To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.
However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.
During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent.
In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice.
Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.
This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.
The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.
Several recommendations are provided for the identification of secondary negative symptoms in clinical settings.
The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.
Patients with schizophrenia spectrum disorders (SSD) have worse physical health and reduced life expectancy compared to the general population. In 2009, the European Psychiatric Association, the European Society of Cardiology and the European Association for the Study of Diabetes published a position paper aimed to improve cardiovascular and diabetes care in patients with severe mental illnesses. However, the initiative did not produce the expected results. Experts in SSD or in cardiovascular and metabolic diseases convened to identify main issues relevant to management of cardiometabolic risk factors in schizophrenia patients and to seek consensus through the Delphi method.
The steering committee identified four topics: 1) cardiometabolic risk factors in schizophrenia patients; 2) cardiometabolic risk factors related to antipsychotic treatment; 3) differences in antipsychotic cardiometabolic profiles; 4) management of cardiometabolic risk. Twelve key statements were included in a Delphi questionnaire delivered to a panel of expert European psychiatrists.
Consensus was reached for all statements with positive agreement higher than 85% in the first round. European psychiatrists agreed on: 1) high cardiometabolic risk in patients with SSD, 2) importance of correct risk management of cardiometabolic diseases, from lifestyle modification to treatment of risk factors, including the choice of antipsychotic drugs with a favourable cardiometabolic profile. The expert panel identified the psychiatrist as the central coordinating figure of management, possibly assisted by other specialists and general practitioners.
This study demonstrates high level of agreement among European psychiatrists regarding the importance of cardiovascular risk assessment and management in subjects with SSD.
To provide evidence to the link between serotonin (5-HT), energy metabolism, and the human obese phenotype, the present study investigated the binding and function of the platelet 5-HT transporter (SERT), in relation to circulating insulin, leptin, and glycolipid metabolic parameters.
Seventy-four drug-free subjects were recruited on the basis of divergent body mass index (BMIs) (16.5-54.8 Kg/m2). All subjects were tested for their blood glycolipid profile together with platelet [3H]-paroxetine ([3H]-Par) binding and [3H]-5-HT reuptake measurements from April 1st to June 30th, 2019.
The [3H]-Par Bmax (fmol/mg proteins) was progressively reduced with increasing BMIs (P < .001), without changes in affinity. Moreover, Bmax was negatively correlated with BMI, waist/hip circumferences (W/HC), triglycerides (TD), glucose, insulin, and leptin, while positively with high-density lipoprotein (HDL) cholesterol (P < .01). The reduction of 5-HT uptake rate (Vmax, pmol/min/109 platelets) among BMI groups was not statistically significant, but Vmax negatively correlated with leptin and uptake affinity values (P < .05). Besides, [3H]-Par affinity values positively correlated with glycemia and TD, while [3H]-5-HT reuptake affinity with glycemia only (P < .05). Finally, these correlations were specific of obese subjects, while, from multiple linear-regression analysis conducted on all subjects, insulin (P = .006) resulting negatively related to Bmax independently from BMI.
Present findings suggest the presence of a possible alteration of insulin/5-HT/leptin axis in obesity, differentially impinging the density, function, and/or affinity of the platelet SERT, as a result of complex appetite/reward-related interactions between the brain, gut, pancreatic islets, and adipose tissue. Furthermore, they support the foremost cooperation of peptides and 5-HT in maintaining energy homeostasis.
Sexual response in obsessive–compulsive disorder (OCD) research and practice is overlooked. According to the Dual Control Model, satisfactory sexual response is based upon a balance of sexual excitation and inhibition. The assessment of sexual response in OCD may have clinical implications, such as the integration of sex therapy in psychotherapeutic intervention. The present study was aimed at comparing sexual excitation and inhibition levels between OCD patients and matched control subjects, and investigating whether obsessive beliefs might predict sexual excitation/inhibition.
Seventy-two OCD patients (mean age ± standard deviation [SD]: 34.50 ± 10.39 years) and 72 matched control subjects (mean age ± SD: 34.25 ± 10.18) were included (62.50% men and 37.50% women in both groups). The Obsessive Compulsive Inventory-Revised (OCI-R), the Obsessive Beliefs Questionnaire-46 (OBQ-46), and the Sexual Inhibition/Sexual Excitation Scales (SIS/SES) were administered.
Patients with OCD showed significantly higher levels of sexual excitation, inhibition due to threat of performance failure, and inhibition due to threat of performance consequences than the controls. In addition, the patients with more severe symptoms showed lower excitation than those with less severe symptoms, and those with higher perfectionism had stronger inhibition due to threat of performance failure than those with lower perfectionism.
This is the first study exploring sexual response in OCD according to the Dual Control Model. Sexual response is an impaired quality of life outcome in OCD that should be assessed in routine clinical practice. These findings support the importance of addressing specific obsessive beliefs to improve sexuality in OCD patients.
While both depression and aging have been associated with oxidative stress and impaired immune response, little is known about redox patterns in elderly depressed subjects. This study investigates the relationship between redox/inflammatory patterns and depression in a sample of elderly adults.
The plasma levels of the advanced products of protein oxidation (AOPP), catalase (CAT), ferric reducing antioxidant power (FRAP), glutathione transferase (GST), interleukin 6 (IL-6), superoxide dismutase (SOD), total thiols (TT), and uric acid (UA) were evaluated in 30 patients with mood disorders with a current depressive episode (depressed patients, DP) as well as in 30 healthy controls (HC) aged 65 years and over. Subjects were assessed with the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Geriatric Depression Rating Scale (GDS), the Scale for Suicide Ideation (SSI), the Reason for Living Inventory (RFL), the Activities of Daily Living (ADL), and the Instrumental Activity of Daily Living (IADL).
DP showed higher levels than HC of AOPP and IL-6, while displaying lower levels of FRAP, TT, and CAT. In the DP group, specific correlations were found among biochemical parameters. SOD, FRAP, UA, and TT levels were also significantly related to psychometric scale scores.
Specific alterations of redox systems are detectable among elderly DP.
Patients with schizophrenia display experiential anomalies in their feelings and cognitions arising in the domain of their lived body. These abnormal bodily phenomena (ABP) are not part of diagnostic criteria for schizophrenia. One of the reasons is the difficulty to assess specific ABP for schizophrenia spectrum disorders. The present study aimed to explore the presence in patients with schizophrenia of specific ABP.
We used a semistructured interview—the Abnormal Bodily Phenomena questionnaire (ABPq), an instrument devised to detect and measure ABP specific to patients with schizophrenia. Fifty-one outpatients affected by schizophrenia and 28 euthymic outpatients affected by bipolar disorder type I with psychotic features (BD-pf-e) were recruited. Before assessing the specificity for schizophrenia of the observed ABP, we tested the internal consistency and the convergent validity of the ABPq in patients with schizophrenia. Specificity was assessed by examining potential differences in ABPq among the patients with schizophrenia in remission (SCZ-r) and BD-pf-e.
The ABPq shows strong internal consistency and convergent validity. As to the specificity, ABP measured by ABPq were more frequent and severe in SCZ-r than in BD-pf-e. In particular, all ABPq dimensions, except “Coherence,” had at least mild severity in over 50% of SCZ-r, while dimensions with at least mild severity were observed in 5–10% of the BD-pf-e.
These findings can contribute to establish more precise phenomenal boundaries between schizophrenia and bipolar disorder, to explore the borders between nonpsychotic and psychotic forms of ABP, between ABP and negative and disorganized symptoms, and to enlighten core aspects of schizophrenia.
Obsessive-compulsive disorder (OCD) and tic disorder (TD) represent highly disabling, chronic and often comorbid psychiatric conditions. While recent studies showed a high risk of suicide for patients with OCD, little is known about those patients with comorbid TD (OCTD). Aim of this study was to characterize suicidal behaviors among patients with OCD and OCTD.
Three hundred and thirteen outpatients with OCD (n = 157) and OCTD (n = 156) were recruited from nine different psychiatric Italian departments and assessed using an ad-hoc developed questionnaire investigating, among other domains, suicide attempt (SA) and ideation (SI). The sample was divided into four subgroups: OCD with SA (OCD-SA), OCD without SA (OCD-noSA), OCTD with SA (OCTD-SA), and OCTD without SA (OCTD-noSA).
No differences between groups were found in terms of SI, while SA rates were significantly higher in patients with OCTD compared to patients with OCD. OCTD-SA group showed a significant male prevalence and higher unemployment rates compared to OCD-SA and OCD-noSA sample. Both OCTD-groups showed an earlier age of psychiatric comorbidity onset (other than TD) compared to the OCD-SA sample. Moreover, patients with OCTD-SA showed higher rates of other psychiatric comorbidities and positive psychiatric family history compared to the OCD-SA group and to the OCD-noSA groups. OCTD-SA and OCD-SA samples showed higher rates of antipsychotics therapies and treatment resistance compared to OCD-noSA groups.
Patients with OCTD vs with OCD showed a significantly higher rate of SA with no differences in SI. In particular, OCTD-SA group showed different unfavorable epidemiological and clinical features which need to be confirmed in future prospective studies.
Structural and functional abnormalities of the left hemisphere, often involving the temporal lobe were frequently observed in schizophrenia. However, negative and discrepant findings were also reported. Our study aimed to investigate the presence of lateralized impairment of event-related potentials, recorded during a tonal dichotic listening task, in a group of clinically stabilized patients with schizophrenia.
The ERP component N100, related to sensory processing of stimuli and generated in the temporal lobe cortex, was investigated. A passive dichotic listening task was used in order to exclude the effect of attention impairment on the observed ERP abnormalities.
Patients with schizophrenia showed a pattern of hemispheric lateralization comparable with that observed in healthy controls. In both groups, dichotic listening inhibited the augmenting pattern of N100 amplitude with increasing tone intensity. However, patients failed to demonstrate the augmenting pattern of the N100 also with monaural tones, over the left temporal leads. This abnormality did not correlate with the severity of psychopathology. A role of antipsychotic treatment was excluded as the N100 showed a normal pattern of amplitude increase over right temporal leads.
Our results suggest a state of functional inhibition of the left auditory cortex, akin to that induced by dichotic listening, in subjects with schizophrenia, indipendent of psychopathology or drug therapy.
Symptomatic remission is increasingly perceived as a realistic objective of pharmacological treatment in patients with schizophrenia (2). However the relationships between symptomatic remission, as defined by standardized criteria, and functional outcome remain controversial. In the present study, we designed a one-year follow-up of clinically stable patients with schizophrenia and examined the relationships of clinical remission with several indices of psychosocial functioning.
Thirty-six patients with schizophrenia were included. All the evaluations were carried out both at baseline (T0) and after a one-year follow-up (T12). The categorization in psychosocial remission/non-remission was done by means of the Psychosocial Remission in Schizophrenia (PSRS) scale.
Both at T0 and at T12, R showed, with respect to NR, a better social functioning and a better quality of life. Correlation analysis revealed that the better the psychosocial functioning, the lower the scores on all psychopathological dimensions, except “anxiety/depression” and “hostility” at T0 as well as “anxiety/depression” at T12. At T0, 65% of R resulted also in psychosocial remission; at T12, this percentage reached 90%.
Our findings suggest that symptomatic remission in schizophrenia is associated to functional outcome in the majority of cases, especially when both symptomatic and chronological criteria are met.
Abnormalities of emotional processing have been reported in both anxiety and depressive disorders. Anxiety might be related to a hyperactive preattentive fear response or to a reduced efficiency of late regulatory processes, whereas depression might be related to a reduced response to positive emotions. In the present study event-related potentials (ERPs) were used to investigate involuntary processing of stimuli with different emotional valence in 33 healthy controls [HC] and 55 clinically stable patients (16 with panic disorder [PD], 15 with obsessive-compulsive disorder [OCD], 13 with unipolar depression [UD] and 11 with bipolar depression [BD]).
The ERPs were recorded during a target detection task, in which erotic, threatening, disgusting and neutral stimuli were used as distracters.
Patients showed abnormalities of the sequence, duration and topography of the ERP components related to emotional processing. Patients with anxiety disorders showed abnormalities of the early components in response to threatening stimuli. Patients with BD showed abnormalities of both early and late ERPs components. OCD and UD patients demonstrated similar abnormalities of the late ERP components in response to erotic stimuli.
According to our results, abnormalities of emotional processing are observed in both anxiety and affective disorders and might have both distinct and shared characteristics in these disorders.
Cognitive impairment in patients with eating disorders was reported by the majority of studies addressing this issue. However, heterogeneous patterns of cognitive dysfunctions were observed and, in a minority of studies, no impairment was found. The present study was aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics influence neurocognitive performance in BN.
Attention, executive control, conditional and incidental learning were evaluated in 83 untreated female patients with BN and 77 healthy controls. Cortisol and 17β-estradiol plasma levels were assessed. Cloninger's Temperament and Character Inventory-Revised (TCI-R), the Eating Disorder Inventory-2 and the Montgomery-Asberg Depression Rating Scale were administered.
No impairment of cognitive performance was found in subjects with BN vs. healthy controls. The higher the cortisol level and “Self-directedness” scores the better the performance on conditional learning, while 17β-estradiol levels showed an opposite pattern of association; “Reward dependence” scores were associated to a worse performance on incidental learning; depressive symptomatology negatively influenced the performance on the WCST.
No cognitive impairment was found in untreated patients with BN in the explored cognitive domains. An influence of neuroendocrine, personality and clinical variables on neurocognitive functioning was found, which might explain discrepancies in literature findings.
An impairment of several cognitive domains has been largely documented in patients with schizophrenia. The present study aimed to investigate the relationships between cognitive functioning, symptomatic remission and functional outcome in schizophrenia.
The performance on the neuropsychological battery “Brief Assessment of Cognition in Schizophrenia (BACS)” has been investigated in clinically remitted (R) and non-remitted (NR) schizophrenic patients. The associations of neuropsychological performance with psychopathological dimensions derived from PANSS and indices of social functioning (as assessed by the Global Assessment of Functioning scale, the Personal and Social Performance scale, the Quality of Life Scale, the UCSD Performance-Based Skills Assessment-Brief Version and the Psychosocial Remission in Schizophrenia scale) were also explored by means of multiple regression (MR) analyses.
Compared with NR, R patients showed a better performance on tests exploring executive functions, processing speed and verbal fluency. Residual negative symptoms and processing speed were independent predictors of functional outcome, while remission status did not enter the MR function.
Our findings suggest that cognitive abilities, in particular processing speed and executive functions, are preserved in patients who are able to reach clinical remission. Independently from the remission state or residual negative symptomatology, processing speed also predicts functional outcome in schizophrenia. Our findings support the view that cognitive dysfunctions in schizophrenia should be targeted by specific treatment intervention, such as neurocognitive rehabilitation.
The most severe forms of conduct disorder (CD) are highly stable and disabling disorders, more likely to persist in time and to evolve into disruptive or antisocial behaviors. One crucial issue in the prognosis of these forms of CD is the high resistence to both non-pharmacological and pharmacological treatments, with antipsychotic drugs being frequently used in refractory cases. Aim of this study was: (1) to explore efficacy and tolerability of olanzapine treatment in adolescents with severe CD; (2) to identify predictors of olanzapine treatment outcome. This was a retrospective study, based on clinical records of the first 23 adolescents diagnosed as having a CD, diagnosed with a clinical interview (K-SADS), either pure or with comorbid diagnoses, and treated with olanzapine. All these patients did not respond satisfactorily to non-pharmacological intervention and to adequate dosages of mood stabilizers (lithium and/or valproate). The sample consisted of 16 males and seven females, 16 inpatients and seven outpatients (mean age 13.6 ± 1.9 years, range 11–17.2 years), followed-up for a period ranging from 6 to 12 months (mean 8.8 ± 2.7 months). Outcome measures included the Modified Overt Aggression Scale (MOAS), Clinical Global Impression-Improvement (CGI-I) and Children Global Assessment Scale (CGAS). During the follow-up, all patients were involved in non-pharmacological treatments (psychotherapy, family therapy, or day-hospital group treatments). Based on both an improvement of at least 50% at MOAS and a score 1 or 2 at CGI-I, 14 out of 23 patients (60.9%) were classified as responders at the end of the follow-up. Significant improvement at the last observation was found in MOAS (P < 0.001) and CGAS (P < 0.001) scores. Olanzapine dosage was 8 ± 3.2 mg/day (range 5–20 mg/day). Mean weight gain at the end of the follow-up was 4.6 ± 3 kg. The predictors of a positive treatment response was an impulsive-affective versus controlled-predatory type of aggression. Age at onset of CD and comorbid disorders did not affect treatment response. These preliminary findings suggest that olanzapine may improve behavior in adolescents with severe and treatment-refractory CD and impulsive aggression.
The term “deficit syndrome” (DS) refers to a diagnostic subtype of schizophrenia characterized by the presence of primary and enduring negative symptoms. Several authors have supported the hypothesis that DS represents the more severe end of the schizophrenia spectrum; however, the empirical evidence did not clarify this interpretation. The present study is aimed to evaluate neuromorphological abnormalities in Deficit (DS) and Nondeficit Schizophrenia (NDS). We investigated a group of 18 patients with a DSM-IV diagnosis of schizophrenia, categorized as DS (N=10) and NDS (N=8), and 8 matched healthy controls. All subjects underwent a high resolution imaging protocol (MPRAGE) and an extensive psychopathological evaluation. Images were segmented by means of the algorithm implemented within the SPM2 software; quantitative measures of gray matter were manually obtained for hippocampal and dorso-lateral prefrontal (DLPF) regions. Gray matter in DLPF cortex was significantly reduced in the NDS group, with respect to both DS and healthy subjects. ANCOVA analyses revealed that the volumetric abnormalities found in DS vs. NDS patients were not related to dose or type of antipsychotic treatment. Our structural neuroimaging findings in subjects with schizophrenia, revealed significant differences between the DS and NDS subtypes, which were not influenced by antipsychotic medication, and suggested that DS does not simply represent the more severe end of the schizophrenia spectrum.
Cognitive impairment is increasingly regarded as a core aspect of schizophrenia. It is associated with poor functional outcome, may represent a rate limiting factor in rehabilitation programs and is not largely influenced by pharmacological interventions.
Several studies suggest the efficacy of cognitive training programs and advice their inclusion in treatment strategies, while others discourage clinical application.
We recently completed a study involving three Mental Health Departments located in the South of Italy and coordinated by the Department of Psychiatry of the University of Naples SUN. Fifty-eight patients with either a diagnosis of schizophrenia or schizoaffective disorder were recruited and randomly allocated to one of two rehabilitation programs: Social Skill Training (SST) + Computerized Cognitive Training (CCT) (Group A) and usual rehabilitation activities of the Department (Group B). The active treatment phase lasted 6 months. Psychopathological aspects, as well as psychosocial and neurocognitive functioning, were assessed both before and after treatment. Group A subjects participated in two one-hour sessions of CCT and one two-hour session of SST. Group B patients spent an equivalent amount of time in the usual rehabilitation activities.
The two groups did not differ on baseline clinical, neurocognitive and psychosocial variables.
At the end of treatment, a worsening of the negative dimension was observed in group B, but not in group A, in which a significant improvement of two psychosocial indices (participation in family life and availability to work) was found.
The experimental program (SST+CCT) was more effective than usual rehabilitation activities of the departments.
A large body of literature supports the hypothesis that high frequency oscillations within the gamma band are involved in the integration of sensory information across different modalities and cortical areas. A reduction of gamma oscillations around 40 Hz has been reported in schizophrenic patients by several authors. This abnormality indicates a poor integration of the neuronal activity within distributed neural networks in schizophrenia, in line with modern conceptualizations of the disorder and its liability.
In the present study we investigated evoked and induced 40-Hz gamma power as well as fronto-parietal and fronto-temporal event-related coherence in patients with deficit and nondeficit schizophrenia and in matched healthy controls. In patients, correlations between gamma oscillations and psychopathological dimensions were also investigated.
We found that abnormalities of both induced gamma power and event-related coherence were present in patients with nondeficit schizophrenia, but not in those with deficit schizophrenia. These findings suggest that schizophrenia heterogeneity should be taken into account when dealing with indices of cortical functional connectivity.
In line with previous findings, in our study an excess of gamma oscillations has been found to correlate with reality distortion and other psychopathological dimensions, indicating that abnormal thoughts, behaviours and perceptions might be related to abnormal connectivity within distributed neural networks.
It has been hypothesized that cognitive remediation with adjunctive psychiatric rehabilitation would be associated with greater improvements in functional outcome than standalone treatment approaches (1).
Moving from these observations our group designed an individualized rehabilitation program including a computerized cognitive training (CCT) and social skills training (SST), which showed promising results (2).
A critical evaluation of recent studies examining standalone and combined treatment approaches included the understanding of the differential impact of the two approaches among crucial areas for future research (3).
The present study compared the effects of CCT and SST on several indices of outcome in psychotic patients. Fifty-eight patients with schizophrenia or schizoaffective disorder were randomly assigned to one of two treatment groups: CCT or SST. Changes in cognitive, psychopathological and psychosocial indices after 6 and 12 months were compared between the two groups.
After both 6 and 12 months, an improvement of psychosocial indices was observed in both groups, while cognitive functions improved only after CCT; the improvement of psychopathological indices, observed in both groups, was greater in the CCT group.
Our findings suggest that CCT is associated with a greater impact than SST on different indices of outcome in psychotic patients. Future research should focus on possible synergistic effects of cognitive remediation and social skills training on functional outcome.