Psychiatric Controls Research Articles

Dysregulated behaviours in bulimia nervosa—A case‐control study

BackgroundBulimia nervosa (BN) is often related to self‐control difficulties and to dysregulated behaviours. This study aimed to evaluate the frequency of self‐injurious behaviour, suicide attempts, and other dysregulated behaviours in BN, using two control groups (a healthy group and a general psychiatric group), and also to examine the association between these behaviours and alleged sexual abuse in BN.MethodWomen (N = 233) aged between 13 and 38 years old were evaluated using a semi‐structured interview.ResultsParticipants with BN reported more self‐injurious behaviours, suicide attempts by drug intake, and poor control in smoking and illicit drugs use compared with participants in both control groups. Participants with BN also reported more spending behaviours when compared with the general psychiatric control group. The use of illegal drugs and medication was significantly related to alleged sexual abuse in BN participants.ConclusionsThis study concluded that BN is often related to dysregulated behaviours, and clinicians must take into account the multi‐impulsive spectrum behaviours of BN in their evaluation and treatment of BN.

Restless Legs Syndrome: Psychiatric Comorbidities Are More Important Than Neuroticism

Restless legs syndrome (RLS) is often associated with psychopathological symptoms. We compared psychiatric diagnoses, psychological complaints, sleep and personality traits in RLS patients and a control group The RLS patients also answered the IRLS, RLS-6, and QoL-RLS. The RLS patients showed more depressive disorders, psychopathological symptoms, and lower well-being than controls, but no differences in personality traits. The slightly, but not significantly, higher neuroticism found in RLS patients can be explained by the higher rates of depression among the patients. It is advisable to screen RLS patients for psychiatric comorbidities. The design using a matched control group without sleep disorders limits the conclusions that can be drawn regarding the frequency of psychiatric diagnoses and controls with sleep problems.

Father–daughter relationship and the severity of eating disorders

BackgroundMother–daughter relationship was the focus of studies on the development of eating disorders (ED) for many years. This study aimed to examine the association between the father–daughter relationship and ED and depressive symptoms. MethodsFifty-three women diagnosed with ED were compared to a psychiatric control group (n=26) and to healthy participants (n=60) regarding their perception of their fathers and the relationship with them. Assessments were done using the Parental Bonding Instrument, the Eating Disorders Questionnaire, the Body Shape Questionnaire, the Eating Attitude Test, and the Beck Depression Inventory as well as narrative-based methods. ResultsFathers’ negative attributes were significantly associated with ED and depressive symptom. Two profiles of father–daughter relationship were found, the “caring and benevolent” relationship and the “overprotective and avoidant” one. In the latter, patients displayed significantly higher levels of food-restraint, more concerns about eating and about their body shape and appearance, and higher levels of depression. DiscussionNegative perception of the father's parenting style as well as the quality of the relationship with him are crucial for the understanding of the development and persistence of ED. Therapeutic programs for ED should focus not only on the relationship with the mother but must also address the relationship with the father.

Functional MRI of pain application in youth who engaged in repetitive non-suicidal self-injury vs. psychiatric controls

Non-suicidal self-injury (NSSI) is increasingly common in young psychiatric patients. It is unclear why pain, which should be aversive, becomes reinforcing in this context. We hypothesized that pain- and/or reward-processing neurocircuitry would be abnormal in NSSI patients compared with non-NSSI patients. Using functional magnetic resonance imaging, we administered a painfully cold and comparison cool stimulus under two conditions: self-administered and experimenter-administered (as a control). Participants comprised 13 NSSI patients and 15 non-NSSI control patients, who were matched for sex, age, medications, symptoms, and diagnoses. Whole-brain analyses of main effects, as well as correlational analyses with subjective pain and “relief” (suggesting reward), were performed. Significant main effects of group showed greater blood oxygenation level-dependent (BOLD) response for NSSI than controls in right midbrain/pons; culmen; amygdala; and parahippocampal, inferior frontal and superior temporal gyri; as well as orbital frontal cortex (OFC). The correlation between BOLD signal and “relief” was greater in NSSI patients in areas associated with reward/pain and addiction including thalamus, dorsal striatum and anterior precuneus. Post hoc analysis showed reduced functional connectivity between right OFC and anterior cingulate cortex in NSSI youth, implying possible deficits in the neuroregulation of emotional behavior. These findings help inform how pain is associated with reward for NSSI patients but not for non-NSSI patients.

History of childhood maltreatment in Intermittent Explosive Disorder and suicidal behavior

Intermittent Explosive Disorder (IED) is a relatively common disorder of impulsive aggression that typically emerges by adulthood. Maltreatment in childhood (CM) may contribute to the development of IED, but little is known about the association between CM and IED, including about how subtypes of CM may specifically relate to IED. This study aimed to test the association between CM and IED diagnosis. A second aim was to examine history of CM in suicide attempters, and to explore whether impulsivity and aggression account for the relationship between CM and suicide attempt (SA). Adults with Intermittent Explosive Disorder (IED; n = 264), with non-IED psychiatric (Axis I or II) disorders (psychiatric controls; PC; n = 199), and with no psychiatric disorder (healthy control subjects; HC; n = 185) were assessed for history of childhood maltreatment, aggression, impulsivity, and history of SA. IED subjects reported significantly greater CM compared to PC and HC subjects, and suicide attempters (n = 62) reported greater CM compared to non-attempters (n = 586). Physical abuse in childhood was independently associated with IED, while sexual abuse and emotional abuse were independently associated with SA. Impulsivity and aggression were potential mediators of the relationship between physical abuse and IED and emotional abuse and SA, but sexual abuse was associated with SA independently of aggression and impulsivity. The results suggest pathways by which environmental factors may influence impulsivity and aggression and, in turn, clinically significant self- and other-directed aggression.

Putative association between the -1415 T/C polymorphism of spermidine/spermine N1-acetyltransferase (SSAT1) gene and alcohol use disorders in women and men

Background: The activity of N-methyl-D-aspartate (NMDA) glutamate receptor, which responds to the levels of polyamines, modifies the neurotoxicity caused by ethanol. We aimed to investigate if the functionality of the spermidine/spermine N1-acetyltransferase (SSAT1) gene could be associated with a differential risk for alcoholism. Methods: We studied a sample of 586 subjects: 104 alcohol-dependent patients, 273 patients with psychiatric disorders but without substance dependence, and 209 healthy controls. After gender stratification, the allele frequency distribution of the SSAT1 gene was compared between these three groups. Results: In females, the TC genotype was significantly more frequent in alcohol-dependent patients than in non-alcohol-dependent psychiatric controls (χ2 = 7.509 df = 2, p = 0.023). A trend was found when alcohol-dependent females were compared with the healthy control group (χ2 = 4.897 df = 2, p = 0.086). No statistical differences were found among the males. Discussion and conclusion: Gender differences in the regulation of SSAT1 gene expression may possibly be due to gender-specific effects of stress, ethanol toxicity, and/or polyamines levels. Further studies are needed to confirm our findings.

Poster #S221 SUICIDALITY IN SCHIZOPHRENIA SPECTRUM DISORDERS: RELATION TO HALLUCINATIONS AND PERSECUTORY DELUSIONS

We recently found marked deficits in sleep spindles, non-rapid eye movement (NREM) sleep oscillations that are generated within the thalamus and then amplified and sustained in the cortex, in patients with schizophrenia compared to both healthy and psychiatric controls. Here, we investigated the thalamic and cortical contributions to these sleep spindle deficits.Anatomical volume of interest analysis (i.e., thalamic volumes) and electroencephalogram (EEG) source modeling (i.e., spindle-related cortical currents) were performed in patients with schizophrenia and healthy comparison subjects.Schizophrenia patients had reduced mediodorsal (MD) thalamic volumes, especially on the left side, compared to healthy controls, whereas whole thalami and lateral geniculate nuclei did not differ between groups. Furthermore, left MD volumes were strongly correlated with the number of scalp-recorded spindles in an anterior frontal region, and cortical currents underlying these anterior frontal spindles were localized in the prefrontal cortex, in Brodmann area (BA) 10. Finally, prefrontal currents at the peak of spindle activity were significantly reduced in schizophrenia patients and correlated with their performance in an abstraction/working memory task.Altogether, these findings point to deficits in a specific thalamo-cortical circuitry in schizophrenia, which is associated with some cognitive deficits commonly reported in those patients.

Cognitive Distortions and Suicide Attempts.

Although theorists have posited that suicidal individuals are more likely than non-suicidal individuals to experience cognitive distortions, little empirical work has examined whether those who recently attempted suicide are more likely to engage in cognitive distortions than those who have not recently attempted suicide. In the present study, 111 participants who attempted suicide in the 30 days prior to participation and 57 psychiatric control participants completed measures of cognitive distortions, depression, and hopelessness. Findings support the hypothesis that individuals who recently attempted suicide are more likely than psychiatric controls to experience cognitive distortions, even when controlling for depression and hopelessness. Fortune telling was the only cognitive distortion uniquely associated with suicide attempt status. However, fortune telling was no longer significantly associated with suicide attempt status when controlling for hopelessness. Findings underscore the importance of directly targeting cognitive distortions when treating individuals at risk for suicide.

Social Cognition and Levels of Personality Organization in Patients With Somatoform Disorders

Social cognition and its association with level of personality organization (PO) were examined in 163 patients with severe somatoform disorders (SFDs) and 151 psychiatric (PSA) control patients. Social cognition was measured with the Social Cognition and Object Relations Scale, which assessed both affective and cognitive facets of social cognition. Levels of PO were assessed using theory-driven profiles of the Dutch Short Form of the Minnesota Multiphasic Personality Inventory (MMPI). The SFD patients exhibited impairments in the cognitive facets of social cognition but not more so than the PSA controls. The results for the affective aspects indicated that the SFD patients exhibited lower levels of emotional investment yet higher affect tone in interactions than the PSA controls. In contrast to the control group, level of PO was not associated with social cognition in SFD. Together, the results indicated that impairments in complexity of mental representations are not specific to SFD patients, yet impairments in emotional investment may be specific to SFD.

Metacognition, social cognition, and symptoms in patients with first episode and prolonged psychoses

While it has been documented that persons with prolonged schizophrenia have deficits in metacognition and social cognition, it is less clear whether these difficulties are already present during a first episode. To explore this issue we assessed and compared metacognition using the Metacognition Assessment Scale—Abbreviated (MAS-A) and social cognition using the Eyes, Hinting and Bell–Lysaker Emotional Recognition Tests (BLERT) in participants with first episode psychosis (FEP; n=26), participants with a prolonged psychosis (n=72), and a psychiatric control group consisting of persons with a substance use disorder and no history of psychosis (n=14). Analyses revealed that both psychosis cohorts scored lower than controls on the MAS-A total and all subscales except metacognitive mastery. Compared to the FEP group, the persons with prolonged psychosis demonstrated greater metacognitive capacities only in those MAS-A domains reflective of the ability to understand the mental state of others and to see that others may have motivations and desires separate from their own. Other domains of metacognition did not differ between psychosis groups. The Eyes, Hinting and BLERT scores of the two psychosis groups did not differ but were poorer than those produced by the control group. Exploratory correlations in the FEP group showed a pattern similar to that previously observed in prolonged psychosis. Taken together, these findings suggest that while certain domains of metacognition could improve with prolonged psychosis, difficulties with global metacognition and social cognition may be stable features of the disorder and perhaps unique to psychosis.

Elevated Plasma Inflammatory Markers in Individuals With Intermittent Explosive Disorder and Correlation With Aggression in Humans

Neurochemical studies in human aggression point to a modulatory role for a variety of central neurotransmitters. Some of these neurotransmitters play an inhibitory role, while others play a facilitatory role modulating aggression. Preclinical studies suggest a facilitatory role for inflammatory markers in aggression. Despite this, to our knowledge, no studies of aggression and inflammatory markers have been reported in psychiatric patients or in individuals with recurrent, problematic, impulsive aggressive behavior. To test the hypothesis that plasma inflammatory markers will correlate directly with aggression and will be elevated in individuals with recurrent, problematic, impulsive aggressive behavior. DESIGN, SETTING, AND PARTICIPANTS Case-control study in a clinical research program in impulsive aggressive behavior at an academic medical center. Participants were physically healthy individuals with intermittent explosive disorder (n = 69), nonaggressive individuals with Axis I and/or II disorders (n = 61), and nonaggressive individuals without history of an Axis I or II disorder (n = 67). Plasma levels of C-reactive protein and interleukin 6 were examined in the context of measures of aggression and impulsivity and as a function of intermittent explosive disorder. Both plasma C-reactive protein and interleukin 6 levels were significantly higher in participants with intermittent explosive disorder compared with psychiatric or normal controls. In addition, both inflammatory markers were directly correlated with a composite measure of aggression and, more specifically, with measures reflecting history of actual aggressive behavior in all participants. These data suggest a direct relationship between plasma inflammatory processes and aggression in humans. This finding adds to the complex picture of the central neuromodulatory role of aggression in humans.

Comprehension of metaphors in patients with schizophrenia-spectrum disorders

BackgroundMetaphors, mainly proverbs and idiomatic expressions of ordinary life are commonly used as a model for concretism. Previous studies have shown impaired metaphor comprehension in patients with schizophrenia-spectrum disorders compared to either psychiatric or non-psychiatric control subject. The aim of this study was to detect possible quantitative differences in figurative processing between patients with schizophrenia-spectrum disorders and healthy controls. MethodsIn order to analyse possible dissociations of different aspects of figurative speech, a range of metaphor tasks was used to distinguish between recognition of familiar metaphors, paraphrasing the meaning of the latter and generating novel metaphors: we used a standard proverb test for conventional metaphors consisting of a multiple-choice and a paraphrasing task, and the Metaphoric Triads Test for the assessment of novel metaphors. We included 40 patients with schizophrenia-spectrum disorders and 43 healthy control subjects. ResultsOur results showed that patients had impaired figurative speech processing regarding novel and conventional metaphors. Associations with cognitive functions were detected. Performance on the paraphrasing task was associated with the severity of negative symptoms. ConclusionWe conclude that patients with schizophrenia-spectrum disorders do exhibit impairments in the recognition and paraphrasing of conventional and the generation of novel metaphors and that some cognitive domains as well the extent of negative symptoms might be associated with these deficits.

Catechol-O-methyltransferase Val158Met polymorphism and altered COMT gene expression in the prefrontal cortex of suicide brains

Catechol-O-methyltransferase (COMT) plays a key role in the degradation of catecholamine neurotransmitters within the brain. A functional polymorphism COMT Val158Met has been associated with psychiatric disorders including suicidal behavior. In the present study we examined whether this polymorphism was related to COMT mRNA expression in frontal cortical regions, and whether the expression of COMT differed between depressed suicide victims and psychiatric healthy controls. The Val158Met polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. The levels of COMT mRNA expression in the frontopolar cortex (FPC; 29 suicides vs. 27 controls) and orbital frontal cortex (OFC; 19 suicides vs. 15 controls) were significantly increased among depressed individuals that died by suicide relative to those of controls, being up-regulated by approximately 60% and 65% in the FPC and OFC, respectively. Furthermore, among individuals with the Met allele (Met/Met and Met/Val genotypes) who died by suicide COMT mRNA expression was elevated relative to that of the nondepressed Met allele carriers. However, significant differences were not detected between suicides (n=49) and controls (n=72) with respect to the Val158Met genotypic distribution and allelic frequencies. These results are consistent with the perspective that altered COMT mRNA expression in frontal cortical brain regions might contribute to suicide and/or depression, further supporting the role of dysregulation of catecholaminergic pathway genes in the pathophysiology of suicide behaviors.

Aggressiveness Across Development and Suicidal Behavior in Depressed Patients

The objective of this study was to determine differences in the pathway of aggressiveness across development between depressive subjects and normal controls, and to examine males and females separately with regard to level of aggression and suicidal behavior among depressed subjects. Participants were classified into 5 groups: depressed suicide attempters (DSA; n = 339), depressed non-suicide attempters (DNSA; n = 92), psychiatric controls who had attempted suicide (PSA; n = 188), psychiatric controls who had not attempted suicide (PNSA; n = 222), and normal controls (NC; n = 532). The level of aggressiveness across development in the different groups was examined using a 5 (DSA vs. DNSA vs. PSA vs. PNSA vs. NC)×3 (Childhood, Adolescence, and Adulthood) MANCOVA. Adjusted and separate models for males and females were conducted. Depressed subjects differed in severity of aggressiveness. The level of aggressiveness in individuals in the NC group remained stable across development, while subjects in the DSA and DNSA groups showed significantly higher levels of aggressiveness. This finding was also observed in subjects of the PSA and PNSA groups. The level of aggressiveness in males with depression significantly increased over time. In women, increasing levels of aggressiveness across development were only observed in depressed suicide attempters. Limitations of this study included use of semi-structured interview for the assessment of risk factors. We found significant differences in severity and in the pathway of aggressiveness across development between depressive subjects and normal controls. In addition, sex differences regarding level of aggression and suicidal behavior among depressed subjects were found.

EPA-0768 – Validation of the personality and life event (PLE) scale in a spanish population

Introduction There is a lack of accurate screening tools for suicide risk in the patients presenting to emergency departments. The Personality and Life Event (PLE) Scale, a set of the 27 most discriminative items from a collection of questionnaires usually employed in the assessment of suicidal behavior, demostrated an elevated accuracy, sensibility, and specificity in classifying suicide attempters. Objectives To validate the self-administered PLE Scale. Material and methods In order to examine its psychometric properties, the PLE scale was administered to 59 suicide attempters, 48 psychiatric controls, and 69 medical patients attending the Puerta de Hierro emergency department. To examine its reliability, we used: 1) Cronbach's coefficient α to evaluate the internal consistency; 2) test-retest reliability to assess if the scale is stable over time. Interrater reliability is not relevant as the PLE is a self-report. To assess its construct validity, we used some of Beck's Suicide Intent Scale (SIS). All analyses were carried out using SPSS v.20 (Macintosh). Results The most frequent criteria for suicide attempters were item 4 (‘I often feel empty inside’; 88.1%) and 20 (‘I act on impulse’; 79,7%). Mean (± SD) of the PLE Scale in suicide attempters, psychiatric controls, and medical controls was 74.49 (± 32.44), 57.19 (± 29.63), and 17.48 (± 21.15), respectively. The PLE had an acceptable internal consistency (Cronbach's alpha =0,674). Conclusions Our preliminary findings support the reliability, construct validity, and ussefulness of the PLE to identify suicide attempters to those attending to emergency departments.

Mental Pain, Communication Difficulties, and Medically Serious Suicide Attempts: A Case-Control Study

Medical severe suicide attempts (MSSA) are epidemiologically very similar to individuals who complete suicide. Thus the investigation of individuals who have made MSSAs may add to our understanding of the risk factors for completed suicide. The aim of this study was to assess the role of mental pain and communication difficulties in MSSA. A total of 336 subjects were divided into 4 groups: 78 meeting criteria for MSSA compared with116 subjects who made a medically non-serious suicide attempt (MNSSA), 47 psychiatric controls with no history of suicidal behavior, and 95 healthy controls. Mental pain variants (e.g., hopelessness), facets of communication difficulties (e.g., self-disclosure), as well as socio-demographic and clinical characteristics were assessed. The MSSA had significantly higher communication difficulties than the other 3 groups. Moreover, the interaction between mental pain and communication difficulties explained some of the variance in suicide lethality, above and beyond the contribution of each component alone. This report underlines the importance of mental pain for suicide attempts in general while difficulties in communication abilities play a critical role in differentiating MSSA from MNSSA. The co-existence of unbearable mental pain with difficulties in communication significantly enhances the risk for more lethal forms of suicidal behavior.

EPA-0777 – Alexithymia, facial emotion identification and social inference in ed patients: a case-control study

Introduction Alexythimia, reduced cognitive empathy and emotion awareness and understanding are present among individuals with Eating Disorders (EDs). Facial expression is a reliable marker of emotion and an important source of social information. Thus, the ability to judge facial expression is essential for successful interpersonal interactions. Objectives To evaluate alexythimia, facial emotion identification and social inference abilities in a sample of ED patients, compared to a sample of patients with another psychiatric diagnosis and a group of healthy controls, matched by gender and age. Aims To describe a specific pattern of emotional dysregulation in ED patients. Methods ED patients and the Psychiatric Control Group are recruited at the Institute of Psychiatry in Novara, while healthy controls are recruited on a community basis. All patients and controls are females, aged 18–65. All patients are undergoing the Structured Clinical Interview for DSM-IV -Patient version (SCID-I-P), healthy controls are administered the Structured Clinical Interview for DSM-IV – Non Patient version (SCID-I-NP). All subjects are undergoing the following: SCID-II, Eating Disorder Inventory − 3 (EDI-3), Binge Eating Scale (BES), Beck Depression Inventory (BDI), Symptom Checklist − 90 (SCL-90), Facial Emotion Identification Test (FEIT), The Awareness of Social Inference Test (TASIT), Temperament and Character Inventory (TCI), Rosenberg Self-Esteem Scale (RSES), Interpersonal Reactivity Index (IRI), Toronto Alexithymia Scale (TAS-20). Results The recruitment and analysis of the samples are ongoing. The ED sample is expected to show greater alexythimia and a poorer performance at FEIT and TASIT, compared to the control samples. Conclusions Clinical implications will be discussed.

Argyrophilic grain disease as a neurodegenerative substrate in late-onset schizophrenia and delusional disorders

To study the relationship between neurodegenerative diseases including argyrophilic grain disease (AGD) and late-onset schizophrenia and delusional disorders (LOSD; onset ≥40 years of age), we pathologically examined 23 patients with LOSD, 71 age-matched normal controls, and 22 psychiatric disease controls (11 depression, six personality disorder, two bipolar disorders, and three neurotic disorders cases). In all LOSD cases (compared to age-matched normal controls), the frequencies of Lewy body disease (LBD), AGD, and corticobasal degeneration (CBD) were 26.1 % (11.3 %), 21.7 % (8.5 %), and 4.3 % (0.0 %), respectively. There was no case of pure Alzheimer's disease (AD). The total frequency of LBD, AGD, and CBD was significantly higher in LOSD cases than in normal controls. Argyrophilic grains were significantly more severe in LOSD than in controls, but were almost completely restricted to the limbic system and adjacent temporal cortex. In LOSD patients whose onset occurred at ≥65 years of age (versus age-matched normal controls), the frequencies of LBD and AGD were 36.4 % (19.4 %) and 36.4 % (8.3 %), respectively, and AGD was significantly more frequent in LOSD patients than in normal controls. In LOSD patients whose onset occurred at <65 years of age, the frequencies of LBD, AGD, and CBD were 16.7, 8.3, and 8.3 %, comparable to those of age-matched normal controls (10.2, 5.1, and 0.0 %). In all psychiatric cases, delusion was significantly more frequent in AGD cases than in cases bearing minimal AD pathology alone. Given these findings, LOSD patients may have heterogeneous pathological backgrounds, and AGD may be associated with the occurrence of LOSD especially after 65 years of age.

Eating and Weight/Shape Criticism as a Specific Life-Event Related to Bulimia Nervosa: A Case Control Study

ABSTRACT The present study aims to evaluate the occurrence of life events preceding the onset of eating problems in bulimia nervosa patients. A case-control design was used involving the comparison of 60 female subjects who meet DSM-IV criteria for bulimia nervosa with 60 healthy control subjects and 60 subjects with other psychiatric disorders. The RFI (Fairburn et al., 1998) subset of factors that represent exposure to life events in the 12 months immediately before the development of eating problems was used. Women with bulimia nervosa reported higher rates of major stress, criticism about eating, weight and shape and also a great number of antecedent life events during the year preceding the development of eating problems than the healthy control group. However, when compared with the general psychiatric control group only the exposure to critical comments about weight, shape, or eating emerged as a specific trigger for bulimia nervosa. Our findings support the fact that eating and shape/weight criticism in the year preceding the development of eating disturbance seems to be specifically related to bulimia nervosa.

Interaction of common genetic variants in the CRF system predicts the risk of comorbid alcoholism

Stress plays a major role in the development of comorbid alcohol use disorder (AUD). AUD in turn worsens the outcome of psychiatric patients with respect to global disease severity, social situation and thus socioeconomic burden. Prediction of persons at-risk of AUD is crucial for future preventive and therapeutic strategies. We investigated whether genetic variants of the corticotropin-releasing factor (CRH) system or their interaction influence the risk of developing AUD in chronic disease populations. Genotype analysis comprising selected single nucleotide polymorphisms (SNPs) within the CRHR1 and CRHBP genes in patients with schizophrenia and in a non-schizophrenic psychiatric disease control sample should allow extracting predictors of comorbid AUD. Gene expression (mRNA) analysis in peripheral blood mononuclear cells (PBMCs) was performed to gain first mechanistic insight. An ideal set-up for the present study was the GRAS (Göttingen Research Association for Schizophrenia) Data Collection of schizophrenic patients, specifically intended to enable association of genetic information with quantifiable phenotypes in a procedure termed PGAS (phenotype-based genetic association study). A total of 1037 schizophrenic patients (GRAS sample) were included, as well as 80 non-schizophrenic psychiatric disease controls as small replicate sample, and 1141 healthy subjects as case control study. Associations of CRHR1 and CRHBP genotypes were determined with: (1) AUD, (2) a here developed alcoholism severity score (ASS; composed of 5 AUD-relevant variables), and (3) quantitative CRHR1 and CRHBP mRNA expression. We found that an interaction of CRHR1 rs110402 and CRHBP rs3811939 predicts high risk of comorbid AUD in schizophrenic patients (odds ratio [OR]= 2.27; 95% CI, 1.56 – 3.30; p < 0.0001) as well as psychiatric disease controls (OR = 4.02; 95% CI, 0.95 – 17.05; p = 0.059) and leads to the highest CRHR1/CRHBP mRNA ratio (p = 0.021; 'dysbalanced' stress axis). The high predictive value of a genetic interaction within the stress axis for the risk of comorbid AUD may be exploited for novel preventive and individualized therapeutic approaches.