Characteristics of older patients in the largest French psychiatric emergency centre.

Despite an increasing number of adults older than 60 years with psychiatric disorders, there are few studies on older patients in psychiatric emergencies and no European data. We aimed to describe the population of patients aged 60 years and older who presented to the main French psychiatric emergency centre and identify predictors of psychiatric hospitalization. This monocentric study included 300 consecutive patients aged 60 years and older. Patients presenting because of psychiatric emergencies were frequently female and lived autonomously. More than 40% had a history of at least one psychiatric hospitalization and 44% had consulted a psychiatrist in the previous 6 months. The most common reasons for consultation were depression, anxiety, sleep disorders and suicidal thoughts. Psychiatric disorders were mainly mood disorders; neurotic, stress-related and somatoform disorders; and schizophrenic, schizotypal and delusional disorders. Only 10% had a diagnosis of organic mental disorders. Overall, 39% of the patients were admitted to the psychiatric hospital. Factors predicting hospitalization were a history of psychiatric hospitalization, suicidal thoughts and a diagnosis of a mood disorder or schizophrenia/schizotypal/delusional disorder. In conclusion, among people aged 60 years and older who consulted for psychiatric emergencies, 39% had to be hospitalized in psychiatry and only psychiatric factors influenced the decision to hospitalize. Our study highlights the need for further studies of older people in psychiatric emergencies in Europe, to anticipate the needs of this specific population and adapt multidisciplinary mental health care.

From psychiatric hospitals to residential facilities: Characteristics of patients who benefited from an institutional partnership.

OBJECTIVES: The population of older adults is growing fast, especially in Europe and Northern America. Old age is often associated with mental health comorbidities. Moreover, life expectancy of people suffering from psychiatric disorders has increased, but with age-related difficulties, such as loss of independence. This represents a challenge for public health policies, as this population requires specific care and living conditions. As a response, a convention was signed between living facilities for dependent elderly (EHPAD) and the GHU Paris Psychiatry and Neurosciences. The agreement included dedicated places in EHPAD for older patients with psychiatric disorders. The aim of the study was to describe the sociodemographic and clinical characteristics of those patients. METHODS: We conducted a cross-sectional study among patients who applied for an EHPAD admission. RESULTS: Between 2016 and 2019, 163 patients applied for placement in an EHPAD, and 117 were admitted (72%). Applicants were 71 years old on average. Admitted patients were older than non-admitted and lived in different Parisian sectors. Among admitted patients, nine in 10 were single, divorced or widowed, and 64.3% were childless. Almost half of them were schizophrenic or had delusional disorders (46.9%), and 65.3% were considered as moderately dependent. At the time of the study, 89 patients still lived in EHPAD. Almost half of them had anxiety and depressive disorders (48.3%), 19.1% had cognitive disorders, and 42.7% manifested agitation. CONCLUSIONS: Our study highlighted older psychiatric patients' specificities regarding their admission status into long-term living facilities.

Gender identity better than sex explains individual differences in episodic and semantic components of autobiographical memory: An fMRI study.

Advances in the literature of sex-related differences in autobiographical memory increasingly tend to highlight the importance of psychosocial factors such as gender identity, which may explain these differences better than sex as a biological factor. To date, however, none of these behavioral studies have investigated this hypothesis using neuroimaging. The purpose of this fMRI study is to examine for the first time sex and gender identity-related differences in episodic and semantic autobiographical memory in healthy participants (M=19, W=18). No sex-related differences were found; however, sex-related effects of masculine and feminine gender identity were identified in men and women independently. These results confirm the hypothesis that differences in episodic and semantic autobiographical memory are best explained by gender but are an interaction between biological sex and gender identity and extend these findings to the field of neuroimaging. We discuss the importance of hormonal factors to be taken into consideration in the future.

Very-late-onset psychotic symptoms: psychosis or dementia? A phenomenological approach. A systematic review.

Very-late-onset psychotic symptoms (PS) are a common gateway to both neurodegenerative dementias and primary psychiatric disorders. Despite similarities in clinical expression, no consensual guidelines or a specific nosographic framework exist. The purpose of this systematic review is to establish a phenomenological classification of PS among the main neurodegenerative dementias and late psychosis. More specifically, to: 1) allow psychotic phenotypes to be considered according to aetiology; 2) help clinicians screen for psychiatric-type dementia, when appropriate; and 3) justify research into very-late-onset PS in patients with dementias at a pre-clinical cognitive stage in order to establish a nosographic framework for these PS based on the prognosis of dementia. METHODS: A literature review was conducted to search for very-late-onset PS (>60 years old) in reports of late-onset (known as primary) psychoses, Alzheimer-type dementia and Lewy body dementia, focusing on the phenomenological data. RESULTS: Very-late-onset schizophrenia-like psychosis appears to be a primary psychiatric diagnosis that is clinically distinct from PS, which emerges among established dementias, but remains a heterogeneous entity due to its age-based syndromic aspect. It is possible to differentiate between the more common phenotypes based on the aetiology of the dementia. CONCLUSION: The results confirm the value of the phenomenological approach in terms of distinguishing between different aetiologies of PS among confirmed cases of dementias. Prospective longitudinal studies are required to examine the early discriminatory characteristics of PS in order to improve prognosis based on the nosographic framework thus established.

[Very late onset psychotic symptoms: psychosis or dementia? A phenomenological approach. A systematic review]. / Symptômes psychotiques d'apparition très tardive chez le sujet âgé : psychose primaire ou démence ? L'apport de l'approche phénoménologique. Une revue de la littérature.

Very-late-onset psychotic symptoms (PS) are a common gateway to both neurodegenerative dementias and primary psychiatric disorders. Despite such similarities of clinical expression, there is no consensual guidelines or specific nosographic frame. The purpose of this systematic review was to establish a phenomenological classification of PS among the main neurodegenerative dementias and late-psychosis. It would allowed 1) the aknowledgement of etiology-specific psychotic phenotypes; 2) where appropriate, it would help the clinician to screen the psychiatric symptoms looking dementias; 3) it would justify the phenomenological research of very-late-onset PS among dementias at a pre-clinical cognitive stage to establish a nosographic frame of these PS based on the prognosis of dementia. METHODS: A literature review was conducted searching for very-late-onset PS (>60 years old) in late-onset psychosis and among Alzheimer dementia type and Lewy bodies dementia, focusing on the phenomenological data. RESULTS: The very-late-onset schizophrenia-like psychosis appears to be a primary psychiatric diagnosis clinically distinct from the PS emerging among established dementias, but remains a heterogeneous entity due to its age-based syndromic aspect. It has been possible to distinguish preferential phenotypes depending on the etiology of the dementia. CONCLUSION: The results confirm the interest of the phenomenological approach to distinguish the etiology of the PS among confirmed dementias. Prospective longitudinal studies must examine the early discriminant characteristics of PS in order to enable a better prognostic prediction of the nosographic frame thereby established.

Gender identity better than sex explains individual differences in episodic and semantic components of autobiographical memory and future thinking.

A recently tested hypothesis suggests that inter-individual differences in episodic autobiographical memory (EAM) are better explained by individual identification of typical features of a gender identity than by sex. This study aimed to test this hypothesis by investigating sex and gender related differences not only in EAM but also during retrieval of more abstract self-knowledge (i.e., semantic autobiographical memory, SAM, and conceptual self, CS), and considering past and future perspectives. No sex-related differences were identified, but regardless of the sex, feminine gender identity was associated with clear differences in emotional aspects that were expressed in both episodic and more abstract forms of AM, and in the past and future perspectives, while masculine gender identity was associated with limited effects. In conclusion, our results support the hypothesis that inter-individual differences in AM are better explained by gender identity than by sex, extending this assumption to both episodic and semantic forms of AM and future thinking.

Amygdala and regional volumes in treatment-resistant versus nontreatment-resistant depression patients.

BACKGROUND: Although treatment-resistant and nontreatment-resistant depressed patients show structural brain anomalies relative to healthy controls, the difference in regional volumetry between these two groups remains undocumented. METHODS: A whole-brain voxel-based morphometry (VBM) analysis of regional volumes was performed in 125 participants' magnetic resonance images obtained on a 1.5 Tesla scanner; 41 had treatment-resistant depression (TRD), 40 nontreatment-resistant depression (non-TRD), and 44 were healthy controls. The groups were comparable for age and gender. Bipolar/unipolar features as well as pharmacological treatment classes were taken into account as covariates. RESULTS: TRD patients had higher gray matter (GM) volume in the left and right amygdala than non-TRD patients. No difference was found between the TRD bipolar and the TRD unipolar patients, or between the non-TRD bipolar and non-TRD unipolar patients. An exploratory analysis showed that lithium-treated patients in both groups had higher GM volume in the superior and middle frontal gyri in both hemispheres. CONCLUSIONS: Higher GM volume in amygdala detected in TRD patients might be seen in perspective with vulnerability to chronicity, revealed by medication resistance.

Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances.

Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging.

Sex Differences in the Neural Correlates of Specific and General Autobiographical Memory.

Autobiographical memory (AM) underlies the formation and temporal continuity over time of personal identity. The few studies on sex-related differences in AM suggest that men and women adopt different cognitive or emotional strategies when retrieving AMs. However, none of the previous works has taken into account the distinction between episodic autobiographical memory (EAM), consisting in the retrieval of specific events by means of mental time travel, and semantic autobiographical memory (SAM), which stores general personal events. Thus, it remains unclear whether differences in these strategies depend on the nature of the memory content to be retrieved. In the present study we employed functional MRI to examine brain activity underlying potential sex differences in EAM and SAM retrieval focusing on the differences in strategies related to the emotional aspects of memories while controlling for basic cognitive strategies. On the behavioral level, there was no significant sex difference in memory performances or subjective feature ratings of either type of AM. Activations common to men and women during AM retrieval were observed in a typical bilateral network comprising medial and lateral temporal regions, precuneus, occipital cortex as well as prefrontal cortex. Contrast analyses revealed that there was no difference between men and women in the EAM condition. In the SAM condition, women showed an increased activity, compared to men, in the dorsal anterior cingulate cortex, inferior parietal and precentral gyrus. Overall, these findings suggest that differential neural activations reflect sex-specific strategies related to emotional aspects of AMs, particularly regarding SAM. We propose that this pattern of activation during SAM retrieval reflects the cognitive cost linked to emotion regulation strategies recruited by women compared to men. These sex-related differences have interesting implications for understanding psychiatric disorders with differential sex prevalence and in which one of key features is overgenerality in AM.

Depression predictors within six months of ischemic stroke: The DEPRESS Study.

BACKGROUND: Depression negatively affects rehabilitation and quality of life after stroke. Identifying in the acute phase patients at high risk for post-stroke depression would facilitate early detection of depressive symptoms. METHODS: The DEPRESS (Depression Predictors after Ischemic Stroke) study was a prospective cohort study designed to identify baseline predictors of depression occurring within six months after ischemic stroke and high-risk patients for post-stroke depression. All patients without aphasia were screened for depression by a neurologist using the Patient Health Questionnaire, and the diagnosis was confirmed by a psychiatrist with the Mini International Neuropsychiatric Interview. In severely aphasic patients, depression was diagnosed using the Aphasic Depression Rating Scale and the Visual Analog Mood Scale. RESULTS: Depression was present in 61 of 251 (24%) patients enrolled in the DEPRESS study. Female gender, prior history of depression, major physical disability, prior history of stroke, stressful life event exposure in the month preceding stroke onset, and pathologic crying were significant predictors of depression within six months after ischemic stroke. Depression was more frequent in patients with left caudate and/or lenticular nucleus lesion (OR = 2.4, 95% confidence interval, 0.97-5.91), but the difference was not significant. The presence of ≥2 predictors identified the largest proportion of depressed patients (62%) in the smallest proportion of the cohort (36%). CONCLUSION: Female gender, prior history of depression, major physical disability, prior history of stroke, recent stressful life event exposure before stroke, and pathologic crying were significant predictors of post-stroke depression occurring within six months after stroke onset.

"The Castle of Remembrance": New insights from a cognitive training programme for autobiographical memory in Alzheimer's disease.

Autobiographical memory deficits are prominent from the early stages of Alzheimer's disease (AD) and result in a loss of personal identity. Nevertheless, standardised methods of autobiographical memory stimulation for the neuropsychological rehabilitation of patients with AD remain underdeveloped. Our aim was to evaluate the impact of a new cognitive training programme for autobiographical memory (REMau) on both the episodic and semantic components of autobiographical memory performance across lifetime periods, as well as on mood. Pre/post evaluations were conducted on two groups of patients with early to moderate AD, assigned to one of two different training activities: either the REMau or a cognitive training programme focused on collective semantic memory. Statistical comparisons showed significant improvement of episodic and semantic autobiographical memory performance in the REMau group, which was more pronounced for the semantic component, as well as improved mood. By contrast, deleterious pre/post differences were observed in the other group. Most interestingly, this study showed that the REMau programme boosted autobiographical memory from the reminiscence bump period, which is considered crucial for the construction and maintenance of personal identity. We discuss the theoretical and practical implications of these results for the reduction of autobiographical memory deficits in AD.

Episodic memory and self-reference via semantic autobiographical memory: insights from an fMRI study in younger and older adults.

Self-referential processing relies mainly on the medial prefrontal cortex (MPFC) and enhances memory encoding (i.e., Self-Reference Effect, SRE) as it improves the accuracy and richness of remembering in both young and older adults. However, studies on age-related changes in the neural correlates of the SRE on the subjective (i.e., autonoetic consciousness) and the objective (i.e., source memory) qualitative features of episodic memory are lacking. In the present fMRI study, we compared the effects of a self-related (semantic autobiographical memory task) and a non self-related (general semantic memory task) encoding condition on subsequent episodic memory retrieval. We investigated encoding-related activity during each condition in two groups of 19 younger and 16 older adults. Behaviorally, the SRE improved subjective memory performance in both groups but objective memory only in young adults. At the neural level, a direct comparison between self-related and non self-related conditions revealed that SRE mainly activated the cortical midline system, especially the MPFC, in both groups. Additionally, in older adults and regardless of the condition, greater activity was found in a fronto-parietal network. Overall, correlations were noted between source memory performance and activity in the MPFC (irrespective of age) and visual areas (mediated by age). Thus, the present findings expand evidence of the role of the MPFC in self-referential processing in the context of source memory benefit in both young and older adults using incidental encoding via semantic autobiographical memory. However, our finding suggests that its role is less effective in aging.

Age-related changes in the functional network underlying specific and general autobiographical memory retrieval: a pivotal role for the anterior cingulate cortex.

Age-related changes in autobiographical memory (AM) recall are characterized by a decline in episodic details, while semantic aspects are spared. This deleterious effect is supposed to be mediated by an inefficient recruitment of executive processes during AM retrieval. To date, contrasting evidence has been reported on the neural underpinning of this decline, and none of the previous studies has directly compared the episodic and semantic aspects of AM in elderly. We asked 20 young and 17 older participants to recall specific and general autobiographical events (i.e., episodic and semantic AM) elicited by personalized cues while recording their brain activity by means of fMRI. At the behavioral level, we confirmed that the richness of episodic AM retrieval is specifically impoverished in aging and that this decline is related to the reduction of executive functions. At the neural level, in both age groups, we showed the recruitment of a large network during episodic AM retrieval encompassing prefrontal, cortical midline and posterior regions, and medial temporal structures, including the hippocampus. This network was very similar, but less extended, during semantic AM retrieval. Nevertheless, a greater activity was evidenced in the dorsal anterior cingulate cortex (dACC) during episodic, compared to semantic AM retrieval in young participants, and a reversed pattern in the elderly. Moreover, activity in dACC during episodic AM retrieval was correlated with inhibition and richness of memories in both groups. Our findings shed light on the direct link between episodic AM retrieval, executive control, and their decline in aging, proposing a possible neuronal signature. They also suggest that increased activity in dACC during semantic AM retrieval in the elderly could be seen as a compensatory mechanism underpinning successful AM performance observed in aging. These results are discussed in the framework of recently proposed models of neural reorganization in aging.

Don't be Too Strict with Yourself! Rigid Negative Self-Representation in Healthy Subjects Mimics the Neurocognitive Profile of Depression for Autobiographical Memory.

Autobiographical memory (AM) comprises representation of both specific (episodic) and generic (semantic) personal information. Depression is characterized by a shift from episodic to semantic AM retrieval. According to theoretical models, this process ("overgeneralization"), would be linked to reduced executive resources. Moreover, "overgeneral" memories, accompanied by a negativity bias in depression, lead to a pervasive negative self-representation. As executive functions and AM specificity are also closely intricate among "non-clinical" populations, "overgeneral" memories could result in depressive emotional responses. Consequently, our hypothesis was that the neurocognitive profile of healthy subjects showing a rigid negative self-image would mimic that of patients. Executive functions and self-image were measured and brain activity was recorded, by means of fMRI, during episodic AMs retrieval in young healthy subjects. The results show an inverse correlation, that is, a more rigid and negative self-image produces lower performances in both executive and specific memories. Moreover, higher negative self-image is associated with decreased activity in the left ventro-lateral prefrontal and in the anterior cingulate cortex, repeatedly shown to exhibit altered functioning in depression. Activity in these regions, on the contrary, positively correlates with executive and memory performances, in line with their role in executive functions and AM retrieval. These findings suggest that rigid negative self-image could represent a marker or a vulnerability trait of depression by being linked to reduced executive function efficiency and episodic AM decline. These results are encouraging for psychotherapeutic approaches aimed at cognitive flexibility in depression and other psychiatric disorders.

Apathy and depression in mild Alzheimer's disease: a cross-sectional study using diagnostic criteria.

Apathy and depression are the most frequent neuropsychiatric symptoms in Alzheimer's disease (AD). In a cross-sectional observational study of 734 subjects with probable mild AD, we evaluated the prevalence of apathy and depression. After the use of specific diagnostic criteria, we tested the interaction between the two syndromes and their relation with specific comorbidities, and different functional outcomes. Depression was diagnosed using the diagnostic criteria for depression in AD, and apathy with the diagnostic criteria for apathy in neuropsychiatric disorders. According to the specific diagnostic criteria, depression had a 47.9% prevalence, while apathy prevalence was 41.6%. Apathy and depression were associated in 32.4% of patients (n = 225). 9.4% (n = 65) had only apathy, 15.4% (n = 107) had only depression, and 42.9% had no apathy and no depression (n = 298). The three most frequent depressive symptoms were fatigue or loss of energy (59.4%), decreased positive affect or pleasure in response to social contacts and activities (46.2%), and psychomotor agitation or retardation (36.9%). Concerning apathy, loss of goal-directed cognition was the most frequently altered (63.6%), followed by loss of goal-directed action (60.6%) and loss of goal-directed emotion (43.8%). Patients with both apathy and depression more frequently required a resource allowance for dependency. Neurological comorbidities were more frequent in the "apathy and depression" and "depression alone" groups (p < 0.001). Apathy and depression overlap considerably, and this might be explained by the presence of some non-specific symptoms in both diagnostic criteria. The need for social support is higher when a patient fulfills the two diagnostic criteria.

Baseline brain metabolism in resistant depression and response to transcranial magnetic stimulation.

Neuroimaging studies of patients with treatment-resistant depression (TRD) have reported abnormalities in the frontal and temporal regions. We sought to determine whether metabolism in these regions might be related to response to repetitive transcranial magnetic stimulation (TMS) in patients with TRD. Magnetic resonance images and baseline resting-state cerebral glucose uptake index (gluMI) obtained using (18)F-fluorodeoxyglucose positron emission tomography were analyzed in TRD patients who had participated in a double-blind, randomized, sham-controlled trial of prefrontal 10 Hz TMS. Among the patients randomized to active TMS, 17 responders, defined as having 50% depression score decrease, and 14 nonresponders were investigated for prestimulation glucose metabolism and compared with 39 healthy subjects using a voxel-based analysis. In nonresponders relative to responders, gluMI was lower in left lateral orbitofrontal cortex (OFC), and higher in left amygdala and uncinate fasciculus. OFC and amygdala gluMI negatively correlated in nonresponders, positively correlated in responders, and did not correlate in healthy subjects. Relative to healthy subjects, both responders and nonresponders displayed lower gluMI in right dorsolateral prefrontal (DLPFC), right anterior cingulate (ACC), and left ventrolateral prefrontal cortices. Additionally, nonresponders had lower gluMI in left DLPFC, ACC, left and right insula, and higher gluMI in left amygdala and uncus. Hypometabolisms were partly explained by gray matter reductions, whereas hypermetabolisms were unrelated to structural changes. The findings suggest that different patterns of frontal-temporal-limbic abnormalities may distinguish responders and nonresponders to prefrontal magnetic stimulation. Both preserved OFC volume and amygdala metabolism might precondition response to TMS.

"Where do auditory hallucinations come from?"--a brain morphometry study of schizophrenia patients with inner or outer space hallucinations.

Auditory verbal hallucinations are a cardinal symptom of schizophrenia. Bleuler and Kraepelin distinguished 2 main classes of hallucinations: hallucinations heard outside the head (outer space, or external, hallucinations) and hallucinations heard inside the head (inner space, or internal, hallucinations). This distinction has been confirmed by recent phenomenological studies that identified 3 independent dimensions in auditory hallucinations: language complexity, self-other misattribution, and spatial location. Brain imaging studies in schizophrenia patients with auditory hallucinations have already investigated language complexity and self-other misattribution, but the neural substrate of hallucination spatial location remains unknown. Magnetic resonance images of 45 right-handed patients with schizophrenia and persistent auditory hallucinations and 20 healthy right-handed subjects were acquired. Two homogeneous subgroups of patients were defined based on the hallucination spatial location: patients with only outer space hallucinations (N=12) and patients with only inner space hallucinations (N=15). Between-group differences were then assessed using 2 complementary brain morphometry approaches: voxel-based morphometry and sulcus-based morphometry. Convergent anatomical differences were detected between the patient subgroups in the right temporoparietal junction (rTPJ). In comparison to healthy subjects, opposite deviations in white matter volumes and sulcus displacements were found in patients with inner space hallucination and patients with outer space hallucination. The current results indicate that spatial location of auditory hallucinations is associated with the rTPJ anatomy, a key region of the "where" auditory pathway. The detected tilt in the sulcal junction suggests deviations during early brain maturation, when the superior temporal sulcus and its anterior terminal branch appear and merge.

Influence of prefrontal target region on the efficacy of repetitive transcranial magnetic stimulation in patients with medication-resistant depression: a [(18)F]-fluorodeoxyglucose PET and MRI study.

It is currently unknown whether the antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) depends on specific characteristics of the stimulated frontal area, such as metabolic changes. We investigated the effect of high-frequency rTMS, administered over the most hypometabolic prefrontal area in depressed patients in a two-site, double-blind, randomized placebo-controlled add-on study. Forty-eight patients with medication-resistant major depression underwent magnetic resonance imaging and [(18)F]-fluorodeoxyglucose positron emission tomography (PET) in order to determine a target area for rTMS. After randomization to PET-guided (n = 16), standard (n = 18), or sham rTMS (n = 14) conditions, the patients received 10 sessions of 10-Hz rTMS (1600 pulses/session) at 90% motor threshold. Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores did not differ between PET-guided, standard and sham groups at 2-wk end-point. Exploratory comparison of left PET-guided (n = 9), right PET-guided, standard, and sham rTMS revealed significant effects. The highest improvement in MADRS scores was observed with left PET-guided (60 + or - 31%), significantly superior to sham (30 + or - 37%, p = 0.01) and right-guided (31 + or - 33%, p = 0.02) stimulation. Comparison between left PET-guided and standard rTMS (49 + or - 28%) was not significant (p = 0.12). Comparison between stimulation over dorsolateral prefrontal cortex (BA 9-46), stimulation of other areas, and sham rTMS was statistically significant. Stimulation over BA 9-46 region (n = 15) was superior to sham rTMS (p = 0.02). The results do not support the general hypothesis of increased antidepressant effects of high-frequency rTMS with prefrontal hypometabolism-related PET guidance. Nonetheless, whether metabolism and anatomy characteristics of left frontal area underneath the coil might account for an increase or speeding up of rTMS effects needs further investigation.

Cortical folding difference between patients with early-onset and patients with intermediate-onset bipolar disorder.

OBJECTIVES: Cerebral abnormalities have been detected in patients with bipolar disorder (BD). In comparison to BD with a later onset, early-onset BD has been found to have a poorer outcome. However, it is yet unknown whether neuroanatomical abnormalities differ between age-at-onset subgroups of the illness. We searched for cortical folding differences between early-onset (before 25 years) and intermediate-onset (between 25 and 45 years) BD patients. METHODS: Magnetic resonance images of 22 early-onset BD patients, 14 intermediate-onset BD patients, and 50 healthy participants were analyzed using a fully automated method to extract, label, and measure the sulcal area in the whole cortex. Cortical folding was assessed by computing global sulcal indices (the ratio between total sulcal area and total outer cortex area) for each hemisphere, and local sulcal indices for 12 predefined regions in both hemispheres. RESULTS: Intermediate-onset BD patients had a significantly reduced local sulcal index in the right dorsolateral prefrontal cortex in comparison to both early-onset BD patients and healthy subjects, and lower global sulcal indices in both hemispheres in comparison to healthy subjects (p < 0.05, Bonferroni corrected). Brain tissue volumes did not differ between groups. CONCLUSIONS: This study provided the first evidence of a neuroanatomic difference between intermediate-onset and early-onset BD, which lends further support to the existence of different age-at-onset subgroups of BD.