Neuroanatomic substrates of lower extremity somatosensory evoked potentials.

After stimulation of the lower extremity nerve (tibial nerve), N21 and N23 are recorded from L4 and T12 spine respectively. The far-field potentials of P31 and N35 are registered from Fpz-C5s (fifth cervical spine) or CPi (ipsilateral with respect to the side of stimulation)-ear derivation. Additional far-field potentials of P17 and P24 may be recorded from the scalp when a noncephalic (knee) reference is used. The major positive peak, P40, is registered at the vertex and the CPi. Preceding P40, there is a small negative peak, N37, recorded at the contralateral (CPc) hemisphere. Neuroanatomic substrates of these somatosensory evoked potential (SSEP) components are less well clarified compared with those of upper extremity (median nerve) SSEPs, primarily because clinical application of lower extremity SSEPs is more difficult, and all of the aforementioned potentials but one (P40) are not obligatory components. The concept of "paradoxical lateralization" complicates the issue further. Accumulating evidence, however, suggests that the far-field potentials of P17 and P31 arise from the distal portion of the sacral plexus and brainstem respectively. These correspond to P9 and P14 of the median nerve SSEPs respectively. The spinal potential of N23 is equivalent to the N13 cervical potential of the median nerve SSEP. N35 recorded from the ipsilateral hemisphere is analogous to N18 of the median nerve. Paradoxically lateralized P40 has been thought to represent the positive end of a dipole field, reflected by the negativity at the mesial surface of the contralateral hemisphere, and has commonly been considered to be equivalent to the first cortical potentials (N20) of the median nerve SSEP. However, more recent evidence suggests that the primary positivity is at the mesial cortical surface, and it more likely corresponds to P26 of the median nerve SSEP. Thus the first cortical potential corresponding to N20 is probably a small and inconsistent N37 recorded on the contralateral hemisphere. These assumptions need to be verified further by more extensive clinical studies applied to various neurologic disorders.     

Electroencephalographic sleep in late-life neuropsychiatric disorders

Late-life depression and dementia of the Alzheimer's type both have profound, although different, effects on electroencephalographic (EEG) sleep patterns. Thus, while depression is associated with REM sleep disinhibition and extreme sleep fragmentation (e.g., sleep onset REM periods and early morning awakenings), Alzheimer's disease is associated with deficits in the production of phasic activity during sleep (e.g., rapid eye movements and K-complexes) and with increased rates of sleep-disordered breathing. These differences have been shown to be reliable in large numbers of patients during the past five years and appear to extend to differences in sleep between depressive pseudodementia and dementia with secondary depression. Preliminary data also suggest that pretreatment sleep onset REM periods may be associated with enhanced vulnerability to recurrent depression. In summary, sleep physiological measures provide useful diagnostic and prognostic indexes in late-life neuropsychiatric disorders.     

Neuroanatomic substrates of sex differences in language dysfunction in schizophrenia: a pilot study

OBJECTIVE: This pilot study investigated whether our previous findings of disrupted normal sexual brain dimorphisms in language-associated regions in schizophrenia were linked with our previously reported sex differences in language dysfunction in schizophrenia. METHOD: Nineteen adults with schizophrenia and 15 normal comparisons were tested on phonology, semantics and grammar and underwent structural MRI. RESULTS: Among males, left hippocampal and left planum temporale (PT) abnormalities were associated with phonological, semantic and grammar deficits, accounting for 17-52% and 27-33%, respectively, of variance in diagnostic group differences. Anterior cingulate gyrus was significantly associated with semantics. Among females, right Heschl's Gyrus (HG) and left PT were significantly associated with phonology, right HG with semantics and grammar and right hippocampus with semantics. CONCLUSIONS: These preliminary findings suggest disrupted sexual brain dimorphisms in schizophrenia are associated with sex-specific language deficits, and left hippocampal abnormalities, in particular, contribute to language dysfunction among men. Abnormalities in right cortical temporal regions showed stronger associations with language dysfunction among females.     

Brief report: Neuroanatomic observations of the brain in pervasive developmental disorders

TheDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994) defines Pervasive Developmental Disorders (PDD) as those syndromes which are characterized by severe and pervasive impairment of reciprocal social skills, communication, or the presence of stereotyped interests and activities. Included under PDD are Autism, Rett's disorder, childhood disintegrative disorder, Asperger's Disorder, and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). To date, detailed neuroanatomic studies have been initiated in only two of these disorders, Autism and Rett syndrome (RS) and some very preliminary data are available for Asperger syndrome (AS).     

Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: patterns of functional MRI activation.

Impairment in semantic processing occurs early in Alzheimer's disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match-mismatch) about word pairs (category-exemplar, category-function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD.     

Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders

The ascending reticular activating system (ARAS) mediates arousal, an essential component of human consciousness. Lesions of the ARAS cause coma, the most severe disorder of consciousness. Because of current methodological limitations, including of postmortem tissue analysis, the neuroanatomic connectivity of the human ARAS is poorly understood. We applied the advanced imaging technique of high angular resolution diffusion imaging (HARDI) to elucidate the structural connectivity of the ARAS in 3 adult human brains, 2 of which were imaged postmortem. High angular resolution diffusion imaging tractography identified the ARAS connectivity previously described in animals and also revealed novel human pathways connecting the brainstem to the thalamus, the hypothalamus, and the basal forebrain. Each pathway contained different distributions of fiber tracts from known neurotransmitter-specific ARAS nuclei in the brainstem. The histologically guided tractography findings reported here provide initialevidence for human-specific pathways of the ARAS. The unique composition of neurotransmitter-specific fiber tracts within each ARAS pathway suggests structural specializations that subserve the different functional characteristics of human arousal. This ARAS connectivity analysis provides proof of principle that HARDI tractography may affect the study of human consciousness and its disorders, including in neuropathologic studies of patients dying in coma and the persistent vegetative state.     

Outcomes of late-life anxiety disorders during 32 weeks of citalopram treatment

BACKGROUND: Anxiety disorders are common in later life, but little is known about the long-term benefits and risks of pharmacotherapy. METHOD: 30 patients aged 60 years and older, with a DSM-IV anxiety disorder, entered a 32-week trial of citalopram. Data gathered at baseline and follow-up included anxiety symptoms using Hamilton Rating Scale for Anxiety (HAM-A) scores, quality of life using the Medical Outcomes Study 36-item Short Form (SF-36), and sleep using the Pittsburgh Sleep Quality Index (PSQI). Data analysis consisted of mixed-effect repeated measures models of HAM-A scores and pre-post comparison of SF-36 and PSQI scores. RESULTS: 30 persons entered treatment; most (27/30) had a primary DSM-IV diagnosis of generalized anxiety disorder (2 had panic disorder; 1 had posttraumatic stress disorder). Three subjects discontinued study medication due to side effects, 5 were terminated because of nonresponse, and 5 dropped out of the study for other reasons; thus, 17 subjects (57%) completed 32 weeks of treatment. Subjects' HAM-A scores improved significantly, with continuing improvements up until about 20 weeks of treatment. On the basis of a criterion of reduction in HAM-A to < 10 during the trial, 60% (18/30) of subjects were responders. Those who completed the 32-week trial had significant improvements in sleep and quality of life-including social functioning, vitality, mental health, and role difficulties due to emotional problems. CONCLUSIONS: In this 32-week study of citalopram for elderly persons with anxiety disorders, 60% responded. Those who received a full course of treatment experience significant improvements in quality of life and sleep quality.     

Medical burden in late-life bipolar and major depressive disorders.

BACKGROUND: Elderly patients with bipolar disorder have been found to have higher mortality than those with major depressive disorder. The authors compare medical burden in elderly patients with bipolar disorder with that in those with major depressive disorder. METHODS: Fifty-four patients with bipolar I or II disorder who were 60 years of age and older were equated 1-to-2 to 108 patients with nonpsychotic, major depressive disorder according to age, sex, race, and lifetime duration of mood disorder illness. Variables examined included the following: Cumulative Illness Rating Scale for Geriatrics (CIRS-G) total scores, body mass index (BMI), and CIRS-G subscale scores. RESULTS: Compared with patients with major depressive disorder, patients with bipolar disorder had similar levels of general medical comorbidity on the CIRS-G total score and number of systems affected but higher BMI. After controlling for multiple comparisons, the endocrine/metabolic and respiratory subscale scores on the CIRS-G were higher for patients with bipolar disorder. CONCLUSION: Although overall medical burden appears comparable in elderly patients with bipolar and those with major depressive disorder, patients with bipolar disorder have higher BMI and greater burden of endocrine/metabolic and respiratory disease.     

Inherited mental disorders

A compilation of all mental disorders with known genetic etiology is presented. Of 139 disorders the gene location is known in 36. Eleven of the genes are located on the X chromosome and 24 on the autosomes. When a gene for a disorder is located, linkage analysis can be used for diagnosis. In the future the gene map will expand and more mental disorders be diagnosed with linkage analysis.     

Boundaries of mental disorders

PURPOSE OF REVIEW: This article reviews the problem of 'boundaries' in psychopathology and its conceptualization in the diagnostic classification of psychiatric disorders. RECENT FINDINGS: A modest number of publications in 2004-2005 contribute concepts, methods and data relevant to several aspects of the problem: scientific 'facts' versus value attribution in the definition of mental disorders; the problem of comorbidity between diagnostic entities; the spurious dichotomy between categorical versus dimensional approaches to diagnosis and classification; and the distinction between validity and pragmatic utility. SUMMARY: The relative paucity of research explicitly addressing these issues should be a reason for concern in the debate leading up to the next revisions of the International Classification of Diseases and the Diagnostic and Statistical Manual of Mental Disorders.     

Neuropathological substrates and structural changes in late-life depression: the impact of vascular burden

A first episode of depression after 65 years of age has long been associated with both severe macrovascular and small microvascular pathology. Among the three more frequent forms of depression in old age, post-stroke depression has been associated with an abrupt damage of cortical circuits involved in monoamine production and mood regulation. Late-onset depression (LOD) in the absence of stroke has been related to lacunes and white matter lesions that invade both the neocortex and subcortical nuclei. Recurrent late-life depression is thought to induce neuronal loss in the hippocampal formation and white matter lesions that affect limbic pathways. Despite an impressive number of magnetic resonance imaging (MRI) studies in this field, the presence of a causal relationship between structural changes in the human brain and LOD is still controversial. The present article provides a critical overview of the contribution of neuropathology in post-stroke, late-onset, and late-life recurrent depression. Recent autopsy findings challenge the role of stroke location in the occurrence of post-stroke depression by pointing to the deleterious effect of subcortical lacunes. Despite the lines of evidences supporting the association between MRI-assessed white matter changes and mood dysregulation, lacunes, periventricular and deep white matter demyelination are all unrelated to the occurrence of LOD. In the same line, neuropathological data show that early-onset depression is not associated with an acceleration of aging-related neurodegenerative changes in the human brain. However, they also provide data in favor of the neurotoxic theory of depression by showing that neuronal loss occurs in the hippocampus of chronically depressed patients. These three paradigms are discussed in the light of the complex relationships between psychosocial determinants and biological vulnerability in affective disorders.     

PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders

OBJECTIVE: To determine whether there are abnormalities in the in vivo status of the serotonin type 2A (5-HT2A) receptor in late-life depression and Alzheimer's disease, the authors used positron emission tomography (PET) to assess patients with these two conditions and healthy subjects. METHOD: PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0). Partial-volume correction of regional specific binding estimates was performed by using a method based on magnetic resonance imaging. RESULTS: No significant abnormalities in [18F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alzheimer's disease group. However, the patients with Alzheimer's disease had significantly lower binding than the normal subjects in several brain regions, including the anterior cingulate, prefrontal cortex, and sensorimotor cortex. CONCLUSIONS: These results suggest that the 5-HT2A receptor is differentially affected in late-life depression and Alzheimer's disease, a finding that has implications for the etiological basis of mood and cognitive features of neuropsychiatric disorders of late life.