Cognitive-behavioral therapy for psychogenic nonepileptic seizures: a pilot RCT.

OBJECTIVE: To compare cognitive-behavioral therapy (CBT) and standard medical care (SMC) as treatments for psychogenic nonepileptic seizures (PNES). METHODS: Our randomized controlled trial (RCT) compared CBT with SMC in an outpatient neuropsychiatric setting. Sixty-six PNES patients were randomized to either CBT (plus SMC) or SMC alone, scheduled to occur over 4 months. PNES diagnosis was established by video-EEG telemetry for most patients. Exclusion criteria included comorbid history of epilepsy, <2 PNES/month, and IQ <70. The primary outcome was seizure frequency at end of treatment and at 6-month follow-up. Secondary outcomes included 3 months of seizure freedom at 6-month follow-up, measures of psychosocial functioning, health service use, and employment. RESULTS: In an intention-to-treat analysis, seizure reduction following CBT was superior at treatment end (group x time interaction p < 0.0001; large to medium effect sizes). At follow-up, the CBT group tended to be more likely to have experienced 3 months of seizure freedom (odds ratio 3.125, p = 0.086). Both groups improved in some health service use measures and on the Work and Social Adjustment Scale. Mood and employment status showed no change. CONCLUSIONS: Our findings suggest that cognitive-behavioral therapy is more effective than standard medical care alone in reducing seizure frequency in PNES patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CBT in addition to SMC, as compared to SMC alone, significantly reduces seizure frequency in patients with PNES (change in median monthly seizure frequency: baseline to 6 months follow-up, CBT group, 12 to 1.5; SMC alone group, 8 to 5).

Impaired spatial working memory in adults with attention-deficit/hyperactivity disorder: comparisons with performance in adults with borderline personality disorder and in control subjects.

OBJECTIVE: This study investigated a previous claim that working memory may be 'particularly impaired' in adult attention-deficit/hyperactivity disorder (ADHD), compared with other psychiatric disorders which affect frontal lobe-mediated executive functions. METHOD: Performance on spatial working memory (SWM) and two additional tasks were investigated for adult patients selected on the basis of DSM-IV ADHD (n = 19), adult patients selected on the basis of borderline personality disorder (BPD) (n = 19), and non-clinical control subjects (n = 19). Groups were matched for age, verbal IQ and gender. RESULTS: Analysis of variance showed that the ADHD group had significant impairment of SWM performance relative to the non-clinical controls. Although there was a trend towards impairment in the BPD group relative to non-clinical controls, this did not reach significance. CONCLUSION: The results are consistent with the claim that aspects of working memory are 'particularly impaired' in adult ADHD. Also, the BPD group had a longer deliberation time for one of the additional tasks, compared with the ADHD group, which indicated that the patient groups may have different patterns of neuropsychological impairments.

Schizophrenia-like psychosis arising de novo following a temporal lobectomy: timing and risk factors.

OBJECTIVES: To clarify risk factors for the development of schizophrenia-like psychotic disorders following temporal lobectomy, and to explore the possibility that the early postoperative period is a time of high risk for the onset of such chronic psychotic disorders. METHODS: Patients who developed schizophrenia-like psychosis were identified from a series of 320 patients who had a temporal lobectomy for medically intractable epilepsy. The relationship of their disorders to both the operation and subsequent seizure activity was examined. Using a retrospective case-control design, risk factors for the development of schizophrenia-like psychosis were established. RESULTS: Eleven patients who developed schizophrenia-like psychosis postoperatively were identified and compared with 33 control subjects who remained free of psychosis postoperatively. The onset of de novo psychotic symptoms was typically in the first year following the operation. No clear relationship between postoperative seizure activity and fluctuations in psychotic symptoms emerged. Compared with the controls, patients who become psychotic had more preoperative bilateral electroencephalogram (EEG) abnormalities, pathologies other than mesial temporal sclerosis in the excised lobe and a smaller amygdala on the unoperated side. CONCLUSIONS: Temporal lobectomy for medically intractable epilepsy may precipitate a schizophrenia-like psychosis. Patients with bilateral functional and structural abnormalities, particularly of the amygdala, may be at particular risk for the development of such psychoses.

Characteristic neurocognitive profile associated with adult attention-deficit/hyperactivity disorder.

BACKGROUND: It is now accepted that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. However, relative to the considerable literature concerning the profile of neurocognitive deficits associated with this disorder in childhood, equivalent investigations in adult populations have been less common. The current study examined cognitive function in adults diagnosed with ADHD employing well-validated neuropsychological tasks. METHOD: Nineteen adult patients who satisfied DSM-IV criteria for ADHD and 19 matched (gender, age and verbal IQ), non-clinical control subjects were recruited. Patients were either unmedicated or had abstained from a psychostimulant medication regime for at least 24 h prior to neurocognitive assessment. A functionally wide-ranging test battery was administered. RESULTS: Relative to controls, ADHD adults performed significantly worse on spatial working memory, planning, and attentional-set shifting tests and were significantly slower to respond to target stimuli on the go/no-go task. In contrast, the two subject groups performed equivalently on decision-making and pattern/spatial recognition memory assessments. CONCLUSIONS: The demonstration of neuropsychological dysfunction in the adult ADHD cohort provides some support for the validity of this diagnosis in adulthood. In particular, there is broad consistency between the cognitive profile revealed in the current investigation and that previously demonstrated in a study of medication-naïve ADHD children. There is evidence that frontostriatal function is especially disrupted.

The specificity of clinical characteristics in adults with attention-deficit/hyperactivity disorder: a comparison with patients with borderline personality disorder.

Characteristics of DSM-IV attention-deficit/hyperactivity disorder (ADHD) in adults can also be found as part of other psychiatric disorders. This study investigated the specificity of adult ADHD features in relation to patients with borderline personality disorder (BPD), a syndrome which shares some of its intrinsic features with ADHD and often co-occurs with ADHD. A group of 20 adult patients selected on the basis of a diagnosis of ADHD and 20 patients selected on the basis of a diagnosis of BPD were assessed by the self-report Attention Deficit Scales for Adults (ADSA). The two groups were matched for age, verbal IQ and gender. Of the nine ADSA scales, seven showed significant inter-group differences, in particular involving attention, organisation and persistence. The 'Consistency/Long-Term' scale, which mainly reflects impaired task and goal persistence, was the best discriminator between the groups. Furthermore, ratings on this scale correlated significantly with the error score of a computer-administered task of spatial working memory, the performance of which has been reported to be impaired in patients with ADHD. The results provide further validation for the ADSA scales and support a previous claim that 'long-term consistencies', i.e., related to task and goal persistence, is 'the centrepiece behavioural issue' for adults with ADHD.

Pseudoseizures and asthma.

BACKGROUND: Sexual abuse and head injury are important risk factors of pseudoseizures, reported in about a third of patients. Clinical experience suggests that asthma is another possible risk factor. OBJECTIVES: To determine the relative prevalence of asthma in patients with pseudoseizures. METHODS: A retrospective record review was undertaken of reported asthma in 102 patients with pseudoseizures and 70 psychotic controls. The pseudoseizure patients were subgrouped according to method of diagnosis: 47 in whom epilepsy was excluded by capturing a typical attack on video-electroencephalographic monitoring (VEEM), and 55 not diagnostically confirmed with VEEM. RESULTS: Asthma was reported in 26.5% of pseudoseizure patients, compared with 8.6% of the psychotic controls (chi(2) = 8.6; p = 0.003). Asthma was reported at similar rates in the VEEM confirmed (29.8%) and non-VEEM confirmed (23.6%) pseudoseizure subgroups. The significant excess of reported asthma held for both the VEEM confirmed subjects (Pearson's chi(2) = 5.4, p = 0.02) and non-VEEM confirmed subjects (Pearson's chi(2) = 8.9, p = 0.003). CONCLUSIONS: There is an association between pseudoseizures and reported asthma. Various models are proposed whereby somatisation, anxiety hyperventilation, and dissociative elaboration may account for the observed association. Both asthma and anxiety hyperventilation may be important risk factors for the development of pseudoseizures. The reported asthma may itself be psychogenic in origin in a proportion of patients. Confirmatory prospective studies are indicated.

Cognitive behaviour therapy with adults with intractable epilepsy and psychiatric co-morbidity: preliminary observations on changes in psychological state and seizure frequency.

Cognitive behaviour therapy (CBT) was undertaken with six adults with chronic, poorly controlled seizures and co-existing psychiatric and/or psychosocial difficulties. During 12 sessions of CBT from an experienced CBT Nurse Specialist, treatment focused concurrently on epilepsy-related problems, associated psychopathology and on the development of psychological strategies to reduce seizure occurrence. At the end of treatment participants rated their initial epilepsy-related problem as having less impact on their daily lives and at one-month follow-up reported less deleterious impact on everyday life in terms of their psychological difficulties. In addition participants demonstrated significant improvements in terms of their self-rated work and social adjustment, and in their decreased use of escape-avoidance coping strategies. These positive findings occurred despite the absence of a significant decrease in seizure frequency. Issues raised by the complexity and severity, both of these patients' psychological/psychosocial difficulties and their epilepsy, are discussed in relation to the optimal length of treatment that may be required when adopting a CBT model in this patient group.

VNS in patients with previous unsuccessful resective epilepsy surgery: antiepileptic and psychotropic effects.

OBJECTIVES: To assess the efficacy of vagus nerve stimulation (VNS) in patients with medically and surgically intractable complex partial seizures (CPS). PATIENTS AND METHODS: Sixteen patients with previous temporal [15] and frontal [one] resections were treated with VNS between 1994 and 1999 at King's College Hospital, London, UK. Post-operative video-electroencephalogram telemetry had shown that CPS started from the operated side in 12 patients, contralaterally in three and bilaterally independently in one. RESULTS: Three patients (18.75%) had 50% or more reduction in seizure frequency, but one showed severe worsening of epilepsy, which remitted upon VNS discontinuation. The antiepileptic effect of VNS was not different with respect to the type of operation (anterior temporal lobectomy vs amygdalohippocampectomy), the side of operation, or the side of seizure onset. We observed psychotropic effects in two patients with post-ictal psychosis, in two others with depression, and in a child with severe behavioral disorder. CONCLUSIONS: VNS may have a rather limited antiepileptic role to play in patients with persistent seizures following epilepsy surgery, but may independently possess useful antipsychotic and mood-stabilizing properties.

Lower prevalence of pre-morbid neurological illness in African-Caribbean than White psychotic patients in England.

BACKGROUND: It has been suggested that the increased incidence of psychosis in African-Caribbeans living in England may be due to illnesses in which social stress plays an important aetiological role. If this is the case, the prevalence of factors associated with psychosis that predate illness onset such as obstetric complications, pre-morbid neurological illness and poor childhood social adjustment may be expected to be lower in African-Caribbean than Whites psychotic patients. METHOD: Details of obstetric complications, pre-morbid neurological illness, and pre-morbid social adjustment were obtained for 337 psychotic patients by patient interview, interviews of mothers and chart review. The proportions of patients with each 'risk factor' in the African-Caribbean (N = 103) and White (N = 184) groups were compared using regression analysis; age, sex, social class, diagnosis and referral status were possible explanatory variables. RESULTS: African-Caribbean patients were less likely to have suffered a pre-morbid neurological disorder than their White counterparts (odds ratio 0.19, 95% CI 0.06-0.61). There was no significant difference in pre-morbid social adjustment or obstetric complications between the two groups, though fewer obstetric complications were reported in the African-Caribbean group (21.5%) than the White group (30.9%). CONCLUSIONS: African-Caribbean patients with psychosis have experienced less pre-morbid neurological illness.

Postictal psychosis after temporal lobectomy.

Three of 282 consecutive patients who had temporal resections for intractable epilepsy developed postoperative postictal psychosis. These three patients had seizure recurrence contralateral to the resection, whereas none of the patients with ipsilateral seizure recurrence developed any psychiatric symptoms after surgery. Two had left amygdalo-hippocampectomy and one right temporal lobectomy. The de novo occurrence of postoperative postictal psychosis is a well-defined complication of surgery for temporal lobe epilepsy, and may relate to contralateral epileptogenesis.

Impaired associative learning in chronic schizophrenics and their first-degree relatives: a study of latent inhibition and the Kamin blocking effect.

The performance of chronic schizophrenic probands (n=21), their first-degree schizotypal (22) and non-schizotypal (19) relatives, and normal controls (24), was measured in two associative learning paradigms, latent inhibition and the Kamin blocking effect. These paradigms assess the effects on learning of initial exposure to other learning contingencies. The normal subjects showed latent inhibition (retarded learning of an association between a burst of white noise and a visually displayed counter increment, if the subject had first been pre-exposed to the white noise without any other consequence) and Kamin blocking (retarded learning of an association between two visual stimuli, if the conditioned stimulus was presented simultaneously with a second, already conditioned stimulus). The schizophrenic probands and both the schizotypal and non-schizotypal relatives were severely impaired in basic associative learning, performing much worse than the normal subjects in the control conditions (i.e. those lacking stimulus pre-exposure of any kind) of both the latent inhibition and the Kamin paradigms and also showed a loss of the normal latent inhibition and Kamin blocking effects. The performance of the three clinically defined groups was statistically indistinguishable. These findings contrast with previous reports of the performance of normal subjects classified as schizotypal by questionnaire, who are not impaired in basic associative learning, and are particularly fast to learn after stimulus pre-exposure. The results question the assumption that high schizotypy, as assessed by questionnaire, is like schizotypy in schizophrenic kin. The severe impairment in basic associative learning in schizophrenic patients and their kin warrants further investigation.

Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms.

OBJECTIVE: Imaging studies of schizophrenia have repeatedly demonstrated global abnormalities of cerebral and ventricular volumes. However, pathological changes at more local levels of brain organization have not yet been so clearly characterized because of the few brain regions of interest heretofore included in morphometric analyses as well as heterogeneity of patient samples. METHOD: Dual echo magnetic resonance imaging (MRI) data were acquired at 1.5 T from 27 right-handed patients who met DSM-IV criteria for schizophrenia with enduring negative symptoms and from 27 healthy comparison subjects. Between-group differences in gray and white matter volume were estimated at each intracerebral voxel after registration of the images in standard space. The relationship between clinical symptom scores and brain structure was also examined within the patient group. Spatial statistics and permutation tests were used for inference. RESULTS: Significant deficits of gray matter volume in the patient group were found at three main locations: 1) the left superior temporal gyrus and insular cortex, 2) the left medial temporal lobe (including the parahippocampal gyrus and hippocampus), and 3) the anterior cingulate and medial frontal gyri. The volume of these three regions combined was 14% lower in the patients relative to the comparison subjects. White matter deficits were found in similar locations in the left temporal lobe and extended into the left frontal lobe. The patient group showed a relative excess of gray matter volume in the basal ganglia. Within the patient group, basal ganglia gray matter volume was positively correlated with positive symptom scores. CONCLUSIONS: Anatomical abnormalities in these schizophrenic patients with marked negative symptoms were most evident in left hemispheric neocortical and limbic regions and related white matter tracts. These data are compatible with models that depict schizophrenia as a supraregional disorder of multiple, distributed brain regions and the axonal connections between them.

Changes in regional cerebral blood flow due to cognitive activation among patients with schizophrenia.

BACKGROUND: The regional cerebral blood flow (rCBF) response to the Wisconsin Card Sort Test (WCST) has been used to assess the functional integrity of the prefrontal cortex in patients with schizophrenia. AIMS: In this study, patients were divided into two groups according to whether they had made few or many perseverative errors on a modified version of the WCST. A control group consisted of normal volunteers. The groups were then compared with respect to rCBF response to WCST activation. METHOD: rCBF was measured during administration of a modified version of the WCST and during a card sorting control task, using single photon emission computerised tomography (SPECT). RESULTS: Performance of the modified WCST was associated with a widespread and substantial increase in rCBF, particularly in the frontal region. The poorly performing group of patients with schizophrenia showed only a modest increase in rCBF in the left anterior cingulate region. CONCLUSION: Subjects with schizophrenia are able to respond to specific neuropsychological challenge with activation of the frontal regions.

Homocysteine, folate, methylation, and monoamine metabolism in depression.

OBJECTIVES: Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. METHODS: In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. RESULTS: Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. CONCLUSIONS: Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement.

Schizophrenia, temporal lobe epilepsy and psychosis: an in vivo magnetic resonance spectroscopy and imaging study of the hippocampus/amygdala complex.

BACKGROUND: We have used proton magnetic resonance imaging and spectroscopy to measure hippocampus/amygdala volumes and anterior hippocampal metabolite concentrations (N-acetyl aspartate (NAA), creatine/phosphocreatine and choline) in subjects with temporal lobe epilepsy (TLE), schizophrenia and in normal controls. METHOD: Four groups of right-handed patients were selected: 12 with TLE and psychosis (EP), 12 with TLE and no psychosis (ENP), 26 with schizophrenia, and 38 normal controls. Imaging and spectroscopy were performed with a 1.5T Signa GE scanner. RESULTS: The schizophrenia group showed a significant left-sided reduction in all metabolites. In the epilepsy groups NAA was reduced bilaterally. The NAA reduction in the EP group was greater than in the ENP group, especially on the left, although the result did not reach significance. Total hippocampus/amygdala volumes showed no significant differences in any of the groups when compared with normal controls. When compared with controls significant, specific regional volume reductions were present bilaterally in the EP group and in the left hippocampus/amygdala in schizophrenia. The regional volume reduction found in schizophrenia was also present in EP but not in ENP. CONCLUSION: Spectroscopic abnormalities were more pronounced in the epilepsy groups and were bilateral, and abnormalities in schizophrenia were left sided. Specific regional hippocampus/amygdala volume reductions were more marked in the EP group and were bilateral. Left-sided regional volume reduction identified in the dominant hemisphere of schizophrenics was also present in EP patients, but not in ENP, suggesting that this region in the left temporal lobe may be significant in the aetiology of psychosis. This is further supported by the predominantly left-sided NAA reduction in schizophrenia. High resolution morphometric studies may identify specific regions of the brain associated with the development of psychosis.

A neuropsychological comparison of schizophrenia and schizophrenia-like psychosis of epilepsy.

BACKGROUND: The schizophrenia-like psychoses of epilepsy (SLPE) might represent a secondary form of schizophrenia in which the pathology is relatively confined to the temporal lobe. To test this possibility we have compared the neuropsychological profile of schizophrenia and SLPE. Our main hypothesis was that both psychotic groups would show deficits of temporal lobe function but that prefrontal impairment, as measured by tests of executive function, would be found only in the primary schi ophrenic group. METHODS: Four groups were studied: (1) patients with SLPE (N = 25); (2) patients with epilepsy but not psychiatric history (N = 24); (3) patients with schizophrenia (N = 22); and (4) healthy volunteers (N = 24). Neuropsychological testing comprised measures of pre-morbid IQ, current verbal and performance IQ, information processing, digit span, motor speed, verbal and visual learning and memory, verbal fluency, the Wisconsin Card Sorting Task, the Stroop test and the trail making task. RESULTS: Patients with schizophrenia and those with SLPE had almost identical neuropsychological profiles, with impairments of attention, episodic memory (verbal > visual) and executive function. The epileptic controls showed similar though less severe impairments of memory and of some tests of executive function. CONCLUSIONS: Our results do not support the hypothesis that the pathophysiology of SLPE and schizophrenia are distinct. While our findings suggest an important role for dominant temporal lobe abnormality in schizophrenia, both in its primary form and in that occurring in patients with epilepsy, they also implicate generalized cognitive impairment, manifest in particular as attentional deficits, in both forms of the disorder.