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

The Lancet Neurology (Impact Factor: 21.9). 03/2006; 5(2):107-8. DOI: 10.1016/S1474-4422(06)70331-3
Source: PubMed
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    • "Depression as a common comorbidity of temporal lobe epilepsy (TLE) is poorly understood [24,25]. In general, evidence for treatment strategies of mood disorders in epilepsy are lacking, and development of management approaches tend to rely on clinical experience rather than evidence-based trials favoring one treatment over another [26]. "
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    ABSTRACT: In Cameroonian traditional medicine various extracts of Gladiolus dalenii Van Geel (Iridaceae) have been used as a cure for various ailments that include headaches, digestive problems, muscle and joint aches, and some central nervous system disorders such as epilepsy, schizophrenia and mood disorders. Owning to this background, the aim of the study was to investigate whether an aqueous macerate of the bulb of Gladiolus dalenii has any antidepressant activity focusing specifically on depression-like behaviours associated with epilepsy. We used the combined administration of atropine and pilocarpine to rats as our animal model of epilepsy. The forced swim test and spontaneous locomotor activity in the open field test were the two tools used to assess the presence of depression-like behaviour in epileptic and control animals. The following depression-related parameters were determined: plasma ACTH, plasma corticosterone, adrenal gland weight and hippocampal levels of brain-derived neurotrophic factor (BDNF). The effects of Gladiolus dalenii were compared to that of fluoxetine. Our results showed that we had a valid animal model of epilepsy-induced depression as all 3 measures of construct, predictive and face validity were satisfied. The data indicated that Gladiolus dalenii significantly reduced the immobility times in the forced swim test and the locomotor activity as assessed in the open field. A similar pattern was observed when the HPA axis parameters were analysed. Gladiolus dalenii significantly reduced the levels of ACTH, corticosterone, but not the adrenal gland weight. Gladiolus dalenii significantly increased the level of BDNF in the hippocampus. In all parameters measured the effects of Gladiolus dalenii were significantly greater than those of fluoxetine. The results show that Gladiolus dalenii has antidepressant-like properties similar to those of fluoxetine in epilepsy-associated depressive states. The antidepressant activity of Gladiolus dalenii is likely to be mediated by restoring the activity of the HPA axis and increasing the levels of BDNF in the hippocampus.
    BMC Complementary and Alternative Medicine 10/2013; 13(1):272. DOI:10.1186/1472-6882-13-272 · 2.02 Impact Factor
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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 · 4.94 Impact Factor
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    • "The NDDI-E was specifically developed to assess depression in epilepsy and also includes one item related to suicidal thoughts ( " I'd be better off dead " ). Abnormal serotonergic neurotransmission is demonstrated in depression as well as in TLE and suicide [30] [31]. It is suggested that common underlying pathways may link depression, suicide, and epilepsy [1] [32] [33] [34]. "
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    ABSTRACT: The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE). Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale. A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures (P=0.012), current major depression (P=0.001), and motor impulsivity (P=0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR=12.82, 95% CI=2.58-63.76, P=0.002) and motor impulsivity (OR=1.21, 95% CI=1.06-1.38, P=0.005) to suicide risk. Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk.
    Epilepsy & Behavior 12/2011; 22(4):745-9. DOI:10.1016/j.yebeh.2011.09.004 · 2.26 Impact Factor
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