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Epilepsy, suicidal behaviour, and depression: Do they share common pathogenic mechanisms?

The Lancet Neurology (Impact Factor: 21.82). 03/2006; 5(2):107-8. DOI: 10.1016/S1474-4422(06)70331-3
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    • "Although many clinicians associate this particularly with mesial Temporal Lobe Epilepsy (mTLE), recent studies have demonstrated that patients with other focal and generalised epilepsy syndromes are similarly affected (Christensen et al., 2007; Adams et al., 2008; Hermann et al., 2008). The increased prevalence of these psychiatric disturbances has been variously attributed to the psychosocial consequences of living with a neurological disorder, to longterm medication effects, to the repeated damaging effects of seizures on the brain, or to a common underlying neurobiological abnormality (Jobe, 2003; Kanner, 2006), explanations which are not mutually exclusive. Of note, several animal models of epilepsy show a range of striking behavioural changes relevant to the psychiatric comorbidities seen in humans with epilepsy, including interictal alterations in anxiety states, depressive-like behaviours and endophenotypes of psychosis (Adamec and Young, 2000; Kalynchuk, 2000; McIntyre et al., 2002; Jobe and Browning, 2007; Mazarati et al., 2007; Jones et al., 2008, 2009, 2010; Mazarati et al., 2009), suggesting that there is at least some biological component to these comorbidities. "
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    ABSTRACT: Psychiatric disorders associated with elevated stress levels, such as depression, are present in many epilepsy patients, including those with mesial Temporal Lobe Epilepsy (mTLE). Evidence suggests that these psychiatric disorders can predate the onset of epilepsy, suggesting a causal/contributory role. Prolonged exposure to elevated corticosterone, used as a model of chronic stress/depression, accelerates limbic epileptogenesis in the amygdala kindling model. The current study examined whether exposure to repeated stress could similarly accelerate experimental epileptogenesis. Female adult non-epileptic Wistar rats were implanted with a bipolar electrode into the left amygdala, and were randomly assigned into stressed (n=18) or non-stressed (n=19) groups. Rats underwent conventional amygdala kindling (two electrical stimulations per day) until 5 Class V seizures had been experienced ('the fully kindled state'). Stressed rats were exposed to 30min restraint immediately prior to each kindling stimulation, whereas non-stressed rats received control handling. Restraint stress increased circulating corticosterone levels (pre-stress: 122±17ng/ml; post-stress: 632±33ng/ml), with no habituation observed over the experiment. Stressed rats reached the 'fully kindled state' in significantly fewer stimulations than non-stressed rats (21±1 vs 33±3 stimulations; p=0.022; ANOVA), indicative of a vulnerability to epileptogenesis. Further, seizure durations were significantly longer in stressed rats (p<0.001; ANOVA). These data demonstrate that exposure to repeated experimental stress accelerates the development of limbic epileptogenesis, an effect which may be related to elevated corticosterone levels. This may have implications for understanding the effects of chronic stress and depression in disease onset and progression of mTLE in humans.
    Psychoneuroendocrinology 06/2012; 38(2). DOI:10.1016/j.psyneuen.2012.06.005
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    • "An association between depression, suicidal behavior, and epilepsy has already been pointed out in another population-based study (Mainio et al., 2007). This association might be related to common pathogenic mechanisms, risk factors for a chronic disease, stigmatization, and pharmacologic treatment (Kanner, 2006; Mazza et al., 2007). "
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    ABSTRACT: To provide information about psychiatric comorbidity and suicidal behavior in people with epilepsy compared to those without epilepsy from a community sample in Brazil. An attempt was made to evaluate all 174 subjects with epilepsy (cases) identified in a previous survey. For every case identified, an individual without epilepsy (control) matched by sex and age was selected in the same neighborhood. A structured interview with validated psychiatric scales was performed. One hundred and fifty-three cases and 154 controls were enrolled in the study. People with epilepsy had anxiety more frequently [39.4% vs. 23.8%, odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.5; p = 0.006], depression (24.4% vs. 14.7%, OR 1.9, 95% CI 1.01-3.5; p = 0.04), and anger (55.6% vs. 39.7%, OR 1.9, 95% CI 1.2-3.1; p = 0.008). They also reported more suicidal thoughts [36.7% vs. 23.8%, OR 1.8, 95% CI 1.1-3.1; p = 0.02), plans (18.2% vs. 3.3%, OR 2.0, 95% CI 1.0-4.0; p = 0.04), and attempts (12.1% vs. 5.3%, OR 2.4, 95% CI 1.1-3.2, p = 0.04) during life than controls. These findings call attention to psychiatric comorbidity and suicidal behavior associated with epilepsy. Suicide risk assessment, mental evaluation, and treatment may improve quality of life in epilepsy and ultimately prevent suicide.
    Epilepsia 11/2009; 51(7):1120-5. DOI:10.1111/j.1528-1167.2009.02386.x
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    • "This has recently also been suggested for the abnormal behavior of epileptic mice in this test (Grçticke et al., 2007). There is increasing evidence that a history of psychiatric diseases, particularly depression along with anxiety, increases the risk of later epilepsy (Kanner, 2006). Furthermore , a history of depression has been reported in up to two-thirds of patients with medically intractable epilepsy (Lambert & Robertson, 1999). "
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    ABSTRACT: Patients with intractable temporal lobe epilepsy (TLE) exhibit an increased risk of psychiatric comorbidity, including depression, anxiety, psychosis, and learning disorders. Furthermore, a history of psychiatric comorbidity has been suggested as a predictor of lack of response to therapy with antiepileptic drugs (AEDs) in patients with epilepsy. However, clinical studies on predictors of pharmacoresistant epilepsy are affected by several confounding variables, which may complicate conclusions. In the present study, we evaluated whether behavioral alterations in epileptic rats are different in AED nonresponders versus responders. For this purpose, we used an animal model of TLE in which AED responders and nonresponders can be selected by prolonged treatment of epileptic rats with phenobarbital (PB). Behavioral and cognitive abnormalities were compared between responders and nonresponders as well as between epileptic rats and nonepileptic controls in a battery of tests. Fifteen epileptic rats with spontaneous recurrent seizures (SRS) either responding (11 rats) or not responding (4 rats) to PB were used for this study. The nonresponders differed markedly in behavioral and cognitive abnormalities from responders and nonepileptic controls in tests of anxiety (open field, elevated-plus maze test), behavioral hyperexcitability (approach-response, touch-response, pick-up tests), and learning and memory (Morris water maze). Our hypothesis that AED-resistant rats will show more severe behavioral and cognitive changes than AED-responsive rats was confirmed by the present experiments. The data substantiate that rodent models of TLE are useful to delineate predictors of pharmacoresistant epilepsy.
    Epilepsia 06/2008; 49(10):1759-76. DOI:10.1111/j.1528-1167.2008.01659.x
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