1. To examine structural brain changes in patients with depression measured using voxel based morphometry(VBM) in comparison with healthy subjects.
2. Relation between grey mater volume (GMV) and other structural changes, and the severity of clinical symptoms.
3. To study if there is structural brain difference between psychotic and non-psychotic depression

Depression is a major psychiatric disorder and a leading cause of disability worldwide. The clinical representation encompasses affective, cognitive and somatic complains such as low mood, anxiety, lack of pleasure and interest, disturbances of sleep and appetite, decreased self-esteem, thoughts of guilt, hopelessness, and even suicide.

Major depressive disorder (MDD) with psychotic features (psychotic depression) is a severe disorder with a lifetime prevalence of 0.35-1% .

Over the last decades, increasing evidence from post-mortem studies and in vivo studies emerged that mood disorder can induce structural and morphometric changes of the brain The development of magnetic resonance imaging (MRI) has allowed for more advanced structural imaging

Several structural magnetic resonance imaging (s MRI) studies have identified key brain areas involved in MDD. In particular, voxel-based morphometry (VBM), it is helpful in quantitatively identifying unexpected anatomic changes studies have found that MDD is associated with widespread local brain abnormalities, mainly affecting the frontal gyrus, insula, temporal lobes and anterior cingulate gyrus . Structural white matter alterations have also been reported within the inferior parietal lobule and frontal gyrus .

Many studies are positive about grey matter (GM) volume reductions in various cortical regions in depressed patients compared to healthy controls . The most consistent findings appear to be related to GM loss in medial frontal cortex (MFC), anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) with less evidence about subcortical structures such as the amygdala and the hippocampus .

Inclusion Criteria:

1. Age 18-60 years old.
2. Based on DSM5 Criteria: MDD with or without psychotic features.

Exclusion Criteria:

1 • Patients under 18 years old or above 60

2• Pregnant or lactating women.

3• Other current or past major psychiatric disorders

4• History or concurrent neurological disease(seizures) or prior head trauma with evidence of consequent cognitive impairment.

5• First degree family history of schizophrenia if the participant is less than 33 years old (mean age of onset of schizophrenia plus two standard deviations) to exclude possible prodromal phase of schizophrenia.

6• Unstable medical condition (i.e., any active illness that may affect the brain as blood dyscrasis, lymphomas, endocrinopathies, renal failure, chronic obstructive lung disease, systemic autoimmune disorders or Malignancy).

7• Patients being treated with steroids or hormonal therapy .

8• Current substances or alcohol use disorders (past diagnosis allowed if in remission for more than 6 months

9• Contraindications for MRI as:

• Metal implants or paramagnetic objects contained within the body (including heart pacemaker or surgical prosthesis)

• Claustrophobia significant enough to interfere with MRI

  10• Refusal of informed consent

The study included two groups:

Group (A): patients' group diagnosed with major depressive disorder (MDD) which include (44) patients aged 18-60 years' old who attended psychiatric outpatient's clinic and who is admitted in psychiatric unit of Assiut university hospitals. This group is further subdivided according to DSM 5 Criteria into 2 subgroups: Major depression with psychotic disorder and Major depression without psychotic disorder.

Group (B): control group which consists of (22) healthy cross matching individuals.