Psychomotor disturbances in bipolar disorder : investigations using structural and functional neuroimaging

Psychomotor disturbances in bipolar disorder are an expression of alterations in volition, cognition, emotion and motor control. While psychomotor disturbances remain a classic hallmark of severe mood disorders, there is limited knowledge about its mediators and neural correlates. The general aim of this thesis was to obtain a better understanding of psychomotor disturbances in bipolar disorder. Our specific objectives were to investigate whether symptoms of psychomotor disturbances in bipolar depression relate to neural activation in frontal-striatal networks that mediate motor function, whether there is a differential activation within these frontal-striatal motor networks between depressed patients with bipolar disorder and healthy controls, and whether morphometric changes in the basal ganglia and thalamus are associated with clinical variables in euthymic bipolar disorder that may predict impairments in psychomotor function. In paper I, we validated a self rating scale with respect to established observer rating scales. In a post-hoc analysis we found a psychomotor factor that we investigated further with functional magnetic resonance imaging (fMRI) in paper II and III. In paper II, we investigated motor execution in patients with bipolar depression. We used task based fMRI to investigate whether self paced finger tapping would reveal any differences in neural activation between groups, and whether neural activation at different levels in the frontal-striatal motor loop is predicted by the functional deafferentiation theory - framework used to explain slowed movement in Parkinson’s disease. We could not confirm our hypotheses. In paper III, we investigated different parts of the production of voluntary movement using fMRI and a motor imagery task. We found significant between-group differences in medial parieto-occipital regions during motor imagery and all other tasks, and in cortical motor areas during motor execution. We also found decreased activations in motor regions when there was an increase in psychomotor disturbances. In paper IV, we investigated whether tests of psychomotor function were associated with morphometric change in the basal ganglia or thalamus. We could not confirm our hypothesis. However, we found significant between-group differences in the shape of the right putamen in the absence of impaired psychomotor function. Shape differences were located in regions connected to frontal executive regions and motor areas. In paper V, we investigated morphometric differences in a subgroup of bipolar disorder characterized by greater impairment of psychomotor function in their euthymic phase. We also investigated clinical variables associated with disease expressions, and the effect of antipsychotic treatment, on morphometric change. We found that antipsychotic medication, the number of manic episodes and duration of illness were associated with local shape changes in the basal ganglia. In summary, we found that psychomotor disturbances may be considered both a symptom and a sign, and that the neural signature of these appear to involve both structural and functional alterations in brain regions of frontal-striatal networks

Differential Effects of Single-Dose Escitalopram on Cognitive and Affective Interference during Stroop Task

Background and objective: Our aim was to study the regulatory role of serotonin [(5-hydroxytryptamine (5-HT)] on two key nodes in the cognitive control networks – the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). We hypothesized that increasing the levels of 5-HT would preferentially modulate the activity in ACC during cognitive control during interference by negative affects compared to cognitive control during interference by a superimposed cognitive task. Methods: We performed a functional magnetic resonance imaging investigation on 11 healthy individuals, comparing the effects of the selective 5-HT reuptake inhibitor escitalopram on brain oxygenation level dependent signals in the ACC and the DLPFC using affective and cognitive counting Stroop paradigms (aStroop and cStroop). Results: Escitalopram significantly decreased the activity in rostral ACC during aStroop compared to cStroop (p < 0.05). In the absence of escitalopram, both aStroop and cStroop significantly activated ACC and DLPFC (Z ≥ 2.3, p < 0.05). Conclusion: We conclude that escitalopram in a region and task specific manner modified the cognitive control networks and preferentially decreased activity induced by affective interference in the ACC

Seizure (Ictal)—EEG Characteristics in Subgroups of Depressive Disorder in Patients Receiving Electroconvulsive Therapy (ECT)—A Preliminary Study and Multivariate Approach

Objectives. Examine frequency distributions of ictal EEG after ECT stimulation in diagnostic subgroups of depression. Methods. EEG registration was consecutively monitored in 33 patients after ECT stimulation. Patients were diagnosed according to DSM IV and subdivided into: (1) major depressive disorder with psychotic features (n = 7), (2) unipolar depression (n = 20), and (3) bipolar depression (n = 6). Results. Results indicate that the diagnostically subgroups differ in their ictal EEG frequency spectrumml: (1) psychotic depression has a high occurrence of delta and theta waves, (2) unipolar depression has high occurrence of delta, theta and gamma waves, and (3) bipolar depression has a high occurrence of gamma waves. A linear discriminant function separated the three clinical groups with an accuracy of 94%. Conclusion. Psychotic depressed patients differ from bipolar depression in their frequency based on probability distribution of ictal EEG. Psychotic depressed patients show more prominent slowing of EEG than nonpsychotic depressed patients. Thus the EEG results may be supportive in classifying subgroups of depression already at the start of the ECT treatment

Glucose metabolism in completed suicide: a forensic-pathological pilot study

Aim To determine whether antemortem blood levels of glycated hemoglobin (HbA1c) and glucose predict completed suicide and, by extension, whether markers of glucose metabolism might be associated with a prosuicidal trait or state. Method From consecutively performed autopsies, samples of blood and vitreous humor from 17 suicide victims and 27 non-suicide controls were compared with regard to levels of glucose, lactate, and HbA1c. Results Mean HbA1c was higher, and mean estimated blood glucose lower, among suicide victims, although tests revealed no significant differences (P = 0.171 and P = 0.395, respectively). HbA1c levels exceeding 48.0 mmol/mol, which were indicative of persistent hyperglycemia, were twice as common in suicide victims (59% vs 30%; P = 0.068). Conclusion The finding of this pilot study suggest that deranged glucose metabolism may reflect biological events antecedent to, or concomitant with, completed suicide, with the following clinical implications: recurring hyperglycemia due to defective glucose transport, which may give rise to depression and suicidal ideation, and elevated HbA1c levels, which may represent an assayable correlate to neurobiological conditions predisposing to suicide

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals

AIMS: Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry. METHODS: We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles. RESULTS: We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex. CONCLUSIONS: We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD

Mega-analysis of association between obesity and cortical morphology in bipolar disorders:ENIGMA study in 2832 participants

Background: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. Methods: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. Results: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. Conclusions: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.</p

Altered Neural and Behavioral Response to Sexually Implicit Stimuli During a Pictorial-Modified Stroop Task in Pedophilic Disorder

Background: Pedophilic disorder (PD) entails sexual attraction to prepubertal children. A risk factor for committing child sexual abuse in PD is impaired cognitive control. However, the underlying neurocognitive mechanisms remain unclear. Methods: We performed a case-control study including 51 self-identified and help-seeking males with PD and 55 matched healthy control subjects. Functional magnetic resonance imaging and a pictorial-modified Stroop task involving computer-generated sexually implicit images were used to measure response time and brain activation. Increases in response time during the pictorial-modified Stroop task are presumably due to image-induced interference in executive functions required for task performance. Results: In PD, during the presentation of images of children compared with adults, we found increased response time (p = .005; 848 ± 92 ms vs. 826 ± 88 ms), and compared with healthy control subjects, we found increased activation in the occipital, temporal (bilateral hippocampus), parietal, frontal, cingulate, and left insular cortices; caudate (bilaterally); thalamus (mediodorsal); and cerebellum. Conclusions: Presentation of child images was associated with response interference in PD and increased engagement of brain regions involved in the processing of sexual stimuli, visual perception, self-referential thought, and executive function. We conclude that processing of child images is associated with functional and behavioral alterations in PD

Seizure (Ictal) – EEG characteristics subgroup depressive disorder in patients receiving ECT – A preliminary study and multivariate approach

Recommended by Fabio Babiloni Objectives. Examine frequency distributions of ictal EEG after ECT stimulation in diagnostic subgroups of depression. Methods. EEG registration was consecutively monitored in 33 patients after ECT stimulation. Patients were diagnosed according to DSM IV and subdivided into: (1) major depressive disorder with psychotic features (n = 7), (2) unipolar depression (n = 20), and (3) bipolar depression (n = 6). Results. Results indicate that the diagnostically subgroups differ in their ictal EEG frequency spectrumml: (1) psychotic depression has a high occurrence of delta and theta waves, (2) unipolar depression has high occurrence of delta, theta and gamma waves, and (3) bipolar depression has a high occurrence of gamma waves. A linear discriminant function separated the three clinical groups with an accuracy of 94%. Conclusion. Psychotic depressed patients differ from bipolar depression in their frequency based on probability distribution of ictal EEG. Psychotic depressed patients show more prominent slowing of EEG than nonpsychotic depressed patients. Thus the EEG results may be supportive in classifying subgroups of depression already at the start of the ECT treatment