Background and Purpose—Previous studies have postulated that poststroke depression (PSD) might be... more Background and Purpose—Previous studies have postulated that poststroke depression (PSD) might be related to cumulative vascular brain pathology rather than to the location and severity of a single macroinfarct. We performed a detailed analysis of all types of microvascular lesions and lacunes in 41 prospectively documented and consecutively autopsied stroke cases. Methods—Only cases with first-onset depression 2 years after stroke were considered as PSD in the present series. Diagnosis of depression was established prospectively using DSM-IV criteria for major depression. Neuropathological evaluation included bilateral semiquantitative assessment of microvascular ischemic pathology and lacunes; statistical analysis included Fisher exact test, Mann-Whitney U test, and regression models. Results—Macroinfarct site was not related to the occurrence of PSD for any of the locations studied. Thalamic and basal ganglia lacunes occurred significantly more often in PSD cases. Higher lacune s...
Journal of Neuropathology & Experimental Neurology
Von Economo neurons (VENs) and fork cells are principally located in the anterior cingulate corte... more Von Economo neurons (VENs) and fork cells are principally located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI). Both of these regions integrate inputs from the autonomic nervous system (ANS) and are involved in decision-making and perception of the emotional states of self and others. Familial dysautonomia (FD) is an orphan disorder characterized by autonomic dysfunction and behavioral abnormalities including repetitive behavior and emotional rigidity, which are also seen in autism spectrum disorder. To understand a possible link between the ANS and the cortical regions implicated in emotion regulation we studied VENs and fork cells in an autonomic disorder. We determined the densities of VENs, fork cells, and pyramidal neurons and the ratio of VENs and fork cells to pyramidal neurons in ACC and FI in 4 FD patient and 6 matched control brains using a stereologic approach. We identified alterations in densities of VENs and pyramidal neurons and their distr...
Background: Schizophrenia is a chronic psychiatric disorder that generally begins in late adolesc... more Background: Schizophrenia is a chronic psychiatric disorder that generally begins in late adolescence or early adulthood. This early onset is often linked with a devastating lifelong impact on both the social network and work capacities of the affected subjects. Beginning in the mid-1990s, several sets of diagnostic criteria aiming to identify “high-risk” patients were developed and applied in clinical studies. Short-term rates of onset of psychosis in this subgroup of subjects ranged from 20% to 40%. However, 20 years later, the proposal to introduce “psychosis risk syndrome” as a coded diagnostic category in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders remained controversial and was finally rejected. Instead, “attenuated psychosis syndrome” was included in section III of the newly published manual as a condition for further studies. Objective: The goal of this article is to review the extant literature concerning the advantages and risks of early assessment of psychotic symptoms (“prodrome” and “psychosis-risk syndrome”) and concerning available therapeutic options, both psychosocial and pharmacological. Conclusions: “Attenuated psychosis syndrome” is a clinically useful concept. It identifies help-seeking individuals with mental health problems who need an intervention and who, if no treatment strategy is proposed, present a higher likelihood of developing a psychosis spectrum disorder in the years following their first contact with a mental health facility. In parallel with the clinical utility of this concept, additional research focused on this group of patients is warranted to further understand the emerging phase of psychotic disorders and to develop effective and efficient evidence-based prevention strategies.
Schweizer Archiv für Neurologie und Psychiatrie (Zurich, Switzerland: 1985)
0 1 1 ; 1 6 2 (6) : 2 4 6 – 5 5 ww w . s a n p . c h | w w w . a s n p . c h Review article 246 S... more 0 1 1 ; 1 6 2 (6) : 2 4 6 – 5 5 ww w . s a n p . c h | w w w . a s n p . c h Review article 246 Summary Initial investigations of the impact of cerebrovascular pathology on cognition and mood predominantly focused on macrovascular lesions. Progressively, however, the role of a chronic accumulation of small vascular and microvascular lesions on both cognitive status and mood regulation came to light. Recent contributions have pointed to the main role of cortical micro-infarcts and subcortical lacunes in dementia, providing the first pathological substrates of mixed dementia. With respect to mood regulation, the research focus has equally shifted from the localisation of macrovascular infarcts to the impact of a chronic cerebrovascular lesion burden. However, empirical results from the wider field of the "vascular depression hypothesis" remain contradictory and the relative contributions of biological and psychosocial factors are still a matter of debate. We review here the ...
The concepts of post-stroke depression and vascular depression have emphasized the bidirectional ... more The concepts of post-stroke depression and vascular depression have emphasized the bidirectional etiologic links that may connect depression and cardiovascular risk factors. In post-stroke depression, the pathogenic role of a chronic cumulative "burden" of subcortical lesions has been well established. In what concerns late-onset depression and the symptomatic profile attributed to "vascular depressions, and despite a growing body of evidence from both neuroimaging and neuropathologic studies, this bilateral causality is still matter of debate. This field of research has highlighted the need for an interdisciplinary view in these traditionally divided fields.
Background and Purpose— Previous studies have postulated that poststroke depression (PSD) might b... more Background and Purpose— Previous studies have postulated that poststroke depression (PSD) might be related to cumulative vascular brain pathology rather than to the location and severity of a single macroinfarct. We performed a detailed analysis of all types of microvascular lesions and lacunes in 41 prospectively documented and consecutively autopsied stroke cases. Methods— Only cases with first-onset depression <2 years after stroke were considered as PSD in the present series. Diagnosis of depression was established prospectively using DSM-IV criteria for major depression. Neuropathological evaluation included bilateral semiquantitative assessment of microvascular ischemic pathology and lacunes; statistical analysis included Fisher exact test, Mann-Whitney U test, and regression models. Results— Macroinfarct site was not related to the occurrence of PSD for any of the locations studied. Thalamic and basal ganglia lacunes occurred significantly more often in PSD cases. Higher l...
Small vessel pathology and microvascular lesions are no longer considered as minor players in the... more Small vessel pathology and microvascular lesions are no longer considered as minor players in the fields of cognitive impairment and mood regulation. Although frequently found in cognitively intact elders, both neuroimaging and neuropathological data revealed the negative impact on cognitive performances of their presence within neocortical association areas, thalamus and basal ganglia. Unlike cognition, the relationship between these lesions and mood dysregulation is still a matter of intense debate. Early studies focusing on the role of macroinfarct location in the occurrence of post-stroke depression (PSD) led to conflicting data. Later on, the concept of vascular depression proposed a deleterious effect of subcortical lacunes and deep white matter demyelination on mood regulation in elders who experienced the first depressive episode. More recently, the chronic accumulation of lacunes in thalamus, basal ganglia and deep white matter has been considered as a strong correlate of PSD. We provide here a critical overview of neuroimaging and neuropathological sets of evidence regarding the affective repercussions of vascular burden in the aging brain and discuss their conceptual and methodological limitations. Based on these observations, we propose that the accumulation of small vascular and microvascular lesions constitutes a common neuropathological platform for both cognitive decline and depressive episodes in old age.
One third of all stroke survivors develop post-stroke depression (PSD). Depressive symptoms adver... more One third of all stroke survivors develop post-stroke depression (PSD). Depressive symptoms adversely affect rehabilitation and significantly increase risk of death in the post-stroke period. One of the theoretical views on the determinants of PSD focuses on psychosocial factors like disability and social support. Others emphasize biologic mechanisms such as disruption of biogenic amine neurotransmission and release of proinflammatory cytokines. The “lesion location” perspective attempts to establish a relationship between localization of stroke and occurrence of depression, but empirical results remain contradictory. These divergences are partly related to the fact that neuroimaging methods, unlike neuropathology, are not able to assess precisely the full extent of stroke-affected areas and do not specify the different types of vascular lesions. We provide here an overview of the known phenomenological profile and current pathogenic hypotheses of PSD and present neuropathological data challenging the classic “single-stroke”-based neuroanatomical model of PSD. We suggest that vascular burden due to the chronic accumulation of small macrovascular and microvascular lesions may be a crucial determinant of the development and evolution of PSD.
The presence of von Economo neurons (VENs) in the frontoinsular cortex (FI) has been linked to a ... more The presence of von Economo neurons (VENs) in the frontoinsular cortex (FI) has been linked to a possible role in the integration of bodily feelings, emotional regulation, and goal-directed behaviors. They have also been implicated in fast intuitive evaluation of complex social situations. Several studies reported a decreased number of VENs in neuropsychiatric diseases in which the “embodied” dimension of
Background and Purpose—Previous studies have postulated that poststroke depression (PSD) might be... more Background and Purpose—Previous studies have postulated that poststroke depression (PSD) might be related to cumulative vascular brain pathology rather than to the location and severity of a single macroinfarct. We performed a detailed analysis of all types of microvascular lesions and lacunes in 41 prospectively documented and consecutively autopsied stroke cases. Methods—Only cases with first-onset depression 2 years after stroke were considered as PSD in the present series. Diagnosis of depression was established prospectively using DSM-IV criteria for major depression. Neuropathological evaluation included bilateral semiquantitative assessment of microvascular ischemic pathology and lacunes; statistical analysis included Fisher exact test, Mann-Whitney U test, and regression models. Results—Macroinfarct site was not related to the occurrence of PSD for any of the locations studied. Thalamic and basal ganglia lacunes occurred significantly more often in PSD cases. Higher lacune s...
Journal of Neuropathology & Experimental Neurology
Von Economo neurons (VENs) and fork cells are principally located in the anterior cingulate corte... more Von Economo neurons (VENs) and fork cells are principally located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI). Both of these regions integrate inputs from the autonomic nervous system (ANS) and are involved in decision-making and perception of the emotional states of self and others. Familial dysautonomia (FD) is an orphan disorder characterized by autonomic dysfunction and behavioral abnormalities including repetitive behavior and emotional rigidity, which are also seen in autism spectrum disorder. To understand a possible link between the ANS and the cortical regions implicated in emotion regulation we studied VENs and fork cells in an autonomic disorder. We determined the densities of VENs, fork cells, and pyramidal neurons and the ratio of VENs and fork cells to pyramidal neurons in ACC and FI in 4 FD patient and 6 matched control brains using a stereologic approach. We identified alterations in densities of VENs and pyramidal neurons and their distr...
Background: Schizophrenia is a chronic psychiatric disorder that generally begins in late adolesc... more Background: Schizophrenia is a chronic psychiatric disorder that generally begins in late adolescence or early adulthood. This early onset is often linked with a devastating lifelong impact on both the social network and work capacities of the affected subjects. Beginning in the mid-1990s, several sets of diagnostic criteria aiming to identify “high-risk” patients were developed and applied in clinical studies. Short-term rates of onset of psychosis in this subgroup of subjects ranged from 20% to 40%. However, 20 years later, the proposal to introduce “psychosis risk syndrome” as a coded diagnostic category in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders remained controversial and was finally rejected. Instead, “attenuated psychosis syndrome” was included in section III of the newly published manual as a condition for further studies. Objective: The goal of this article is to review the extant literature concerning the advantages and risks of early assessment of psychotic symptoms (“prodrome” and “psychosis-risk syndrome”) and concerning available therapeutic options, both psychosocial and pharmacological. Conclusions: “Attenuated psychosis syndrome” is a clinically useful concept. It identifies help-seeking individuals with mental health problems who need an intervention and who, if no treatment strategy is proposed, present a higher likelihood of developing a psychosis spectrum disorder in the years following their first contact with a mental health facility. In parallel with the clinical utility of this concept, additional research focused on this group of patients is warranted to further understand the emerging phase of psychotic disorders and to develop effective and efficient evidence-based prevention strategies.
Schweizer Archiv für Neurologie und Psychiatrie (Zurich, Switzerland: 1985)
0 1 1 ; 1 6 2 (6) : 2 4 6 – 5 5 ww w . s a n p . c h | w w w . a s n p . c h Review article 246 S... more 0 1 1 ; 1 6 2 (6) : 2 4 6 – 5 5 ww w . s a n p . c h | w w w . a s n p . c h Review article 246 Summary Initial investigations of the impact of cerebrovascular pathology on cognition and mood predominantly focused on macrovascular lesions. Progressively, however, the role of a chronic accumulation of small vascular and microvascular lesions on both cognitive status and mood regulation came to light. Recent contributions have pointed to the main role of cortical micro-infarcts and subcortical lacunes in dementia, providing the first pathological substrates of mixed dementia. With respect to mood regulation, the research focus has equally shifted from the localisation of macrovascular infarcts to the impact of a chronic cerebrovascular lesion burden. However, empirical results from the wider field of the "vascular depression hypothesis" remain contradictory and the relative contributions of biological and psychosocial factors are still a matter of debate. We review here the ...
The concepts of post-stroke depression and vascular depression have emphasized the bidirectional ... more The concepts of post-stroke depression and vascular depression have emphasized the bidirectional etiologic links that may connect depression and cardiovascular risk factors. In post-stroke depression, the pathogenic role of a chronic cumulative "burden" of subcortical lesions has been well established. In what concerns late-onset depression and the symptomatic profile attributed to "vascular depressions, and despite a growing body of evidence from both neuroimaging and neuropathologic studies, this bilateral causality is still matter of debate. This field of research has highlighted the need for an interdisciplinary view in these traditionally divided fields.
Background and Purpose— Previous studies have postulated that poststroke depression (PSD) might b... more Background and Purpose— Previous studies have postulated that poststroke depression (PSD) might be related to cumulative vascular brain pathology rather than to the location and severity of a single macroinfarct. We performed a detailed analysis of all types of microvascular lesions and lacunes in 41 prospectively documented and consecutively autopsied stroke cases. Methods— Only cases with first-onset depression <2 years after stroke were considered as PSD in the present series. Diagnosis of depression was established prospectively using DSM-IV criteria for major depression. Neuropathological evaluation included bilateral semiquantitative assessment of microvascular ischemic pathology and lacunes; statistical analysis included Fisher exact test, Mann-Whitney U test, and regression models. Results— Macroinfarct site was not related to the occurrence of PSD for any of the locations studied. Thalamic and basal ganglia lacunes occurred significantly more often in PSD cases. Higher l...
Small vessel pathology and microvascular lesions are no longer considered as minor players in the... more Small vessel pathology and microvascular lesions are no longer considered as minor players in the fields of cognitive impairment and mood regulation. Although frequently found in cognitively intact elders, both neuroimaging and neuropathological data revealed the negative impact on cognitive performances of their presence within neocortical association areas, thalamus and basal ganglia. Unlike cognition, the relationship between these lesions and mood dysregulation is still a matter of intense debate. Early studies focusing on the role of macroinfarct location in the occurrence of post-stroke depression (PSD) led to conflicting data. Later on, the concept of vascular depression proposed a deleterious effect of subcortical lacunes and deep white matter demyelination on mood regulation in elders who experienced the first depressive episode. More recently, the chronic accumulation of lacunes in thalamus, basal ganglia and deep white matter has been considered as a strong correlate of PSD. We provide here a critical overview of neuroimaging and neuropathological sets of evidence regarding the affective repercussions of vascular burden in the aging brain and discuss their conceptual and methodological limitations. Based on these observations, we propose that the accumulation of small vascular and microvascular lesions constitutes a common neuropathological platform for both cognitive decline and depressive episodes in old age.
One third of all stroke survivors develop post-stroke depression (PSD). Depressive symptoms adver... more One third of all stroke survivors develop post-stroke depression (PSD). Depressive symptoms adversely affect rehabilitation and significantly increase risk of death in the post-stroke period. One of the theoretical views on the determinants of PSD focuses on psychosocial factors like disability and social support. Others emphasize biologic mechanisms such as disruption of biogenic amine neurotransmission and release of proinflammatory cytokines. The “lesion location” perspective attempts to establish a relationship between localization of stroke and occurrence of depression, but empirical results remain contradictory. These divergences are partly related to the fact that neuroimaging methods, unlike neuropathology, are not able to assess precisely the full extent of stroke-affected areas and do not specify the different types of vascular lesions. We provide here an overview of the known phenomenological profile and current pathogenic hypotheses of PSD and present neuropathological data challenging the classic “single-stroke”-based neuroanatomical model of PSD. We suggest that vascular burden due to the chronic accumulation of small macrovascular and microvascular lesions may be a crucial determinant of the development and evolution of PSD.
The presence of von Economo neurons (VENs) in the frontoinsular cortex (FI) has been linked to a ... more The presence of von Economo neurons (VENs) in the frontoinsular cortex (FI) has been linked to a possible role in the integration of bodily feelings, emotional regulation, and goal-directed behaviors. They have also been implicated in fast intuitive evaluation of complex social situations. Several studies reported a decreased number of VENs in neuropsychiatric diseases in which the “embodied” dimension of
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Papers by Carla Micaela Santos Brosch