Platelet number is negatively and independently associated with carotid intima-media thickness in apparently healthy overweight/obese subjects.

BACKGROUND AND AIM: A significant change of platelet number may be a risk factor for atherosclerotic cardiovascular disease. The aim of this study was to investigate the association between platelet number and early signs of atherosclerosis, evaluated by carotid intima-media thickness (c-IMT), in a apparently healthy population mainly represented by obese subjects. METHODS AND RESULTS: As many as 961 subjects, 686 women and 275 men, aged between 18 and 74 years, were enrolled in the study. Of these, 54 individuals (5.6% of all subjects) were normal weight, 259 individuals (27.0% of all subjects) were overweight, and 648 individuals (67.4% of all subjects) were obese. Waist circumference (WC) and blood glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol, triglycerides and platelet count were also detected in all subjects, who underwent carotid echo color doppler ultrasound to measure c-IMT. c-IMT was significantly and positively associated to age (r = 0.204, P < 0.0001), fasting glucose (r = 0.073, P < 0.0240), total cholesterol (r = 0.096, P = 0.0031), and systolic and diastolic blood pressure (r = 0.140, P < 0.0001 and r = 0.119, P < 0.0003 respectively); c-IMT was significantly and negatively correlated with platelet count (r = -0.165, P < 0.0001). Only age (P < 0.0001) and systolic blood pressure (P = 0.0393), positively, and platelet number (P < 0.0001), negatively, were significantly and independently associated to c-IMT in a final multiple regression analysis. CONCLUSION: Lower platelet number represented an independent determinant of c-IMT in a population, mainly represented by obese patients. These results suggest that a decrease of platelet number may well be an early defensive mechanism in subjects developing the thickening of carotid artery.

Improved executive functioning following repetitive transcranial magnetic stimulation.

The cognitive effects of active and sham repetitive transcranial magnetic stimulation (rTMS) were examined in 19 middle-aged and elderly patients with refractory depression. Patients received either active (n = 9) or sham (n = 10) rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients in the active rTMS group improved significantly on a test of cognitive flexibility and conceptual tracking (Trail Making Test-B).

A controlled study of repetitive transcranial magnetic stimulation as a treatment of depression in the elderly.

Rapid transcranial magnetic stimulation (rTMS) applied to the left dorsal lateral frontal cortex has been shown to produce antidepressant effects. Older depressed patients, however, in one study showed a lower response rate than younger patients. The current study examined treatment response in 20 depressed, treatment-refractory patients (mean age 60.7 +/- 9.8 years) given five sessions of rTMS at 20 Hz for 2 seconds over 20 trains at 80% of motor threshold or identical placebo stimulation, after patients had been withdrawn from their antidepressants. There were no significant differences in Hamilton Depression Scale scores either before or after treatment at 7 days' follow-up. There were three responders to active treatment and three to sham treatment and responders had significantly greater frontal lobe volume than nonresponders (p = .03). These findings suggest that the stimulation parameters used in this study were probably insufficient to produce treatment response and that frontal atrophy may interfere with the effectiveness of rTMS.

Gender differences in depression associated with neurologic illness: clinical correlates and pharmacologic response.

Functional depression (i.e., depression without neuropathology) occurs approximately twice as often in women as in men. A review of the literature from the period 1966-1999 on the prevalence, clinical correlates, and treatment of depression in neurologic disease revealed a female preponderance of depression in diffuse neurologic disease, including Alzheimer's disease. In focal neurologic disease, the data were consistent for men and women, with a 1:1 ratio. Treatment data on depression in neurologic disease are scant, with the exception of poststroke depression. Although gender-based outcome data on the treatment of functional depression reveal better tolerability and response to serotonin reuptake inhibitors in women than in men, this phenomenon cannot be generalized to depression in neurologic disease. Men seem to consistently respond better than premenopausal women to tricyclic antidepressants in both functional and neurologic disease. Understanding how gender influences depression in neurologic illness and its response to treatment is a necessary step to improve the specificity of psychiatric treatment for depression.

Neural mechanisms of anhedonia in schizophrenia: a PET study of response to unpleasant and pleasant odors.

CONTEXT: Loss of the capacity to experience pleasure (anhedonia) is a core clinical feature of schizophrenia. Although functional imaging techniques have been successful in identifying the neural basis of cognitive impairments in schizophrenia, no attempts to date have been made to investigate neural systems underlying emotional disturbances. OBJECTIVE: To study the neural basis of emotional processing in schizophrenia by exploring the pattern of brain responses to olfactory stimuli in patients and healthy volunteers. DESIGN: Positron emission tomographic study of patients with schizophrenia and healthy volunteers. Positron emission tomographic data were collected between July 21, 1995, and September 11, 1997, and data analyses were conducted in 1999-2001. SETTING: The Mental Health Clinical Research Center at the University of Iowa, Iowa City. PARTICIPANTS: Sixteen healthy volunteers with a mean age of 29.5 years and 18 patients with schizophrenia and a mean age of 30.0 years. MAIN OUTCOME MEASURE: Areas of relative increase or decrease in regional cerebral blood flow, measured using positron emission tomography and the [(15)O]water method while participants performed an emotion-induction olfactory task to determine response to pleasant (vanillin) and unpleasant (4-methylvaleric acid) odors, compared between patients and healthy volunteers. RESULTS: Patients with schizophrenia subjectively experienced unpleasant odors in a manner similar to healthy volunteers but showed impairment in the experience of pleasant odors. The analysis of the regional cerebral blood flow revealed that patients failed to activate limbic/paralimbic regions (eg, insular cortex, nucleus accumbens, and parahippocampal gyrus) during the experience of unpleasant odors, recruiting a compensatory set of frontal cortical regions instead. CONCLUSION: Abnormalities in the complex functional interactions between mesolimbic and frontal regions may underlie emotional disturbances in schizophrenia.

Impact of depressed mood on neuropsychological status in temporal lobe epilepsy.

OBJECTIVES: Depression is a common psychiatric complication of temporal lobe epilepsy. This study examined the effect of depressed mood on neuropsychological performance among patients with chronic temporal lobe epilepsy. METHODS: Seventy consecutive surgery candidates for medication resistant complex partial seizures of unilateral temporal lobe origin were assessed for psychiatric symptoms and underwent comprehensive neuropsychological assessment. RESULTS: Standardised psychiatric interview disclosed that 34% of the patient sample exhibited significant depression. Controlling for seizure frequency, patients with comorbid depression at the time of neuropsychological assessment exhibited significantly poorer performance on measures of intelligence, language, visuoperceptual ability, memory, and executive function. Within lateralised temporal lobe epilepsy groups, the adverse effects of depression on cognitive function were greater in patients with left temporal lobe compared with those with right temporal lobe epilepsy. In addition, depression seemed to be underrecognised and undertreated as none of the patients with epilepsy and comorbid depression were treated for their psychiatric condition at the time of admission for monitoring. CONCLUSIONS: Depression, a common psychiatric comorbidity among patients with chronic temporal lobe epilepsy, seems to be undertreated and to have adverse effects on cognitive functioning.

Cerebral blood flow changes associated with attribution of emotional valence to pleasant, unpleasant, and neutral visual stimuli in a PET study of normal subjects.

OBJECTIVE: To assist in the development of a model for the psychopathology of emotions, the present study sought to identify the neural circuits associated with the evaluation of visual stimuli for emotional valence. METHOD: Seventeen healthy individuals were shown three sets of emotionally laden pictures carrying pleasant, unpleasant, and neutral content. While subjects evaluated the picture set for emotional valence, regional cerebral blood flow was measured with the use of [15O] water positron emission tomography. Subjective ratings of the emotional valence of the picture sets were recorded. Data were analyzed by comparing the images acquired during the neutral condition with the unpleasant and pleasant image sets and the unpleasant and pleasant conditions with each other. RESULTS: Processing of pleasant stimuli was associated with increased blood flow in the dorsal-lateral, orbital, and medial frontal cortex relative to the unpleasant condition and in the cingulate, precuneus, and visual cortex relative to the neutral condition. Evaluation of unpleasant stimuli activated the amygdala, visual cortex, and cerebellum relative to the pleasant condition and the nucleus accumbens, precuneus, and visual cortex relative to the neutral condition. CONCLUSIONS: Observing and assigning emotional value to unpleasant stimuli produced activations in subcortical limbic regions, whereas evaluation of pleasant stimuli produced activations in cortical limbic areas. These findings are consistent with the notion of a subcortical and archaic danger recognition system and a system detecting pleasantness in events and situations that is phylogenetically younger, involving primarily the prefrontal cortex.

Frontal lobe syndrome reassessed: comparison of patients with lateral or medial frontal brain damage.

Examination of mood and behaviour changes after frontal damage may contribute to understanding the functional role of distinct prefrontal areas in depression and anxiety. Depression and anxiety disorders, symptoms, and behaviour were compared in eight patients with single lateral and eight patients with single medial frontal lesions matched for age, sex, race, education, socioeconomic status, side, and aetiology of lesion 2 weeks and 3 months after brain injury. DSM IV major depressive and generalised anxiety disorders were more frequent in patients with lateral compared with medial lesions at 2 weeks but not at 3 months. At 3 months, however, patients with lateral damage showed greater severity of depressive symptoms, and greater impairment in both activities of daily living and social functioning. At initial evaluation depressed mood and slowness were more frequent, whereas at 3 months slowness, lack of energy, and social unease were more frequent in the lateral than the medial group. Patients with lateral lesions showed greater reduction of emotion and motivation (apathy) during both examinations. Medial frontal injury may fail to produce emotional dysregulation or may inhibit experience of mood changes, anxiety, or apathy. Lateral prefrontal damage may disrupt mood regulation and drive while leaving intact the ability to experience (negative) emotions.

Minor depression after stroke: an initial validation of the DSM-IV construct.

Using 141 patients with a single left- or right-hemisphere stroke, the authors investigated the distinction between major and minor depression after stroke. Major- and minor-depression patients and nondepressed control patients were compared, and a logistic-regression model suggested that major and minor depressions may be cross-sectionally distinguishable disorders. Minor depression was associated with younger age, left-hemisphere lesion location, and more caudal hemisphere lesions. There was an association between minor depression and pathoanatomical variables, with results generally consistent with the categorical vs. the continuum hypothesis of mood disorders in stroke victims. Authors discuss the significance of damage in left-hemisphere posterior portions of the brain for the development of minor depression after stroke.

Neglect after right insular cortex infarction.

BACKGROUND AND PURPOSE: Case reports have shown an association between right insular damage and neglect. The aim of this study was to examine the incidence of neglect among patient groups with right or left insular infarction. METHODS: We examined neglect in 9 right-handed subjects with insular stroke as evidenced by CT and/or MRI scans (4 with right insular and 5 with left insular cerebrovascular accident) between 4 and 8 weeks after acute stroke with tests of visual, tactile, and auditory perception. RESULTS: Compared with patients with left insular lesions, patients with right insular lesions showed significant neglect in the tactile, auditory, and visual modalities. CONCLUSIONS: The right insular cortex seems to have a role in awareness of external stimuli, and infarction in this area may lead to neglect in multisensory modalities.

Recalling word lists reveals "cognitive dysmetria" in schizophrenia: a positron emission tomography study.

OBJECTIVE: This study explored the neural circuitry used during recall of unstructured verbal material in schizophrenic patients and healthy volunteer subjects. METHOD: The subjects were 13 healthy volunteers and 14 schizophrenic patients. All patients were free of medication, and all subjects were right-handed. Two experimental cognitive conditions were used: recall of novel and practiced word lists (two 15-item lists from the Rey Auditory Verbal Learning Test). Both active recall tasks were compared with an eyes-closed resting baseline condition. A nonparametric randomization test was used to determine within- and between-group differences in regional cerebral blood flow. RESULTS: Performance on both the practiced and novel memory tasks was nonsignificantly different in the patients and control subjects. During the novel memory task, the patients showed decreased flow in the right anterior cingulate, right thalamus, and bilateral cerebellum (left greater than right) relative to the control subjects. When recalling the practiced word lists, the patients showed decreased flow in the left dorsolateral prefrontal cortex, bilateral medial frontal cortex, left supplementary motor area, left thalamus, left cerebellar regions, anterior vermis, and right cuneus. CONCLUSIONS: Patients with schizophrenia fail to activate cortical-cerebellar-thalamic-cortical circuitry during recall of both well-learned and novel word lists.

The cerebellum plays a role in conscious episodic memory retrieval.

The cerebellum has traditionally been considered to be primarily dedicated to motor functions. Its phylogenetic development and connectivity suggest, however, that it also may play a role in cognitive processes in the human brain. In order to examine a potential cognitive role for the cerebellum in human beings, a positron emission tomography (PET) study was conducted during a "pure thought experiment": subjects intentionally recalled a specific past personal experience (consciously retrieved episodic memory). Since there was no motor or sensory input or output, the design eliminated the possibility that cerebellar changes in blood flow were due to motor activity. During silent recall of a consciously retrieved episodic memory, activations were observed in the right lateral cerebellum, left medial dorsal thalamus, medial and left orbital frontal cortex, anterior cingulate, and a left parietal region. These activations confirm a cognitive role for the cerebellum, which may participate in an interactive cortical-cerebellar network that initiates and monitors the conscious retrieval of episodic memory.

Neuropsychiatric effects of insular stroke.

The neuropsychiatric effects of insular damage in humans have not previously been examined. We therefore examined the neuropsychiatric impairment in seven patients with left insular stroke, six patients with right insular stroke, six patients with left hemisphere noninsular stroke, and six patients with right hemisphere noninsular stroke. Between 4 and 8 weeks after acute stroke, patients were administered a neuropsychiatric battery. Patients with right insular lesions had a greater frequency of subjective anergia and underactivity (Fisher's exact p = .002) as well as tiredness (Fisher's exact p < .002) compared with patients with non-insular lesions or left insular lesions. Subjective feelings of impaired energy or drive after right insular damage may result from disconnection between the insula and the frontal lobe or the anterior cingulate cortex, structures that have been associated with willed action and motor behavior.

"Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry?

Earlier efforts to localize the symptoms of schizophrenia in a single brain region have been replaced by models that postulate a disruption in parallel distributed or dynamic circuits. Based on empirical data derived from both magnetic resonance and positron emission tomography, we have developed a model that implicates connectivity among nodes located in prefrontal regions, the thalamic nuclei, and the cerebellum. A disruption in this circuitry produces "cognitive dysmetria," difficulty in prioritizing, processing, coordinating, and responding to information. This "poor mental coordination" is a fundamental cognitive deficit in schizophrenia and can account for its broad diversity of symptoms.

Gender differences in poststroke depression.

In stroke and other medical illnesses, secondary depression may be associated with different factors in women than in men. The authors examined 301 consecutive admissions for acute treatment of cerebrovascular accident for gender differences in depression, psychosocial factors, physical impairment, and lesion location. Women were twice as frequently diagnosed with major depression as men. Women with major depression had a greater frequency of left hemisphere lesions than men. In men, major depression was associated with greater impairment in activities of daily living, and greater severity of depression was associated with greater impairment in daily activities and social functioning. In women, greater severity of depression was associated with prior diagnosis of psychiatric disorder and cognitive impairment. These findings suggest a different nature of poststroke depression in men and women and may have implications for its treatment.

Brain activity assessed with PET during recall of word lists and narratives.

This study investigated the functional neuroanatomy involved in retrieval of structured versus unstructured verbal information. We compared cerebral blood flow using PET with the [15O]water method while subjects engaged in recall of novel and practised narratives and lists of unrelated words. Left orbital frontal cortex was activated during recall of both novel and practised unrelated words. Right parietal cortex was relatively more active during recall of the novel word list. Right orbital frontal cortex and anterior cingulate were relatively more active during recall of the practised but not the novel word list. These results are consistent with the role of left orbital frontal cortex in retrieval of unstructured verbal information. Right orbital frontal activity suggests that cognitive strategies may be involved in retrieval of well-practised words.

Emotional activation of limbic circuitry in elderly normal subjects in a PET study.

OBJECTIVE: This study was undertaken to identify brain structures associated with emotion in normal elderly subjects. METHOD: Eight normal subjects aged 55-78 years were shown film clips intended to provoke the emotions of happiness, fear, or disgust as well as a neutral state. During emotional activation, regional cerebral blood flow was measured with the use of [15O]H2O positron emission tomography imaging, and subjective emotional responses were recorded. Data were analyzed by subtracting the values during the neutral condition from the values in the various emotional activations. RESULTS: The stimuli produced a general activation in visual pathways that included the primary and secondary visual cortex, involving regions associated with object and spatial recognition. In addition, the specific emotions produced different regional limbic activations, which suggests that different pathways may be used for different types of emotional stimuli. CONCLUSIONS: Emotional activation in normal elderly subjects was associated with increases in blood flow in limbic and paralimbic brain structures. Brain activation may be specific to the emotion being elicited but probably involves complex sensory, association, and memory circuitry. Further studies are needed to identify activations that are specific for emotion.

Cerebellar size and cognition: correlations with IQ, verbal memory and motor dexterity.

The objective of this study was to examine the structure/function relationship between in vivo cerebellar size and higher cognitive function in a sample of healthy young subjects. The design of the study involved correlation of in vivo cerebellar volume measurements with measures of general intelligence (WAIS-R V&P FSIQ, Vocabulary, Block Design, and Digit Span subtests), motor dexterity (Halstead-Reitan Finger Tapping), verbal (WMS Logical Memory), and visual (Rey-Osterrieth Figure) memory covaring for cerebrum size. A similar analysis was performed using left temporal lobe volumes as a control region. The sample consisted of 62 healthy subjects (30 females, 32 males) enrolled as controls at the MHCRC at the University of Iowa Hospitals and Clinics. This independent sample does not overlap with the groups studied in our previous report on the relationship between cerebellar and brain size and IQ. Cerebellar and total brain size were estimated through automatic, atlas-based volume measurements using MR images obtained with a T1-weighted three-dimensional SPGR sequence on a 1.5-T GE Signa scanner and locally developed software. Cerebellar volume significantly correlated with Finger Tapping (left hand: r = 0.218, p < 0.05; right hand: r = 0.211, p < 0.05) and with memory retention of complex narrative material (r = 0.27, p < 0.02). Cerebellar volume correlated with general intelligence in the expected direction (r = 0.19, p < 0.07). This study confirms previous work indicating that the cerebellum may make a contribution to several aspects of cognition. Cerebellar volume significantly correlated with the ability to retain already encoded information in the verbal domain and with fine motor dexterity. Cerebellar volume positively correlated with general but the relationship did not reach statistical significance. The structural/functional relationship between cerebellum and verbal memory abilities is consistent with evolutionary theory for the phylogenetical increase in the size of the cerebellum.

Vegetative and psychological symptoms associated with depressed mood over the first two years after stroke.

INTRODUCTION: In patients with acute physical illness, symptoms used in the diagnosis of major depression such as sleep or appetite disturbance may be nonspecific for depression. This study was undertaken to examine the association of depressed mood with other depressive symptoms to determine which symptoms were most useful in the accurate diagnosis of major depression after stroke. METHODS: Using a structured mental status examination, 142 patients with acute stroke were followed at three, six, twelve, and twenty-four months. RESULTS: The median number of vegetative and psychological symptoms among patients with depressed mood was more than three times the respective rates among nondepressed patients at all time points over two years. Autonomic anxiety, morning depression, subjective anergia, worrying, brooding, loss of interest, hopelessness, and lack of self-confidence were significantly more frequent among depressed patients than nondepressed patients throughout the entire two-year period. Some symptoms such as anxious foreboding and loss of libido, as well as self-depreciation, feelings of guilt, and irritability were no longer significantly more common among depressed compared with nondepressed patients after six months. Standard DSM-IV diagnostic criteria and modified DSM-IV diagnostic criteria which included only specific symptoms of depression (i.e., symptoms which were significantly more frequent among depressed than nondepressed mood patients) yielded similar frequencies of major depression diagnosis. There were only a few patients (i.e., 2% to 3%) with depressive symptoms without a depressed mood (perhaps "masked" depression). CONCLUSIONS: Vegetative and psychological depressive symptoms are significantly more common in depressed patients over the first two years after stroke and DSM-IV criteria do not overdiagnose major depression even in this population with chronic physical illness. The symptoms which characterize major depression appear to change between the subacute and chronic post-stroke periods.

Social impairment and depression after traumatic brain injury.

OBJECTIVE: Previous studies have shown that social impairment is associated with major depression throughout the first year after traumatic brain injury (TBI). This study examined the specific social factors that were associated with post-TBI depression. METHOD: A consecutive series of 65 patients with closed head injuries were cross-sectionally and longitudinally examined using a semistructured psychiatric interview, the Hamilton Depression Rating Scale, and the Social Functioning Exam during in-hospital care and at 3-, 6-, 9-, and 12-month follow-ups. RESULTS: Depressed subjects showed poorer social functioning at the initial evaluation, and at 6, 9, and 12 months. Measures of preinjury job dissatisfaction and fear of job loss were significantly associated with depression at the initial evaluation. Concurrent impaired close personal relationships as well as continued fear of job loss were associated with depression at 6, 9, and 12 months after TBI. CONCLUSIONS: These findings suggest that two of the psychosocial factors associated with depression during the acute TBI period (patient's satisfaction with work and fear of job loss) are the same as those operant during the chronic period, but an additional psychosocial factor (close interpersonal relationships) is also operant during the chronic period. These findings support the need for early targeted social intervention in cases of TBI.