Schizophrenia (SCH) and bipolar affective disorder (BP) are complex disorders that overlapping both in their clinical symptoms and certain familiar characteristics. They share some common characteristcs but there are also key differences. The frequency of overlapping symptoms between these diseases could give us more information about the current validity of the diagnosis based on existing diagnostic criteria. Similarities within and between these two disorders in the future, can possibly redefine greater reliability of diagnosis.

The aim of the study was to investigate the frequency of overlapping symptoms between BP and SCH.

The sample included 159 patients diagnosed with SCH and 61 with BP who were followed over a two year period. The research was conducted at the UCCS Psychiatric Clinic. Assessment of clinical symptoms and diagnosis were performed using a structured clinical interview (SCID I), a list of operationalized criteria (OPSCRIT), a scale for the assessment of positive and negative symptoms (PANSS), a scale for the assessment of manic symptoms (YMRS).

The overall PANSS score was significantly higher in patients with SCH compared to patients with BP, but on the general psychopatology there are no significant differences betwen SCH and BP. Symptoms of mania are significantly more pronounced in patients with BP compared to those with SCH.

Our results of overlapping of individual symptoms between SCH and BP can speak infavor of the theory of disease continuum. And can also help us in understanding symptoms and guide us to develop optimal treatment strategies.

No significant relationships.

Suicide is one of the most frequent causes of death in schizophrenia patients, but the low insight in this pathology makes it difficult to identify persons at risk. The clinical picture of schizophrenia includes a wide variety of signs and symptoms, which make it hard to properly assess suicidal ideation.

Our study was aimed at comparing tendencies among the clinical presentation and sociodemographic factors of schizophrenic patients with and without suicide attempts in their medical history.

We analysed the clinical data of 60 patients admitted to the Psychiatry Clinic of Timisoara with the diagnosis of Schizophrenia during 2020-2021. The PANNS-R scale was used for every patient, and each item was compared to the clinical data gathered.

A positive history of suicide attempts was corelated to blunted affect, stereotyped thinking, lack of spontanety and flow of conversation, somatic concern, tension, unsual tought content, lack of judgment and insight. Total negative symptoms were correlated with psychiatric family history.

Considering a history of suicide attempts is a risk factor for suicide, more studies are needed to evaluate patients with such a history in order to identify the constelation of risk factors with a high predictibility value for suicide. This could help implement prophylactic measures in clinical practice that would decrease suicidal behaviour in schizophrenia.

No significant relationships.

The six-item Positive And Negative Syndrome Scale (PANSS-6) is short psychometric valid scale quantifying the severity of core schizophrenia symptoms. Using PANSS-6 to guide treatment decision-making requires that staff members’ ratings are valid and reliable.

The objective of the study was to evaluate whether such valid and reliable PANSS-6 ratings can be obtained through a video-based training program.

One-hundred-and-four staff members from Aarhus University Hospital - Psychiatry, Denmark participated in the training. Participants conducted baseline PANSS-6 ratings based on a video of a patient being interviewed using the Simplified Positive And Negative Symptoms interview (SNAPSI). Subsequently, a theoretical introduction video was displayed followed by five SNAPSI patient interviews. After each SNAPSI video, individual ratings were performed before a video providing the gold standard scores was displayed. The validity of ratings was estimated by calculating the proportion of participants not deviating from the gold standard scores with >2 points on individual items or >6 points on the PANSS-6 total score. Reliability was evaluated after each step in the training by means of Gwet’s Agreement Coefficient (Gwet).

By the end of the training, 72% of the participants rated within the acceptable deviations of the gold standard, ranging from 60% (nurses) to 91% (medical doctors/psychologists). The reliability improved (Gwet baseline vs. endpoint) for all PANSS-6 items, except for Blunted affect.

The majority of the staff members conducted valid PANSS-6 ratings after a brief standardized training program, supporting the implementation of PANSS-6 in clinical settings to facilitate measurement-based care.

Dr. Opler is a full-time employee of MedAvante-ProPhase Inc. Dr. Correll has been a consultant and/or advisor to or have received honoraria from: Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular T

Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC–thalamus network.

We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA).

We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers.

We found altered effective and structural connectivity within the ACC–thalamus network in SZ. Our results indicate that ACC–thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.

Auditory hallucinations are resistant to pharmacotherapy in about 25% of adults with schizophrenia. Treatment with noninvasive brain stimulation would provide a welcomed additional tool for the clinical management of auditory hallucinations. A recent study found a significant reduction in auditory hallucinations in people with schizophrenia after five days of twice-daily transcranial direct current stimulation (tDCS) that simultaneously targeted left dorsolateral prefrontal cortex and left temporo-parietal cortex.

We hypothesized that once-daily tDCS with stimulation electrodes over left frontal and temporo-parietal areas reduces auditory hallucinations in patients with schizophrenia.

We performed a randomized, double-blind, sham-controlled study that evaluated five days of daily tDCS of the same cortical targets in 26 outpatients with schizophrenia and schizoaffective disorder with auditory hallucinations.

We found a significant reduction in auditory hallucinations measured by the Auditory Hallucination Rating Scale (F2,50 = 12.22, P < 0.0001) that was not specific to the treatment group (F2,48 = 0.43, P = 0.65). No significant change of overall schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale was observed.

The lack of efficacy of tDCS for treatment of auditory hallucinations and the pronounced response in the sham-treated group in this study contrasts with the previous finding and demonstrates the need for further optimization and evaluation of noninvasive brain stimulation strategies. In particular, higher cumulative doses and higher treatment frequencies of tDCS together with strategies to reduce placebo responses should be investigated. Additionally, consideration of more targeted stimulation to engage specific deficits in temporal organization of brain activity in patients with auditory hallucinations may be warranted.

Schizophrenia research based on traditional assessment measures for negative symptoms appears to be, to some extent, unreliable. The limitations of the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) have been extensively acknowledged and should be taken into account. The aim of this study is to show how the PANSS and the SANS conflate negative symptoms and cognition and to offer alternatives for the limitations found.

A sample of 117 participants with schizophrenia from two independent studies was retrospectively investigated. Linear regression models were computed to explore the effect of negative symptoms and illness duration as predictors of cognitive performance.

For the PANSS, the item “abstract thinking” accounted for the association between negative symptoms and cognition. For the SANS, the “attention” subscale predicted the performance in verbal memory, but illness duration emerged as a stronger predictor than negative symptoms for outcomes of processing speed, verbal and working memory.

Utilizing alternative models to the traditional PANSS and SANS formats, and accounting for illness duration, provide more precise evidence on the relationship between negative symptoms and cognition. Since these measures are still extensively utilized, we recommend adopting more rigorous approaches to avoid misleading results.

Negative symptoms in schizophrenia are heterogeneous and multidimensional; effective treatments are lacking. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, was significantly more effective than risperidone in treating negative symptoms in a prospectively designed trial in patients with schizophrenia and persistent, predominant negative symptoms.

Using post hoc analyses, we evaluated change from baseline at week 26 in individual items of the Positive and Negative Syndrome Scale (PANSS) and PANSS-derived factor models using a mixed-effects model for repeated measures (MMRM) in the intent-to-treat (ITT) population (cariprazine = 227; risperidone = 227).

Change from baseline was significantly different in favor of cariprazine versus risperidone on PANSS items N1-N5 (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking) (P <.05), but not on N6 (lack of spontaneity/flow of conversation) or N7 (stereotyped thinking). On all PANSS-derived negative symptom factor models evaluated (PANSS-Factor Score for Negative Symptoms, Liemburg factors, Khan factors, Pentagonal Structure Model Negative Symptom factor), statistically significant improvement was demonstrated for cariprazine versus risperidone (P <.01). Small and similar changes in positive/depressive/EPS symptoms suggested that negative symptom improvement was not pseudospecific. Change from baseline was significantly different for cariprazine versus risperidone on PANSS-based factors evaluating other relevant symptom domains (disorganized thoughts, prosocial function, cognition; P <.05).

Since items representing different negative symptom dimensions may represent different fundamental pathophysiological mechanisms, significant improvement versus risperidone on most PANSS Negative Subscale items and across all PANSS-derived factors suggests broad-spectrum efficacy for cariprazine in treating negative symptoms of schizophrenia.

Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.

This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).

Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.

Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Review efficacy, safety, and tolerability of brexpiprazole in patients with schizophrenia in short- and long-term phase 3 studies.

Patients experiencing a current exacerbation of schizophrenia received brexpiprazole in two fixed-dose (2 and 4 mg), 6-week, placebo-controlled studies, one flexible-dose (2–4 mg), 6-week, placebo-control and active reference study, and one fixed-dose (1–4 mg), 52-week, placebo-controlled maintenance study.

The efficacy of brexpiprazole was demonstrated in the two short-term fixed-dose studies with statistically significant improvements from baseline in Positive and Negative Syndrome Scale (PANSS) total score compared with placebo. In the flexible-dose short-term study, treatment with brexpiprazole resulted in numerically greater improvements in PANSS total score than with placebo that approached statistical significance (p=0.056). A meta-analysis of these short-term studies showed a mean change in PANSS total score of −20.1, reflecting a clinically meaningful reduction in symptoms. In the maintenance study, brexpiprazole had a beneficial effect relative to placebo on time to exacerbation of psychotic symptoms/impending relapse (p<0.0001). For all studies, brexpiprazole demonstrated clinically meaningful treatment effects on the Personal and Social Performance scale. Brexpiprazole had a favourable safety profile, with a relatively low prevalence of activating and sedating side effects. Weight gain in the short-term studies was ~1 kg greater than placebo. No safety concerns were observed with brexpiprazole in laboratory values, electrocardiogram, or vital signs.

Overall, the results indicate brexpiprazole, used either short-term or as part of a long-term maintenance treatment programme, is an efficacious therapy option in adults with schizophrenia and has a favourable safety/tolerability profile.

We investigated cerebral structural connectivity and its relationship to symptoms in never-medicated individuals with first-onset schizophrenia using diffusion tensor imaging (DTI).

We recruited subjects with first episode DSM-IV schizophrenia who had never been exposed to antipsychotic medication (n=34) and age-matched healthy volunteers (n=32). All subjects received DTI and structural magnetic resonance imaging scans. Patients' symptoms were assessed on the Positive and Negative Syndrome Scale. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values significantly correlated with symptom scores.

In patients with first-episode schizophrenia, positive symptoms correlated positively with FA scores in white matter associated with the right frontal lobe, left anterior cingulate gyrus, left superior temporal gyrus, right middle temporal gyrus, right middle cingulate gyrus, and left cuneus. Importantly, FA in each of these regions was lower in patients than controls, but patients with more positive symptoms had FA values closer to controls. We found no significant correlations between FA and negative symptoms.

The newly-diagnosed, neuroleptic-naive patients had lower FA scores in the brain compared with controls. There was positive correlation between FA scores and positive symptoms scores in frontotemporal tracts, including left fronto-occipital fasciculus and left inferior longitudinal fasciculus. This implies that white matter dysintegrity is already present in the pre-treatment phase and that FA is likely to decrease after clinical treatment or symptom remission.