and BDI scores (ρ=0.299, p=0.004). In the subgroup of patients with temporal lobe epilepsy, the correlation between age at onset of the seizures and constricted affect scores was less evident (ρ=−0.291, p=0.022).

Patients with temporal lobe epilepsy had higher scores than patients without temporal lobe epilepsy for SPQ total scores, and subscales disorganized, interpersonal, cognitive-perceptual, ideas of references, unusual perceptions, no friends, odd speech, and suspiciousness ( Table 3 ). Logistic regression models including SPQ total scores, the three factors (disorganized, interpersonal, cognitive-perceptual), and the subscales ideas of references, unusual perceptions, no friends, odd speech, and suspiciousness showed that temporal lobe epilepsy diagnosis correlated specifically with SPQ total (OR=1.03; 95% CI=1.01–1.06, p=0.009), cognitive-perceptual (OR=1.10; 95% CI=1.03–1.17, p=0.004), and suspiciousness scores (OR=1.34; 95% CI=1.12–1.61, p=0.001).

To the best of our knowledge, this study is the first one to investigate associations between epilepsy and different dimensions of schizotypy using a validated psychometric instrument such as the Schizotypal Personality Questionnaire (SPQ). Our results suggest that SPQ-derived schizotypal symptoms are common in adult patients with epilepsy, particularly when compared with the normative sample of healthy subjects. 12, 14 Specifically, epilepsy seems to be associated with higher scores on the interpersonal factor, which includes symptoms of excessive social anxiety, no close friendships, and constricted affect. Particularly, those with constricted affect showed a significant negative correlation with age of onset of the epilepsy (OR=−3.04; 95% CI=−5.32 to −1.48, p=0.001). In the group of patients with temporal lobe epilepsy, this correlation was still present but weaker than that reported in the whole population. This is likely to be related to the small number of subjects investigated and might be more noticeable in larger samples. However, this association needs to be discussed in the light of previous literature. 7, 8

There seems to be general agreement that patients with epilepsy and psychosis have an age of onset of seizures within early adolescence, 7, 8, 15, 16 but no studies clearly pointed out a relationship with a specific dimension of schizophrenia. Affective flattening is one of the diagnostic criteria for schizophrenia according to DSM-IV, being, together with alogia and avolition, one of the major negative symptoms. Literature about negative symptoms in seizure patients is scanty and our findings are consistent with a previous study supporting the hypothesis that negative symptoms are stable features of the interictal behavior in epilepsy. 17 Thus, someone would infer that our results further support the hypothesis that psychosis in epilepsy may have a strong biological basis as a consequence of early brain damage. However, the observed correlation of constricted affect scores with measures of anxiety and depression (STAI and BDI scores) raises a number of issues. The most important one is whether this SPQ subscale, namely constricted affect, truly reflects the affective blunting usually seen in psychotic and schizotypal patients and not merely the effects of depressed mood or avoidant personality features. Although depression is in general overrepresented among epilepsy patients, there was no correlation between age at onset of the epilepsy and BDI or STAI scores, making it unlikely that our findings represent just a bias due to the pervasive effect of mood disturbances. This further suggests that negative symptoms of schizophrenia are connected with the age at onset of the seizures in patients with epilepsy.

We need to consider the overlap between schizotypal and avoidant personality features. Conceptually, avoidant patients yearn for social relationships but require an unusually strong degree of acceptance before engaging in them because of their anxiety, while schizotypal individuals do not actively want or seek these relationships. In clinical practice, these distinctions can be difficult to make, especially when avoidant patients appear aloof and distant and there is a significant degree of cognitive impairment. 2 In our opinion, it is impossible to rule out that our data may reflect severe avoidant personality features due to poor self-esteem and a certain degree of cognitive impairment as a consequence of an early-onset seizure disorder. It is therefore evident that the significance of schizotypal features in epilepsy at a phenomenological level deserves further investigation.

The correlations between a diagnosis of temporal lobe epilepsy and total SPQ, cognitive-perceptual, and suspiciousness scores are much more in line with the hypothesis that psychoses in epilepsy have a strong biological component. Few controlled studies have demonstrated an increased incidence of psychoses in patients with TLE, 18 and it has been argued that TLE preponderance on interictal psychoses may be a bias and that patients with partial epilepsy, regardless of the localization of the focus, share similar processes in the development of psychiatric symptoms. 7, 8, 19 We agree that psychoses are multimodal phenomena and that other factors, not necessarily epileptogenic zones, are of relevance. 8 However, our findings support the assumption that temporal lobe dysfunction represents a fertile neurobiological ground for the development of schizophrenia-related personality features such as schizotypy and may be, therefore, of relevance for the development of a thought disorder. The temporal cortex, the frontal cortex, the striatum, and the thalamus have been particularly implicated, as regions of interests, in both schizophrenia and schizotypal personality disorder. 3 In particular, reduced size of the temporal cortex has been reported in schizotypal patients involving the superior temporal gyrus, 20 Heschl’s gyrus, 21 as well as the inferior and middle temporal gyri. 22 Although we fail to show that SPQ scores correlated with any major structural abnormalities in the temporal lobes, as detected with our routine MRI protocols, it has been suggested that these structures may be affected by developmental aberrations that can be detected with more sophisticated investigations. 23 However, our findings further support that temporal lobe alterations are associated with the core symptom profile of schizophrenia disorders, and this is further corroborated by correlations with the cognitive-perceptual factor (OR=1.10; 95% CI=1.03–1.17, p=0.004) that most closely parallels Jaspers’ concept of psychosis. 24

Limitations of our study need to be acknowledged. First, the small sample size reduces the statistical power of our study. Second, our findings may not be representative of epilepsy patients in general because our population represents a selected sample coming mainly from a university-based referral center. It is possible that an individual with both epilepsy and schizotypal features is more likely to be referred to our clinic, and correspondingly patients in our clinic may represent individuals with more severe epilepsy and behavioral problems. Furthermore, psychosocial problems that arise from living with, and adapting to, a still stigmatized disorder such as epilepsy need to be taken into account, because these problems may contribute to the severity of associated psychopathology.

In conclusion, our study showed that schizotypal symptoms are common in adult patients with epilepsy and correlate with an early onset of the seizures and a diagnosis of temporal lobe epilepsy. At a theoretical level it is plausible that epilepsy and schizotypy may share a common pathoetiology, and our results are in line with a number of publications showing a complex relation between epilepsy and psychosis. 7 However, further studies are needed to replicate our findings and to shed light on the neurobiology of schizotypy, schizophrenia spectrum disorders, and epilepsy.