ABSTRACT
The onset of schizophrenia is determined by biological and social risk factors operating predominantly during development. These result in subtle deviations in brain structure and cognitive function. Striatal dopamine dysregulation follows, causing abnormal salience and resultant psychotic symptoms. Most people diagnosed as having schizophrenia do not progressively deteriorate; many improve or recover. However, poor care can allow a cycle of deterioration to be established, stress increasing dopamine dysregulation, leading to more stress consequent on continuing psychotic experiences, and so further dopamine release. Additionally, long-term antipsychotics can induce dopamine supersensitivity with resultant relapse and eventually treatment resistance. Some patients suffer loss of social and cognitive function, but this is a consequence of the hazards that afflict the person with schizophrenia, not a direct consequence of genetic predisposition. Thus, brain health and cognition can be further impaired by chronic medication effects, cardiovascular and cerebrovascular events, obesity, poor diet, and lack of exercise; drug use, especially of tobacco and cannabis, are likely to contribute. Poverty, homelessness and poor nutrition which become the lot of some people with schizophrenia, can also affect cognition. Regrettably, the model of progressive deterioration provides psychiatry and its funders with an alibi for the effects of poor care.
Subject(s)
Antipsychotic Agents , Psychotic Disorders , Schizophrenia , Antipsychotic Agents/adverse effects , Child , Developmental Disabilities/complications , Dopamine/physiology , Humans , Psychotic Disorders/complicationsABSTRACT
Aberrant emotion processing is a well-established component of psychotic disorders and is already present at the first episode of psychosis (FEP). However, the role of emotion processing abnormalities in the emergence of psychosis and the underlying neurobiology remain unclear. Here, we systematically reviewed functional magnetic resonance studies that used emotion processing task paradigms in FEP patients, and in people at clinical high-risk for psychosis (CHRp). Image-based meta-analyses with Seed-based d Mapping on available studies (n = 6) were also performed. Compared to controls, FEP patients showed decreased neural responses to emotion, particularly in the amygdala and anterior cingulate cortex. There were no significant differences between CHRp subjects and controls, but a high degree of heterogeneity was identified across studies. The role of altered emotion processing in the early phase of psychosis may be clarified through more homogenous experimental designs, particularly in the CHRp population.
Subject(s)
Magnetic Resonance Imaging , Psychotic Disorders , Amygdala , Brain/diagnostic imaging , Emotions , Gyrus Cinguli , Humans , Psychotic Disorders/diagnostic imagingABSTRACT
Data from animal models and from postmortem studies suggest that schizophrenia is associated with brain GABAergic dysfunction. The extent to which this is reflected in data from in vivo studies of GABA function in schizophrenia is unclear. The Medline database was searched to identify articles published until 21 October 2016. The search terms included GABA, proton magnetic resonance spectroscopy (1H-MRS), positron emission tomography (PET), single photon emission computed tomography (SPECT), schizophrenia and psychosis. Sixteen GABA 1H-MRS studies (538 controls, 526 patients) and seven PET/SPECT studies of GABAA/benzodiazepine receptor (GABAA/BZR) availability (118 controls, 113 patients) were identified. Meta-analyses of 1H-MRS GABA in the medial prefrontal cortex (mPFC), parietal/occipital cortex (POC) and striatum did not show significant group differences (mFC: g=-0.3, 409 patients, 495 controls, 95% confidence interval (CI): -0.6 to 0.1; POC: g=-0.3, 139 patients, 111 controls, 95% CI: -0.9 to 0.3; striatum: g=-0.004, 123 patients, 95 controls, 95% CI: -0.7 to 0.7). Heterogeneity across studies was high (I2>50%), and this was not explained by subsequent moderator or meta-regression analyses. There were insufficient PET/SPECT receptor availability studies for meta-analyses, but a systematic review did not suggest replicable group differences in regional GABAA/BZR availability. The current literature does not reveal consistent alterations in in vivo GABA neuroimaging measures in schizophrenia, as might be hypothesized from animal models and postmortem data. The analysis highlights the need for further GABA neuroimaging studies with improved methodology and addressing potential sources of heterogeneity.
Subject(s)
Brain/diagnostic imaging , Receptors, GABA-A/metabolism , Schizophrenia/diagnostic imaging , gamma-Aminobutyric Acid/metabolism , Brain/metabolism , Humans , Neuroimaging , Positron-Emission Tomography , Proton Magnetic Resonance Spectroscopy , Schizophrenia/metabolism , Tomography, Emission-Computed, Single-PhotonABSTRACT
Animal models and human neuroimaging studies suggest that altered levels of glutamatergic metabolites within a corticolimbic circuit have a major role in the pathophysiology of schizophrenia. Rodent models propose that prefrontal glutamate dysfunction could lead to amygdala hyper-response to environmental stress and underlie hippocampal overdrive in schizophrenia. Here we determine whether changes in brain glutamate are present in individuals with high schizotypy (HS), which refers to the presence of schizophrenia-like characteristics in healthy individuals, and whether glutamate levels are related to altered corticolimbic response to emotion. Twenty-one healthy HS subjects and 22 healthy subjects with low schizotypy (LS) were selected based on their Oxford and Liverpool Inventory of Feelings and Experiences rating. Glutamate levels were measured in the anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, followed by a functional magnetic resonance imaging (fMRI) scan to measure corticolimbic response during emotional processing. fMRI results and fMRI × glutamate interactions were considered significant after voxel-wise P<0.05 family-wise error correction. While viewing emotional pictures, HS individuals showed greater activation than did subjects with LS in the caudate, and marginally in the ACC, hippocampus, medial prefrontal cortex (MPFC) and putamen. Although no between-group differences were found in glutamate concentrations, within the HS group ACC glutamate was negatively correlated with striatal activation (left: z=4.30, P=0.004 and right: z=4.12 P=0.008 caudate; left putamen: z=3.89, P=0.018) and marginally with MPFC (z=3.55, P=0.052) and amygdala (left: z=2.88, P=0.062; right: z=2.79, P=0.079), correlations that were not present in LS subjects. These findings provide, to our knowledge, the first evidence that brain glutamate levels are associated with hyper-responsivity in brain regions thought to be critical in the pathophysiology of psychosis.
Subject(s)
Cerebral Cortex/diagnostic imaging , Emotions/physiology , Glutamic Acid/metabolism , Limbic System/diagnostic imaging , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Multimodal Imaging/methods , Schizotypal Personality Disorder/diagnostic imaging , Adolescent , Adult , Animals , Brain/diagnostic imaging , Brain/metabolism , Cerebral Cortex/metabolism , Cerebral Cortex/physiology , Female , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/metabolism , Hippocampus/diagnostic imaging , Hippocampus/metabolism , Humans , Limbic System/metabolism , Limbic System/physiology , Male , Middle Aged , Models, Animal , Neuroimaging/methods , Prefrontal Cortex/metabolism , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/metabolism , Psychotic Disorders/physiopathology , Schizophrenia/diagnostic imaging , Schizophrenia/metabolism , Schizophrenia/physiopathology , Schizotypal Personality Disorder/metabolism , Schizotypal Personality Disorder/physiopathology , Young AdultABSTRACT
Impaired working memory is a core feature of schizophrenia and is linked with altered engagement the lateral prefrontal cortex. Although altered PFC activation has been reported in people with increased risk of psychosis, at present it is not clear if this neurofunctional alteration differs between familial and clinical risk states and/or increases in line with the level of psychosis risk. We addressed this issue by using functional MRI and a working memory paradigm to study familial and clinical high-risk groups. We recruited 17 subjects at ultra-high-risk (UHR) for psychosis, 10 non-affected siblings of patients with schizophrenia (familial high risk [FHR]) and 15 healthy controls. Subjects were scanned while performing the N-back working memory task. There was a relationship between the level of task-related deactivation in the medial PFC and precuneus and the level of psychosis risk, with deactivation weakest in the UHR group, greatest in healthy controls, and at an intermediate level in the FHR group. In the high-risk groups, activation in the precuneus was associated with the level of negative symptoms. These data suggest that increased vulnerability to psychosis is associated with a failure to deactivate in the medial PFC and precuneus during a working memory task, and appears to be most evident in subjects at clinical, as opposed to familial high risk.
Subject(s)
Memory, Short-Term , Prefrontal Cortex/pathology , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology , Adult , Brain Mapping/methods , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Parietal Lobe , Schizophrenic Psychology , Young AdultABSTRACT
BACKGROUND: The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown. METHOD: We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses. RESULTS: The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive-compulsive disorder symptoms. CONCLUSIONS: Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state.
Subject(s)
Brain Mapping/methods , Gray Matter/pathology , Magnetic Resonance Imaging/methods , Mood Disorders/pathology , Psychotic Disorders/pathology , Adult , Comorbidity , Depressive Disorder, Major/pathology , Female , Gyrus Cinguli/pathology , Humans , Image Processing, Computer-Assisted/methods , London/epidemiology , Male , Mood Disorders/epidemiology , Psychotic Disorders/epidemiology , RiskABSTRACT
BACKGROUND: Schizotypy is conceptualized as a subclinical manifestation of the same underlying biological factors that give rise to schizophrenia and other schizophrenia spectrum disorders. Individuals with psychometric schizotypy (PS) experience subthreshold psychotic signs and can be psychometrically identified among the general population. Previous research using magnetic resonance imaging (MRI) has shown gray-matter volume (GMV) abnormalities in chronic schizophrenia, in subjects with an at-risk mental state (ARMS) and in individuals with schizotypal personality disorder (SPD). However, to date, no studies have investigated the neuroanatomical correlates of PS. METHOD: Six hundred first- and second-year university students completed the Community Assessment of Psychic Experiences (CAPE), a self-report instrument on psychosis proneness measuring attenuated positive psychotic experiences. A total of 38 subjects with high and low PS were identified and subsequently scanned with MRI. Voxel-based morphometry (VBM) was applied to examine GMV differences between subjects with high and low positive PS. RESULTS: Subjects with high positive PS showed larger global volumes compared to subjects with low PS, and larger regional volumes in the medial posterior cingulate cortex (PCC) and the precuneus. There were no regions where GMV was greater in low than in high positive PS subjects. CONCLUSIONS: These regions, the PCC and precuneus, have also been sites of volumetric differences in MRI studies of ARMS subjects and schizophrenia, suggesting that psychotic or psychotic-like experiences may have common neuroanatomical correlates across schizophrenia spectrum disorders.
Subject(s)
Brain/pathology , Psychotic Disorders/pathology , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Organ Size , RiskABSTRACT
OBJECTIVE: To determine the usefulness of an interactive multimedia internet-based system (IMIS) for the cognitive stimulation of Alzheimer's disease. METHODS: This is a 24-week, single-blind, randomised pilot study conducted on 46 mildly impaired patients suspected of having Alzheimer's disease receiving stable treatment with cholinesterase inhibitors (ChEIs). The patients were divided into three groups: (1) those who received 3 weekly, 20-min sessions of IMIS in addition to 8 h/day of an integrated psychostimulation program (IPP); (2) those who received only IPP sessions; and (3) those who received only ChEI treatment. The primary outcome measure was the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Secondary outcome measures were: Mini-Mental State Examination (MMSE), Syndrom Kurztest, Boston Naming Test, Verbal Fluency, and the Rivermead Behavioral Memory Test story recall subtest. RESULTS: After 12 weeks, the patients treated with both IMIS and IPP had improved outcome scores on the ADAS-Cog and MMSE, which was maintained through 24 weeks of follow-up. The patients treated with IPP alone had better outcome than those treated with ChEIs alone, but the effects were attenuated after 24 weeks. All patients had improved scores in all of the IMIS individual tasks, attaining higher levels of difficulty in all cases. CONCLUSION: Although both the IPP and IMIS improved cognition in patients with Alzheimer's disease, the IMIS program provided an improvement above and beyond that seen with IPP alone, which lasted for 24 weeks.
Subject(s)
Alzheimer Disease/rehabilitation , Cognition Disorders/therapy , Cognition , Internet , Multimedia , User-Computer Interface , Aged , Aged, 80 and over , Alzheimer Disease/complications , Cognition Disorders/etiology , Female , Humans , Male , Mental Status Schedule , Single-Blind Method , Treatment OutcomeABSTRACT
INTRODUCTION: The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a screening instrument for the evaluation of behavioral disturbances in Alzheimer's patients. Our aim was to validate the BEHAVE-AD test in Spanish, intended for use in routine clinical practice. METHOD: We assessed the validity of the BEHAVEAD in 79 nursing-home patients with diagnosis criteria of dementia, scoring 4 or higher on the Global Deterioration Scale (GDS) scale, by developing a crossed validated form between the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and BEHAVE-AD tests. Both instruments were rated by an expert clinician. In order to study the concurrent validity of some of the BEHAVE-AD subscales, we compared the Cohen-Mansfield Agitation Inventory (CMAI) and the Hamilton Depression Rating Scale (HDRS) tests. RESULTS: The Pearson correlation index between the BEHAVE-AD test and the NPI-Q, was significant but moderate (r=0.694). Pearson's correlation between BEHAVEAD's symptoms scale and NPI-Q's severity scale was r=0.698. When comparing BEHAVE-AD's global evaluation scale (caregiver's disturbance) and NPI-Q's distress scale, the correlation index was 0.535. CONCLUSIONS: The BEHAVE-AD Spanish version offers the possibility to use a screening tool for the detection of neuropsychiatric symptoms in dementia patients, also applicable to nursing home residents, administered by an expert clinician.
Subject(s)
Alzheimer Disease/physiopathology , Behavioral Symptoms , Psychiatric Status Rating Scales , Aged , Aged, 80 and over , Female , Humans , Male , Mass Screening , Middle Aged , Neuropsychological Tests , Reproducibility of Results , SpainABSTRACT
Introducción. La Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) es un instrumento de cribado para la detección de sintomatología conductual en pacientes con demencia de tipo Alzheimer. El objetivo fue la validación española de la BEHAVE-AD para su incorporación en la práctica clínica diaria. Método. Estudio de la validez de la BEHAVE-AD en 79 pacientes con criterios diagnósticos de demencia en régimen de residencia, con puntuación de 4 o superior en la Global Deterioration Scale (GDS), mediante una validación cruzada entre el Neuropsychiatric Inventory-Questionnaire (NPI-Q) y la BEHAVE-AD. Administración de ambas escalas por parte de un clínico entrenado. Administración de las escalas Inventario de Agitación del Anciano de Cohen-Mansfield (IAACM) y Hamilton Depression Rating Scale (HDRS) para estudiar la validez convergente de dos de los dominios de la BEHAVE-AD. Resultados. índice de correlación de Pearson entre la BEHAVE-AD y el NPI-Q moderadamente significativo (r=0,694). Correlación de Pearson entre la escala de sintomatología de la BEHAVE-AD y la escala de gravedad del NPI-Q de 0,698 y entre la escala de evaluación global (perturbación en el cuidador) y la escala de estrés del NPI-Q de 0,535 puntos. Conclusiones. Esta versión en español de la BEHAVE-AD ofrece la posibilidad de aplicar un test de cribado de la sintomatología neuropsiquiátrica en pacientes con demencia, siendo también aplicable a usuarios de residencia, administrado por un clínico entrenado
Introduction. The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHA VE-AD) is a screening instrument for the evaluation of behavioral disturbances in Alzheimer's patients. Our aim was to validate the BEHA VE-AD test in Spanish, intended for use in routine clinical practice. Method. We assessed the validity of the BEHA VEAD in 79 nursing-home patients with diagnosis criteria of dementia, scoring 4 or higher on the Global Deterioration Scale (GDS) scale, by developing a crossed validated form between the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and BEHA VE-AD tests. Both instruments were rated by an expert clinician. In order to study the concurrent validity of some of the BEHA VE-AD subscales, we compared the Cohen-Mansfield Agitation Inventory (CMAI) and the Hamilton Depression Rating Scale (HDRS) tests. Results. The Pearson correlation index between the BEHA VE-AD test and the NPI-Q, was significant but moderate (r = 0.694). Pearson's correlation between BEHA VEAD's symptoms scale and NPI-Q's severity scale was r=0.698. When comparing BEHA VE-AD's global evaluation scale (caregiver's disturbance) and NPI-Q's distress scale, the correlation index was 0.535. Conclusions. The BEHA VE-AD Spanish version offers the possibility to use a screening tool for the detection of neuropsychiatric symptoms in dementia patients, also applicable to nursing home residents, administered by an expert clinician
Subject(s)
Male , Female , Aged , Middle Aged , Humans , Alzheimer Disease/physiopathology , Psychiatric Status Rating Scales , Behavioral Symptoms , Mass Screening , Reproducibility of Results , SpainABSTRACT
INTRODUCTION: The Neuropsychiatric Inventory-Nursing Home version (NPI-NH) is a screening instrument to be used by the nursing staff to evaluate neuropsychiatric symptoms in dementia patients in the nursing home setting. The aim of the present study was to validate the NPI-NH in Spanish. METHODS: We assessed the validity of the NPI-NH in 80 patients who were also nursing home residents, comparing the responses of nursing home staff on the NPI-NH with that filled out by the external observer. We developed a crossed validated form between the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and both NPI-NH. We determined the concurrent validity of the domains "depression" and "agitation/aggression" of the NPI-NH with the Cohen-Mansfield Agitation Inventory (IAACM, Spanish version) and the Hamilton Depression Rating Scale (HDRS). RESULTS: Among the totals of the NPI-NH of the nursing staff and the NPI-Q, the convergent validity was r = 0.536 and r = 0.669 for the occupational disruptiveness scale (distress in NPI-Q). The Pearson correlation index between the NPI-Q and NPI-NH of the observations was r = 0.342. The convergent validity between the NPINH of the nursing home staff and NPI-NH of the observers with the Pearson correlation index was r = 0.274. CONCLUSIONS: The NPI-NH Spanish version offers the possibility to use a screening tool for detecting neuropsychiatric symptoms in dementia patients in the nursing home setting. It should be administered by adequately trained staff to avoid limitations in the evolutive control of behavioral changes.
Subject(s)
Geriatric Assessment , Neuropsychological Tests , Nursing Homes , Aged , Aged, 80 and over , Dementia/physiopathology , Humans , Middle Aged , Reproducibility of Results , Spain , Surveys and QuestionnairesABSTRACT
Introducción. El Neuropsychiatric Inventory-Nursing Home version (NPI-NH) es un instrumento de cribado para evaluar por el personal de enfermería o auxiliar la sintomatología neuropsiquiátrica en pacientes con demencia ingresados en residencia. El objetivo del presente estudio fue validar la versión española del NPI-NH. Métodos. Estudio de la validez del NPI-NH en 80 pacientes con demencia ingresados en residencia mediante la comparación entre la escala contestada por el auxiliar y la cumplimentada por el observador externo. Validación cruzada entre el Neuropsychiatric Inventory-Questionnaire (NPI-Q) y ambos NPI-NH. Estudio de la validez convergente de los dominios «depresión» y «agitación/agresividad» del NPI-NH con las escalas Inventario de Agitación del Anciano Cohen-Mansfield (lAACM) y Hamilton Depression Rating Scale (HDRS). Resultados. Entre los totales del NPI-NH auxiliares y el NPI-Q la validez convergente fue de r = 0,536 Y de r = 0,669 para la escala de interrupción ocupacional (estrés en NPI-Q). Entre el NPI-Q y el NPI-NH de las observaciones el índice de correlación de Pearson fue de r = 0,342. La validez convergente entre el NPI-NH de los auxiliares y NPI-NH de los observadores mediante el índice de correlación de Pearson fue de r = 0,273. Conclusiones. La versión española del NPI-NH ofrece la posibilidad de aplicar un test de cribado de sintomatología neuropsiquiátrica en pacientes con demencia alojados en una residencia geriátrica. Debe ser administrado por personal debidamente entrenado para evitar limitaciones en el control evolutivo de los cambios de conducta
Introduction. The Neuropsychiatric Inventory-Nursing Horne version (NPI-NH) is a screening instrument to be used by the nursing staff to evaluate neuropsychiatric symptoms in dementia patients in the nursing home setting. The aim of the present study was to validate the NPI-NH in Spanish. Methods. We assessed the validity of the NPI-NH in 80 patients who were also nursing home residents, comparing the responses of nursing home staff on the NPI-NH with that filled out by the external observer. We developed a crossed validated form between the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and both NPI-NH. We determined the concurrent validity of the domains «depression» and «agitation/aggression» of the NPI-NH with the Cohen-Mansfield Agitation Inventory (IAACM, Spanish version) and the Hamilton Depression Rating Scale (HDRS). Results. Among the totals of the NPI-NH of the nursing staff and the NPI-Q, the convergent validity was r = 0.536 and r = 0.669 for the occupational disruptiveness scale (distress in NPI-Q). The Pearson correlation index between the NPI-Q and NPI-NH of the observations was r = 0.342. The convergent validity between the NPINH of the nursing home staff and NPI-NH of the observers with the Pearson correlation index was r = 0.274. Conclusions. The NPI-NH Spanish version offers the possibility to use a screening tool for detecting neuropsychiatric symptorns in dementia patients in the nursing home setting. It should be administered by adequately trained staff to avoid limitations in the evolutive control of behavioral changes
