Sergio Paradiso

Cognitive impairment in the euthymic phase of chronic unipolar depression

Cognitive functioning in the nonsymptomatic phase and the long-term cognitive outcome of patients with mood disorders are both heuristic and important clinical issues in the study of mood disorders. Literature findings are inconsistent because of design confounds. We tried to address these issues while controlling for several confounds including age, education, gender differences in neurobehavioral functioning, and diagnosis. Nonsymptomatic patients with a history of chronic unipolar depression and bipolar affective disorder and healthy male individuals were administered neuropsychological tests to assess attention, visual-motor tracking, executive abilities, and immediate verbal memory. Subjects had comparable depression scores at the time of testing. Disease duration was 7.5 years (SD 5.1) for unipolar and 11 years (SD 7.3) for bipolar patients. Unipolar patients were more impaired than healthy normal comparison subjects on measures of visual-motor sequencing (Trail Making Test A, p < .05), executive function (Trail Making Test B, Stroop Test Color/Word Trial, p < .05), and immediate memory and attention (CERAD 1st trial, WAIS Digit Symbol subtest, p < .05). Differences between bipolar patients and normal comparison subjects did not reach significance in any of the selected measures. Male patients with a history of chronic unipolar disorder are at risk for cognitive impairment in the nonsymptomatic phase of their disease. Cognitive disturbance is the type seen with prefrontal dysfunction and may be assessed with standard neuropsychological assessments.

The Cerebellum and Emotional Experience

While the role of the cerebellum in motor coordination is widely accepted, the notion that it is involved in emotion has only recently gained popularity. To date, functional neuroimaging has not been used in combination with lesion studies to elucidate the role of the cerebellum in the processing of emotional material. We examined six participants with cerebellar stroke and nine age and education matched healthy volunteers. In addition to a complete neuropsychological, neurologic, and psychiatric examination, participants underwent [15O]water positron emission tomography (PET) while responding to emotion-evoking visual stimuli. Cerebellar lesions were associated with reduced pleasant experience in response to happiness-evoking stimuli. Stroke patients reported an unpleasant experience to frightening stimuli similar to healthy controls, yet showed significantly lower activity in the right ventral lateral and left dorsolateral prefrontal cortex, amygdala, thalamus, and retrosplenial cingulate gyrus. Frightening stimuli led to increased activity in the ventral medial prefrontal, anterior cingulate, pulvinar, and insular cortex. This suggests that alternate neural circuitry became responsible for maintaining the evolutionarily critical fear response after cerebellar damage.

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. Hum. Brain Mapping 8:226–234, 1999.

Cognitive and neurological impairment in mood disorders

Disorders of mood are accompanied by a range of cognitive and neurological impairments. Similar types of cognitive deficits are shared by patients with unipolar depression and bipolar disorder. Given the disparate clinical nature of these two disorders, it is interesting and informative to understand that they share common impairments in cognition. Neuro-imaging studies indicate that these impairments in both patient populations may be subserved by disruptions of the dorsal lateral and ventral medial PFC. An important problem that remains for clinicians is that some neurological symptoms are linked specifically to the adverse pharmacological effects of antidepressant agents, mood stabilizers, and neuroleptic agents. Research has shown a relation between mood and cognitive ability. Studies also have shown an association between mood and specific types of neurological dysfunction. Although few studies have examined all three symptom domains within one investigation, preliminary reports indicate that mood, cognition, and motor function may be linked to one another by complex mechanisms. Moreover, either type of abnormality that persists in the euthymic state suggests that a fundamental neural dysfunction is unaffected by treatment with existing means. Understanding the neural mechanisms that underlie mood, cognition, and movements may help to devise better treatments that do not influence cognitive or neurological functions,yet treat mood successfully.

Improved executive functioning following repetitive transcranial magnetic stimulation.

Abstract—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).

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 (patients 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.

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.

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” depressions). 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.

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.

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 (Fishers exact p = .002) as well as tiredness (Fishers 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.