Structural and functional neuroimaging correlates of depression in temporal lobe epilepsy

Depression is commonly experienced among persons with temporal lobe epilepsy (TLE). Although evidence exists implicating dysfunction of distributed neural structure and circuitry among depressed persons without epilepsy, little is known regarding the neural correlates of depression in TLE. We examined the relationship between self-reported depression severity and both structural MRI volumetry and [(18)F]fluorodeoxyglucose positron emission tomography (PET)-measured resting metabolism of the amygdala and hippocampus of 18 patients with TLE. Significant positive relationships were noted between right and left amygdala volumes and depression. No other significant relationships were observed between amygdala PET measures, hippocampal volumes, or hippocampal PET measures and degree of depressive symptomatology. These findings indicate that both right and left amygdala volumes are associated with depression severity among persons with TLE. Future studies examining the potential role of extended neural regions may clarify the observed structural relationship between depressive symptoms and the amygdala.     

Ovulatory Function in Epilepsy

Summary Women with epilepsy have lower fertility rates than women without epilepsy. We hypothesized that limbic dysfunction in temporal lobe epilepsy (TLE) alters the release of hypothalamic trophic hormones that secondarily affect release of the pituitary gonadotropins, causing ovulatory failure. We assessed ovulatory function over three consecutive menstrual cycles in 17 women with partial seizures arising from the temporal lobe (TLE), 7 women with primary generalized epilepsy (PGE), and 12 controls. We devised scores to reflect ovulatory function that were based on daily basal body tem perature and monthly serum progesterone levels. Seizure frequency, antiepileptic drugs (AEDs), and depressive symptomatology were also evaluated. Anovulation was more frequent in subjects with TLE (35.3%) than in subjects with PGE (0%) or in controls (8.3%). Anovulatory cycles tended to occur more frequently in subjects with TLE who were treated with polytherapy than in those receiving monotherapy, but this result was not statistically significant. Seizure frequency and symptoms of depression did not affect ovulatory function. Although AED polytherapy may increase the likelihood of anovulation, our results suggest a mechanism of infertility related to temporal lobe dysfunction.     

Depression and Anxiety in Patients with Epilepsy

The aim of this investigation was to study the interaction between depression/anxiety and epilepsy. One hundred fifty individuals with partial epilepsy, 70 with idiopathic generalized epilepsy, and 100 controls were administered two self-rating mood questionnaires (Zung and Stai) for the evaluation of depression and anxiety, respectively. The group with epilepsy was much more severely impaired than the controls according to both mood questionnaires; the patients with partial epilepsy, especially those with temporal lobe epilepsy (TLE), were more depressed and anxious than the patients with generalized epilepsy. The group with left TLE appeared to have the highest levels of depression and anxiety. The final results of our study confirmed that some mood disorders are common throughout the epilepsy population, especially in patients with left TLE. No correlation was noted between the frequency of seizures and onset of epilepsy and the results of the mood questionnaires. Moreover, no differences were found in depression and anxiety between males and females among both left focus and right focus epilepsy patients.     

Secondary depression in panic disorder and agoraphobia. I. Frequency, severity, and response to treatment

Depressive symptomatology in 481 subjects with panic disorder and phobic avoidance was studied as part of an investigation of the efficacy of alprazolam in panic disorder. Subjects who had a major depressive episode (MDE) before the onset of their panic disorder were not included in the trial. With this exclusion criterion, 31% of subjects had a secondary MDE occurring after the onset of the panic disorder. The occurrence of secondary MDE was related to the length of time subjects were ill with panic disorder. Compared with the subjects without depression, those subjects with current MDE had higher scores on measures of anxiety and depression but not on the number of panic attacks per week. The presence of depression and the degree of phobic avoidance contributed independently to measures of the severity of the panic illness. Alprazolam was effective in reducing panic and depressive symptomatology in both depressed and nondepressed subjects with panic disorder. The presence of an MDE was not predictive of the outcome of treatment for the panic and phobic symptoms. Subjects with or without depression responded similarly to alprazolam.     

Depressive personality and its relationship to depressed mood,interpersonal loss,negative parental perceptions,and perfectionism

Eighty veteran psychiatric outpatients were evaluated for depressive personality disorder on the Depressive Personality Disorder Inventory (DPDI). It was predicted that those classified with depressive personality would report higher levels of interpersonal loss, negative perceptions of their parents, and higher levels of perfectionism than psychiatric control subjects. Nine of the 12 measures of these variables were significantly greater in those with depressive personality compared with psychiatric control subjects. When statelike depression was controlled for, seven of the nine variables still significantly differed between the two groups. Hierarchical regression analysis and discriminant function analysis found that these variables predicted 9% of the variance in the DPDI above and beyond statelike depression, and that a combination of these variables correctly classified 91% of the depressive personalities and 88% of the psychiatric control subjects. It is concluded that, as hypothesized, depressive personality disorder is associated with loss, negative parental perceptions, and perfectionism, and that these relationships are not accounted for exclusively by a depressed mood.     

Depression and anxiety before and after temporal lobe epilepsy surgery.

PURPOSE: To examine the course of depression and anxiety in patients with temporal lobe epilepsy (TLE) treated with epilepsy surgery (and anticonvulsant drugs) or medical means alone. METHODS: Of 94 TLE patients evaluated for epilepsy surgery, 76 underwent a resective procedure, 18 continued on medical treatment alone. Depression (Beck Depression Inventory (BDI)) and anxiety scores (Self-Rating Anxiety Scale (SRAS)) were examined during presurgical evaluation (T1) and after a mean of 16 months (T2), or 12 months after surgery. Depression and anxiety scores were related to type of intervention, underlying epileptogenic lesion, change of seizure control and anticonvulsant therapy. RESULTS: At T1, depression and anxiety scores were higher in patients with TLE than scores in published normal populations. At T2, depression but not anxiety scores were significantly lower than at T1. Change of depression scores interacted with improvements of seizure control. CONCLUSIONS: Evidence of depression and anxiety is commonly found in patients with TLE. Depression improves not because of epilepsy surgery per se, but because of improved seizure control. This is more commonly achieved by surgery than medical treatment. The results are consistent with the hypothesis that depression in TLE is caused by pathological epileptic activity rather than a fixed structural defect.     

Sexual abuse and psychiatric symptoms in an epileptic population.

One hundred and seven consecutive patients attending the outpatient epilepsy clinic at a teaching general hospital were assessed by clinical interview for a history of sexual abuse. Questionnaires dealing with overall psychiatric symptomatology i.e., (SCL-90), (TSC-40) and depression (ZSRDS) were also used. The majority of subjects were single (60%), living at home (76.6%) and had an average age of 29 years. The mean duration of epilepsy was 18.8 years and the seizures were controlled with medication in 65.2% of patients. Ten (9.3%) of the subjects had been sexually abused. This frequency of sexual abuse is lower than in the general population and among psychiatric patients. The specific form of sexual abuse consisted of sexual intercourse (n = 4), fondling (n = 4) and oral sex (n = 2). The sexually abused subjects had significantly higher scores on the anxiety subscale of the SCL-90 and depression score on the ZSRDS than non-abused subjects.     

Do neurological disorders in childhood pose a risk for mental health in young adulthood?

To assess whether juvenile-onset epilepsy or motor disability is complicated by an increased number of mental health disorders or experience of psychosomatic symptoms in young adulthood, we studied 81 subjects with epilepsy and 52 with motor disabilities at the age of 19 to 25 years and compared them with 211 controls. The main diagnostic tool, the Present State Examination, was administered to those attending the interviews in person who were of normal intelligence; there were 62, 38, and 123 subjects in the three categories, respectively. Compared with the controls, the subjects with epilepsy showed an equal prevalence of psychiatric disorders whereas those with motor disabilities had a significantly higher prevalence, particularly of depressive disorders. The reported prevalence of psychosomatic symptoms confirmed this main result. Psychological illness affected everyday life of two out of five subjects with motor disabilities, but only half of those in the other two groups. It is concluded that motor disability since childhood, but not epilepsy, could be a factor that increases susceptibility to psychiatric morbidity, especially depression, and causes a large number of psychosomatic symptoms. The results challenge staff of clinics working with such adolescents to find individual approaches in preventing the negative influence of psychological disorders on social life.     

Prevalence of Psychopathology in Dutch Epilepsy Inpatients: A Comparative Study

The purpose of this study was to determine the prevalence of psychiatric disorders in Dutch patients with epilepsy in comparison with epidemiological data on a representative sample of the Dutch population. The Composite International Diagnostic Interview (CIDI) was used to determine the prevalence of psychiatric disorders in 209 epilepsy patients and compared with findings in the general Dutch population. The prevalence in temporal lobe epilepsy (TLE) and extra-temporal lobe epilepsy (extra-TLE) was also compared. Psychiatric disorders most frequently found in patients with epilepsy were anxiety and mood disorders. The last-year prevalence of these disorders was 25% for anxiety disorders and 19% for mood disorders. Compared with the general Dutch population, the prevalence of these disorders was significantly higher in epilepsy. No differences were found between patients with TLE and extra-TLE. It can be concluded that patients with epilepsy admitted to a tertiary epilepsy center suffer more often from mood and anxiety disorders than the general population.     

The neuropsychological and emotional consequences of living with intractable temporal lobe epilepsy: implications for clinical management.

PURPOSE: To investigate and document the neuropsychological and emotional effects of epilepsy in people with intractable temporal lobe epilepsy (TLE). METHODS: 273 patients with a diagnosis of TLE underwent a complete neuropsychological and psychological examination as a routine part of their investigation for epilepsy surgery. Neuropsychological assessment included measures of intellect, memory, language functioning, higher executive functioning, emotional well-being and the psychosocial impact of epilepsy and its treatment. RESULTS: The sample comprised 135 females and 138 males with a clearly lateralised epileptogenic focus. Patients were mildly anxious but not depressed, although many reported that epilepsy and its treatment had a marked effect on their daily lives. Current reading ability was in the average range; the mean obtained full scale IQ was 88 (low average range). Verbal memory functioning was within the borderline impaired range with visual memory functioning within the average range. Mean language performance was between the 5-10th percentile. Higher executive functioning results were in the normal range.Multiple univariate analyses were performed according to onset laterality. There were no significant differences between the groups on measures of psychological or emotional functioning. Participants with left TLE scored significantly lower than those in the right temporal group on measures of verbal intelligence, general intelligence, attention span and expressive language functioning. CONCLUSIONS: Patients with intractable epilepsy suffer significant neuropsychological difficulties in terms of their intellect, memory and language. Higher executive functioning appears unaffected. In addition, there is also evidence of emotional distress. These all impact upon their day-to-day functioning, which can be improved by the application of various psychological therapies and interventions.     

Systematic Literature Review of Psychiatric Comorbidities in Adults with Epilepsy

Background and PurposeMental illness is disproportionately common in people with epilepsy (PWE). This systematic literature review identified original research articles that reported the prevalence of psychiatric comorbidities based upon clinical assessments in a sample of PWE and assessed the clinical features of the populations found in studies included in our review of mental health comorbidity.MethodsThe included articles were written in English and published from 2008 to 2018, and focused on adults aged ≥18 years who had psychiatric diagnoses determined in clinical assessments, such as those found in medical records, clinician psychiatric evaluations, structured diagnostic interviews, and mental health screening questionnaires specific for a psychiatric disorder. The primary outcome was the prevalence of psychiatric comorbidities as a percentage of the total sample of PWE. Additional data included the overall sample size, mean age, epilepsy type, study design, and method of diagnosis. A modified Newcastle Ottawa Scale was used to assess the quality of the studies. All 23 articles that were consistent with the inclusion criteria were related to observational studies.ResultsMood disorders and anxiety disorders were the most common psychiatric comorbidities, with prevalence rates of 35.0% and 25.6%, respectively. Major depressive disorder was the most common mood disorder, with a prevalence of 24.2%. Post-traumatic stress disorder (PTSD) had the highest reported prevalence among anxiety disorders, at 14.2%, followed by general anxiety disorder at 11.1%. Other comorbidities included psychosis (5.7%), obsessivecompulsive disorder (3.8%), schizophrenia (1.7%), bipolar disorder (6.2%), and substance abuse (7.9%). The pooled prevalence of suicidality, as reported for two studies, was 9.3%. Temporal lobe epilepsy (TLE) was associated with higher levels of psychiatric comorbidity. Two (8.7%) of the 23 studies compared psychiatric comorbidities in TLE with that of extratemporal lobe epilepsy (ETLE), and one of these two studies found that depression was more common in TLE (53.8%) than in ETLE (25%). Regarding seizure types, partial seizures were associated with a higher prevalence of depression vs generalized seizures.ConclusionsThis systematic literature review of recent original research found a relatively high prevalence of mental health comorbidities in PWE. Mood and anxiety disorders are the most common comorbidities, while psychotic spectrum conditions such as schizophrenia and bipolar disorder are much rarer. The prevalence of comorbidity may vary with the epilepsy type and treatment responsiveness. These findings suggest that screening tools for depression and anxiety should be included as part of the training for epilepsy care, while resources for other relatively common conditions such as PTSD and substance abuse disorders should be readily available to neurology specialists who treat PWE.     

Anger and hostility in depression

The present study examined the relationship between depression and various dimensions of anger using multiple measures of anger and hostility and comparing depressed subjects with both a normal sample and a clinical sample with predominant anger difficulties. Three groups of subjects were obtained: a normal sample of 120 parents of elementary school children, 36 psychiatric inpatients meeting Research Diagnostic Criteria for major depressive episode, and 54 hospitalized veterans meeting Diagnostic Interview Schedule criteria for posttraumatic stress disorder (PTSD). The three groups differed significantly on all measures of anger experience, hostility, anger suppression, and anger expression. The depressed group reported greater levels of hostility and anger experience than the normal group but less than the PTSD group. On measures of anger suppression and expression, the depressed group exhibited more suppression than either the normal or the PTSD group and generally reported levels of anger expression comparable with the normal group's. The PTSD group reported the highest levels of anger expression. Within the depressed group, severity of depression was positively associated with levels of hostility and anger experience but was not related to measures of anger expression and was only partially related to anger suppression. These results are discussed as they relate to the "anger turned in" hypothesis of psychodynamic theories of depression, and directions for future research are noted.     

Neuroendocrine and amine studies in affective illness.

(1) There are limitations to some of these studies because of the small number of patients involved, but our data suggest that maximal Growth Hormone (GH) levels after induced hypoglycemia were lower in depressed patients than in control subjects. (2) Manic patients showed low GH peaks during the Insulin Tolerance Test (ITT), and furthermore urinary 3-methoxy-4-hydroxyphenylene glycol (MHPG) excretion rates in mania were indistinguishable from normals but higher than in depressed patients. (3) The apomorphine-induced GH response was essentially normal in affective disorder patients, while acute schizophrenic patients showed hypersensitivity of postsynaptic dopamine receptors. (4) Confirming previous studies by Maas et al. (1968, 1972), patients with depressive illness were found to have signicantly lower urinary MHPG excretion, whereas borderline patients with depressive symptomatology had MHPG values similar to control subjects.     

Rates of depressive and anxiety disorders in a residential mother-infant unit for unsettled infants

OBJECTIVE: Depression and anxiety are known to be common among women presenting to residential mother-infant programmes for unsettled infant behaviour but most studies have used self-report measures of psychological symptomatology rather than diagnostic interviews to determine psychiatric diagnoses. The aim of the present study was to determine rates of depressive and anxiety disorders and rates of comorbidity among clients of the Karitane residential mother-infant programme for unsettled infant behaviour. METHOD: One hundred and sixty women with infants aged 2 weeks-12 months completed the Edinburgh Postnatal Depression Scale and were interviewed for current and lifetime history of depressive and anxiety disorders using the Structured Clinical Interview for DSM-IV diagnosis (Research version). RESULTS: A total of 25.1% of the sample met criteria for a current diagnosis of major depression, 31.7% had met criteria for major depression since the start of the pregnancy, and 30.5% of clients met criteria for a current anxiety disorder. Of note were the 21.6% who met criteria for generalized anxiety disorder or anxiety disorder not otherwise specified (worry confined to the topics of the baby or being a mother). High levels of comorbidity were confirmed in the finding that 60.8% of those with an anxiety disorder had experienced major or minor depression since the start of their pregnancy and 46.3% of those who had experienced depression since the start of their pregnancy also met criteria for a current anxiety disorder. CONCLUSIONS: There are high levels of psychiatric morbidity among clients attending residential mother-infant units for unsettled infant behaviour, highlighting the importance of providing multifaceted interventions in order to address both infant and maternal psychological issues.     

Effect of comorbid anxiety disorders on the hypothalamic-pituitary-adrenal axis response to a social stressor in major depression.

BACKGROUND: Major depressive disorder (MDD) is often complicated by anxiety symptoms, and anxiety disorders occur in approximately 30% of mood cases. This study examined the influence of anxiety comorbidity on the hypothalamic-pituitary-adrenal (HPA) axis response to stress in patients with MDD. METHODS: Untreated subjects with pure MDD (n = 15), MDD with comorbid anxiety disorders (n = 18), and pure anxiety disorders (n = 15) were recruited by advertising. Age- and gender-matched control subjects were recruited for each subject with a psychiatric diagnosis (n = 48). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for adrenocorticotropic hormone (ACTH) and cortisol assay. RESULTS: When all depressed patients (n = 33) were compared with their matched control subjects (n = 33), they showed a significantly greater ACTH response to the stressor; however, this exaggerated ACTH response was exclusively due to the depressed group with comorbid anxiety disorders. A similar but nonsignificant effect was observed in the cortisol response. Subjects with pure mood or pure anxiety disorders showed normal ACTH and cortisol responses to the TSST. All patient groups showed similar levels of TSST-induced anxiety. CONCLUSIONS: Comorbid anxiety disorders might play a role in the increased activation of the HPA axis observed in patients with major depression.     

Differences in heart rate and blood pressure in children with conduct disorder, major depression, and separation anxiety

Heart rate and blood pressure of children and adolescents admitted to a psychiatric hospital were compared among those diagnosed conduct disorder, major depressive disorder, and separation anxiety disorder. Subjects with conduct disorder had a lower heart rate compared to subjects without a conduct disorder diagnosis; and subjects with separation anxiety disorder had higher heart rate and systolic blood pressure compared to subjects without an anxiety disorder diagnosis. Subjects with major depressive disorder had higher systolic blood pressure than subjects with conduct disorder but no difference in heart rate. The findings are consistent with conduct disorder being associated with decreased noradrenergic function and anxiety/depressive disorder being associated with increased noradrenergic function.     

Relationship between post-operative depression/anxiety and hippocampal/amygdala volumes in temporal lobectomy for epilepsy

PURPOSE: Patients with temporal lobe epilepsy (TLE) often present mood disturbances, which may either exacerbate or remit following surgery. The objective of the study was to investigate the relationship between post-operative depressive/anxiety symptoms and hippocampal/amygdala volumes following anterior temporal lobectomy. METHODS: Thirty-five patients operated for TLE were assessed for mood disturbances by the Beck depression inventory (BDI) and Beck anxiety inventory (BAI). Post-operative MRI data were collected and volumetric analysis of the hippocampi (HV) and amygdala (AV) was performed. Correlations between volumetric data, measures of mood, and demographic and clinical data were calculated. RESULTS: BDI scores significantly correlated with the intact HV (p=0.029) as well as the absolute difference between the intact and remnant HV (p=0.021). This was evident in left-side resections (p=0.049); in right-side resections the correlation was marginally non- significant (p=0.057). Depressed patients also had smaller remnant AV (p=0.002). Furthermore, BAI was negatively correlated with the HV remnant in left-side resections (p=0.038). No other significant associations between post-operative mood disturbances and various demographic and clinical variables were observed. CONCLUSION: The severity of depressive symptomatology in operated epilepsy patients correlates with the extent of hippocampal and amygdala resection; this association appears to be more evident in left-side resections.     

Is interictal EEG activity a biomarker for mood disorders in temporal lobe epilepsy?

Objective

Psychiatric comorbidities are frequent in temporal lobe epilepsy (TLE), and symptoms of these comorbidities may be related to epilepsy activity. Here we evaluated interictal EEG activity in TLE patients with or without psychiatric comorbidities.

Methods

A cohort study of 78 patients with TLE, with evaluation of wake/sleep interictal scalp EEG. All subjects were submitted to a psychiatric structured clinical interview (SCID) for the diagnosis of lifetime psychiatric comorbidities. Three major diagnostic categories were studied: mood disorders, anxiety disorders, and psychosis. We then evaluated differences in interictal EEG activity between patients with and without these psychiatric comorbidities.

Results

Infrequent EEG interictal spikes, defined as less than one event per minute, were significantly associated with mood disorders in TLE (p = 0.02).

Conclusions

Low intensity seizure disorder has been associated with a decrease in interictal EEG discharges and with an increase in psychiatric symptoms in TLE, a phenomenon known as forced normalization. In our study, we observed a low interictal spike frequency on EEG in TLE patients with mood disorders.

Significance

A low spike index might be a neurophysiological marker for depression in temporal lobe epilepsy.     

Psychopathological profile in patients with severe bilateral hippocampal atrophy and temporal lobe epilepsy: evidence in support of the Geschwind syndrome?

Bilateral symmetrical hippocampal atrophy (BHA) has been implicated as a possible causal element in various neuropsychiatric disorders, in particular depressive disorder and schizophrenia. To test the hypothesis that bilateral symmetrical severe volume loss of the hippocampi is of causal relevance to these psychiatric syndromes rather than an epiphenomenon we assessed the psychopathology in a group of patients with temporal lobe epilepsy (TLE) and very severe bilateral symmetrical hippocampal atrophy and compared it with that of a patient control group. Patients with TLE and hippocampal volumes smaller than three standard deviations below the mean of a control population were identified and compared with a matched patient population with normal hippocampal volumes. Psychopathology was assessed by blinded trained psychiatrists using the Present State Examination and Neurobehavioral Inventory. The prevalence of psychiatric syndromes was high in both patient groups; however, there was no significant difference between the two groups. With use of the more specific Neurobehavioral Inventory a psychopathological pattern reminiscent of the Geschwind syndrome emerged when patients with BHA were characterized by caregivers. While BHA does not result in an increased prevalence of specific psychiatric syndromes, specific symptoms that characterize the Geschwind syndrome like hypergraphia and hyposexuality might be pathogenically related to hippocampal atrophy.     

难治性颞叶癫(癎)的相关基因表达谱

目的 筛选难治性颞叶癫(癎)相关基因表达谱,并通过对表达谱筛选所发现的差异基因进行验证,从分子水平探讨颞叶癫(癎)可能的发病机制.方法 在利用基因芯片对难治性颞叶癫(癎)患者手术切除颞叶组织与对照间行基因表达谱分析研究的基础上,扩大样本量,应用RT.PCR方法,验证SH3GL2、BTN2A2、KCNJ4基因的mRNA在颞叶癫(癎)患者脑内的表达差异.结果 芯片研究结果显示,颞叶癫(癎)脑组织标本与对照组相比,表达趋势一致的已知基因包括:免疫相关因子、离子通道相关因子、信号转导相关基因、细胞增殖周期因子、细胞凋亡相关基因等;经RT.PCR证实,颞叶癫(癎)组突触重建调控因子SH3GL2的mRNA表达水平(1.022±0.547)明显高于对照组(0.446±0.171,t=-3.181),免疫调控基因BTN2A2的mRNA表达在颞叶癫(癎)组(0.481±0.196)同样高于对照组(0.243±0.111,t=3.351),而编码内向整流钾通道亚单位基因KCNJ4 mRNA的表达水平在颞叶癫疴组(0.438±0.178)则明显低于对照组(0.795±0.112),差异均有统计学意义(P<0.05).结论 在颞叶癫(癎)发生发展各个阶段均有基因的参与,是一个复杂的调控过程;芯片试验结果对进一步探讨疾病可能的发病机制以及为探求疾病治疗的新靶点提供了依据.