Abnormal reward functioning is central to anhedonia and amotivation symptoms of schizophrenia (SCZ). Reward processing encompasses a series of psychological components. This systematic review and meta-analysis examined the brain dysfunction related to reward processing of individuals with SCZ spectrum disorders and risks, covering multiple reward components.

After a systematic literature search, 37 neuroimaging studies were identified and divided into four groups based on their target psychology components (i.e. reward anticipation, reward consumption, reward learning, effort computation). Whole-brain Seed-based d Mapping (SDM) meta-analyses were conducted for all included studies and each component.

The meta-analysis for all reward-related studies revealed reduced functional activation across the SCZ spectrum in the striatum, orbital frontal cortex, cingulate cortex, and cerebellar areas. Meanwhile, distinct abnormal patterns were found for reward anticipation (decreased activation of the cingulate cortex and striatum), reward consumption (decreased activation of cerebellum IV/V areas, insula and inferior frontal gyri), and reward learning processing (decreased activation of the striatum, thalamus, cerebellar Crus I, cingulate cortex, orbitofrontal cortex, and parietal and occipital areas). Lastly, our qualitative review suggested that decreased activation of the ventral striatum and anterior cingulate cortex was also involved in effort computation.

These results provide deep insights on the component-based neuro-psychopathological mechanisms for anhedonia and amotivation symptoms of the SCZ spectrum.

Excessive cortical cerebrospinal fluid (CSF) has been acknowledged as a possible marker of a gray matter loss. This excess in schizophrenia is found predominantly in the prefrontal and temporal regions. We hypothesized that the poorer global outcome and treatment response in males with schizophrenia are related to a greater cortical volume loss as compared to females.

In order to test this hypothesis we have used magnetic resonance imaging (MRI) to study the cortical (prefrontal, temporal, and hemispheric) CSF values in a group of 85 patients with schizophrenia, of whom 56 were males and 29, females. We calculated the residual values of CSF in the patients based on the data pertaining to 45 control subjects and linear regression, from which the normal effects of age and intracranial volume were discounted. These residual scores constitute a quantitative measurement of the excess of CSF due to the disease.

Males, but not females, presented a trend-level significant excess of left prefrontal CSF. The prefrontal and temporal residual values were significantly associated with illness duration in males, but not in females.

These results conform to the worse outcome and the higher severity of structural abnormalities generally found in schizophrenia in male subjects.

Our data support the hypothesis of accelerated prefrontal cortical loss in males, but not in females with schizophrenia.

Cognitive models of obsessive–compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala–prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala–prefrontal connections. However, abnormalities in amygdala–prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly.

Amygdala–prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples.

During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala–ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest.

Our finding of abnormal amygdala–prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala–prefrontal coupling in affective models of OCD.

Children with a history of maltreatment suffer from altered emotion processing but the neural basis of this phenomenon is unknown. This pioneering functional magnetic resonance imaging (fMRI) study investigated the effects of severe childhood maltreatment on emotion processing while controlling for psychiatric conditions, medication and substance abuse.

Twenty medication-naive, substance abuse-free adolescents with a history of childhood abuse, 20 psychiatric control adolescents matched on psychiatric diagnoses but with no maltreatment and 27 healthy controls underwent a fMRI emotion discrimination task comprising fearful, angry, sad happy and neutral dynamic facial expressions.

Maltreated participants responded faster to fearful expressions and demonstrated hyper-activation compared to healthy controls of classical fear-processing regions of ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex, which survived at a more lenient threshold relative to psychiatric controls. Functional connectivity analysis, furthermore, demonstrated reduced connectivity between left vmPFC and insula for fear in maltreated participants compared to both healthy and psychiatric controls.

The findings show that people who have experienced childhood maltreatment have enhanced fear perception, both at the behavioural and neurofunctional levels, associated with enhanced fear-related ventromedial fronto-cingulate activation and altered functional connectivity with associated limbic regions. Furthermore, the connectivity adaptations were specific to the maltreatment rather than to the developing psychiatric conditions, whilst the functional changes were only evident at trend level when compared to psychiatric controls, suggesting a continuum. The neurofunctional hypersensitivity of fear-processing networks may be due to childhood over-exposure to fear in people who have been abused.

Se ha reconocido una cantidad mayor de líquido cefalorraquídeo (LCR) cortical como un posible marcador de una pérdida de sustancia gris. Esta cantidad mayor en la esquizofrenia se encuentra predominantemente en las regiones prefrontal y temporal. Planteamos la hipótesis de que la evolución global y la respuesta al tratamiento peores en los varones con esquizofrenia se relacionan con una pérdida mayor de volumen cortical comparado con las mujeres.

Para comprobar esta hipótesis hemos utilizado imágenes de resonancia magnética (IRM) para estudiar los valores de LCR cortical (prefrontal, temporal y hemisférico) en un grupo de 85 pacientes con esquizofrenia, 56 de los cuales eran varones y 29, mujeres. Calculamos los valores residuales de LCR en los pacientes a partir de los datos relativos a 45 sujetos de control y regresión lineal, de los que se descontaron los efectos normales de la edad y el volumen intracraneal. Estas puntuaciones residuales constituyen una medida cuantitativa de la cantidad mayor de LCR debida a la enfermedad.

Los hombres, pero no las mujeres, presentaron una cantidad mayor significativa en el nivel de tendencia de LCR prefrontal izquierdo. Los valores residuales prefrontales y temporales se asociaban significativamente con la duración de la enfermedad en los varones, pero no en las mujeres.

Estos resultados son compatibles con la peor evolución y la mayor gravedad de las anomalías estructurales encontradas por lo general en la esquizofrenia en los sujetos varones.

Nuestros datos apoyan la hipótesis de una pérdida cortical prefrontal acelerada en los varones, pero no en las mujeres con esquizofrenia.